2022/05/08 更新

写真a

ヒラサワ アキラ
平沢 晃
HIRASAWA Akira
所属
医歯薬学域 教授
職名
教授
外部リンク

学位

  • 博士(医学) ( 2004年3月   慶應義塾大学 )

研究分野

  • ライフサイエンス / システムゲノム科学

  • ライフサイエンス / 腫瘍診断、治療学

  • ライフサイエンス / 腫瘍生物学

学歴

  • 慶應義塾大学大学院   医学研究科博士課程  

    - 2004年3月

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  • 慶應義塾大学   School of Medicine  

    1989年4月 - 1995年3月

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経歴

  • 岡山大学大学院医歯薬学総合研究科 病態制御科学専攻 腫瘍制御学講座 (臨床遺伝子医療学分野)   教授

    2018年6月 - 現在

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  • 慶應義塾大学医学部産婦人科 専任講師

    2015年4月

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  • 日本学術振興会二国間交流事業オープンパートナーシップ共同研究 日本側研究代表者, Institute for Molecular Medicine Finland, Senior Researcher (フィンランドアカデミー)

    2014年7月

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  • 慶應義塾大学医学部産婦人科 特任講師

    2013年1月

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  • 日本学術振興会 特定国派遣研究者事業 平成24年度特定国派遣研究者 Institute for Molecular Medicine Finland, visiting researcher

    2012年4月

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  • 日本学術振興会 組織的な若手研究者等海外派遣プログラムInstitute for Molecular Medicine Finland, 日本学術振興会 組織的な若手研究者等海外派遣プログラム Institute for Molecular Medicine Finland, visiting researcher

    2011年10月

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  • 慶應義塾大学医学部臨床遺伝学センター センター員(併任)

    2011年8月

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  • 慶應義塾大学医学部産婦人科学助教(助手)・診療医長(婦人科)

    2005年9月

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  • 独立行政法人国立病院機構東京医療センター(産婦人科)

    2004年4月 - 2005年8月

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  • 栃木県立がんセンター研究所(研修医)

    2002年7月

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  • 東京医科歯科大学難治疾患研究所遺伝疾患研究部門 (分子細胞遺伝)共同研究者

    2000年6月

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  • 慶應義塾大学医学部助手(専修医)

    1999年11月 - 2004年3月

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  • 芳賀赤十字病院(産婦人科)

    1999年9月 - 1999年10月

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  • 慶應義塾大学医学部助手(専修医)(産婦人科学)

    1998年6月 - 1999年8月

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  • 大田原赤十字病院(産婦人科)

    1997年6月 - 1998年5月

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  • 国立埼玉病院(産婦人科)

    1996年6月 - 1997年5月

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  • 慶應義塾大学医学部研修医(産婦人科)

    1995年5月 - 1996年5月

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所属学協会

  • 日本女性医学学会

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  • 日本臨床薬理学会

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  • 日本人類遺伝学会

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  • 日本癌治療学会

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  • 日本婦人科腫瘍学会

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  • 日本臨床腫瘍学会

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  • 日本臨床細胞学会

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  • 日本産婦人科乳腺医学会

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  • 日本遺伝性腫瘍学会

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  • 一般社団法人日本遺伝性乳癌卵巣癌総合診療制度機構

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  • 日本医療安全学会

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  • 日本遺伝カウンセリング学会

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  • 日本遺伝子診療学会

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  • 日本産科婦人科遺伝診療学会

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  • Ovarian Cancer Association Consortium (OCAC)

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  • Asian Society of Gynecologic Oncology

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  • Taiwan Precision Medicine Society

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  • Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

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  • European Society of Human Genetics

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  • American Society of Human Genetics

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  • 日本癌学会

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  • 日本産科婦人科学会

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  • American Association for Cancer Research

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委員歴

  • 厚生労働省   がんゲノム医療中核拠点病院等の指定要件に関するワーキンググループ 構成員  

    2021年12月   

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    団体区分:政府

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  • 日本学術会議   連携会員  

    2020年10月   

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  • 一般社団法人日本遺伝性乳癌卵巣癌総合診療制度機構   理事・広報部会長  

    2020年6月   

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  • 日本婦人科腫瘍学会   がんゲノム医療、HBOC診療の適正化に関するWG委員  

    2020年6月   

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  • HBOC診療ガイドライン作成委員   遺伝診断・遺伝カウンセリング 領域リーダー  

    2020年3月   

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  • 日本癌学会   評議員  

    2020年1月   

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  • 日本産科婦人科学会   PGT-Mに関する倫理審議会 委員  

    2019年12月   

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  • 日本産科婦人科遺伝診療学会   理事  

    2019年12月   

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  • 日本人類遺伝学会   理事  

    2019年10月   

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  • 日本婦人科腫瘍学会   卵巣がん治療ガイドライン2020年版評価委員  

    2019年5月   

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  • 日本遺伝カウンセリング学会   倫理問題検討委員会 委員  

    2019年4月   

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  • 日本遺伝カウンセリング学会   遺伝学的検査委員会 委員  

    2019年4月   

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  • 成人・小児進行固形がんにおける臓器横断的ゲノム診療のガイドライン   作成委員  

    2019年4月   

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  • クリニカルバイオバンク学会   理事  

    2019年3月   

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  • 日本臨床薬理学会   指導医  

    2018年10月   

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  • 全国遺伝子医療部門連絡会議   理事  

    2018年10月   

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  • 日本家族性腫瘍学会 (現 日本遺伝性腫瘍学会)   学術・教育委員会 委員長  

    2018年6月   

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  • 厚生労働科学研究費補助金(がん対策推進総合研究事業) 「希少癌診療ガイドラインの作成を通した医療提供体制の質向上」「進行固形腫瘍患者におけるDNAミスマッチ修復機能欠損検査ガイドライン作成プロジェクト」   プロジェクトメンバー  

    2018年1月   

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  • 日本家族性腫瘍学会(現 日本遺伝性腫瘍学会)   家族性腫瘍指導医(現 遺伝性腫瘍指導医)  

    2017年10月   

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  • 日本婦人科腫瘍学会   修練カリキュラム・教育プログラム改訂委員  

    2017年9月   

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  • 日本婦人科腫瘍学会   PARP阻害薬使用における遺伝学的検査の実施体制等に関する検討委員会  

    2017年9月   

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  • 日本産科婦人科遺伝診療学会   認定制度ワーキンググループ  

    2017年4月   

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  • 日本家族性腫瘍学会   学術・教育委員会委員  

    2017年4月   

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  • Ovarian Cancer Association Consortium (OCAC)   委員  

    2017年1月   

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  • 日本婦人科腫瘍学会   査読委員  

    2016年8月   

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  • 日本家族性腫瘍学会   編集委員会委員  

    2016年6月   

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  • 遺伝性乳癌卵巣癌症候群診療の手引き(厚生労働科研 がん対策推進総合研究事業「わが国における遺伝性乳癌卵巣癌の臨床遺伝学的特徴の解明と遺伝子情報を用いた生命予後の改善に関する研究」研究班)   作製委員  

    2016年6月   

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  • 日本遺伝性腫瘍学会   評議員  

    2016年6月   

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  • ホルモン補充療法ガイドライン2017年度版   作成委員  

    2016年4月   

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  • Taiwan Precision Medicine Society   Honor board member  

    2015年12月   

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  • 日本女性医学学会   代議員  

    2015年11月   

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  • 日本人類遺伝学会   評議員  

    2015年10月   

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  • 遺伝性大腸癌診療ガイドライン   作成委員  

    2015年9月   

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  • 日本産科婦人科遺伝診療学会   幹事  

    2015年7月   

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  • Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)   委員  

    2015年7月   

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  • 日本産科婦人科学会 婦人科腫瘍委員会 遺伝性乳癌卵巣癌(HBOC)の啓発および取り扱い小委員会   委員  

    2015年4月   

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  • 東京産科婦人科学会   評議員  

    2015年4月   

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  • 日本産科婦人科学会ガイドライン婦人科外来編 ガイドライン   作成員  

    2014年11月   

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  • 日本HBOCコンソーシアム   評議員  

    2013年1月   

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  • 日本婦人科腫瘍学会 婦人科腫瘍   専門医  

    2013年1月   

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  • 日本女性医学学会   認定医  

    2011年10月   

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    団体区分:学協会

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  • 日本がん治療認定医機構   がん治療認定医  

    2009年3月   

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    団体区分:その他

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  • 日本がん治療認定医機構   暫定教育医  

    2007年8月   

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    団体区分:その他

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  • 日本臨床細胞学会   評議員  

    2007年4月   

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    団体区分:学協会

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  • 日本産科婦人科学会東京地方部会   編集幹事  

    2006年4月 - 2011年8月   

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    団体区分:学協会

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  • 日本婦人科腫瘍学会   評議員  

    2006年4月   

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    団体区分:学協会

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  • 日本人類遺伝学会   臨床遺伝専門医制度専門医  

    2004年12月   

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    団体区分:学協会

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  • 日本臨床細胞学会   細胞診専門医  

    2003年12月   

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    団体区分:学協会

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  • 日本産科婦人科学会   専門医  

    2000年10月   

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    団体区分:学協会

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論文

  • Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey. 国際誌

    Akari Minamoto, Takahiro Yamada, Saki Shimada, Ichiro Kinoshita, Yoko Aoki, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

    Journal of human genetics   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.

    DOI: 10.1038/s10038-022-01028-x

    PubMed

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  • Hemothorax and Bloody Ascites Caused by Vascular Ehlers-Danlos Syndrome. 国際誌

    Shuichi Tanaka, Hiroyuki Honda, Kou Hasegawa, Koji Tomita, Reimi Sogawa, Hideki Yamamoto, Takao Hiraki, Akira Hirasawa, Fumio Otsuka

    The American journal of medicine   2022年3月

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  • Hereditary gynecologic tumors and precision cancer medicine. 国際誌

    Chikako Ogawa, Akira Hirasawa, Naoyuki Ida, Keiichiro Nakamura, Hisashi Masuyama

    The journal of obstetrics and gynaecology research   48 ( 5 )   1076 - 1090   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.

    DOI: 10.1111/jog.15197

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  • ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors. 国際誌

    Sayaka Ueno, Tamotsu Sudo, Akira Hirasawa

    International journal of molecular sciences   23 ( 1 )   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.

    DOI: 10.3390/ijms23010523

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  • Homologous Recombination Deficiencies and Hereditary Tumors. 国際誌

    Hideki Yamamoto, Akira Hirasawa

    International journal of molecular sciences   23 ( 1 )   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor.

    DOI: 10.3390/ijms23010348

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  • Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report. 国際誌

    Mashu Futagawa, Hideki Yamamoto, Mariko Kochi, Yusaku Urakawa, Reimi Sogawa, Fumino Kato, Mika Okazawa-Sakai, Daisuke Ennishi, Katsunori Shinozaki, Hirofumi Inoue, Hiroyuki Yanai, Akira Hirasawa

    Hereditary cancer in clinical practice   19 ( 1 )   48 - 48   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. CASE PRESENTATION: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. CONCLUSIONS: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.

    DOI: 10.1186/s13053-021-00205-x

    PubMed

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  • MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma. 国際誌

    Eun Young Kang, Joshua Millstein, Gordana Popovic, Nicola S Meagher, Adelyn Bolithon, Aline Talhouk, Derek S Chiu, Michael S Anglesio, Betty Leung, Katrina Tang, Neil Lambie, Marina Pavanello, Annalyn Da-Anoy, Diether Lambrechts, Liselore Loverix, Siel Olbrecht, Christiani Bisinotto, Jesus Garcia-Donas, Sergio Ruiz-Llorente, Monica Yagüe-Fernandez, Robert P Edwards, Esther Elishaev, Alexander Olawaiye, Sarah Taylor, Beyhan Ataseven, Andreas du Bois, Philipp Harter, Jenny Lester, Claus K Høgdall, Sebastian M Armasu, Yajue Huang, Robert A Vierkant, Chen Wang, Stacey J Winham, Sabine Heublein, Felix K F Kommoss, Daniel W Cramer, Naoko Sasamoto, Lilian van-Wagensveld, Maria Lycke, Constantina Mateoiu, Janine Joseph, Malcolm C Pike, Kunle Odunsi, Chiu-Chen Tseng, Celeste L Pearce, Sanela Bilic, Thomas P Conrads, Arndt Hartmann, Alexander Hein, Michael E Jones, Yee Leung, Matthias W Beckmann, Matthias Ruebner, Minouk J Schoemaker, Kathryn L Terry, Mona A El-Bahrawy, Penny Coulson, John L Etter, Katherine LaVigne-Mager, Juergen Andress, Marcel Grube, Anna Fischer, Nina Neudeck, Greg Robertson, Rhonda Farrell, Ellen Barlow, Carmel Quinn, Anusha Hettiaratchi, Yovanni Casablanca, Ramona Erber, Colin J R Stewart, Adeline Tan, Yu Yu, Jessica Boros, Alison H Brand, Paul R Harnett, Catherine J Kennedy, Nikilyn Nevins, Terry Morgan, Peter A Fasching, Ignace Vergote, Anthony J Swerdlow, Francisco J Candido Dos Reis, G Larry Maxwell, Susan L Neuhausen, Arantzazu Barquin-Garcia, Francesmary Modugno, Kirsten B Moysich, Philip J Crowe, Akira Hirasawa, Florian Heitz, Beth Y Karlan, Ellen L Goode, Peter Sinn, Hugo M Horlings, Estrid Høgdall, Karin Sundfeldt, Stefan Kommoss, Annette Staebler, Anna H Wu, Paul A Cohen, Anna DeFazio, Cheng-Han Lee, Helen Steed, Nhu D Le, Simon A Gayther, Kate Lawrenson, Paul D P Pharoah, Gottfried Konecny, Linda S Cook, Susan J Ramus, Linda E Kelemen, Martin Köbel

    Virchows Archiv : an international journal of pathology   480 ( 4 )   855 - 871   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

    DOI: 10.1007/s00428-021-03232-0

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  • Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients.

    Naomi Iwasa-Inoue, Hiroyuki Nomura, Fumio Kataoka, Tatsuyuki Chiyoda, Tomoko Yoshihama, Yoshiko Nanki, Kensuke Sakai, Yusuke Kobayashi, Wataru Yamagami, Tohru Morisada, Akira Hirasawa, Daisuke Aoki

    International journal of clinical oncology   27 ( 2 )   441 - 447   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. METHODS: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III-IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. RESULTS: Twenty-four patients were included in this study. The median age was 55.5 years (37-80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7-92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. CONCLUSIONS: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

    DOI: 10.1007/s10147-021-02050-3

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  • Hereditary pancreatic cancer.

    Kodai Abe, Minoru Kitago, Yuko Kitagawa, Akira Hirasawa

    International journal of clinical oncology   26 ( 10 )   1784 - 1792   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

    DOI: 10.1007/s10147-021-02015-6

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  • Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger.

    Takeshi Makabe, Wataru Yamagami, Akira Hirasawa, Izumi Miyabe, Tomokazu Wakatsuki, Mari Kikuchi, Akemi Takahashi, Junko Noda, Go Yamamoto, Daisuke Aoki, Kiwamu Akagi

    International journal of clinical oncology   26 ( 9 )   1767 - 1774   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    [Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

    DOI: 10.1007/s10147-021-01953-5

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  • Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report. 国際誌

    Kohei Taniguchi, Hiroyuki Yanai, Tatsuya Kaji, Toshio Kubo, Daisuke Ennishi, Akira Hirasawa, Tadashi Yoshino

    Journal of cutaneous pathology   48 ( 8 )   1069 - 1074   2021年8月

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    記述言語:英語  

    Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.

    DOI: 10.1111/cup.14028

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  • Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer.

    Naohiro Tomita, Hideyuki Ishida, Kohji Tanakaya, Tatsuro Yamaguchi, Kensuke Kumamoto, Toshiaki Tanaka, Takao Hinoi, Yasuyuki Miyakura, Hirotoshi Hasegawa, Tetsuji Takayama, Hideki Ishikawa, Takeshi Nakajima, Akiko Chino, Hideki Shimodaira, Akira Hirasawa, Yoshiko Nakayama, Shigeki Sekine, Kazuo Tamura, Kiwamu Akagi, Yuko Kawasaki, Hirotoshi Kobayashi, Masami Arai, Michio Itabashi, Yojiro Hashiguchi, Kenichi Sugihara

    International journal of clinical oncology   26 ( 8 )   1353 - 1419   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.

    DOI: 10.1007/s10147-021-01881-4

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  • Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling. 国際誌

    Arisa Ueki, Kokichi Sugano, Kumiko Misu, Eriko Aimono, Kohei Nakamura, Shigeki Tanishima, Nobuyuki Tanaka, Shuji Mikami, Akira Hirasawa, Miho Ando, Teruhiko Yoshida, Mototsugu Oya, Hiroshi Nishihara, Kenjiro Kosaki

    International journal of molecular sciences   22 ( 15 )   2021年7月

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    記述言語:英語  

    Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.

    DOI: 10.3390/ijms22157962

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  • Preclinical diagnosis and identification of the chimeric CYP11B1/CYP11B2 gene in two pediatric cases of a Japanese family with glucocorticoid-remediable aldosteronism. 国際誌

    Yasuhiro Nakano, Nahoko Iwata, Kanako Ogura-Ochi, Kosei Hasegawa, Akira Hirasawa, Fumio Otsuka

    Hypertension research : official journal of the Japanese Society of Hypertension   44 ( 7 )   891 - 893   2021年7月

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  • SMAD4 Germline Pathogenic Variant-Related Gastric Juvenile Polyposis with Adenocarcinoma Treated with Laparoscopic Total Gastrectomy: A Case Report. 国際誌

    Yuya Sakurai, Satoru Kikuchi, Kunitoshi Shigeyasu, Yoshihiko Kakiuchi, Takehiro Tanaka, Hibiki Umeda, Masaki Sakamoto, Sho Takeda, Shuya Yano, Mashu Futagawa, Fumino Kato, Reimi Sogawa, Hideki Yamamoto, Shinji Kuroda, Yoshitaka Kondo, Fuminori Teraishi, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Akira Hirasawa, Toshiyoshi Fujiwara

    The American journal of case reports   22   e932241   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

    DOI: 10.12659/AJCR.932241

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  • Best practices for the extraction of genomic DNA from formalin-fixed paraffin-embedded tumor tissue for cancer genomic profiling tests. 国際誌

    Hirofumi Inoue, Shuta Tomida, Shigeru Horiguchi, Hironari Kato, Hiromi Matsuoka, Etsuko Sanehira, Masashi Matsuoka, Hiroyuki Yanai, Akira Hirasawa, Shinichi Toyooka

    Pathology international   71 ( 5 )   360 - 364   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recently, two cancer genomic profiling tests have been approved in Japan and implemented in routine clinical practice: the FDA-approved FoundationOne CDx test, and the OncoGuide NCC Oncopanel test. The quality and quantity of DNA significantly affects the sequencing results; therefore, preparing a sufficient amount of high-quality DNA for clinical cancer genomic profiling tests is important. We examined the best practices for the extraction of cancer genomic DNA from formalin-fixed paraffin-embedded (FFPE) tumor tissues of pancreatic, lung and colon cancer specimens. We found that the quality of cancer genomic DNA extracted from 10-μm-thick FFPE samples improved significantly, compared with that from 4-μm-thick FFPE samples, suggesting that 10-μm-thick FFPE samples are preferable for clinical cancer genomic profiling tests. For convenience, we created a quick reference table for calculating the required number of FFPE slides.

    DOI: 10.1111/pin.13086

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  • 遺伝性平滑筋腫症-腎細胞癌症候群関連腎細胞癌の術後骨転移に対してイピリムマブ・ニボルマブ併用療法が有効であった1例

    渡部 智文, 榮枝 一磨, 津川 昌也, 関戸 崇了, 富永 悠介, 高本 篤, 定平 卓也, 小林 泰之, 荒木 元朗, 渡邉 豊彦, 小田 和歌子, 黒田 直人, 十川 麗美, 山本 英喜, 平沢 晃, 那須 保友

    西日本泌尿器科   83 ( 1 )   31 - 36   2021年4月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    症例は45歳,男性。X-1年9月に肉眼的血尿と右腰痛を主訴に当院を受診し,単純CTで右腎上極に長径5cm大の腫瘤を認めた。腹部造影CTでは動脈相で早期濃染,後期相でwashout patternを伴う内部不整な腫瘤を同部位に認めたが,明らかなリンパ節・他臓器転移を認めなかった。右腎癌cT1bN0M0 Stage Iと診断し,同年10月に腹腔鏡下右腎摘除術を施行した。病理所見は,腫瘍細胞は淡明細胞や好酸性細胞が乳頭状・管状の構造を取り,細胞質に好酸性の核小体および核周囲明庭を認めた。Fumarate hydratase(FH)免疫染色陰性でFH欠損腎細胞癌と診断した。術後2ヵ月で多発骨転移を認め,International Metastatic RCC Database Consortium(IMDC) intermediate riskと判断し,イピリムマブ・ニボルマブ併用療法を開始した。4コース施行後,CT上新規の転移巣や転移巣の増大を認めなかった。遺伝学的検査でFH遺伝子の病的バリアントを認め,腎細胞癌の家族歴と合わせ,遺伝性平滑筋腫症-腎細胞癌症候群(hereditary leiomyomatosis and renal cell carcinoma syndrome;HLRCC)関連腎細胞癌と診断した。現在ニボルマブ単剤投与を継続中で,骨転移増悪や新規遠隔転移は認めていない。(著者抄録)

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  • Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome 国際誌

    Tomoko Yoshihama, Akira Hirasawa, Kokichi Sugano, Teruhiko Yoshida, Mineko Ushiama, Arisa Ueki, Tomoko Akahane, Yoshiko Nanki, Kensuke Sakai, Takeshi Makabe, Wataru Yamagami, Nobuyuki Susumu, Kaori Kameyama, Kenjiro Kosaki, Daisuke Aoki

    International Cancer Conference Journal   10 ( 1 )   6 - 10   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a <italic>BRCA2</italic> pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic <italic>BRCA2</italic> variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer.

    DOI: 10.1007/s13691-020-00449-9

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    その他リンク: http://link.springer.com/article/10.1007/s13691-020-00449-9/fulltext.html

  • 最新産婦人科遺伝診療ABC 10.婦人科腫瘍領域における遺伝診療総論

    坂井美佳, 坂井美佳, 竹原和宏, 平沢晃

    産科と婦人科   88 ( 1 )   65 - 72   2021年

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    担当区分:責任著者   記述言語:日本語   出版者・発行元:(株)診断と治療社  

    遺伝性乳がん卵巣がん症候群(HBOC)やLynch症候群を代表とする遺伝性腫瘍は婦人科腫瘍とのかかわりが深い。特にごく最近では2019年のBRCA1/2遺伝学的検査のコンパニオン診断とがんゲノム医療の保険診療化、そして2020年4月のHBOC診療の一部保険診療化に伴い、産婦人科医にとって遺伝性腫瘍の知識は不可欠なものとなっている。個々の遺伝情報を知ることは、がん治療および予防の観点から有用性が高い。(著者抄録)

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  • Molecular Features and Clinical Management of Hereditary Gynecological Cancers. 国際誌

    Arisa Ueki, Akira Hirasawa

    International journal of molecular sciences   21 ( 24 )   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.

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  • Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan 国際誌

    Mio Tsuchiya, Takahiro Yamada, Rina Akaishi, Haruka Hamanoue, Akira Hirasawa, Maki Hyodo, Issei Imoto, Tomoki Kosho, Kenji Kurosawa, Hiromi Murakami, Kaname Nakatani, Fumio Nomura, Aiko Sasaki, Kenji Shimizu, Mariko Tamai, Hiroshi Umemura, Atsushi Watanabe, Akiko Yoshida, Hiroshi Yoshihashi, Junko Yotsumoto, Shinji Kosugi

    JOURNAL OF HUMAN GENETICS   65 ( 12 )   1045 - 1053   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGERNATURE  

    The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

    DOI: 10.1038/s10038-020-0802-2

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  • Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution. 国際誌

    Yusuke Kobayashi, Akira Hirasawa, Tatsuyuki Chiyoda, Arisa Ueki, Kenta Masuda, Kumiko Misu, Miho Kawaida, Shigenori Hayashi, Fumio Kataoka, Kouji Banno, Kenjiro Kosaki, Daisuke Aoki

    Japanese journal of clinical oncology   51 ( 2 )   213 - 217   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS: To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS: The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS: Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

    DOI: 10.1093/jjco/hyaa173

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  • Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing. 国際誌

    Yoshiko Nanki, Tatsuyuki Chiyoda, Akira Hirasawa, Aki Ookubo, Manabu Itoh, Masaru Ueno, Tomoko Akahane, Kaori Kameyama, Wataru Yamagami, Fumio Kataoka, Daisuke Aoki

    Scientific reports   10 ( 1 )   12581 - 12581   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.

    DOI: 10.1038/s41598-020-69488-9

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  • Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology.

    Yoichi Naito, Saori Mishima, Kiwamu Akagi, Ataru Igarashi, Masafumi Ikeda, Susumu Okano, Shunsuke Kato, Tadao Takano, Katsuya Tsuchihara, Keita Terashima, Hiroshi Nishihara, Hiroyki Nishiyama, Eiso Hiyama, Akira Hirasawa, Hajime Hosoi, Osamu Maeda, Yasushi Yatabe, Wataru Okamoto, Shigeru Ono, Hiroaki Kajiyama, Fumio Nagashima, Yutaka Hatanaka, Mitsuru Miyachi, Yasuhiro Kodera, Takayuki Yoshino, Hiroya Taniguchi

    International journal of clinical oncology   25 ( 3 )   403 - 417   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we published provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors. Recently, efficacy of tropomyosin receptor kinase inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors have been established as the second tumor-agnostic treatment, making it necessary to develop the guideline prioritized for these patients. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO) and Japanese Society of Medical Oncology (JSMO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and Japanese Society of Pediatric Hematology/Oncology, and the public comments among all Societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 15 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: In the NTRK guideline, the committee proposed 15 recommendations for performing NTRK testing properly to select patients who are likely to benefit from tropomyosin receptor kinase inhibitors.

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  • Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition. 査読

    Saori Mishima, Hiroya Taniguchi, Kiwamu Akagi, Eishi Baba, Yutaka Fujiwara, Akira Hirasawa, Masafumi Ikeda, Osamu Maeda, Kei Muro, Hiroshi Nishihara, Hiroyki Nishiyama, Tadao Takano, Katsuya Tsuchihara, Yasushi Yatabe, Yasuhiro Kodera, Takayuki Yoshino

    International journal of clinical oncology   25 ( 2 )   217 - 239   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Novel therapeutic agents have improved survival outcomes in patients with advanced solid tumors. In parallel, the development of predictive biomarkers to identify patients who are likely to benefit from a certain treatment has also contributed to the improvement of survival. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. METHODS: Clinical questions (CQs) regarding medical care were formulated for patients with dMMR advanced solid tumors, and evidence to the CQs was collected by manual search to prepare recommendations. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors. RESULTS: The current guideline, which we consider a provisional clinical opinion at this point, describes the 11 requirements to be considered in terms of patients for whom dMMR testing is recommended, the timing and methods of dMMR testing, and clinical care systems required to perform dMMR testing properly and to administer immune checkpoint inhibitors safely. CONCLUSION: This provisional clinical opinion proposes the requirements for performing dMMR testing properly to select patients who are likely to benefit from immune checkpoint inhibitors and administering them safely.

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  • 多発小腸GISTに対し手術を施行した神経線維腫症1型の1例 査読

    母里 淑子, 重安 邦俊, 吉岡 貴裕, 永坂 岳司, 原賀 順子, 香川 俊輔, 寺石 文則, 豊岡 伸一, 平沢 晃, 藤原 俊義

    家族性腫瘍   19 ( 2 )   77 - 82   2020年2月

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    記述言語:日本語   出版者・発行元:日本家族性腫瘍学会  

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  • Identification of a novel uterine leiomyoma GWAS locus in a Japanese population. 国際誌

    Kensuke Sakai, Chizu Tanikawa, Akira Hirasawa, Tatsuyuki Chiyoda, Wataru Yamagami, Fumio Kataoka, Nobuyuki Susumu, Chikashi Terao, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Michiaki Kubo, Nobuo Fuse, Takako Takai-Igarashi, Atsushi Shimizu, Akimune Fukushima, Aya Kadota, Kokichi Arisawa, Hiroaki Ikezaki, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Daisuke Aoki, Koichi Matsuda

    Scientific reports   10 ( 1 )   1197 - 1197   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10-25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.

    DOI: 10.1038/s41598-020-58066-8

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  • Establishment and characterization of a new malignant peritoneal mesothelioma cell line, KOG-1, from the ascitic fluid of a patient with pemetrexed chemotherapy resistance.

    Tomoko Akahane, Akira Hirasawa, Issei Imoto, Aki Okubo, Manabu Itoh, Yoshiko Nanki, Tomoko Yoshihama, Eichiro Tominaga, Daisuke Aoki

    Human cell   33 ( 1 )   272 - 282   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Malignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time was 13.7 h. Karyotypic and molecular genetic analyses showed that chromosome numbers ranged from 62 to 142, with a peak of 73 with complicated copy number alterations. No germline BAP1 pathogenic variant was detected. Cells expressed various tumor markers of mesothelioma, such as calretinin, podoplanin, and Wilms tumor 1 (WT-1). Drug sensitivity and resistance testing with a set of 36 drugs using 2D and three-dimensional (3D) culture models demonstrated that KOG-1 cells showed high and low sensitivity to pemetrexed under 2D and 3D culture conditions, respectively, whereas control ovarian cancer cell lines showed low sensitivity to pemetrexed under both culture conditions. This newly established cell line will be a valuable biological resource to expand the feasibility of functional studies as well as drug testing for potential therapeutic purposes in MPeM.

    DOI: 10.1007/s13577-019-00286-w

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  • Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome. 国際誌

    Tomoko Kaneyasu, Seiichi Mori, Hideko Yamauchi, Shozo Ohsumi, Shinji Ohno, Daisuke Aoki, Shinichi Baba, Junko Kawano, Yoshio Miki, Naomichi Matsumoto, Masao Nagasaki, Reiko Yoshida, Sadako Akashi-Tanaka, Takuji Iwase, Dai Kitagawa, Kenta Masuda, Akira Hirasawa, Masami Arai, Junko Takei, Yoshimi Ide, Osamu Gotoh, Noriko Yaguchi, Mitsuyo Nishi, Keika Kaneko, Yumi Matsuyama, Megumi Okawa, Misato Suzuki, Aya Nezu, Shiro Yokoyama, Sayuri Amino, Mayuko Inuzuka, Tetsuo Noda, Seigo Nakamura

    NPJ breast cancer   6   25 - 25   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.

    DOI: 10.1038/s41523-020-0163-1

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  • ゲノム医療におけるデータサイエンティストの役割と育成

    冨田秀太, 森田瑞樹, 山下範之, 平沢晃, 豊岡伸一

    薬学雑誌(Web)   140 ( 5 )   657 - 661   2020年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1248/yakushi.19-00217-2

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  • DV200 Index for Assessing RNA Integrity in Next-Generation Sequencing. 国際誌

    Takehiro Matsubara, Junichi Soh, Mizuki Morita, Takahiro Uwabo, Shuta Tomida, Toshiyoshi Fujiwara, Susumu Kanazawa, Shinichi Toyooka, Akira Hirasawa

    BioMed research international   2020   9349132 - 9349132   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Poor quality of biological samples will result in an inaccurate analysis of next-generation sequencing (NGS). Therefore, methods to accurately evaluate sample integrity are needed. Among methods for evaluating RNA quality, the RNA integrity number equivalent (RINe) is widely used, whereas the DV200, which evaluates the percentage of fragments of >200 nucleotides, is also used as a quality assessment standard. In this study, we compared the RINe and DV200 RNA quality indexes to determine the most suitable RNA index for the NGS analysis. Seventy-one RNA samples were extracted from formalin-fixed paraffin-embedded tissue samples (n = 30), fresh-frozen samples (n = 25), or cell lines (n = 16). After assessing RNA quality using the RINe and DV200, we prepared two kinds of stranded mRNA sequencing libraries. Finally, we calculated the correlation between each RNA quality index and the amount of library product (1st PCR product per input RNA). The DV200 measure showed stronger correlation with the amount of library product than the RINe (R2 = 0.8208 for the DV200 versus 0.6927 for the RINe). Receiver operating characteristic curve analyses revealed that the DV200 was the better marker for predicting efficient library production than the RINe using a threshold of >10 ng/ng for the amount of the 1st PCR product per input RNA (cutoff value for the RINe and DV200, 2.3 and 66.1%; area under the curve, 0.99 and 0.91; sensitivity, 82% and 92%; and specificity, 93% and 100%, respectively). Our results indicate that NGS libraries prepared using RNA samples with the DV200 value > 66.1% exhibit greater sensitivity and specificity than those prepared with the RINe values > 2.3. These findings suggest that the DV200 is superior to the RINe, especially for low-quality RNA, because it is a more consistent assessment of the amount of the 1st NGS library product per input.

    DOI: 10.1155/2020/9349132

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  • PALB2およびNBNの病的バリアントを認めた家族生膵癌家系の一例 査読 国際誌

    阿部紘大, 植木有紗, 浦川優作, 北郷実, 吉浜智子, 南木佳子, 北川雄光, 青木大輔, 小崎健次郎, 平沢晃

    日本癌学会学術総会抄録集(Web)   79th ( 1 )   5 - 5   2020年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s13053-020-00160-z

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    その他リンク: http://link.springer.com/article/10.1186/s13053-020-00160-z/fulltext.html

  • がんゲノム医療と実地臨床での課題

    平沢 晃

    日本婦人科腫瘍学会雑誌   37 ( 4 )   666 - 667   2019年10月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • BRCA1/2遺伝子バリアントとがん発症・臨床病理学的特徴および発症リスク因子を明らかにするための卵巣がん未発症を対象としたバイオバンク・コホート研究(JGOG3024)

    平沢 晃

    第17回婦人科悪性腫瘍研究機構年次会議(総会)記録集   18th   67 - 69   2019年8月

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    記述言語:日本語  

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  • Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer. 国際誌

    Takeshi Makabe, Eri Arai, Takuro Hirano, Nanako Ito, Yukihiro Fukamachi, Yoriko Takahashi, Akira Hirasawa, Wataru Yamagami, Nobuyuki Susumu, Daisuke Aoki, Yae Kanai

    Carcinogenesis   40 ( 5 )   611 - 623   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among 'transcriptional factors'. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

    DOI: 10.1093/carcin/bgz046

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  • 遺伝子情報を用いた遺伝性乳癌卵巣癌の予防と治療 査読

    平沢 晃

    病理と臨床   37 ( 6 )   522 - 527   2019年6月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • 女性がんの化学予防 査読

    平沢 晃

    産科と婦人科 増刊号   86 ( Suppl. )   350 - 353   2019年4月

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

    <POINT!>◆遺伝性腫瘍関連遺伝子の病的バリアント保持者に対して、がん一次予防として化学予防が選択肢とされることがある。◆BRCA1/2病的バリアント保持者に対する現時点で提唱されている確実ながん予防法はリスク低減卵管卵巣摘出術(RRSO)である。◆低用量経口避妊薬は卵巣癌予防効果があり、RRSOを選択しないBRCA1/2病的バリアント保持者に対しては卵巣癌一次予防法の選択肢となり得る。(著者抄録)

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  • Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2017 edition. 国際誌

    Ryuji Kawaguchi, Koji Matsumoto, Shigeo Akira, Ken Ishitani, Kazuhiro Iwasaku, Yutaka Ueda, Ryugo Okagaki, Hiroya Okano, Toshimichi Oki, Kaori Koga, Michiko Kido, Takumi Kurabayashi, Yasushi Kuribayashi, Yuichi Sato, Kaori Shiina, Yasushi Takai, Satoshi Tanimura, Osamu Chaki, Masakazu Terauchi, Yukiharu Todo, Yasuyuki Noguchi, Sayaka Nose-Ogura, Tsukasa Baba, Akira Hirasawa, Takuma Fujii, Tsuneo Fujii, Tetsuo Maruyama, Etsuko Miyagi, Kaoru Yanagida, Osamu Yoshino, Mitsutoshi Iwashita, Tsugio Maeda, Takashi Minegishi, Hiroshi Kobayashi

    The journal of obstetrics and gynaecology research   45 ( 4 )   766 - 786   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated.

    DOI: 10.1111/jog.13831

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  • がんゲノム医療と女性ヘルスケア 査読

    平沢 晃

    医学のあゆみ   269 ( 1 )   85 - 88   2019年4月

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    記述言語:日本語   出版者・発行元:医歯薬出版(株)  

    がん診療のエンドポイントは"がん死の低減"であるが、女性においては集学的治療やリスク低減手術によって女性ホルモンの欠落をきたし、quality of life(QOL)低下を余儀なくされるケースがある。近年のがんゲノム医療の急速な進展は、実地臨床においてがん薬物療法の標的となる遺伝子病的バリアント(変異)のみならず、遺伝性腫瘍の原因となる生殖細胞系列バリアントも明らかにしてきている。2人に1人ががんに罹患するという今日、医療人はがんの"診断・予防・治療"のみならず、女性ヘルスケアについてもシームレスに行う体制を構築する必要がある。(著者抄録)

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  • 婦人科がんとがんゲノム医療 査読

    平沢 晃

    Pharma Medica   37 ( 2 )   9 - 14   2019年2月

  • 婦人科における遺伝性腫瘍 査読

    平沢 晃

    産婦人科の実際   68 ( 2 )   187 - 191   2019年2月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

    <文献概要>遺伝性腫瘍診療のエンドポイントは「がん死の低減」であり,遺伝性腫瘍の病的バリアント(変異)を同定することで,がん予防策を構築することを目指す。婦人科領域における遺伝性腫瘍としては遺伝性乳癌卵巣癌症候群(HBOC),リンチ症候群などが代表である。近年はがん診療のなかで生殖細胞系列病的バリアントが同定される機会が多くなってきている。婦人科癌ではほかのがん種と比較しても生殖細胞系列病的バリアントが潜在している頻度が高いことから,遺伝性腫瘍診療において産婦人科が担う役割は大きい。さらに,病的バリアント同定後のがん治療やがん予防のサーベイランスを施行する立場としても産婦人科実地臨床は重要な立場にある。

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  • Genome-wide DNA methylation profile of young-onset endometrial cancer

    Makabe Takeshi, Arai Eri, Hirasawa Akira, Yamagami Wataru, Susumu Nobuyuki, Aoki Daisuke, Kanai Yae

    CANCER SCIENCE   109   1304 - 1304   2018年12月

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    記述言語:英語  

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  • 遺伝性乳癌卵巣癌に対するリスク低減卵管卵巣摘出後のQOLに関する検討 査読

    谷本 慧子, 平沢 晃, 牧田 和也, 岩田 卓, 堀場 裕子, 横田 めぐみ, 小川 真里子, 弟子丸 亮太, 柳本 茂久, 高松 潔, 青木 大輔

    日本女性医学学会雑誌   26 ( 1 )   45 - 47   2018年11月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    遺伝性乳癌卵巣癌(hereditary breast cancer ovarian cancer syndrome、HBOC)は、BRCA1またはBRCA2(BRCA1/2)の生殖細胞系列病的変異(バクアント)が原因であり、家系内に乳癌・卵巣癌・卵管癌・腹膜癌などが好発し、BRCA1/2遺伝子変異保持者では70歳までに卵巣癌発症例が40%以上であると報告されている。BRCA1/2遺伝子変異保持者に対するマネージメントとして、リスク低減卵管卵巣摘出術(risk reduction salpingo-oophorectomy、RRSO)は卵巣癌や卵管癌の発症リスクを減少させ、全死亡率を低下することも報告されているが、閉経前の両側卵巣摘出術は医原性の卵巣欠落症状を惹起するため、その管理が重要である。本検討では、当院でRRSOを施行した8症例を対象に、RRSO後の諸症状より女性QOLについて後方視的に検討した。8例のうち6例で乳癌の既往があった。術後に薬物治療を必要とする卵巣欠落症状を呈した症例は3例で漢方治療を行っていた。またRRSO後早期に脂質異常症を発症した例もあった。BRCA1/2遺伝子変異保持者に対するRRSOは本邦の実臨床に導入されてきているが、RRSO実施例では短期的には卵巣欠落症状、長期的には脂質異常症や骨粗鬆症などを発症してQOL低下をもたらす可能性が高い。海外の各種ガイドラインでは術後卵巣欠落症状に対するホルモン補充療法(HRT)が提唱されているものの、乳癌既往例などではHRTが禁忌な例が存在し、症例には漢方療法が有効である。RRSO後はがんサーベイランスとともに、女性医学の観点から将来的なQOLに関係する項目を経時的に追跡することが重要である。(著者抄録)

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  • Synchronous endometrial and ovarian cancer in Lynch syndrome with a MSH2 germline mutation: A case report. 査読 国際誌

    Takashi Takeda, Kouji Banno, Megumi Yanokura, Mayuka Anko, Arata Kobayashi, Asako Sera, Takayuki Takahashi, Masataka Adachi, Yusuke Kobayashi, Shigenori Hayashi, Hiroyuki Nomura, Akira Hirasawa, Eiichiro Tominaga, Daisuke Aoki

    Molecular and clinical oncology   9 ( 5 )   479 - 484   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Synchronous endometrial and ovarian cancer (SEOC) is a rare entity among gynecological cancers, which exhibits endometrioid histology in its early stages and generally has a good prognosis. However, diagnosis is difficult and recent reports have demonstrated that most clinically diagnosed cases of SEOC have clonally related cancers, indicating metastatic cancer. The association of SEOC with Lynch syndrome is also not clearly understood. We herein present the case of a 41-year-old SEOC patient with MSH2 mutation. The endometrial cancer was an endometrioid adenocarcinoma and the ovarian cancer was mainly endometrioid, but also included a clear cell carcinoma with a borderline clear cell adenofibromatous component, indicating primary ovarian cancer. Both tumors exhibited microsatellite instability (MSI) and loss of expression of MSH2 and MSH6. The patient had a family history of colorectal and gastric cancers. Genetic analysis revealed a germline mutation in exon 6 of MSH2 (c.1042C>T, p.Gln348*) and the patient was diagnosed with Lynch syndrome. This MSH2 mutation has only been registered in one case in the InSiGHT variant databases and has not been reported in a gynecological tumor or SEOC to date. This case is a rare example of a patient with genetically diagnosed Lynch syndrome who also developed SEOC. This synchronous cancer is not common, but it may be caused by Lynch syndrome. Testing for MSI and immunohistochemistry for mismatch repair deficiency is necessary in cases with suspected SEOC.

    DOI: 10.3892/mco.2018.1723

    PubMed

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  • 遺伝性腫瘍・家族性腫瘍

    平沢 晃

    日本医師会雑誌   147 ( 7 )   1401 - 1406   2018年10月

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    記述言語:日本語   出版者・発行元:(公社)日本医師会  

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  • GENOME-WIDE DNA METHYLATION ANALYSIS IN YOUNG-ONSET ENDOMETRIAL CANCER

    Makabe T, Arai E, Hirasawa A, Yamagami W, Nobuyuki S, Aoki D, Kanai Y

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28   79 - 79   2018年9月

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    記述言語:英語  

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  • THE EFFICACY OF REPEATED HORMONAL THERAPY FOR INTRAUTERINE RECURRENCE FOLLOWING FERTILITY PRESERVING HORMONAL THERAPY FOR ENDOMETRIAL CANCER OR ATYPICAL ENDOMETRIAL HYPERPLASIA. 査読

    Hirano T, Yamagami W, Susumu N, Makabe T, Sakai K, Ninomiya T, Chiyoda T, Nomura H, Kataoka F, Hirasawa A, Banno K, Aoki D

    INTERNATIONAL JOURNAL OF GYNECOLOGIC CANCER   28 ( S2 )   1092 - 1092   2018年9月

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    記述言語:英語   掲載種別:研究論文(研究会,シンポジウム資料等)  

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  • UNSUCCESSFUL HIGH-DOSE HORMONAL THERAPY FOR ENDOMETRIAL CANCER OR ATYPICAL ENDOMETRIAL HYPERPLASIA. 査読

    Tamagawa M, Yamagami W, Hirano T, Makabe T, Sakai K, Ninomiya T, Chiyoda T, Nomura H, Kataoka F, Hirasawa A, Banno K, Susumu N, Aoki D

    INTERNATIONAL JOURNAL OF GYNECOLOGIC CANCER   28 ( S2 )   1189 - 1189   2018年9月

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    記述言語:英語   掲載種別:研究論文(研究会,シンポジウム資料等)  

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  • がんゲノム医療とHBOC

    平沢 晃

    日本HBOCコンソーシアムニュースレター   6   2018年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 婦人科疾患ゲノム異常の探索と女性ヘルスケアの個別化

    平沢 晃

    公益社団法人日本産婦人科医会 研修ノート   101   64 - 67   2018年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy: a comprehensive analysis using targeted resequencing of 100 pharmacogenes. 査読 国際誌

    Yoshihama T, Fukunaga K, Hirasawa A, Nomura H, Akahane T, Kataoka F, Yamagami W, Aoki D, Mushiroda T

    Oncotarget   9 ( 51 )   29789 - 29800   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18632/oncotarget.25712

    PubMed

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  • 有害事象によりベバシズマブ投与を中止した婦人科がん症例の検討 査読

    大野 あゆみ, 千代田 達幸, 野村 弘行, 同前 愛, 早乙女 啓子, 冨永 英一郎, 岩田 卓, 山上 亘, 片岡 史夫, 平沢 晃, 田中 守, 青木 大輔

    東京産科婦人科学会会誌   67 ( 3 )   396 - 400   2018年7月

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    ベバシズマブは婦人科がんにおいて日常的に用いられる分子標的薬となっているが、特有の有害事象により投与継続が困難となるケースを経験する。そこで本研究ではベバシズマブ投与中止の原因となった重篤な有害事象と臨床的背景を明らかにすることを目的とした。ベバシズマブ併用化学療法を2013年12月から開始した上皮性卵巣癌、卵管癌、腹膜癌(以下卵巣癌)48例および2017年1月から開始した子宮頸癌12例の計60例について後方視的に有害事象とその発現時期を検討した。卵巣癌は初発投与19例、再発投与29例の計48例、子宮頸癌は初発投与1例、再発投与11例の計12例を組み入れた。卵巣癌の年齢中央値は54歳(37〜76歳)、ベバシズマブ投与サイクル数中央値は15回(1〜68回)であった。子宮頸癌の年齢中央値は50歳(33〜68歳)、ベバシズマブ投与サイクル数中央値は5.5回(1〜10回)であった。卵巣癌48例中有害事象による投与中止例は4例あり、内訳は高度蛋白尿・ネフローゼ2例(4.2%)、腸炎1例(2.08%)、血栓塞栓症1例(2.08%)であった。子宮頸癌12例中有害事象による投与中止例は3例あり、全例血栓塞栓症(25%)であった。血液毒性、高血圧による投与中止例は認めず、出血および消化管穿孔、瘻孔は認めなかった。有害事象の発現時期について高度蛋白尿・ネフローゼは17、23サイクル終了時、血栓塞栓症はそれぞれ1、1、2、8サイクル終了時に認めた。高度蛋白尿・ネフローゼは投与数を重ねてから出現し、血栓塞栓症は投与開始後早期に認めた。検討した症例数は少ないものの、子宮頸癌では卵巣癌に比較して血栓塞栓症を多く認める可能性が示唆され、今後症例の蓄積が必要である。(著者抄録)

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  • 遺伝性腫瘍に対するリスク低減卵管卵巣摘出術 -RRSOの臨床試験やその適応、手技の実際と留意すべきポイント-

    植木有紗, 平沢 晃, 青木大輔

    産婦人科の実際   67 ( 5 )   549 - 556   2018年5月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

    <文献概要>遺伝性腫瘍における臨床目標の1つが,「病的バリアント保持者※(遺伝子変異保持者)に対するがん死低減」である。遺伝性腫瘍に対するリスク低減手術はわが国においても実施施設では着実に実地臨床に導入されている。本稿においては,リスク低減卵管卵巣摘出術の効果およびその対象となる遺伝性腫瘍の概要を中心に,実際の手術手技のポイントについて述べる。その実施にあたっては,オカルト癌の可能性を念頭に病理学的に詳細な検討を行うことや,遺伝診療部門との堅実な連携体制を構築し,十分な遺伝カウンセリングを行うなど,他診療科との体制整備が必要である。※アメリカ臨床遺伝学会(ACMG)ガイドラインの表記に従い,最近では,「変異(mutation)」の代わりに「バリアント(variant)」が使われるようになってきている。もともと変異という言葉に否定的な響きがあり,また定義そのものがあいまいで混乱をきたすということを理由に,最近はこうした表現をやめ,代わりにバリアント(多様体)という言葉を使うことが推奨されており,本稿ではバリアントという表記に統一する。

    J-GLOBAL

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00535&link_issn=&doc_id=20180525020017&doc_link_id=10.18888%2Fsp.0000000437&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fsp.0000000437&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 遺伝性乳がん

    植木有紗, 平沢 晃, 青木大輔

    White   6 ( 1 )   15 - 22   2018年5月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

    遺伝性乳がんに関連するさまざまな原因遺伝子が同定されてきた。中でも遺伝性乳癌卵巣癌症候群(HBOC)の原因遺伝子であるBRCA1/2遺伝子の関連は25%を占める。遺伝性乳がんに関わる疾患として、臨床的に重要視されつつあるHBOCを中心に、Li Fraumeni症候群、Cowden病について解説した。また、Multi-gene panel検査、NCCNガイドラインを参照にしたマネジメントについて述べた。さらに、主治医が理解しておくべき遺伝学的検査の特徴、結果による治療戦略、家族への影響について触れた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06305&link_issn=&doc_id=20180620100003&doc_link_id=%2Fai1whitc%2F2018%2F000601%2F003%2F0015-0022%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1whitc%2F2018%2F000601%2F003%2F0015-0022%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 遺伝性乳癌卵巣癌症候群に対するリスク低減卵管卵巣摘出後の漢方療法に関する検討 査読

    平沢 晃, 牧田 和也, 岩田 卓, 堀場 裕子, 横田 めぐみ, 小川 真里子, 弟子丸 亮太, 柳本 茂久, 青木 大輔

    産婦人科漢方研究のあゆみ   35 ( 35 )   189 - 191   2018年4月

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer syndrome:HBOC)は、BRCA1またはBRCA2(BRCA1/2)の生殖細胞系列変異(病的バリアント)が原因であり、家系内に乳癌や卵巣癌(卵管癌・腹膜癌含む)などが好発する。BRCA1/2遺伝子変異保持者では70歳までに卵巣癌発症例が40%以上であり、現時点ではリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)が卵巣癌発症リスクを減少させ全死亡率の低下を可能とすることから、最も確実な癌予防法とされている。しかしながら閉経前のRRSOは医原性の卵巣欠落症状を惹起するため、その術後の管理が重要である。本検討では当院でRRSOを施行した症例における術後の女性QOL管理について検討した。2008年から2016年までに当院にてRRSOを施行した8例を調査対象として、RRSO後の卵巣欠落症状の有無・血清脂質・骨密度検査について検討した。特に卵巣欠落症状に対する漢方薬を含めた介入につき後方視的に検討した。8例のうち7例が継続的に当院女性健康維持外来に受診をしており、7例全例(100%)で介入を施行されていた。術後に薬物治療を必要とする卵巣欠落症状を呈したのは5例(71%)で、いずれも術後に漢方治療を行っていた。なお6例で乳癌の既往があった。BRCA1/2遺伝子変異保持者に対するRRSOはわが国の実臨床に導入されてきているが、RRSO実施例では短期的には卵巣欠落症状、長期的には脂質異常症や骨粗鬆症などを発症してQOL低下をもたらす可能性が高い。海外の各種ガイドラインでは術後卵巣欠落症状に対するホルモン補充療法(HRT)が提唱されているものの、乳癌既往例などET療法が困難な例が存在し、症例によっては漢方療法が有効であると考えられた。(著者抄録)

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  • Is repeated high-dose medroxyprogesterone acetate (MPA) therapy permissible for patients with early stage endometrial cancer or atypical endometrial hyperplasia who desire preserving fertility? 査読 国際誌

    Wataru Yamagami, Nobuyuki Susumu, Takeshi Makabe, Kensuke Sakai, Hiroyuki Nomura, Fumio Kataoka, Akira Hirasawa, Kouji Banno, Daisuke Aoki

    JOURNAL OF GYNECOLOGIC ONCOLOGY   29 ( 2 )   e21   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY  

    Objective: Reports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1.Methods: Patients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400-600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed.Results: Complete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%).Conclusion: Repeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1.

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  • 婦人科疾患ゲノム異常の探索と女性ヘルスケアの個別化 招待 査読

    平沢 晃

    日本女性医学学会雑誌   25 ( 2 )   156 - 158   2018年2月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    がん診療のエンドポイントは生存率(survival)の向上であるが、がん治療にともなうQOLも重要な課題である。近年の婦人科がん罹患数の増加と集学的治療法の進歩は、将来における婦人科がんサーバイバー(がん生存者)の増加を意味しており、女性がんサバイバーのQOLに対して系統的に早期介入する体制を確立することは喫緊の課題である。さらに近年はがん罹患者のみならず、がん高危険群に対する予防的治療も現実のものとなってきている。遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer:HBOC)の原因遺伝子であるBRCA1またはBRCA2(BRCA1/2)遺伝子の病的バリアント(遺伝子変異)保持者に対するリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)は、国内の実施臨床に確実に導入されてきている。しかしながらRRSOは閉経前に施行することが多いため、短期的には卵巣欠落症状、皮膚・泌尿器症状など、長期的には脂質異常症や骨粗鬆症の高危険群となる。さらに最近は「生活習慣病としてのがん」という観点から、女性医学と腫瘍学のクロストークが注目を浴びつつある。このような背景のもと、我々は質の高い臨床データ、家系員情報をともなった婦人科疾患バイオバンク試料をもとに、リスクの層別化に基づいた個別化がん予防戦略を構築し、最終的に女性のQOLの臨床に還元する臨床と研究を行ってきた。(著者抄録)

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  • ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death 査読 国際誌

    Mari Ueno, Takayuki Shiomi, Satsuki Mochizuki, Miyuki Chijiiwa, Masayuki Shimoda, Yae Kanai, Fumio Kataoka, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki, Yasunori Okada

    CANCER SCIENCE   109 ( 2 )   471 - 482   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in carcinomas than in control non-neoplastic ovarian tissue. Among the histological subtypes of serous, endometrioid, mucinous and clear cell carcinomas, ADAM9m expression was highest in clear cell carcinomas. Immunohistochemistry showed that all the clear cell carcinoma samples displayed ADAM9m primarily on the carcinoma cell membrane. By immunoblotting, ADAM9m was detected mainly in an active form in the clear cell carcinoma tissues. When two clear cell carcinoma cell lines (RMG-I and TOV21G cells) with ADAM9m expression were treated with cisplatin, viability was significantly reduced and apoptosis increased in ADAM9m knockdown cells compared with mock transfectants. In addition, treatment of the cells with neutralizing anti-ADAM9m antibody significantly decreased viability compared with non-immune IgG, whereas ADAM9m over-expression significantly increased viability compared with mock transfectants. Our data show, to the best of our knowledge, for the first time, that ADAM9m is over-expressed in an activated form in human ovarian clear cell carcinomas, and suggest that ADAM9m plays a key role in cisplatin resistance.

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  • Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (Translated Version). 査読

    Hideyuki Ishida, Tatsuro Yamaguchi, Kohji Tanakaya, Kiwamu Akagi, Yasuhiro Inoue, Kensuke Kumamoto, Hideki Shimodaira, Shigeki Sekine, Toshiaki Tanaka, Akiko Chino, Naohiro Tomita, Takeshi Nakajima, Hirotoshi Hasegawa, Takao Hinoi, Akira Hirasawa, Yasuyuki Miyakura, Yoshie Murakami, Kei Muro, Yoichi Ajioka, Yojiro Hashiguchi, Yoshinori Ito, Yutaka Saito, Tetsuya Hamaguchi, Megumi Ishiguro, Soichiro Ishihara, Yukihide Kanemitsu, Hiroshi Kawano, Yusuke Kinugasa, Norihiro Kokudo, Keiko Murofushi, Takako Nakajima, Shiro Oka, Yoshiharu Sakai, Akihiko Tsuji, Keisuke Uehara, Hideki Ueno, Kentaro Yamazaki, Masahiro Yoshida, Takayuki Yoshino, Narikazu Boku, Takahiro Fujimori, Michio Itabashi, Nobuo Koinuma, Takayuki Morita, Genichi Nishimura, Yuh Sakata, Yasuhiro Shimada, Keiichi Takahashi, Shinji Tanaka, Osamu Tsuruta, Toshiharu Yamaguchi, Kenichi Sugihara, Toshiaki Watanabe

    Journal of the anus, rectum and colon   2 ( Suppl I )   S1-S51   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non-polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

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  • Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group. 査読 国際誌

    Sarah M Nielsen, Diana M Eccles, Iris L Romero, Fahd Al-Mulla, Judith Balmaña, Michela Biancolella, Rien Bslok, Maria Adelaide Caligo, Mariarosaria Calvello, Gabriele Lorenzo Capone, Pietro Cavalli, T L Chris Chan, Kathleen B M Claes, Laura Cortesi, Fergus J Couch, Miguel de la Hoya, Simona De Toffol, Orland Diez, Susan M Domchek, Ros Eeles, Anna Efremidis, Florentia Fostira, David Goldgar, Andreas Hadjisavvas, Thomas V O Hansen, Akira Hirasawa, Claude Houdayer, Petra Kleiblova, Sophie Krieger, Conxi Lázaro, Maria Loizidou, Siranoush Manoukian, Arjen R Mensenkamp, Setareh Moghadasi, Alvaro N Monteiro, Luigi Mori, April Morrow, Nadia Naldi, Henriette R Nielsen, Olufunmilayo I Olopade, Nicholas S Pachter, Edenir I Palmero, Inge S Pedersen, Maria Piane, Marianna Puzzo, Mark Robson, Maria Rossing, Maria Christina Sini, Angela Solano, Jana Soukupova, Gianluca Tedaldi, Manuel Teixeira, Mads Thomassen, Maria Grazia Tibiletti, Amanda Toland, Therese Törngren, Erica Vaccari, Liliana Varesco, Ana Vega, Yvonne Wallis, Barbara Wappenschmidt, Jeffrey Weitzel, Amanda B Spurdle, Arcangela De Nicolo, Encarna B Gómez-García

    JCO precision oncology   2   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Methods: Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Results: Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Conclusion: Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.

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  • Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. 招待 査読 国際誌

    Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Hiroyuki Nomura, Kiyoshi Masuda, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki

    Oncotarget   8 ( 68 )   112258 - 112267   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:(in press)  

    Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

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  • Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer 査読 国際誌

    Tomoko Yoshihama, Hiroyuki Nomura, Naomi Iwasa, Fumio Kataoka, Shiho Hashimoto, Yoshiko Nanki, Takuro Hirano, Takeshi Makabe, Kensuke Sakai, Wataru Yamagami, Akira Hirasawa, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   47 ( 11 )   1019 - 1023   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) is currently one of the preferred treatment options for advanced ovarian, fallopian tube or peritoneal cancer. This study was conducted to evaluate the clinical efficacy and safety of dose-dense paclitaxel plus carboplatin therapy (ddTC therapy) as NAC for these cancers.A retrospective study was conducted in 25 patients with Stage III/IV ovarian, fallopian tube or peritoneal cancer who received ddTC therapy as NAC. For ddTC therapy, paclitaxel (80 mg/m(2)) was administered intravenously on Days 1, 8 and 15 and carboplatin (AUC 6.0 mg/ml x min) was administered intravenously on Day 1 every 3 weeks. IDS was performed after three cycles of ddTC therapy, and ddTC therapy was also continued after surgery.With ddTC therapy as NAC, the response rate was 92% and disease progression did not occur in any patient. Grade 4 hematologic toxicity and >= Grade 3 non-hematologic toxicity both occurred in 8% of the patients, but no patient discontinued NAC because of adverse events. When IDS was performed, the complete surgery rate was 64% and the optimal surgery rate was 96%. >= Grade 3 perioperative complications occurred in 16% of the patients, but there were no perioperative deaths. Median overall survival was 35.7 months and median progression-free survival was 17.7 months.This study showed that ddTC therapy was considerably effective and tolerable as NAC. The complete surgery rate was high with IDS, and perioperative complications were acceptable.

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  • 治療薬解説 PARP阻害薬

    平沢 晃, 青木大輔

    カレントテラピー   35 ( 9 )   74 - 77   2017年9月

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    記述言語:日本語  

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  • A Comparison of Dye Versus Fluorescence Methods for Sentinel Lymph Node Mapping in Endometrial Cancer 査読 国際誌

    Wataru Yamagami, Nobuyuki Susumu, Fumio Kataoka, Takeshi Makabe, Kensuke Sakai, Tomomi Ninomiya, Michiko Wada, Hiroyuki Nomura, Akira Hirasawa, Kouji Banno, Tadaki Nakahara, Kaori Kameyama, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 ( 7 )   1517 - 1524   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective Sentinel nodes (SNs) have been observed in several reports from Japan and overseas in cases with endometrial cancer; however, no consensus has been reached regarding the types of tracers or the method of their injection. A combination of the radioisotope (RI) and dye method is considered to be desirable. We assessed SN mapping using either dye or near-infrared fluorescence imaging to clarify a suitable method in cases of endometrial cancer.Methods Patients were enrolled from 92 patients diagnosed with endometrial cancer and having no extrauterine metastasis by the preoperative imaging between 2009 and 2014 at our institution. To identify the SNs, we performed 3 methods using either dye or fluorescence solutions in conjunction with a RI method. In the dye method, we injected indocyanine green in the uterine subserosa, visually identifying SNs as stained green. In the fluorescence method, a dilute indocyanine green solution (0.5 mg, fluorescence A or 0.25 mg, fluorescence B, each per 10 mL of solvent) was injected and the SN identified by the HyperEye Medical System.Results The SN detection rates were 100%, 100%, and 96% using dye and fluorescence A or B solution, respectively. Pelvic SNs were detected by the 3 methods in 98%, 100%, and 96% of cases and para-aortic SNs in 65%, 88%, and 74%, respectively. Fluorescence A solution was somewhat better than dye in detecting para-aortic SNs, although not significantly so (P = 0.07). The sensitivity and negative predictive values for detecting SNs with metastases with the dye method were 92% and 98% compared with 100% and 100%, respectively, for both fluorescence solutions.Conclusions Although both dye and fluorescence methods performed well, no method perfectly identified para-aortic SNs. The concomitant use of the RI method is required to detect para-aortic SNs.

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  • 遺伝性卵巣がん

    千代田達幸, 平沢 晃, 青木大輔

    成人病と生活習慣病   47 ( 7 )   861 - 866   2017年7月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

    がんは遺伝因子と環境因子の双方が関与して発症するが、卵巣癌の約10〜15%は遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer;HBOC)の原因遺伝子であるBRCA1もしくはBRCA2(BRCA1/2)の生殖細胞系列変異に基づく。BRCA1/2変異保持者は卵巣癌のリスクが高く、がん予防策を講じる必要がある。もっとも確実なリスク低減策はリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy;RRSO)であり、発癌リスクを80%減らすことができる。BRCA1/2変異のある癌に対しては合成致死作用によりPARP阻害薬が奏効する。PARP阻害薬のコンパニオン診断としてBRCA1/2遺伝子検査が行われるようになり、precision medicineの先駆けとしてゲノム医療の実用化が始まっている。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03723&link_issn=&doc_id=20170807200010&doc_link_id=%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 医療機器に生じたトラブル

    冨永英一郎, 小林佑介, 平沢 晃, 阪埜浩司, 末岡 浩, 青木大輔

    産婦人科の実際   66 ( 6 )   767 - 771   2017年6月

  • Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer. 国際誌

    Kenta Masuda, Akira Hirasawa, Haruko Irie-Kunitomi, Tomoko Akahane, Arisa Ueki, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Japanese journal of clinical oncology   47 ( 5 )   401 - 406   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients. Method: Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups. Results: A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91). Conclusions: In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

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  • Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer. 査読 国際誌

    Kenta Masuda, Akira Hirasawa, Haruko Irie-Kunitomi, Tomoko Akahane, Arisa Ueki, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Japanese journal of clinical oncology   47 ( 5 )   473 - 473   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    This study shows that the newly designed self-administered questionnaire is a useful tool to assess the risk of hereditary cancer for patients with gynecologic cancer.A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients.
    Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups.
    A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91).
    In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

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  • Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report. 査読 国際誌

    Masataka Adachi, Kouji Banno, Kenta Masuda, Megumi Yanokura, Moito Iijima, Takashi Takeda, Haruko Kunitomi, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Kaori Kameyama, Kokichi Sugano, Daisuke Aoki

    The journal of obstetrics and gynaecology research   43 ( 2 )   416 - 420   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46-year-old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer history met the revised Bethesda criteria, we examined microsatellite instability and the result was negative, but loss of the MSH6 expression was detected by immunohistochemistry. Genetic testing revealed deleterious germline mutation of MSH6, which was compatible with Lynch syndrome. To our knowledge, this is the first case of endometrial carcinoma of the LUS with MSH6 germline mutation.

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  • UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan 査読 国際誌

    Tomoko Yoshihama, Akira Hirasawa, Hiroyuki Nomura, Tomoko Akahane, Yoshiko Nanki, Wataru Yamagami, Fumio Kataoka, Eiichiro Tominaga, Nobuyuki Susumu, Taisei Mushiroda, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   47 ( 2 )   170 - 174   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    We investigated whether UGT1A1 polymorphisms are associated with the prognosis of ovarian cancer patients treated with irinotecan. UGT1A1 genotypes were analyzed in 11 stage I ovarian clear cell carcinoma patients who received irinotecan as first-line therapy. Progression-free survival, overall survival and adverse events were also assessed for each genotype. Three patients harbored UGT1A1*1/*6 while another three harbored UGT1A1*1/*28. Two patients with a wildtype genotype experienced recurrence and one died, whereas no recurrence or death was observed in patients with heterozygous genotypes. Adverse events tended to be more severe in patients with UGT1A1*6 and *28, although progression-free survival and overall survival rates tended to be better than in wild-type; the differences were not significant. We conclude that UGT1A1 polymorphisms have the potential to be a prognostic marker of irinotecan treatment.

    DOI: 10.1093/jjco/hyw163

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  • Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report 査読

    Masataka Adachi, Kouji Banno, Kenta Masuda, Megumi Yanokura, Moito Iijima, Takashi Takeda, Haruko Kunitomi, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Kaori Kameyama, Kokichi Sugano, Daisuke Aoki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   43 ( 2 )   416 - 420   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46-year-old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer history met the revised Bethesda criteria, we examined microsatellite instability and the result was negative, but loss of the MSH6 expression was detected by immunohistochemistry. Genetic testing revealed deleterious germline mutation of MSH6, which was compatible with Lynch syndrome. To our knowledge, this is the first case of endometrial carcinoma of the LUS with MSH6 germline mutation.

    DOI: 10.1111/jog.13202

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  • 遺伝性乳癌卵巣癌症候群と女性ヘルスケア 招待

    平沢 晃, 青木大輔

    更年期と加齢のヘルスケア   16 ( 1 )   42 - 45   2017年

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    記述言語:日本語   出版者・発行元:更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)  

    遺伝性乳癌卵巣癌症候群(hereditary breast and ovarian cancer syndrome:HBOC)はBRCA1またはBRCA2遺伝子(BRCA1/2)の生殖細胞系列変異によるもので、BRCA1遺伝子変異保持者女性の卵巣癌発症リスクは39〜46%、BRCA2遺伝子変異保持者女性では12〜27%であると報告されている。HBOCは常染色体優性遺伝性疾患であり、血縁者にその関連疾患が多発することから、家族歴の聴取が発見の端緒となる。BRCA1/2変異保持者に対しては、がん発症リスクを理解した上で適切な対策を講じる必要がある。腫瘍遺伝学の臨床におけるエンドポイントは「遺伝子変異保持者におけるがん死の低減」である。その目的のため遺伝子変異保持者に対してはがん予防策をとることが必要となる。がん一次予防法としてはリスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)、リスク低減乳房切除術(risk-reducing mastectomy:RRM)、経口避妊薬による卵巣癌予防およびタモキシフェンによる乳癌予防などが挙げられる。そのなかでもRRSOは卵巣癌発症のリスク低減効果のみならず、乳癌発症リスク、さらには卵巣癌や乳癌による死亡率のみならず全死亡も低減すると報告されており、現時点でBRCA1/2遺伝子変異保持者に対する最も効果が高いがん一次予防法である。BRCA1/2遺伝子変異保持者に対するRRSOは本邦の実臨床に導入されてきている。しかしながらRRSOは閉経前に施行されることが多く、術後短期的には卵巣欠落症状、長期的には脂質異常症や骨粗鬆症などを発症してQOL低下をもたらす可能性が高い。海外の各種ガイドラインでは術後卵巣欠落症状に対するホルモン補充療法(ET療法)が提唱されているものの、乳癌既往例などET療法が困難な例が存在し、そのような場合は漢方療法が有効な場合がある。RRSO施行後は乳癌や腹膜癌などの発生についての「がんサーベイランス」とともに、女性ヘルスケアの観点からも経時的に追跡することが重要である。(著者抄録)

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  • 手術前禁忌薬(経口避妊薬,低用量エストロゲン-プロゲスチン配合薬)に関する医療安全対策 査読

    高柳裕子, 冨永英一郎, 小林佑介, 仲村 勝, 片岡史夫, 平沢 晃, 阪埜浩司, 田中 守, 青木大輔

    東京産科婦人科学会会誌   66 ( 3 )   424 - 428   2017年

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    当科において手術前禁忌薬である経口女性ホルモン製剤(OC・LEP)を内服している患者に、術前休薬の指示がされなかったために発生したインシデント事例について、後方視的に検討した。2015年1月から12月に、当院で入院のうえ手術を施行した1,250例のうち、OC・LEPを内服していた症例は17例であり、そのうち3例は術前に内服中止の指示がされず、手術延期となった。院内における対策として医療者への教育強化、医師への注意喚起、看護師・薬剤師によるダブルチェックなどのチェック機構強化を図った。その結果、当科においては手術前禁忌薬に関する同様のインシデント発生を防ぐことが可能となった。防御システムを多重化すること、医療者の認識を高めることが、インシデント発生を防止するために重要であると考えられた。(著者抄録)

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  • 一般病院における家族性腫瘍相談外来とハイリスク外来の開設 –一般病院み求められる家族性腫瘍診療の意義についての考察- . 招待 査読

    植木有紗, 中田さくら, 安斎純子, 麻薙美香, 嶋田恭輔, 久保内光一, 三須久美子, 平沢 晃, 阪埜浩司, 菅野康吉, 小崎健次郎, 青木大輔

    家族性腫瘍   16 ( 2 )   38 - 43   2017年

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    記述言語:日本語   出版者・発行元:(一社)日本遺伝性腫瘍学会  

    本邦における家族性腫瘍の遺伝カウンセリング体制は近年急速に整備されつつあるが,その多くは大学病院やセンター病院といった大規模病院である.今回我々は,地域がん診療連携拠点病院における家族性腫瘍相談外来開設の経験をもとに,一般市中病院での遺伝カウンセリング体制の課題などについて当院での現状を紹介し,考察する.依頼元の内訳は乳腺外科からの受診相談が約30%にのぼり,さらに遺伝学的検査の内訳で見ると43%が乳癌の術前依頼であり,受診動機として癌罹患者の術式選択が大きな要因になっていることが示唆された.また,受診された遺伝子変異保持者および血縁者を対象にハイリスク外来を同時に開設し,心理的支援とサーベイランスを継続している.今後もクライエントのために,一般市中病院の立場で家族性腫瘍に関する正しい情報提供およびサーベイランスや,診断後の治療を含む実地診療との密な協力体制の構築を目標に,よりクライエント中心型のカウンセリング体制の整備が必要と考える.(著者抄録)

    DOI: 10.18976/jsft.16.2_38

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03931&link_issn=&doc_id=20170714280003&doc_link_id=%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • BRCA1またはBRCA2遺伝子変異陽性女性へのHRT 招待

    平沢 晃, 高松 潔, 青木大輔

    産科と婦人科   84 ( 12 )   1468 - 1471   2017年

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

    近年、遺伝性乳癌卵巣癌症候群の原因遺伝子であるBRCA1またはBRCA2(BRCA1/2)遺伝子の遺伝学的検査が実地臨床に導入されてきている。今後はがん治療や予防の領域においてはBRCA1/2遺伝子のステータスに応じて、PARP(poly ADP ribose polymerase)阻害薬を用いた個別化治療法や、リスク低減卵管卵巣摘出術(risk-reducing salpingo-oophorectomy:RRSO)などの個別化予防法が実用化されることは確実である。そこで、BRCA1/2遺伝子変異保持者女性に対するHRTは女性医学、臨床腫瘍学、臨床遺伝学知見に基づいた統合的対応が必要である。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00525&link_issn=&doc_id=20171124130011&doc_link_id=%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Consistency in drug response profiling. 査読 国際誌

    John Patrick Mpindi, Bhagwan Yadav, Päivi Östling, Prson Gautam, Disha Malani, Astrid Murumägi, Akira Hirasawa, Sara Kangaspeska, Krister Wennerberg, Olli Kallioniemi, Tero Aittokallio

    Nature   540 ( 7631 )   E5-E6 - E6   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    DOI: 10.1038/nature20171

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  • Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis. 査読 国際誌

    Takashi Takeda, Kouji Banno, Megumi Yanokura, Masataka Adachi, Moito Iijima, Haruko Kunitomi, Kanako Nakamura, Miho Iida, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

    Genes   7 ( 10 )   e86   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

    DOI: 10.3390/genes7100086

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  • 遺伝性腫瘍領域の新たな潮流

    平沢 晃, 青木大輔

    実験医学   34 ( 16 )   2671 - 2674   2016年10月

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    記述言語:日本語  

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  • 婦人科悪性腫瘍に脳梗塞を合併したTrousseau症候群5例の検討

    沖山 愛, 山上 亘, 坂井健良, 真壁 健, 二宮委美, 野村弘行, 片岡史夫, 平沢 晃, 阪埜浩司, 進 伸幸, 青木大輔

    日本婦人科腫瘍学会雑誌   34 ( 4 )   620 - 625   2016年10月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

    Trousseau症候群は悪性腫瘍に伴う血液凝固線溶異常により血栓塞栓症を生じる病態であり、進行例が多く予後不良である。当科でも2006〜2014年に5例の脳梗塞を発症したTrousseau症候群を経験した。年齢の中央値は63歳(54〜69歳)で、合併悪性腫瘍は子宮体癌2例、卵巣癌2例、子宮頸癌1例であり、組織型は類内膜腺癌2例、漿液性腺癌2例、扁平上皮癌1例であった。4例は進行再発癌、1例は早期癌であった。病態はいずれも多発脳梗塞によるものであり、脳出血の症例はなかった。感染性心内膜炎との鑑別に難渋した進行再発例の1例を除く全症例でヘパリンナトリウムによる抗凝固療法を開始したが、手術不能な進行再発癌の4例は原疾患の治療が奏効せず、発症後約2ヵ月以内に死亡した。手術で腫瘍を完全摘出できた早期の卵巣癌の1例は予後良好であり、手術可能な症例では原疾患の摘除により予後改善の可能性があることが示唆された。(著者抄録)

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  • Symptoms and effects of physical factors in Japanese middle-aged women. 国際誌

    Megumi Yokota, Kazuya Makita, Akira Hirasawa, Takashi Iwata, Daisuke Aoki

    Menopause (New York, N.Y.)   23 ( 9 )   974 - 83   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Lippincott Williams and Wilkins  

    OBJECTIVE: The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI). METHODS: The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups. RESULTS: The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms. CONCLUSIONS: The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms.

    DOI: 10.1097/GME.0000000000000660

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  • Symptoms and effects of physical factors in Japanese middle-aged women 査読

    Megumi Yokota, Kazuya Makita, Akira Hirasawa, Takashi Iwata, Daisuke Aoki

    MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY   23 ( 9 )   974 - 983   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective:The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI).Methods:The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups.Results:The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms.Conclusions:The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms.

    DOI: 10.1097/GME.0000000000000660

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  • Retrospective Analysis on the Feasibility and Efficacy of Docetaxel-Cisplatin Therapy for Recurrent Endometrial Cancer. 国際誌

    Tomomi Ninomiya, Wataru Yamagami, Nobuyuki Susumu, Takeshi Makabe, Kensuke Sakai, Michiko Wada, Aya Takigawa, Tatsuyuki Chiyoda, Hiroyuki Nomura, Fumio Kataoka, Akira Hirasawa, Kouji Banno, Daisuke Aoki

    Anticancer research   36 ( 4 )   1751 - 8   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    AIM: There is poor evidence regarding effective treatment for recurrent endometrial cancer. We treated patients with recurrent endometrial cancer with docetaxel-cisplatin (DP) therapy as second-line or third-line chemotherapy. We aimed to evaluate the feasibility and efficacy of DP therapy for patients with recurrent endometrial cancer. PATIENT AND METHODS: We included 26 patients diagnosed with recurrent endometrial cancer, who underwent DP chemotherapy at our Institution. Docetaxel at 70 mg/m(2)and cisplatin at 60 mg/m(2)were administered by intravenous injection every 3 weeks. We retrospectively analyzed the clinicopathological factors associated with the response rate (RR) and prognosis. We also analyzed the adverse effects of DP therapy. RESULTS: Median follow-up was 33.8 months and the median number of therapy cycles was six. Grade 3 or 4 adverse effects included leukopenia (66%), neutropenia (81%), anemia (9%), diarrhea (12%), general fatigue (12%), liver dysfunction (4%), peripheral neuropathy (4%), and hyponatremia (4%). RR was 58% and the median progression-free survival (PFS) was 7.5 months. The group with a treatment-free interval of 6 months or more tended to have better PFS than that with less than 6 months (p=0.01). The group with a platinum-free interval of 6 months or more had significantly better PFS than that with less than 6 months (p=0.09). Although the history of taxane usage was not relevant to prognosis, a taxane-free interval of 12 months or more was associated with a tendency for better PFS (p=0.06). CONCLUSION: DP therapy was fully feasible and demonstrated efficacy for patients with recurrent endometrial cancer.

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  • 婦人科疾患における自覚症状としての「冷え」,疾患単位としての「冷え症」の合併頻度についての検討

    渡辺 賢治, 堀場裕子, 吉野鉄大, 平沢晃, 牧田和也, 横田めぐみ, 岩田卓, 青木大輔

    日本産科婦人科学会雑誌   68 ( 2 )   677 - 677   2016年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 遺伝性乳がん卵巣がんに対するリスク低減卵管卵巣摘出術と術後ヘルスケア

    横田めぐみ, 平沢 晃, 堀場裕子, 岩田 卓, 牧田和也, 青木大輔

    更年期と加齢のヘルスケア   14 ( 2 )   316 - 318   2016年2月

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    記述言語:日本語   出版者・発行元:更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)  

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  • Factors affecting pregnancy outcomes in young women treated with fertility-preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia. 査読 国際誌

    Osamu Inoue, Toshio Hamatani, Nobuyuki Susumu, Wataru Yamagami, Seiji Ogawa, Takashi Takemoto, Akira Hirasawa, Kouji Banno, Naoaki Kuji, Mamoru Tanaka, Daisuke Aoki

    Reproductive biology and endocrinology : RB&E   14 ( 1 )   2 - 2   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    BACKGROUND: Patients hoping to preserve their fertility receive conservative treatment with high-dose medroxyprogesterone acetate (MPA) for well-differentiated endometrioid adenocarcinoma (EC) or atypical endometrial hyperplasia (AEH) . Such treatment generally involves frequent intrauterine operations, including dilation and curettage (D&C) and endometrial biopsy (EMB), which could result in endometritis, endometrial thinning, or intrauterine adhesion. In turn, any of these outcomes could adversely affect implantation and pregnancy development. The current study thus aimed to identify factors that might affect pregnancy following conservative treatment by MPA. METHODS: We compared a pregnancy group (45 patients) with a non-pregnancy group (53 patients) of MPA-treated patients to evaluate the factors affecting clinical pregnancy establishment. We undertook a multivariate logistic regression analysis based on factors shown by univariate analysis to be significantly different between the groups. Univariate analysis identified number of D&C, endometrial thickness, duration of MPA administration, age of pregnancy permission (the age at which a patient was first allowed to attempt pregnancy after disappearance of the lesion), period of disappearance of lesions, and recurrence as independent variables. RESULTS: The odds ratios (95 % confidence interval) of multivariate analysis for disease recurrence, endometrial thickness during ovulation, and age of pregnancy permission were 0.283 (0.102-0.785), 1.677 (1.251-2.248), and 0.889 (0.792-0.998), respectively. There was no significant difference in the other independent variables between groups. CONCLUSIONS: We identified three factors considered to affect pregnancy establishment following conservative treatment with MPA: recurrence, endometrial thickness during ovulation, and the age of the pregnancy permission. Introduction of infertility treatment including assisted reproductive technology (ART) soon after achieving tumor disappearance by MPA would therefore be beneficial for patients with disease recurrence, thin endometrium, or a higher age of pregnancy permission.

    DOI: 10.1186/s12958-015-0136-7

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  • バイオリソースを用いた研究基盤整備に関する国内外の動き 招待 査読

    平沢 晃, 青木大輔

    産科と婦人科   83 ( 1 )   13 - 19   2016年

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

    基礎研究、トランスレーショナルリサーチ、臨床研究の連携と推進にはバイオリソース、すなわち研究に用いる生物資源が必要であり、バイオバンクがその橋渡し機能を担う。バイオバンクの役割は、単に試料を採取・保管するのみならず、臨床情報、ゲノム解析情報、画像情報をはじめとした重層オミクスのビックデータを扱うことにより、医歯学、保健、基礎生命科学の発展や創薬開発研究のハブ機能にある。がんをはじめとした難治性疾患の個別化治療の実現ためにバイオバンクは不可欠であり、各国とも国をあげてその整備に取り組んでいる。ヒト試料のバンキングは人類が希求する難治性疾患の画期的な診断法・治療法・予防法の開発、さらには知財形成や創薬研究における研究基盤となるため、率先して取り組むべき課題である。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00525&link_issn=&doc_id=20160108220002&doc_link_id=%2Fae4sanke%2F2016%2F008301%2F003%2F0013-0019%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2016%2F008301%2F003%2F0013-0019%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 遺伝性乳がん卵巣がん; 遺伝性腫瘍-実地臨床での対応を目指して 招待

    平沢 晃, 青木大輔

    日本医師会雑誌   145 ( 4 )   705 - 709   2016年

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    記述言語:日本語   出版者・発行元:(公社)日本医師会  

    J-GLOBAL

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  • 卵巣・卵管の良性腫瘍・類腫瘍 招待

    日本女性医学学会編

    女性医学ガイドブック 思春期・性成熟期編2016年度版   151 - 154   2016年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 両側卵巣摘出術を施行した婦人科がんサバイバーのQOL向上を目指した疫学因子および遺伝因子の解析. 招待 査読

    平沢 晃

    日本女性医学学会雑誌   24 ( 1 )   48 - 52   2016年

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

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  • 子宮体部・卵巣同時発生重複癌40症例の臨床病理学的検討. 査読

    小笠原 淳, 小林佑介, 野村弘行, 山上 亘, 片岡史夫, 平沢 晃, 冨永英一郎, 鈴木 淳, 阪埜浩司, 進 伸幸, 田中 守, 青木大輔

    東京産科婦人科学会会誌   65 ( 3 )   436 - 439   2016年

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    重複癌は2つ以上の臓器または組織に異なる種類の癌腫が発生するものであり、子宮体部および卵巣に同時発生する例もしばしば経験される。臨床的には一方の癌による転移との鑑別に苦慮することも少なくないが、両者では臨床的な取扱いや経過が異なるため、その鑑別は重要である。そこで、2002年から2015年に当院において経験した子宮体部・卵巣同時発生重複癌40症例の臨床病理学的背景を検討した。臨床的には診断時の平均年齢は48.5歳と比較的若年者が多く、病理学的には高分化、早期の症例が多数を占め、組織型は子宮体部・卵巣ともに類内膜腺癌が最も多かった。類内膜腺癌重複癌の症例では85.1%で子宮内膜症の併存を認めた。(著者抄録)

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  • 遺伝性腫瘍 招待 査読

    平沢 晃, 山上 亘, 青木大輔

    産婦人科の実際   65 ( 6 )   653 - 659   2016年

  • Characterization of the STK11 splicing variant as a normal splicing isomer in a patient with Peutz-Jeghers syndrome harboring genomic deletion of the STK11 gene. 査読 国際誌

    Kenta Masuda, Yusuke Kobayashi, Tokuhiro Kimura, Kiyoko Umene, Kumiko Misu, Hiroyuki Nomura, Akira Hirasawa, Kouji Banno, Kenjiro Kosaki, Daisuke Aoki, Kokichi Sugano

    Human genome variation   3   16002 - 16002   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report a STK11 splicing variant comprising a 131-bp insertion that is derived from intron 1, which has previously been reported to possess potent pathogenicity. The same variant was detected in a Peutz-Jeghers syndrome patient harboring a genomic deletion in the vicinity of exon 1 of the STK11 gene, which indicated that this variant was derived from the wild-type allele. We also found the same variant in other normal subjects. This variant corresponds to the predicted transcript variant of STK11 (XM_011528209), which is derived from the genomic sequence of Chr19 (NT_011295.12). Therefore, we concluded that the splicing variant was not pathogenic.

    DOI: 10.1038/hgv.2016.2

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  • Profiling of Epithelial Ovarian Cancer as BRCAness Status with MLPA Method. 査読

    Hirasawa A, Akahane T, Masuda K, Ninomiya T, Yamagami W, Nomura H, Kataoka F, Banno K, Susumu N, Aoki D

    Curr Oncol   23 ( 3 )   e305   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • [Free fatty acid receptors as therapeutic targets for metabolic disorders].

    Akira Hirasawa, Masato Takeuchi, Ryouhei Shirai, Zao Chen, Shota Ishii, Keiko Iida

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica   146 ( 6 )   296 - 301   2015年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1254/fpj.146.296

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  • EVALUATION OF PRE- OR INTRA-OPERATIVE DIAGNOSTIC METHOD FOR UTERINE CARCINOSARCOMA

    T. Makabe, W. Yamagami, N. Susumu, K. Sakai, T. Yoshihama, N. Iwasa, N. Nakadaira, S. Hashimoto, T. Ninomiya, M. Wada, A. Takigawa, H. Nomura, F. Kataoka, A. Hirasawa, K. Banno, D. Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   25 ( 9 )   1107 - 1107   2015年10月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • 子宮体がんの予防とヘルスケア

    進 伸幸, 平沢 晃, 山上 亘, 青木大輔

    産婦人科の実際 女性ヘルスケア 集中講義!   61 ( 10月臨時増刊号 )   399 - 408   2015年10月

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    記述言語:日本語  

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  • 若年子宮体癌、および子宮内膜異型増殖症に対して妊孕性温存治療を施行することによる精神的影響

    横田 めぐみ, 山上 亘, 坂井 健良, 真壁 健, 二宮 委美, 和田 美智子, 野村 弘行, 片岡 史夫, 平澤 晃, 牧田 和也, 阪埜 浩司, 進 伸幸, 青木 大輔, 白波瀬 丈一郎

    日本女性医学学会雑誌   23 ( Suppl. )   140 - 140   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

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  • Intratumoral CD8(+) Lymphocyte Infiltration as a Prognostic Factor and Its Relationship With Cyclooxygenase 2 Expression and Microsatellite Instability in Endometrial Cancer 査読

    Tomohiro Suemori, Nobuyuki Susumu, Takashi Iwata, Kouji Banno, Wataru Yamagami, Akira Hirasawa, Kokichi Sugano, Eri Matsumoto, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   25 ( 7 )   1165 - 1172   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer.
    Methods The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8(+) T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses.
    Results The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (&lt;10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression.
    Conclusions The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

    DOI: 10.1097/IGC.0000000000000482

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  • High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer. 国際誌

    Reiko Iwadate, Jun Inoue, Hitoshi Tsuda, Masashi Takano, Kenichi Furuya, Akira Hirasawa, Daisuke Aoki, Johji Inazawa

    The American journal of pathology   185 ( 9 )   2523 - 33   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    High expression of SQSTM1/p62 (p62) protein, which functions as a hub of oncogenic signaling pathways, has been detected in several human cancers. However, the clinicopathological and functional contribution of p62 expression is largely unknown in endometrial cancers (ECs). In this study, we assessed the expression status of p62 in primary ECs (n = 194) by immunohistochemistry and analyzed its clinical significance. Although p62 was expressed in the cytoplasm and/or nucleus in primary ECs, we observed that an expression subtype, high expression of cytoplasmic p62 but low expression of nuclear p62 (cytoplasm(High)/nucleus(Low)), significantly correlated with nonendometrioid types (P = 0.002), high grade (P < 0.001), deep myometrial invasion (P = 0.025), vascular invasion (P = 0.012), and poor prognosis (P < 0.001), and may be an independent prognostic marker of ECs (P = 0.011). Furthermore, RNA interference-mediated inhibition of p62 expression in the HEC-1A EC cell line led to the reduction of invasiveness and resistance to oxidative stress in vitro, as well as the suppression of in vivo tumor growth in an orthotopic mouse model of ECs. High expression of cytoplasmic p62 is a novel prognostic biomarker of ECs, and excess p62 expression may functionally contribute to the acquirement of malignant phenotypes in EC cells.

    DOI: 10.1016/j.ajpath.2015.05.008

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  • Intratumoral CD8+ Lymphocyte Infiltration as a Prognostic Factor and Its Relationship With Cyclooxygenase 2 Expression and Microsatellite Instability in Endometrial Cancer. 国際誌

    Tomohiro Suemori, Nobuyuki Susumu, Takashi Iwata, Kouji Banno, Wataru Yamagami, Akira Hirasawa, Kokichi Sugano, Eri Matsumoto, Daisuke Aoki

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society   25 ( 7 )   1165 - 72   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer. METHODS: The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8 T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses. RESULTS: The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression. CONCLUSIONS: The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

    DOI: 10.1097/IGC.0000000000000482

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  • Polymorphisms of estrogen metabolism-related genes ESR1, UGT2B17, and UGT1A1 are not associated with osteoporosis in surgically menopausal Japanese women. 査読 国際誌

    Megumi Yokota, Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Kensuke Sakai, Takeshi Makabe, Yuko Horiba, Wataru Yamagami, Mariko Ogawa, Takashi Iwata, Shigehisa Yanamoto, Ryota Deshimaru, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Przeglad menopauzalny = Menopause review   14 ( 3 )   161 - 7   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Termedia Publishing House Ltd.  

    INTRODUCTION: Bilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve their quality of life. MATERIAL AND METHODS: This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 (ESR1) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated. RESULTS: No significant association was found between osteoporosis and polymorphisms in ESR1, UGT2B17, or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations. CONCLUSIONS: These results suggest that the ESR1, UGT2B17, and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

    DOI: 10.5114/pm.2015.54339

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  • 一般病院における家族性腫瘍相談外来とハイリスク外来の開設

    植木 有紗, 安齋 純子, 中田 さくら, 麻薙 美香, 嶋田 恭輔, 久保内 光一, 三須 久美子, 平沢 晃, 阪埜 浩司, 菅野 康吉, 小崎 健次郎, 青木 大輔

    家族性腫瘍   15 ( 2 )   A96 - A96   2015年5月

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    記述言語:日本語   出版者・発行元:(一社)日本遺伝性腫瘍学会  

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  • 当科健康維持外来初診患者に認められた甲状腺機能異常の現状

    横田めぐみ, 牧田和也, 堀場裕子, 平沢 晃, 小川真里子, 弟子丸亮太, 柳本茂久, 高松 潔, 青木大輔

    日本女性医学学会雑誌   22 ( 2 )   133 - 137   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    【目的】当科「健康維持外来」では、2007年5月より初診時の血液検査項目に、甲状腺刺激ホルモン(TSH)と遊離サイロキシン(fT4)の2項目を甲状腺機能のスクリーニングのために加えている。今回我々は、当外来初診患者に認められた甲状腺機能異常について、潜在性甲状腺機能異常も含めて検証したので報告する。【対象と方法】2007年5月より2014年4月末までの7年間に当外来を受診した初診患者537例(平均年齢51.7歳)に施行した血清TSHおよびfT4の値から、各症例の甲状腺機能を評価した。そしてこれらの測定値が当院で規定されている基準範囲を逸脱している症例については、当外来初診後の甲状腺機能に関する診療経過等について、外来診療録より追跡調査を行った。【結果】(1)症例全体としては、甲状腺機能および血清脂質はいずれも基準範囲であり、体格因子に関しても同様であった。(2)537例中499例(92.9%)は、TSH値とfT4値いずれもが基準範囲であった。甲状腺機能低下症と臨床診断された症例が1例(0.2%)、甲状腺の機能亢進状態であった症例は6例(1.1%)認められた。(3)潜在性甲状腺機能亢進症と診断された症例は、537例中4例(0.7%)に認められた。(4)潜在性甲状腺機能低下症と診断された症例は、537例中23例(4.4%)に認められ、2項目ともに基準範囲であった症例以外では最も多かった。(5)基準範囲例と潜在性甲状腺機能低下症例の2群間では、年齢・体格因子・血清脂質に有意差を認めなかった。【考察】当外来受診患者の9割以上の症例で甲状腺機能は正常であったが、潜在性甲状腺機能低下症例が少なからず存在することが判明し、その罹患率はわが国における人間ドック受診者を対象とした報告に匹敵するものであった。従って、主に更年期女性を対象としている当外来において甲状腺機能のスクリーニング検査を行うことは、有用であると考えられた。(著者抄録)

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  • 子宮体がんの予防とへするケア-妊孕性温存と術後のQOL改善を目指して-

    進 伸幸, 平沢 晃, 山上 亘, 片岡史夫, 岩田 卓, 牧田和也, 阪埜浩司, 青木大輔

    日本女性医学学会雑誌   22 ( 2 )   282 - 104   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

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  • Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer. 査読 国際誌

    Masataka Adachi, Kouji Banno, Megumi Yanokura, Miho Iida, Kanako Nakamura, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Iori Kisu, Arisa Ueki, Akira Hirasawa, Eiichiro Tominaga, Daisuke Aoki

    Molecular and clinical oncology   3 ( 2 )   267 - 273   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Risk-reducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingo-oophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer.

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  • Clinicopathologic Analysis With Immunohistochemistry for DNA Mismatch Repair Protein Expression in Synchronous Primary Endometrial and Ovarian Cancers 査読

    Yusuke Kobayashi, Kanako Nakamura, Hiroyuki Nomura, Kouji Banno, Haruko Irie, Masataka Adachi, Miho Iida, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Iori Kisu, Arisa Ueki, Wataru Yamagami, Fumio Kataoka, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   25 ( 3 )   440 - 446   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers.
    Methods: Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers.
    Results: Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II.
    Conclusions: These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

    DOI: 10.1097/IGC.0000000000000377

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  • Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers. 国際誌

    Yusuke Kobayashi, Kanako Nakamura, Hiroyuki Nomura, Kouji Banno, Haruko Irie, Masataka Adachi, Miho Iida, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Iori Kisu, Arisa Ueki, Wataru Yamagami, Fumio Kataoka, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society   25 ( 3 )   440 - 6   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. METHODS: Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. RESULTS: Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. CONCLUSIONS: These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

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  • 遺伝性乳癌・卵巣癌とLynch症候群のリスク低減手術

    安達将隆, 阪埜浩司, 増田健太, 植木有紗, 平沢 晃, 冨永英一郎, 青木大輔

    産婦人科の実際   64 ( 3 )   377 - 383   2015年3月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia. 国際誌

    Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Wataru Yamagami, Takeshi Makabe, Megumi Yokota, Yuko Horiba, Mariko Ogawa, Shigehisa Yanamoto, Rhota Deshimaru, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Japanese journal of clinical oncology   45 ( 1 )   127 - 31   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

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  • Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia 査読

    Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Wataru Yamagami, Takeshi Makabe, Megumi Yokota, Yuko Horiba, Mariko Ogawa, Shigehisa Yanamoto, Rhota Deshimaru, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   45 ( 1 )   127 - 131   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

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  • Polymorphisms of estrogen metabolism-related genes ESR1, UGT2B17, and UGT1A1 are not associated with osteoporosis in surgically menopausal Japanese women

    Megumi Yokota, Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Kensuke Sakai, Takeshi Makabe, Yuko Horiba, Wataru Yamagami, Mariko Ogawa, Takashi Iwata, Shigehisa Yanamoto, Ryota Deshimaru, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    MENOPAUSE REVIEW-PRZEGLAD MENOPAUZALNY   14 ( 3 )   161 - 167   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TERMEDIA PUBLISHING HOUSE LTD  

    Introduction: Bilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve their quality of life.Material and methods: This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 (ESR1) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated.Results: No significant association was found between osteoporosis and polymorphisms in ESR1, UGT2B17, or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations.Conclusions: These results suggest that the ESR1, UGT2B17, and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

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  • BRCA1/2遺伝子変異保持者に対するリスク低減卵管卵巣摘出術とサーベイランス 招待 査読

    平沢 晃, 増田健太, 青木大輔

    産科と婦人科   82 ( 6 )   639 - 643   2015年

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

    遺伝性乳癌卵巣癌(HBOC)の原因遺伝子であるBRCA1またはBRCA2(BRCA1/2)の遺伝子変異保持者(mutant carrier)に対する有効な卵巣癌スクリーニング法は確立されていない。BRCA1/2遺伝子変異保持者に対してリスク低減卵管卵巣摘出術(RRSO)を実施することにより卵巣癌や卵管癌の発症リスクが低減することは確実である。また卵巣癌や乳癌による死亡率を低減することもほぼ確実とされている。RRSOの検体からはoccult cancerが見つかることもあるため病理医との連携が重要である。RRSO施行後は腹膜癌の発症リスクが残るため引き続きサーベイランスが必要であるとともに、卵巣摘出に伴うエストロゲン欠落症状にも対応する。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00525&link_issn=&doc_id=20150603110007&doc_link_id=%2Fae4sanke%2F2015%2F008206%2F008%2F0639-0643%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2015%2F008206%2F008%2F0639-0643%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer. 査読

    Iwadate R, Inoue J, Tsuda H, Takano M, Furuya K, Hirasawa A, Aoki D, Inazawa J

    Am J Pathol   185 ( 9 )   2523 - 2533   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ajpath.2015.05.008

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  • 遺伝性乳癌卵巣癌の遺伝子検査 査読

    平沢 晃, 増田健太, 青木大輔

    産科と婦人科   82 ( Sup )   202 - 205   2015年

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

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  • 臓器・領域別家族性腫瘍の臨床 卵巣癌 招待 査読

    植木有紗, 増田健太, 平沢 晃, 中田さくら, 青木大輔

    日本臨床   73 ( 6 )   462 - 466   2015年

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • 遺伝性乳癌卵巣癌 招待 査読

    平沢 晃, 増田健太, 青木大輔

    臨床画像   31 ( 10 )   220 - 221   2015年

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    記述言語:日本語   出版者・発行元:(株)メジカルビュー社  

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  • 子宮体癌の予防とヘルスケア 招待 査読

    進 伸幸, 平沢 晃, 山上 亘, 青木大輔

    産婦人科の実際   64 ( 1 )   1741 - 1750   2015年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Features of ovarian cancer in Lynch syndrome (Review). 査読 国際誌

    Kanako Nakamura, Kouji Banno, Megumi Yanokura, Miho Iida, Masataka Adachi, Kenta Masuda, Arisa Ueki, Yusuke Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Eiichiro Tominaga, Daisuke Aoki

    Molecular and clinical oncology   2 ( 6 )   909 - 916   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

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  • Clinicopathological study on para-aortic lymph node metastasis without pelvic lymph node metastasis in endometrial cancer. 査読 国際誌

    Shoko Tomisato, Wataru Yamagami, Nobuyuki Susumu, Michiko Kuwahata, Aya Takigawa, Hiroyuki Nomura, Fumio Kataoka, Akira Hirasawa, Kouji Banno, Daisuke Aoki

    The journal of obstetrics and gynaecology research   40 ( 6 )   1733 - 9   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    AIM: One of the important risk factors for recurrence of endometrial cancer is lymph node metastasis. The regional lymph nodes are pelvic lymph nodes (PLN) and para-aortic lymph nodes (PAN). PAN metastasis was often detected in the cases with PLN metastasis. However, PAN metastasis not associated with PLN metastasis was identified in a few cases. We focused on nine cases with PAN metastasis and without PLN metastasis. MATERIAL AND METHODS: The subjects of this study were 260 cases that were diagnosed with endometrial cancer. The initial treatments were surgery, including pelvic and para-aortic lymphadenectomy. Nine of these cases had PAN metastasis but did not have PLN metastasis. We retrospectively analyzed the clinicopathological factors and prognosis in cases with PLN-PAN+ cases. RESULTS: A total of 91 (35%) cases were identified as positive for either PLN or PAN. PAN metastases were detected in 62.6% of the cases that had some regional lymph node metastases and 3.5% of all cases were PLN- and PAN+. In all PLN-PAN+ cases, PAN swelling was not detected by preoperative chest-abdominal computed tomography scan. There were no clear trends among risk factors of regional lymph node metastasis. The 5-year progression-free survival was 87.1% for PLN-PAN- cases, 67.5% for PLN+PAN- cases, 44.4% for PLN-PAN+ cases, and 33.2% for PLN+PAN+ cases. CONCLUSION: During diagnosis and treatment for endometrial cancer, PLN-PAN+ cases should also be considered because the prognosis in PLN-PAN+ cases tended to be lower than that in PLN-PAN- cases and PLN+PAN- cases.

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  • Clinicopathological study on para-aortic lymph node metastasis without pelvic lymph node metastasis in endometrial cancer

    Shoko Tomisato, Wataru Yamagami, Nobuyuki Susumu, Michiko Kuwahata, Aya Takigawa, Hiroyuki Nomura, Fumio Kataoka, Akira Hirasawa, Kouji Banno, Daisuke Aoki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   40 ( 6 )   1733 - 1739   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Aim One of the important risk factors for recurrence of endometrial cancer is lymph node metastasis. The regional lymph nodes are pelvic lymph nodes (PLN) and para-aortic lymph nodes (PAN). PAN metastasis was often detected in the cases with PLN metastasis. However, PAN metastasis not associated with PLN metastasis was identified in a few cases. We focused on nine cases with PAN metastasis and without PLN metastasis. Material and Methods The subjects of this study were 260 cases that were diagnosed with endometrial cancer. The initial treatments were surgery, including pelvic and para-aortic lymphadenectomy. Nine of these cases had PAN metastasis but did not have PLN metastasis. We retrospectively analyzed the clinicopathological factors and prognosis in cases with PLN-PAN+ cases. Results A total of 91 (35%) cases were identified as positive for either PLN or PAN. PAN metastases were detected in 62.6% of the cases that had some regional lymph node metastases and 3.5% of all cases were PLN- and PAN+. In all PLN-PAN+ cases, PAN swelling was not detected by preoperative chest-abdominal computed tomography scan. There were no clear trends among risk factors of regional lymph node metastasis. The 5-year progression-free survival was 87.1% for PLN-PAN- cases, 67.5% for PLN+PAN- cases, 44.4% for PLN-PAN+ cases, and 33.2% for PLN+PAN+ cases. Conclusion During diagnosis and treatment for endometrial cancer, PLN-PAN+ cases should also be considered because the prognosis in PLN-PAN+ cases tended to be lower than that in PLN-PAN- cases and PLN+PAN- cases.

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  • A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region

    Yusuke Kobayashi, Kenta Masuda, Tokuhiro Kimura, Hiroyuki Nomura, Akira Hirasawa, Kouji Banno, Nobuyuki Susumu, Kokichi Sugano, Daisuke Aoki

    FUTURE ONCOLOGY   10 ( 2 )   171 - 177   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FUTURE MEDICINE LTD  

    Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma.

    DOI: 10.2217/FON.13.180

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  • A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region. 査読 国際誌

    Yusuke Kobayashi, Kenta Masuda, Tokuhiro Kimura, Hiroyuki Nomura, Akira Hirasawa, Kouji Banno, Nobuyuki Susumu, Kokichi Sugano, Daisuke Aoki

    Future oncology (London, England)   10 ( 2 )   171 - 7   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FUTURE MEDICINE LTD  

    Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma.

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  • Family History and BRCA1/BRCA2 Status Among Japanese Ovarian Cancer Patients and Occult Cancer in a BRCA1 Mutant Case 査読

    Akira Hirasawa, Kenta Masuda, Tomoko Akahane, Arisa Ueki, Megumi Yokota, Tomohiko Tsuruta, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Kazuya Makita, Nobuyuki Susumu, Kokichi Sugano, Kenjiro Kosaki, Kaori Kameyama, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   44 ( 1 )   49 - 56   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer.
    One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer.
    Nine of 102 (8.8) families were regarded as having hereditary breastovarian cancer syndrome, two families (2.0) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case.
    Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

    DOI: 10.1093/jjco/hyt171

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  • Family history and BRCA1/BRCA2 status among Japanese ovarian cancer patients and occult cancer in a BRCA1 mutant case. 国際誌

    Akira Hirasawa, Kenta Masuda, Tomoko Akahane, Arisa Ueki, Megumi Yokota, Tomohiko Tsuruta, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Kazuya Makita, Nobuyuki Susumu, Kokichi Sugano, Kenjiro Kosaki, Kaori Kameyama, Daisuke Aoki

    Japanese journal of clinical oncology   44 ( 1 )   49 - 56   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    BACKGROUND: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. METHODS: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. RESULTS: Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. CONCLUSIONS: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

    DOI: 10.1093/jjco/hyt171

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  • 遺伝性乳がん卵巣がん(HBOC)への対応 査読

    増田健太, 阪埜浩司, 植木有紗, 平沢 晃, 青木大輔

    産婦人科の実際   63 ( 7 )   973 - 980   2014年

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

    Reiko Iwadate, Jun Inoue, Hitoshi Tsuda, Masashi Takano, Kenichi Furuya, Akira Hirasawa, Daisuke Aoki, Johji Inazawa

    ACTA HISTOCHEMICA ET CYTOCHEMICA   47 ( 6 )   295 - 301   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY  

    High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary E0Cs, and an expression subtype (Cyto(High)/Nuc(Low)), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P&lt;0.001), advanced stage (P=0.005), presence of residual tumor (P&lt;0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto(High)/Nuc(Low) subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.

    DOI: 10.1267/ahc.14048

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  • Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients. 国際誌

    Akira Hirasawa, Takeru Zama, Tomoko Akahane, Hiroyuki Nomura, Fumio Kataoka, Koichiro Saito, Keisuke Okubo, Eiichiro Tominaga, Kazuya Makita, Nobuyuki Susumu, Kenjiro Kosaki, Yusuke Tanigawara, Daisuke Aoki

    Journal of human genetics   58 ( 12 )   794 - 8   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Irinotecan is a key chemotherapeutic drug used to treat many tumors, including cervical and ovarian cancers; however, irinotecan can cause toxicity, particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity. Here, we investigated the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan-induced adverse events in patients with gynecologic cancer, who are treated with lower doses of irinotecan than patients with other types of solid tumors. Fifty-three female patients treated with irinotecan and 362 female patients not treated with irinotecan were screened for UGT1A1*6, UGT1A1*27 and UGT1A1*28. Homozygosity for UGT1A1*6 or heterozygosity for UGT1A1*6/*28 was associated with a high risk of severe absolute neutrophil count decrease or diarrhea (odds ratios: 16.03 and 31.33, respectively). In contrast, serum bilirubin levels were not associated with irinotecan toxicity. Homozygosity for UGT1A1*6/*6 and heterozygosity for UGT1A1*6/*28 were associated with an increased risk of absolute neutrophil count and/or diarrhea in Japanese gynecologic cancer patients, despite the lower doses of irinotecan used in these patients. UGT1A1*6 and UGT1A1*28 are potential predictors of severe absolute neutrophil decrease and diarrhea caused by low-dose irinotecan in gynecologic cancer patients.

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  • Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients

    Akira Hirasawa, Takeru Zama, Tomoko Akahane, Hiroyuki Nomura, Fumio Kataoka, Koichiro Saito, Keisuke Okubo, Eiichiro Tominaga, Kazuya Makita, Nobuyuki Susumu, Kenjiro Kosaki, Yusuke Tanigawara, Daisuke Aoki

    Journal of Human Genetics   58 ( 12 )   794 - 798   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Irinotecan is a key chemotherapeutic drug used to treat many tumors, including cervical and ovarian cancers
    however, irinotecan can cause toxicity, particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity. Here, we investigated the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan-induced adverse events in patients with gynecologic cancer, who are treated with lower doses of irinotecan than patients with other types of solid tumors. Fifty-three female patients treated with irinotecan and 362 female patients not treated with irinotecan were screened for UGT1A1*6, UGT1A1*27 and UGT1A1*28. Homozygosity for UGT1A1*6 or heterozygosity for UGT1A1*6/*28 was associated with a high risk of severe absolute neutrophil count decrease or diarrhea (odds ratios: 16.03 and 31.33, respectively). In contrast, serum bilirubin levels were not associated with irinotecan toxicity. Homozygosity for UGT1A1*6/*6 and heterozygosity for UGT1A1*6/*28 were associated with an increased risk of absolute neutrophil count and/or diarrhea in Japanese gynecologic cancer patients, despite the lower doses of irinotecan used in these patients. UGT1A1*6 and UGT1A1*28 are potential predictors of severe absolute neutrophil decrease and diarrhea caused by low-dose irinotecan in gynecologic cancer patients. © 2013 The Japan Society of Human Genetics All rights reserved 1434-5161/13.

    DOI: 10.1038/jhg.2013.105

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  • Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients 査読

    Akira Hirasawa, Takeru Zama, Tomoko Akahane, Hiroyuki Nomura, Fumio Kataoka, Koichiro Saito, Keisuke Okubo, Eiichiro Tominaga, Kazuya Makita, Nobuyuki Susumu, Kenjiro Kosaki, Yusuke Tanigawara, Daisuke Aoki

    Journal of Human Genetics   58 ( 12 )   794 - 798   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Irinotecan is a key chemotherapeutic drug used to treat many tumors, including cervical and ovarian cancers
    however, irinotecan can cause toxicity, particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity. Here, we investigated the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan-induced adverse events in patients with gynecologic cancer, who are treated with lower doses of irinotecan than patients with other types of solid tumors. Fifty-three female patients treated with irinotecan and 362 female patients not treated with irinotecan were screened for UGT1A1*6, UGT1A1*27 and UGT1A1*28. Homozygosity for UGT1A1*6 or heterozygosity for UGT1A1*6/*28 was associated with a high risk of severe absolute neutrophil count decrease or diarrhea (odds ratios: 16.03 and 31.33, respectively). In contrast, serum bilirubin levels were not associated with irinotecan toxicity. Homozygosity for UGT1A1*6/*6 and heterozygosity for UGT1A1*6/*28 were associated with an increased risk of absolute neutrophil count and/or diarrhea in Japanese gynecologic cancer patients, despite the lower doses of irinotecan used in these patients. UGT1A1*6 and UGT1A1*28 are potential predictors of severe absolute neutrophil decrease and diarrhea caused by low-dose irinotecan in gynecologic cancer patients. © 2013 The Japan Society of Human Genetics All rights reserved 1434-5161/13.

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  • Hereditary gynecological tumors associated with Peutz-Jeghers syndrome 査読

    Kouji Banno, Iori Kisu, Megumi Yanokura, Kenta Masuda, Arisa Ueki, Yusuke Kobayashi, Akira Hirasawa, Daisuke Aoki

    ONCOLOGY LETTERS   6 ( 5 )   1184 - 1188   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

    DOI: 10.3892/ol.2013.1527

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  • Hypertriglyceridemia is Frequent in Endometrial Cancer Survivors

    Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Megumi Yokota, Wataru Yamagami, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   43 ( 11 )   1087 - 1092   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Objective: Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic.
    Methods: This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed.
    Results: Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls.
    Conclusions: Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors.

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  • Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review). 国際誌

    Kouji Banno, Iori Kisu, Megumi Yanokura, Kenta Masuda, Arisa Ueki, Yusuke Kobayashi, Akira Hirasawa, Daisuke Aoki

    Oncology letters   6 ( 5 )   1184 - 1188   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

    DOI: 10.3892/ol.2013.1527

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  • Hereditary gynecological tumors associated with Peutz-Jeghers syndrome

    Kouji Banno, Iori Kisu, Megumi Yanokura, Kenta Masuda, Arisa Ueki, Yusuke Kobayashi, Akira Hirasawa, Daisuke Aoki

    ONCOLOGY LETTERS   6 ( 5 )   1184 - 1188   2013年11月

     詳細を見る

    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

    DOI: 10.3892/ol.2013.1527

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  • Hypertriglyceridemia is frequent in endometrial cancer survivors. 査読 国際誌

    Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Megumi Yokota, Wataru Yamagami, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Japanese journal of clinical oncology   43 ( 11 )   1087 - 92   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    OBJECTIVE: Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. METHODS: This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. RESULTS: Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. CONCLUSIONS: Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors.

    DOI: 10.1093/jjco/hyt125

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  • Hypertriglyceridemia is Frequent in Endometrial Cancer Survivors

    Akira Hirasawa, Kazuya Makita, Tomoko Akahane, Megumi Yokota, Wataru Yamagami, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   43 ( 11 )   1087 - 1092   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Objective: Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic.
    Methods: This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed.
    Results: Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls.
    Conclusions: Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors.

    DOI: 10.1093/jjco/hyt125

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  • Distinguishing between lymphangioleiomyomatosis and carcinomatous peritonitis in a patient with ovarian cancer. 国際誌

    Akira Hirasawa, Takashi Sato, Mari Ueno, Tomoko Akahane, Nobuyuki Susumu, Tomoko Betsuyaku, Daisuke Aoki

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology   31 ( 28 )   e427-9 - E429   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • Distinguishing Between Lymphangioleiomyomatosis and Carcinomatous Peritonitis in a Patient With Ovarian Cancer

    Akira Hirasawa, Takashi Sato, Mari Ueno, Tomoko Akahane, Nobuyuki Susumu, Tomoko Betsuyaku, Daisuke Aoki

    JOURNAL OF CLINICAL ONCOLOGY   31 ( 28 )   E427 - E429   2013年10月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2012.45.3019

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  • Distinguishing Between Lymphangioleiomyomatosis and Carcinomatous Peritonitis in a Patient With Ovarian Cancer 査読

    Akira Hirasawa, Takashi Sato, Mari Ueno, Tomoko Akahane, Nobuyuki Susumu, Tomoko Betsuyaku, Daisuke Aoki

    JOURNAL OF CLINICAL ONCOLOGY   31 ( 28 )   E427 - E429   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer

    Koichiro Saito, Koji Inagaki, Takahiro Kamimoto, Yoko Ito, Toshiaki Sugita, Satoko Nakajo, Akira Hirasawa, Arifumi Iwamaru, Takashi Ishikura, Hideki Hanaoka, Keisuke Okubo, Tokio Onozaki, Takeru Zama

    PLOS ONE   8 ( 8 )   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue-or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary.
    Methodology/Principal Findings: To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model.
    Conclusions/Significance: Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.

    DOI: 10.1371/journal.pone.0071480

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  • MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer

    Koichiro Saito, Koji Inagaki, Takahiro Kamimoto, Yoko Ito, Toshiaki Sugita, Satoko Nakajo, Akira Hirasawa, Arifumi Iwamaru, Takashi Ishikura, Hideki Hanaoka, Keisuke Okubo, Tokio Onozaki, Takeru Zama

    PLOS ONE   8 ( 8 )   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue-or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary.
    Methodology/Principal Findings: To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model.
    Conclusions/Significance: Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.

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  • β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation

    Villacorte M, Suzuki K, Hirasawa A, Ohkawa Y, Suyama M, Maruyama T, Aoki D, Ogino Y, Miyagawa S, Terabayashi T, Tomooka Y, Nakagata N, Yamada G

    Oncogene   32 ( 29 )   3477 - 3482   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    &lt;p&gt;The Wnt/β-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated β-catenin signaling is associated with the formation of endometrial adenocarcinomas (EACs), which is considered as the common form of endometrial cancer in women. In the current study, we investigate the downstream target of Wnt/β-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of β-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that β-catenin regulates Foxa2 with its candidate upstream region for the uterine epithelia. Furthermore, knockdown of Foxa2 leads to defects in cell cycle regulation, suggesting a possible function of Foxa2 in the control of cell proliferation. We also observe that β-catenin and Foxa2 expression levels are augmented in the human specimens of complex atypical endometrial hyperplasia, which is considered to have a greater risk of progression to EACs. Thus, our study indicates that β-catenin regulates Foxa2 expression,

    DOI: 10.1038/onc.2012.376

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  • β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation. 査読

    Villacorte M, Suzuki K, Hirasawa A, Ohkawa Y, Suyama M, Maruyama T, Aoki D, Ogino Y, Miyagawa S, Terabayashi T, Tomooka Y, Nakagata N, Yamada G

    Oncogene   32 ( 29 )   3477 - 3482   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/onc.2012.376

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  • β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation

    Villacorte M, Suzuki K, Hirasawa A, Ohkawa Y, Suyama M, Maruyama T, Aoki D, Ogino Y, Miyagawa S, Terabayashi T, Tomooka Y, Nakagata N, Yamada G

    Oncogene   32 ( 29 )   3477 - 3482   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    &lt;p&gt;The Wnt/β-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated β-catenin signaling is associated with the formation of endometrial adenocarcinomas (EACs), which is considered as the common form of endometrial cancer in women. In the current study, we investigate the downstream target of Wnt/β-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of β-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that β-catenin regulates Foxa2 with its candidate upstream region for the uterine epithelia. Furthermore, knockdown of Foxa2 leads to defects in cell cycle regulation, suggesting a possible function of Foxa2 in the control of cell proliferation. We also observe that β-catenin and Foxa2 expression levels are augmented in the human specimens of complex atypical endometrial hyperplasia, which is considered to have a greater risk of progression to EACs. Thus, our study indicates that β-catenin regulates Foxa2 expression,

    DOI: 10.1038/onc.2012.376

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  • Experience of risk-reducing salpingo-oophorectomy for a BRCA1 mutation carrier and establishment of a system performing a preventive surgery for hereditary breast and ovarian cancer syndrome in Japan: our challenges for the future. 国際誌

    Akira Hirasawa, Kenta Masuda, Tomoko Akahane, Tomohiko Tsuruta, Kouji Banno, Kazuya Makita, Nobuyuki Susumu, Hiromitsu Jinno, Yuko Kitagawa, Kokichi Sugano, Kenjiro Kosaki, Daisuke Aoki

    Japanese journal of clinical oncology   43 ( 5 )   515 - 9   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    BACKGROUND: Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan. METHODS: We developed the first system in Japan for performing risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008. RESULTS: The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan. CONCLUSIONS: Recent treatment guidelines for breast cancer in Japan recommended risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingo-oophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future.

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  • Experience of Risk-reducing Salpingo-oophorectomy for a BRCA1 Mutation Carrier and Establishment of a System Performing a Preventive Surgery for Hereditary Breast and Ovarian Cancer Syndrome in Japan: Our Challenges for the Future

    Akira Hirasawa, Kenta Masuda, Tomoko Akahane, Tomohiko Tsuruta, Kouji Banno, Kazuya Makita, Nobuyuki Susumu, Hiromitsu Jinno, Yuko Kitagawa, Kokichi Sugano, Kenjiro Kosaki, Daisuke Aoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   43 ( 5 )   515 - 519   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan.
    We developed the first system in Japan for performing risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008.
    The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan.
    Recent treatment guidelines for breast cancer in Japan recommended risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingo-oophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future.

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  • 高用量黄体ホルモン療法後に妊娠に至った若年性子宮体癌および複雑型子宮内膜異型増殖症43例の妊娠予後と分娩後のサーベイランス 査読

    山上 亘, 進 伸幸, 市川 義一, 桑波田 美智子, 野村 弘行, 平沢 晃, 峰岸 一宏, 冨永 英一郎, 宮越 敬, 阪埜 浩司, 青木 大輔, 吉村 泰典

    日本産科婦人科学会雑誌   65 ( 2 )   574 - 574   2013年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • The origin of stroma surrounding epithelial ovarian cancer cells. 国際誌

    Tomoko Akahane, Akira Hirasawa, Hiroshi Tsuda, Fumio Kataoka, Sadako Nishimura, Hideo Tanaka, Eiichiro Tominaga, Hiroyuki Nomura, Tatsuyuki Chiyoda, Yoko Iguchi, Wataru Yamagami, Nobuyuki Susumu, Daisuke Aoki

    International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists   32 ( 1 )   26 - 30   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

    DOI: 10.1097/PGP.0b013e3182518533

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  • 遺伝性乳癌・卵巣癌に対する婦人科の取り組み 招待

    平沢 晃, 青木大輔

    化療ニュース   22 ( 2 )   13 - 19   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • ホルモンによるがんの化学予防 招待 査読

    平沢 晃, 鶴田智彦, 青木大輔

    産科と婦人科   80 ( Sup )   164 - 168   2013年

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

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  • 遺伝性乳癌・卵巣癌女性への遺伝カウンセリング 招待 査読

    平沢 晃, 青木大輔

    産科と婦人科   80 ( 11 )   1465 - 1472   2013年

  • 当科健康維持外来患者からみためまいの現状 招待

    牧田和也, 橫田めぐみ, 堀場裕子, 平沢 晃, 小川真里子, 弟子丸亮太, 柳本茂久, 高松 潔, 青木大輔, 吉村泰典

    日本女性医学学会雑誌   21 ( 1 )   54 - 59   2013年

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    【目的】めまいは、古くはKuppermanの閉経期指数にも取り上げられているが、その真の原因が同定出来ないケースも少なくなく、更年期障害の一症状として治療するとしても、その対応に苦慮するケースが少なくない。今回我々は、当科「健康維持外来」受診者に認められためまいの現状について検証を行ったので報告する。【対象と方法】2007年10月より2010年9月末までの3年間に、当外来を受診した初診患者443例の初診時の40症状から成る「健康維持外来調査票」の記入結果を検証した。各症状について、症状なし、(症状)弱、中、強の4段階で評価していくが、今回はめまいに関して「中」ないし「強」と回答した64例を抽出し、これら全症例の初診後の臨床経過について外来診療録より追跡調査を行った。【結果】(1)めまいに対して、443例中48例(10.8%)が「中」、16例(3.6%)が「強」と回答した。(2)当外来受診後、12例が耳鼻咽喉科に、4例が神経内科に、3例が精神神経科に診療依頼を行った。精神神経科を受診した3例は、めまい自体も精神症状由来のものと判断されたが、それ以外の16例のうちめまいに対する明らかな病名診断を得たのは、耳鼻咽喉科に依頼した2例(良性発作性頭位めまい症)に過ぎなかった。(3)依頼した診療科でめまいの治療を行った5例を除く59例中38例は、元々自覚的には気になるめまいを認めず、11例はその後の外来受診時には、めまいは完全に消失していた。(4)「めまい」を含めた各症状の程度を点数化した上で、「めまい」を従属変数、他の39項目を独立した変数として重回帰分析を行った結果、有意差(p<0.05)をもって関連が深い症状は、「動悸」および「吐き気」のみであった。【考察】更年期周辺女性に認められるめまいの(真の)病態解明に当たっては、耳鼻咽喉科医や神経内科医などとの綿密な病診連携が必要であると考える。(著者抄録)

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  • 子宮峡部癌の臨床病理学的特徴とLynch症候群との関連 招待 査読

    増田健太, 阪埜浩司, 矢野倉恵, 小林佑介, 辻 浩介, 木須伊織, 植木有紗, 野村弘行, 平沢 晃, 進 伸幸, 青木大輔

    家族性腫瘍   13 ( 1 )   1 - 5   2013年

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    記述言語:日本語   出版者・発行元:(一社)日本遺伝性腫瘍学会  

    子宮体癌は子宮体部や底部から発生することが一般的であるが,まれに体部下部から頸部上部,つまりlower uterine segment(LUS)もしくは峡部と呼ばれる領域から発生する子宮体癌が存在する.子宮峡部から発生する子宮体癌(以降,子宮峡部癌)は子宮体癌全体の3〜3.5%とまれであり,これまで小規模の報告しか存在しない.近年,子宮峡部癌が遺伝性腫瘍であるLynch症候群との関連があると報告され注目されている.一般的な子宮体癌でのLynch症候群の頻度は1〜2%といわれているが,米国の報告によると子宮峡部癌のうち29%がLynch症候群とされ,高頻度にMSH2の変異が存在するとしている.今後わが国をはじめ,より大規模な調査において子宮峡部癌の臨床病理学的特徴やLynch症候群との関連についてさらに検討する必要がある.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J03931&link_issn=&doc_id=20130830390001&doc_link_id=%2Fcg3kazok%2F2013%2F001301%2F001%2F0001-0005%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2013%2F001301%2F001%2F0001-0005%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 子宮体がんとエストロゲン 招待 査読

    進 伸幸, 山上 亘, 二宮委美, 桑波田美智子, 片岡史夫, 平沢 晃, 阪埜浩司, 青木大輔

    産婦人科の実際   62 ( 9 )   1181 - 1187   2013年

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • MicroRNA-196a is a putative diagnostic biomarker and therapeutic target for laryngeal cancer. 査読 国際誌

    Koichiro Saito, Koji Inagaki, Takahiro Kamimoto, Yoko Ito, Toshiaki Sugita, Satoko Nakajo, Akira Hirasawa, Arifumi Iwamaru, Takashi Ishikura, Hideki Hanaoka, Keisuke Okubo, Tokio Onozaki, Takeru Zama

    PloS one   8 ( 8 )   e71480   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    BACKGROUND: MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary. METHODOLOGY/PRINCIPAL FINDINGS: To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model. CONCLUSIONS/SIGNIFICANCE: Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.

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  • Establishment of a system for performing risk-reducing salpingo-oophorectomy for BRCA1 or BRCA2 mutation carriers in Japan: Our challenges for the future. 査読

    Hirasawa A, Masuda K, Akahane T, Tsuruta T, Banno K, Makita K, Susumu N, Sugano K, Kosaki K, Aoki D

    Jpn J Clin Oncol   43 ( 5 )   515-519   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Lobular endocervical glandular hyperplasia and peritoneal pigmentation associated with Peutz-Jeghers syndrome due to a germline mutation of STK11

    A. Hirasawa, T. Akahane, T. Tsuruta, Y. Kobayashi, K. Masuda, K. Banno, T. Fujii, N. Susumu, T. Itsubo, K. Kameyama, K. Sugano, D. Aoki

    ANNALS OF ONCOLOGY   23 ( 11 )   2990 - 2992   2012年11月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    DOI: 10.1093/annonc/mds492

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  • Lobular endocervical glandular hyperplasia and peritoneal pigmentation associated with Peutz-Jeghers syndrome due to a germline mutation of STK11

    A. Hirasawa, T. Akahane, T. Tsuruta, Y. Kobayashi, K. Masuda, K. Banno, T. Fujii, N. Susumu, T. Itsubo, K. Kameyama, K. Sugano, D. Aoki

    ANNALS OF ONCOLOGY   23 ( 11 )   2990 - 2992   2012年11月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

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  • Relationship of lower uterine segment cancer with Lynch syndrome: a novel case with an hMLH1 germline mutation. 査読 国際誌

    Kenta Masuda, Kouji Banno, Akira Hirasawa, Megumi Yanokura, Kosuke Tsuji, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Hiroyuki Nomura, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

    Oncology reports   28 ( 5 )   1537 - 43   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Lynch syndrome is a genetic disease that often develops in patients with endometrial cancer and is caused by abnormal DNA mismatch repair (MMR) genes. In the United States, it was recently reported that the prevalence of Lynch syndrome with an hMSH2 mutation in patients with endometrial cancer in the lower uterine segment (LUS) is much greater than that in patients with endometrial cancer, although no such reports have been published in Asia. In this study, we examined the correlation between endometrial cancer in LUS and abnormalities in MMR genes. We examined 625 patients, who were diagnosed with endometrial cancer and underwent a hysterectomy. Nine patients (1.4%) had cancer based on pathological confirmation of a tumor in the lower part of the uterus and no cancer in the upper part. These cases were compared with 27 cases of sporadic endometrial (non-LUS) cancer. The age and BMI of the patients with LUS cancer were significantly lower than those of the patients with non-LUS cancer. No differences were observed in the pathological characteristics. The microsatellite instability (MSI)-positive rates were similar. Immunohistochemistry showed a decreased expression of hMLH1 and hMSH6 in patients with LUS cancer. In contrast with earlier reports from the United States, hMSH2 was expressed in all the cases. Of the 2 patients with LUS cancer who exhibited high MSI, 1 patient showed abnormal methylation of hMLH1, while the other patient was diagnosed with Lynch syndrome with a mutation in the hMLH1 gene. This is the second report on the relationship of LUS cancer and Lynch syndrome, and the first to describe an Asian patient with LUS cancer with Lynch syndrome induced by an hMLH1 mutation.

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  • Relationship of lower uterine segment cancer with Lynch syndrome: A novel case with an hMLH1 germline mutation

    Kenta Masuda, Kouji Banno, Akira Hirasawa, Megumi Yanokura, Kosuke Tsuji, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Hiroyuki Nomura, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

    ONCOLOGY REPORTS   28 ( 5 )   1537 - 1543   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Lynch syndrome is a genetic disease that often develops in patients with endometrial cancer and is caused by abnormal DNA mismatch repair (MMR) genes. In the United States, it was recently reported that the prevalence of Lynch syndrome with an hMSH2 mutation in patients with endometrial cancer in the lower uterine segment (LUS) is much greater than that in patients with endometrial cancer, although no such reports have been published in Asia. In this study, we examined the correlation between endometrial cancer in LUS and abnormalities in MMR genes. We examined 625 patients, who were diagnosed with endometrial cancer and underwent a hysterectomy. Nine patients (1.4%) :lad cancer based on pathological confirmation of a tumor in the lower part of the uterus and no cancer in the upper part. These cases were compared with 27 cases of sporadic endometrial (non-LUS) cancer. The age and BMI of the patients with LUS cancer were significantly lower than those of the patients with non-LUS cancer. No differences were observed in the pathological characteristics. The microsatellite instability (MSI)-positive rates were similar. Immunohistochemistry showed a decreased expression of hMLH1 and hMSH6 in patients with LUS cancer. In contrast with earlier reports from the United States, hMSH2 was expressed in all the cases. Of the 2 patients with LUS cancer who exhibited high MSI, 1 patient showed abnormal methylation of hMLH1, while the other patient was diagnosed with Lynch syndrome with a mutation in the hMLH1 gene. This is the second report on the relationship of LUS cancer and Lynch syndrome, and the first to describe an Asian patient with LUS cancer with Lynch syndrome induced by an hMLH1 mutation.

    DOI: 10.3892/or.2012.2008

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  • Lobular endocervical glandular hyperplasia and peritoneal pigmentation associated with Peutz-Jeghers syndrome due to a germline mutation of STK11 査読

    A. Hirasawa, T. Akahane, T. Tsuruta, Y. Kobayashi, K. Masuda, K. Banno, T. Fujii, N. Susumu, T. Itsubo, K. Kameyama, K. Sugano, D. Aoki

    ANNALS OF ONCOLOGY   23 ( 11 )   2990 - 2992   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    DOI: 10.1093/annonc/mds492

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  • Blood-direct InvaderPlus® as a new method for genetic testing 国際誌

    Hirasawa Akira, Akahane Tomoko, Tanigawara Yusuke, Aoki Daisuke

    Personalized Medicine   9 ( 6 )   657 - 663   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    &lt;p&gt;Aim: This study compared the efficiency of Blood-direct InvaderPlus® with existing methods for detecting genetic polymorphisms by using clinical samples, and to determine whether this new method can be used for future clinical studies. Materials &amp; methods: We developed a new method, called Blood-direct InvaderPlus, for detecting genetic polymorphisms. Whole-blood samples were subjected to genetic analysis with the new method and also the conventional method. Results: The results obtained with the new method were consistent with those of direct sequencing. Blood-direct InvaderPlus was able to detect gene polymorphisms of UGT1A16,27,28,60, VKORC1 -1639G&gt;A, VKORC1 1173T&gt;C and CYP2C92 and3 much faster than the conventional methods. Conclusion: Blood-direct InvaderPlus allowed accurate, simple and rapid detection of genetic polymorphisms. © 2012 Future Medicine Ltd.&lt;/p&gt;

    DOI: 10.2217/pme.12.71

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  • Blood-direct InvaderPlus (R) as a new method for genetic testing 査読

    Akira Hirasawa, Tomoko Akahane, Yusuke Tanigawara, Daisuke Aoki

    PERSONALIZED MEDICINE   9 ( 6 )   657 - 663   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FUTURE MEDICINE LTD  

    Aim: This study compared the efficiency of Blood-direct InvaderPlus (R) with existing methods for detecting genetic polymorphisms by using clinical samples, and to determine whether this new method can be used for future clinical studies. Materials & methods: We developed a new method, called Blood-direct InvaderPlus, for detecting genetic polymorphisms. Whole-blood samples were subjected to genetic analysis with the new method and also the conventional method. Results: The results obtained with the new method were consistent with those of direct sequencing. Blood-direct InvaderPlus was able to detect gene polymorphisms of UGT1A1*6, *2Z *28, *60, VKORC1 -1639G&gt;A, VKORC1 1173T&gt;C and CYP2C9 *2 and *3 much faster than the conventional methods. Conclusion: Blood-direct InvaderPlus allowed accurate, simple and rapid detection of genetic polymorphisms.

    DOI: 10.2217/PME.12.71

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  • Blood-direct InvaderPlus® as a new method for genetic testing

    Hirasawa Akira, Akahane Tomoko, Tanigawara Yusuke, Aoki Daisuke

    Personalized Medicine   9 ( 6 )   657 - 663   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    &lt;p&gt;Aim: This study compared the efficiency of Blood-direct InvaderPlus® with existing methods for detecting genetic polymorphisms by using clinical samples, and to determine whether this new method can be used for future clinical studies. Materials &amp; methods: We developed a new method, called Blood-direct InvaderPlus, for detecting genetic polymorphisms. Whole-blood samples were subjected to genetic analysis with the new method and also the conventional method. Results: The results obtained with the new method were consistent with those of direct sequencing. Blood-direct InvaderPlus was able to detect gene polymorphisms of UGT1A16,27,28,60, VKORC1 -1639G&gt;A, VKORC1 1173T&gt;C and CYP2C92 and3 much faster than the conventional methods. Conclusion: Blood-direct InvaderPlus allowed accurate, simple and rapid detection of genetic polymorphisms. © 2012 Future Medicine Ltd.&lt;/p&gt;

    DOI: 10.2217/PME.12.71

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  • 当科健康維持外来受診者における大腿骨近位部骨密度の検討

    牧田 和也, 横田 めぐみ, 堀場 裕子, 平沢 晃, 小川 真里子, 弟子丸 亮太, 柳本 茂久, 青木 大輔

    Osteoporosis Japan   20 ( 3 )   489 - 491   2012年7月

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    2008年12月〜2011年4月に当外来を初診した26〜85歳の女性252名を対象に、大腿骨近位部骨密度(F-BMD)と腰椎骨密度(L-BMD)との相関性について検討した。その結果、YAM値表記(%)によるF-BMD値とL-BMD値との間に5%超の差を認めた人が168名(67%)おり、このうちF-BMD値のほうが高い人が34名(全体の13%)、L-BMDのほうが高い人134名(53%)であった。L-BMD値から「原発性骨粗鬆症診断基準(2000年度改訂版)」に従い診断したところ、骨粗鬆症が5名(2%)、骨量減少が25名(10%)、骨量正常が222名(88%)となった。F-BMD値から同様に診断したところ、骨粗鬆症が19名(8%)、骨量減少35名(14%)、骨量正常198名(79%)となり、L-BMD値から診断した結果との一致率をみると、骨量正常群では95%の人が一致したが、骨粗鬆症群では16%、骨量減少群では29%しか一致しなかった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J03021&link_issn=&doc_id=20120815130024&doc_link_id=%2Fai6ostoe%2F2012%2F002003%2F025%2F0489-0491%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2012%2F002003%2F025%2F0489-0491%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 子宮体癌の家族発生と遺伝子診断

    平沢 晃, 鶴田友彦, 阪埜浩司, 進 伸幸, 青木大輔

    日本臨床 婦人科がん-最新の研究動向-   70 ( 増刊号4 )   292-296 - 296   2012年6月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • [Hereditary endometrial cancer and genetic testing].

    Akira Hirasawa, Tomohiko Tsuruta, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

    Nihon rinsho. Japanese journal of clinical medicine   70 Suppl 4   292 - 6   2012年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • [Hereditary endometrial cancer and genetic testing].

    Hirasawa Akira, Tsuruta Tomohiko, Banno Kouji, Susumu Nobuyuki, Aoki Daisuke

    Nihon rinsho. Japanese journal of clinical medicine   70 Suppl 4   292 - 296   2012年6月

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    記述言語:英語  

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  • EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy

    Fumio Kataoka, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Hideo Tanaka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Akira Hirasawa, Tomoko Akahane, Hiroshi Nishio, Kazuto Nishio, Daisuke Aoki

    GENES CHROMOSOMES & CANCER   51 ( 3 )   300 - 312   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Stromal components interact with cancer cells to promote growth and metastasis. The purpose of this study was to identify genes expressed in stroma, which could provide prognostic information in epithelial ovarian cancer (EOC). Seventy-four patients were included. We performed gene expression profiling and confirmed array data using RT-PCR and immunohistochemistry. By microarray analysis, 52 candidate genes associated with progression free survival (PFS) were identified (P &lt; 0.005). Expression of the early growth response 1 (EGR1) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) genes was further analyzed. Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC. Immunohistochemically, EGR1 protein is localized in cancer cells and a-smooth muscle actin positive stromal fibroblasts. The EGR1 and FOSB expression in stromal cells and EGR1 expression in cancer cells are prognostic indicators in EOC. (c) 2011 Wiley Periodicals, Inc.

    DOI: 10.1002/gcc.21916

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  • EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy 査読

    Fumio Kataoka, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Hideo Tanaka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Akira Hirasawa, Tomoko Akahane, Hiroshi Nishio, Kazuto Nishio, Daisuke Aoki

    GENES CHROMOSOMES & CANCER   51 ( 3 )   300 - 312   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Stromal components interact with cancer cells to promote growth and metastasis. The purpose of this study was to identify genes expressed in stroma, which could provide prognostic information in epithelial ovarian cancer (EOC). Seventy-four patients were included. We performed gene expression profiling and confirmed array data using RT-PCR and immunohistochemistry. By microarray analysis, 52 candidate genes associated with progression free survival (PFS) were identified (P &lt; 0.005). Expression of the early growth response 1 (EGR1) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) genes was further analyzed. Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC. Immunohistochemically, EGR1 protein is localized in cancer cells and a-smooth muscle actin positive stromal fibroblasts. The EGR1 and FOSB expression in stromal cells and EGR1 expression in cancer cells are prognostic indicators in EOC. (c) 2011 Wiley Periodicals, Inc.

    DOI: 10.1002/gcc.21916

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  • EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy

    Fumio Kataoka, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Hideo Tanaka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Akira Hirasawa, Tomoko Akahane, Hiroshi Nishio, Kazuto Nishio, Daisuke Aoki

    GENES CHROMOSOMES & CANCER   51 ( 3 )   300 - 312   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Stromal components interact with cancer cells to promote growth and metastasis. The purpose of this study was to identify genes expressed in stroma, which could provide prognostic information in epithelial ovarian cancer (EOC). Seventy-four patients were included. We performed gene expression profiling and confirmed array data using RT-PCR and immunohistochemistry. By microarray analysis, 52 candidate genes associated with progression free survival (PFS) were identified (P &lt; 0.005). Expression of the early growth response 1 (EGR1) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) genes was further analyzed. Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC. Immunohistochemically, EGR1 protein is localized in cancer cells and a-smooth muscle actin positive stromal fibroblasts. The EGR1 and FOSB expression in stromal cells and EGR1 expression in cancer cells are prognostic indicators in EOC. (c) 2011 Wiley Periodicals, Inc.

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  • 発現解析による子宮体部癌肉腫の生物学的特性の解明.

    千代田達幸, 津田浩史, 片岡史夫, 野村弘行, 田中英雄, 平沢 晃, 進 伸幸, 佐谷秀行, 青木大輔

    日本分子腫瘍マーカー研究会誌   27   23-34 - 24   2012年

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • Aberrant DNA Methylation in Endometrial Cancer

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Kosuke Tsuji, Iori Kisu, Arisa Ueki, Yusuke Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Epigenetics in Human Disease   471 - 480   2012年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Elsevier Inc.  

    DOI: 10.1016/B978-0-12-388415-2.00023-8

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  • 遺伝性乳癌卵巣癌 招待 査読

    平沢 晃, 青木大輔

    日本産科婦人科学会雑誌   64 ( 4 )   292 - 296   2012年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 発現解析による子宮体癌再発予測モデルの開発.

    津田浩史, 井口蓉子, 片岡史夫, 野村弘行, 田中英雄, 千代田達幸, 平沢 晃, 進 伸幸, 青木大輔

    日本分子腫瘍マーカー研究会誌   27   45-46 - 46   2012年

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • 子宮体がんの術後補助療法

    山上 亘, 進 伸幸, 津田浩史, 平沢 晃, 阪埜浩司, 青木大輔

    腫瘍内科   8 ( 6 )   563-571 - 571   2011年12月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • Immunofluorescence-Detected Infiltration of CD4(+)FOXP3(+) Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer 査読

    Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   21 ( 9 )   1628 - 1634   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8(+) cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.
    Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4(+) FOXP3(+) cells were identified as Tregs in this study. The numbers of CD8(+) cells, CD4(+) cells, and Tregs as well as the Treg/CD8(+) and Treg/CD4(+) ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.
    Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8(+) and CD4(+) cell counts, Treg count, and Treg/CD8(+) and Treg/CD4(+) ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8(+) ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8(+) ratios (P &lt; 0.05).
    Conclusions: The Treg count and Treg/CD8(+) ratio may be new prognostic factors for endometrial cancer.

    DOI: 10.1097/IGC.0b013e31822c271f

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  • Immunofluorescence-Detected Infiltration of CD4(+)FOXP3(+) Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer

    Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   21 ( 9 )   1628 - 1634   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8(+) cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4(+) FOXP3(+) cells were identified as Tregs in this study. The numbers of CD8(+) cells, CD4(+) cells, and Tregs as well as the Treg/CD8(+) and Treg/CD4(+) ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8(+) and CD4(+) cell counts, Treg count, and Treg/CD8(+) and Treg/CD4(+) ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8(+) ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8(+) ratios (P < 0.05).Conclusions: The Treg count and Treg/CD8(+) ratio may be new prognostic factors for endometrial cancer.

    DOI: 10.1097/IGC.0b013e31822c271f

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  • Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer. 国際誌

    Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society   21 ( 9 )   1628 - 34   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. METHODS: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4FOXP3 cells were identified as Tregs in this study. The numbers of CD8 cells, CD4 cells, and Tregs as well as the Treg/CD8 and Treg/CD4 ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. RESULTS: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 and CD4 cell counts, Treg count, and Treg/CD8 and Treg/CD4 ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 ratios (P < 0.05). CONCLUSIONS: The Treg count and Treg/CD8 ratio may be new prognostic factors for endometrial cancer.

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  • Narrow band imaging hysteroscopy: A comparative study using randomized video images 査読

    Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   39 ( 5 )   1057 - 1062   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of A EH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P&lt;0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

    DOI: 10.3892/ijo.2011.1131

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  • Narrow band imaging hysteroscopy: a comparative study using randomized video images. 国際誌

    Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

    International journal of oncology   39 ( 5 )   1057 - 62   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of AEH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P<0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

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  • Narrow band imaging hysteroscopy: A comparative study using randomized video images

    Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   39 ( 5 )   1057 - 1062   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of A EH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P&lt;0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

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  • miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. 国際誌

    Tomohiko Tsuruta, Ken-Ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa

    Cancer research   71 ( 20 )   6450 - 62   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer.

    DOI: 10.1158/0008-5472.CAN-11-0364

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  • miR-152 Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer

    Tomohiko Tsuruta, Ken-ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa

    CANCER RESEARCH   71 ( 20 )   6450 - 6462   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer. Cancer Res; 71(20); 6450-62. (C) 2011 AACR.

    DOI: 10.1158/0008-5472.CAN-11-0364

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  • 妊産婦への向精神薬の投与

    牧田和也, 平沢 晃, 青木大輔

    産婦人科治療   103 ( 4 )   417-421 - 421   2011年10月

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    記述言語:日本語   出版者・発行元:(株)永井書店  

    妊産婦に対する薬物治療に関しては、妊娠4ヵ月末までは胎児への催奇形性に、5ヵ月以降は胎児の機能的発育への影響に留意しなければならない。可能ならば妊娠が判明した時点で、向精神薬による治療の中止もしくは減量が望ましいが、薬物治療の継続が必要な場合は、患者自身に薬物治療の必要性を十分に理解してもらうよう努めるとともに、どの週数であっても胎児への影響が出来る限り少ない薬剤を単剤から投与することが肝要である。(著者抄録)

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  • Magnifying hysteroscopy with narrow-band imaging for visualization of endometrial lesions

    青木 大輔

    Int J Gynaecol Obstet   115 ( 1 )   74-75   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • miR-152 Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer 査読

    Tomohiko Tsuruta, Ken-ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa

    CANCER RESEARCH   71 ( 20 )   6450 - 6462   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer. Cancer Res; 71(20); 6450-62. (C) 2011 AACR.

    DOI: 10.1158/0008-5472.CAN-11-0364

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  • 遺伝性乳癌・卵巣がんの取扱いとリスク低減卵管卵巣摘出術

    平沢 晃, 青木大輔

    産科と婦人科   78 ( 9 )   1064-1068 - 1068   2011年9月

  • 婦人科疾患と遺伝カウンセリング

    平沢 晃, 鶴田智彦, 青木大輔

    産婦人科の実際   60 ( 9 )   1331-1338 - 1338   2011年9月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • 遺伝性腫瘍の基礎知識と遺伝子診断および予防法 ~遺伝性乳がん・卵巣がんに着目して~.

    平沢 晃, 青木大輔

    がん看護   16 ( 6 )   631-635 - 635   2011年9月

  • 発現解析による子宮体部癌肉腫の生物学的特性の解明

    千代田 達幸, 津田 浩史, 片岡 史夫, 野村 弘行, 田中 英雄, 平沢 晃, 進 伸幸, 佐谷 秀行, 青木 大輔

    日本分子腫瘍マーカー研究会プログラム・講演抄録   31回   46 - 47   2011年9月

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • 発現解析による子宮体癌の再発予測モデルの開発

    津田 浩史, 井口 蓉子, 片岡 史夫, 野村 弘行, 田中 英雄, 千代田 達幸, 平沢 晃, 進 伸幸, 青木 大輔

    日本分子腫瘍マーカー研究会プログラム・講演抄録   31回   68 - 69   2011年9月

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • 家系内の遺伝子検査が契機となり早期介入を行ったLynch症候群の1例

    中村加奈子, 平沢 晃, 赤羽智子, 鶴田智彦, 冨永英一郎, 阪埜浩司, 藤井多久磨, 進 伸幸, 青木大輔, 吉村泰典

    東京産科婦人科学会会誌   60 ( 2 )   293-297 - 297   2011年6月

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    Lynch症候群(Lynch syndrome:hereditary non-polyposis colon cancer,HNPCC)は常染色体優性遺伝の遺伝性腫瘍症候群であり、70歳までに子宮体癌を発症するリスクが一般集団では2.7%であるのに対し、Lynch症候群では20%〜60%と報告されている。我々は、詳細な家族歴の聴取によりLynch症候群家系を疑い、遺伝子検査を経て早期治療が可能となった1例を経験した。症例は46歳未経妊未経産、不正性器出血および遺伝性腫瘍に関する精査を希望し当院を受診した。家族歴の聴取によりLynch症候群が疑われたため遺伝子検査を施行し、原因遺伝子の一つであるMLH1に変異が認められた。その後複数回の子宮内膜検査により子宮内膜異型増殖症を認めたため、拡大子宮全摘出術および両側付属器摘出術を施行した。当該例では遺伝子検査ののちに適切なサーベイランスを行うことで前がん病変の段階で縮小手術を施行したことにより結果的に手術による侵襲を最小限にし、術後合併症やQOL低下を防ぐことが可能であった。現在も外来で定期的にフォローアップを行っており、再発なく経過している。(著者抄録)

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  • 産婦人科臨床における遺伝性乳癌卵巣癌の位置づけ

    平沢 晃, 鶴田智彦, 阪埜浩司, 進 伸幸, 三須久美子, 矢崎久妙子, 武田祐子, 菅野康吉, 青木大輔

    家族性腫瘍   11 ( 2 )   48-51 - 51   2011年5月

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    記述言語:日本語   出版者・発行元:(一社)日本遺伝性腫瘍学会  

    婦人科領域においても遺伝性腫瘍が存在する.遺伝性乳癌卵巣癌(hereditary breast and ovarian cancer:HBOC)にともなう卵巣癌ではBRCA1またはBRCA2(BRCA1/2)がその責任遺伝子として知られており,BRCA1の変異遺伝子を有する場合,70歳までに卵巣癌発症の確率が40%との報告もある.またLynch症候群家系に子宮体癌が高率に発生することが知られており,近年ではその診断基準に子宮体癌も組み入れられるようになった.さらにPeutz-Jeghers症候群例において子宮頸部腺癌(悪性腺腫)を合併することが以前より知られている.ところで卵巣はがん検診の対象臓器となっておらず,悪性の場合は自覚症状発現時に病変がすでに進行していることが多い.また卵巣腫瘍は多くの場合術前に良悪性の診断をすることが困難である.そこでBRCA1/2遺伝子変異保持例に対しては適切なサーベイランスの手法が存在しないことから,がん一次予防法としてリスク低減卵管卵巣摘出術(Risk-Reducing Salpingo-Oophorectomy:RRSO)が現在のところ最も確実性の高い卵巣癌予防策であるとみなされている.しかしながらRRSO施行後には急速なエストロゲンによる卵巣欠落症状を来すことがあり,さらに長期的には脂質異常症や骨粗鬆症の高危険群となるため,適切な管理が必要である.慶應義塾大学病院産婦人科では女性のトータルヘルスケアを目的とした女性健康維持外来を開設して女性の卵巣機能低下にともなう諸症状を多角的に検証している.さらに遺伝性腫瘍の遺伝子変異保持例は常に異時性発症癌や重複癌発症の不安と共存していかなくてはならず,卵巣機能低下に対する対策と並行して,心理的不安の解消を含めたQOL低下防止策が必要である.卵巣癌BRCA1/2遺伝子変異保持例に対してPARP阻害薬であるOlaparib投与が考慮されており,治験が進められている.(著者抄録)

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  • 老人性腟炎

    牧田和也, 平沢 晃, 青木大輔

    臨床婦人科産科   65 ( 4(増大号) )   568-571   2011年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Flexible hysteroscopy with narrow band imaging (NBI) for endoscopic diagnosis of malignant endometrial lesions

    Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   38 ( 3 )   613 - 618   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Narrow band imaging (NBI) for detection of blood vessels and microstructures on the mucosal surface is used in gastrointestinal endoscopy since it can improve qualitative diagnosis and detection of lesion. However, there are no studies on flexible hysteroscopy using NBI. We performed flexible hysteroscopy with NBI for outpatients to investigate the sensitivity and specificity of endoscopic diagnosis of malignant endometrial lesions. Of patients who attended our hospital for suspected lesions in the uterine cavity between April 2009 and May 2010, 104 subjects underwent hysteroscopy with NBI, in addition to white light. Using the pathological diagnosis as the gold-standard, we evaluated the sensitivity and specificity of NBI hysteroscopy for detecting atypical endometrial hyperplasia (AEH) or carcinoma. The results were also compared with historical data (n=209) for conventional hysteroscopy using white light only in 2008. The sensitivities were 97.2% [95% confidence interval (95% CI): 90.3-99.7%] and 82.6% (95% Cl: 74.4-89.0%) for NBI hysteroscopy and conventional hysteroscopy, respectively. The 95% CIs for the two methods did not overlap and the sensitivity of lesion detection was higher with NB! hysteroscopy. Specificities were comparable, 90.6% (95% CI: 75.0-98.0%) and 85.1% (95% CI: 76.3-91.6%) between the methods. NBI hysteroscopy has increased sensitivity for detection of atypical endometrial hyperplasia (AEH) or carcinoma. A comparison with historical data suggested that NBI may be useful for diagnosis of malignant endometrial lesions. As far as we are aware, this is the first evaluation of flexible hysteroscopy with NBI for diagnosis of malignant endometrial lesions.

    DOI: 10.3892/ijo.2011.903

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  • Flexible hysteroscopy with narrow band imaging (NBI) for endoscopic diagnosis of malignant endometrial lesions. 国際誌

    Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

    International journal of oncology   38 ( 3 )   613 - 8   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Narrow band imaging (NBI) for detection of blood vessels and microstructures on the mucosal surface is used in gastrointestinal endoscopy since it can improve qualitative diagnosis and detection of lesion. However, there are no studies on flexible hysteroscopy using NBI. We performed flexible hysteroscopy with NBI for outpatients to investigate the sensitivity and specificity of endoscopic diagnosis of malignant endometrial lesions. Of patients who attended our hospital for suspected lesions in the uterine cavity between April 2009 and May 2010, 104 subjects underwent hysteroscopy with NBI, in addition to white light. Using the pathological diagnosis as the gold-standard, we evaluated the sensitivity and specificity of NBI hysteroscopy for detecting atypical endometrial hyperplasia (AEH) or carcinoma. The results were also compared with historical data (n=209) for conventional hysteroscopy using white light only in 2008. The sensitivities were 97.2% [95% confidence interval (95% CI): 90.3-99.7%] and 82.6% (95% CI: 74.4-89.0%) for NBI hysteroscopy and conventional hysteroscopy, respectively. The 95% CIs for the two methods did not overlap and the sensitivity of lesion detection was higher with NBI hysteroscopy. Specificities were comparable, 90.6% (95% CI: 75.0-98.0%) and 85.1% (95% CI: 76.3-91.6%) between the methods. NBI hysteroscopy has increased sensitivity for detection of atypical endometrial hyperplasia (AEH) or carcinoma. A comparison with historical data suggested that NBI may be useful for diagnosis of malignant endometrial lesions. As far as we are aware, this is the first evaluation of flexible hysteroscopy with NBI for diagnosis of malignant endometrial lesions.

    DOI: 10.3892/ijo.2011.903

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  • Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    CURRENT GENOMICS   12 ( 1 )   25 - 29   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

    DOI: 10.2174/138920211794520169

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  • Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome. 国際誌

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Current genomics   12 ( 1 )   25 - 9   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

    DOI: 10.2174/138920211794520169

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  • Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    CURRENT GENOMICS   12 ( 1 )   25 - 29   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

    DOI: 10.2174/138920211794520169

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  • 腫瘍間質の遺伝子発現解析を用いた進行上皮性卵巣癌に対する新規バイオマーカーの探索

    片岡史夫, 津田浩史, 野村弘行, 千代田達幸, 平沢 晃, 冨永英一郎, 鈴木 淳, 進 伸幸, 青木大輔

    日本分子腫瘍マーカー研究会誌   26   32-33 - 33   2011年1月

  • ホルモン補充療法が腰椎骨密度に及ぼす長期的な効果の検討 -当科健康維持外来における10年継続投与例からの検証- .

    牧田和也, 松村聡子, 堀場裕子, 平沢 晃, 小川真里子, 弟子丸亮太, 柳本茂久, 高松 潔, 青木大輔

    Osteoporosis Japan   18 ( 3 )   83-85 - 539   2011年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    外来で更年期障害、卵巣欠落症状、閉経後骨粗鬆症を主な適応としてホルモン補充療法(HRT)を10年以上継続して施行した49例について、HRTの腰椎骨密度に対する長期的な効果を検討した。24例はHRTを終了したが25例は継続中である。HRT開始時に使用したエストロゲン製剤は結合型エストロゲン9割、経皮吸収剤(エストラジオール貼付剤)1割であった。HRT施行後18ヵ月迄は有意な増加傾向を示したが、その後はHRTを継続している限りプラトーになることが判明した。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J03021&link_issn=&doc_id=20100816080038&doc_link_id=%2Fai6ostoe%2F2010%2F001803%2F038%2F0537-0539%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2010%2F001803%2F038%2F0537-0539%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • MicroRNA in endometrial cancer 査読

    平沢 晃

    Trends in Cancer Research   7   49-55   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Relationship between DNA Mismatch Repair Deficiency and Endometrial Cancer. 査読 国際誌

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Nana Asahara, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Molecular biology international   2011   256063 - 256063   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Lynch syndrome is thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene. An aberration in the MMR gene prevents accurate repair of base mismatches produced during DNA replication. This phenomenon can lead to an increased frequency of errors in target genes involved in carcinogenesis, resulting in cancerization of the cell. On the other hand, aberrant DNA methylation is thought to play a key role in sporadic endometrial carcinogenesis. Hypermethylation of unmethylated CpG islands in the promoter regions of cancer-related genes associated with DNA repair leads to the cell becoming cancerous. Thus, both genetic and epigenetic changes are intricately involved in the process through which cells become cancerous. In this review, we introduce the latest findings on the DNA mismatch repair pathway in endometrial cancer.

    DOI: 10.4061/2011/256063

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  • Visual Analogue Scale(VAS)を用いた呉茱萸湯の片頭痛に対する治療効果の検討.

    堀場裕子, 牧田和也, 松村聡子, 平沢 晃, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   28 ( 28 )   80-83 - 83   2011年

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    前兆のない片頭痛と診断された15例に呉茱萸湯の内服を行い、VASを用いて治療効果を評価した。全く痛みなしを「0」、死ぬほど耐えられない痛みを「10」とし、内服後1ヵ月ごとにその期間に認めた全ての頭痛発作時のVAS値を測定し、その平均を内服前VAS値と比較した。その結果、15例中11例で片頭痛の発作回数の減少や発作時の疼痛緩和など何らかの効果がみられた。この11例を有効群、残り4例を無効群とし、内服前後のVAS値の推移をみたところ、有効群の平均VAS値は内服前8.1が内服1ヵ月後2.9と有意に低下し、内服2ヵ月後でも2.7と維持されていたが、無効群の平均VAS値は内服前8.8が内服1ヵ月後8.3、2ヵ月後8.2と明らかな変化はみられなかった。有効群におけるNSAIDsもしくはトリプタン製剤の使用錠数をみたところ、内服前は1ヵ月平均6.7錠であったが、内服後1ヵ月間では平均3.8錠に減少した。なお、無効群では内服前後で使用錠数に変化はみられなかった。

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  • 当科「健康維持外来」におけるホルモン補充療法施行症例についての検証.

    牧田和也, 松村聡子, 堀場裕子, 平沢 晃, 小川真里子, 弟子丸亮太, 柳本茂久, 高松 潔, 青木大輔, 吉村泰典

    日本女性医学学会雑誌   19 ( 1 )   18-23 - 24   2011年

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    (目的)エストロゲン低下を主因とする種々の退行期疾患の予防と早期治療を指向した当科「健康維持外来」におけるホルモン補充療法(HRT)施行例について、これまで得られたデータを再検証する。(対象・方法)1991年4月から2008年12月末までに当外来を受診した全初診患者3,210例の中から、臨床治験や男女混合ホルモンの筋肉注射を施行した例などを除き、HRTを6ヵ月以上に亘り連続して施行した経験のある症例および現在も施行中の計454例(開始時の平均年齢50.9歳)を調査対象とした。これらの症例のHRT開始時から既に終了している症例ではその時点までの、現在も継続中の症例については2009年6月末までの状況について、診療記録を下に調査を行った。(結果)454例中127例が現在HRTを施行中であり、最長継続例は約17年、10年以上継続している症例が37例存在した。HRTの主たる適応は、更年期不定愁訴が最も多かった。HRT開始時の投与方法は、エストロゲンと黄体ホルモンの併用持続投与が最も多かった。HRT開始時に経口剤を用いたものが353例であり、結合型エストロゲン剤が最も多かった。一方経皮吸収剤を用いた101例中85例がエストラジオールパッチ剤であった。HRTの施行終了に至った理由は、患者自らの申し出によるものが最も多かった。HRT施行時に発生した有害事象では、悪性腫瘍の発症が10例と最も多く、そのうち8例は乳癌であった。(考察)わが国においてHRTが本格的に導入されたのは、当外来が開設された時期とほぼ一致する。当外来においてHRTを施行し続けたことで、中高年女性のQuality of lifeの向上の一助となっていることを再確認した。(著者抄録)

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  • 家系内の遺伝子検査が契機となり早期介入に至ったリンチ症候群の1例.

    中村加奈子, 平沢 晃, 赤羽智子, 鶴田智彦, 冨永英一郎, 阪埜浩司, 藤井多久磨, 進 伸幸, 青木大輔, 吉村泰典

    日本産科婦人科学会東京地方部会会誌   60 ( 2 )   293-297   2011年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 大腿骨頸部骨密度測定は腰椎骨骨密度測定の代用となり得るか?—当科健康維持外来受診者からの比較検討—

    牧田和也, 松村聡子, 堀場裕子, 平沢 晃, 小川真里子, 弟子丸亮太, 柳本茂久, 青木大輔

    Osteoporosis Japan   19 ( 3 )   481-483 - 483   2011年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    健康維持外来初診患者に対して、腰椎骨骨密度と大腿骨頸部骨密度を同時に測定し、その両者の相関について検証した。健康維持外来を受診した初診患者205例を対象とした。腰椎骨骨密度値からみた診断では、第2から第4までの平均の骨密度値(L2-4BMD)から原発性骨粗霧症診断基準に従い診断すると、骨粗鬆症例が5例、骨量減少例が20例、骨量正常例が180例となるが測定部位全体の骨密度値(F-To BMD)からの診断と疾患名が一致したのは、骨粗鬆症例が5例中3例、骨量減少例20例中7例、骨量正常例180例中155例であった。大腿骨頸部骨密度値からみた診断では、F-To BMD値からの診断で、骨粗鬆症例が16例、骨量減少例が26例、骨量正常例が163例となるが、L2-4BMD値からの診断と疾患名が一致したのは、骨粗鬆症例が16例中3例、骨量減少例26例中7例、骨量正常例163例中155例であった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J03021&link_issn=&doc_id=20110825190033&doc_link_id=%2Fai6ostoe%2F2011%2F001903%2F035%2F0481-0483%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2011%2F001903%2F035%2F0481-0483%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer 査読

    Kisu I, Banno K, Yanokura M, Kobayashi Y, Ueki A, Ono A, Masuda K, Yamagami W, Nomura H, HIRASAWA AKIRA, Susumu N, Aoki D

    Journal of Cancer Therapy   2 ( 4 )   458-462   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Gynecological tumors in patients with Peutz-Jeghers syndrome (PJS). 査読

    Ueki A, Kisu I, Banno K, Yanokura M, Masuda K, Kobayashi Y, HIRASAWA AKIRA, Aoki D

    Open Journal of Genetics   1 ( 3 )   65-69   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • ASSOCIATION BETWEEN COPY NUMBER VARIATIONS OF ESTROGEN MATABOLISM-RELATED GENE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN OF JANANESE 査読

    A. Hirasawa, K. Makita, T. Akahane, K. Banno, N. Susumu, D. Aoki

    OSTEOPOROSIS INTERNATIONAL   21 ( 5 )   S722 - S723   2010年12月

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    記述言語:英語   掲載種別:研究論文(研究会,シンポジウム資料等)   出版者・発行元:SPRINGER LONDON LTD  

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  • 遺伝性乳癌卵巣癌-婦人科の観点より-

    平沢 晃, 野村 弘行, 青木 大輔

    乳癌の臨床   25 ( 5 )   523-527 - 527   2010年11月

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    記述言語:日本語   出版者・発行元:篠原出版新社(東京)  

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  • MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications

    Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Kennta Masuda, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    ONCOLOGY LETTERS   1 ( 6 )   935 - 940   2010年11月

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    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 base pairs that regulate the expression of genes by targeting messenger RNA with complementarity with the miRNA base sequence. Regulation of gene expression by miRNAs is crucial in cellular development and differentiation, and recent studies suggest a relationship between human diseases and the breakdown of gene silencing mechanisms induced by miRNA abnormalities. In particular, abnormal miRNA expression has been detected in various types of cancer and the target genes have been identified. These results indicate that miRNAs act in a manner equivalent to oncogenes or tumor suppressors. miRNAs may also serve as diagnostic biomarkers and therapeutic targets. In this review, we introduce the latest findings on miRNAs in human endometrial cancer, a common malignancy, and discuss the potential of miRNAs as biomarkers and targets for molecular therapy.

    DOI: 10.3892/ol.2010.173

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  • MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications (Review). 査読 国際誌

    Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Kennta Masuda, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Oncology letters   1 ( 6 )   935 - 940   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 base pairs that regulate the expression of genes by targeting messenger RNA with complementarity with the miRNA base sequence. Regulation of gene expression by miRNAs is crucial in cellular development and differentiation, and recent studies suggest a relationship between human diseases and the breakdown of gene silencing mechanisms induced by miRNA abnormalities. In particular, abnormal miRNA expression has been detected in various types of cancer and the target genes have been identified. These results indicate that miRNAs act in a manner equivalent to oncogenes or tumor suppressors. miRNAs may also serve as diagnostic biomarkers and therapeutic targets. In this review, we introduce the latest findings on miRNAs in human endometrial cancer, a common malignancy, and discuss the potential of miRNAs as biomarkers and targets for molecular therapy.

    DOI: 10.3892/ol.2010.173

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  • MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications

    Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Kennta Masuda, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    ONCOLOGY LETTERS   1 ( 6 )   935 - 940   2010年11月

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    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 base pairs that regulate the expression of genes by targeting messenger RNA with complementarity with the miRNA base sequence. Regulation of gene expression by miRNAs is crucial in cellular development and differentiation, and recent studies suggest a relationship between human diseases and the breakdown of gene silencing mechanisms induced by miRNA abnormalities. In particular, abnormal miRNA expression has been detected in various types of cancer and the target genes have been identified. These results indicate that miRNAs act in a manner equivalent to oncogenes or tumor suppressors. miRNAs may also serve as diagnostic biomarkers and therapeutic targets. In this review, we introduce the latest findings on miRNAs in human endometrial cancer, a common malignancy, and discuss the potential of miRNAs as biomarkers and targets for molecular therapy.

    DOI: 10.3892/ol.2010.173

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  • 腫瘍間質の遺伝子発現解析を用いた進行上皮性卵巣癌に対する新規バイオマーカーの探索

    片岡 史夫, 津田 浩史, 野村 弘行, 千代田 達幸, 平沢 晃, 冨永 英一郎, 鈴木 淳, 進 伸幸, 青木 大輔

    日本分子腫瘍マーカー研究会プログラム・講演抄録   30回   52 - 53   2010年9月

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • 女性の片頭痛

    牧田和也, 平沢 晃, 青木大輔

    産婦人科治療   101 ( 2 )   135-139 - 139   2010年8月

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    記述言語:日本語   出版者・発行元:(株)永井書店  

    片頭痛は、周期的に認められる激しい頭痛発作により著しいquality of lifeの低下を招く一次性頭痛であり、女性においては月経周期、妊娠・出産・授乳、閉経といったライフステージに伴う女性ホルモンの変動との関連性が高く、とくに月経は最大のトリガーとされている。産婦人科外来に頭痛を主訴として来院する患者は少ないが、月経に関連して認められる頭痛などに着目することで、潜在的な片頭痛患者の掘り起こしが可能である。(著者抄録)

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  • Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer. 国際誌

    Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

    Gynecologic oncology   118 ( 2 )   160 - 6   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    OBJECTIVES: The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy. METHODS: We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin+paclitaxel) as primary therapy. RESULTS: Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p=0.01) and (12/383 vs. 32/13656, p=1.3 x 10(-)(16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM_000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p=0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS. CONCLUSIONS: Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC.

    DOI: 10.1016/j.ygyno.2010.03.010

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  • 無結紮手術(BiClamp,Ligasure,ハーモニック)-広汎子宮全摘出術におけるBiClamp使用の実際

    進 伸幸, 片岡史夫, 野村弘行, 平沢 晃, 藤井多久磨, 青木大輔

    産婦人科の実際   59 ( 8 )   1195-1200 - 1200   2010年8月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. 査読 国際誌

    Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

    Nature genetics   42 ( 8 )   707 - 10   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.

    DOI: 10.1038/ng.612

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  • A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese

    Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

    NATURE GENETICS   42 ( 8 )   707 - U88   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.

    DOI: 10.1038/ng.612

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  • A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese

    Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

    NATURE GENETICS   42 ( 8 )   707 - U88   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.

    DOI: 10.1038/ng.612

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  • Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer 査読

    Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

    GYNECOLOGIC ONCOLOGY   118 ( 2 )   160 - 166   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.Methods. We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy.Results. Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p 0.01) and (12/383 vs. 32/13656, p = 1.3 x 10(-16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM__000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p = 0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS.Conclusions. Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ygyno.2010.03.010

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  • Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer

    Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

    GYNECOLOGIC ONCOLOGY   118 ( 2 )   160 - 166   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.
    Methods. We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy.
    Results. Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p&lt;0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p 0.01) and (12/383 vs. 32/13656, p = 1.3 x 10(-16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM__000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p = 0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS.
    Conclusions. Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ygyno.2010.03.010

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  • Relationship Between ABCF2 Expression and Response to Chemotherapy or Prognosis in Clear Cell Adenocarcinoma of the Ovary 査読

    Hiroshi Tsuda, Kiyoshi Ito, Nobuo Yaegashi, Akira Hirasawa, Tamotsu Sudo, Tsunekazu Kita, Yoshito Terai, Junzo Kigawa, Toru Sugiyama, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   20 ( 5 )   794 - 797   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary.Methods: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery.Results: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24).Conclusions: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.

    DOI: 10.1111/IGC.0b013e3181a835fc

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  • Relationship between ABCF2 expression and response to chemotherapy or prognosis in clear cell adenocarcinoma of the ovary. 国際誌

    Hiroshi Tsuda, Kiyoshi Ito, Nobuo Yaegashi, Akira Hirasawa, Tamotsu Sudo, Tsunekazu Kita, Yoshito Terai, Junzo Kigawa, Toru Sugiyama, Daisuke Aoki

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society   20 ( 5 )   794 - 7   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVES: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary. METHODS: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery. RESULTS: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24). CONCLUSIONS: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.

    DOI: 10.1111/IGC.0b013e3181a835fc

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  • Relationship Between ABCF2 Expression and Response to Chemotherapy or Prognosis in Clear Cell Adenocarcinoma of the Ovary

    Hiroshi Tsuda, Kiyoshi Ito, Nobuo Yaegashi, Akira Hirasawa, Tamotsu Sudo, Tsunekazu Kita, Yoshito Terai, Junzo Kigawa, Toru Sugiyama, Daisuke Aoki

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   20 ( 5 )   794 - 797   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary.
    Methods: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery.
    Results: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24).
    Conclusions: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.

    DOI: 10.1111/IGC.0b013e3181a835fc

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  • 家族性乳癌・遺伝性乳癌の現状と課題 遺伝相談外来を受診したBRCA1/2遺伝子変異を有する遺伝性乳がん卵巣がん家系の臨床遺伝学的特徴

    菅野 康吉, 牧島 恵子, 友田 茉莉, 安藤 二郎, 矢崎 久妙子, 武田 祐子, 平澤 晃, 神野 浩光, 北川 雄光, 和泉 秀子, 古賀 範子, 木下 貴之

    日本乳癌学会総会プログラム抄録集   18回   260 - 260   2010年5月

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    記述言語:日本語   出版者・発行元:(一社)日本乳癌学会  

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  • 月経関連片頭痛に対する呉茱萸湯の周期的投与の試み.

    牧田和也, 堀場裕子, 平沢 晃, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   27 ( 27 )   73-75 - 75   2010年

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    症例は月経の3〜4日目に頭痛発作が出現する25歳女性(症例1)と、月経周期の不順に伴い片頭痛発作が月経時に出現しやすくなった46歳女性(症例2)で、両者に対し予定月経日5日前から月経が終了するまでの間、ツムラ呉茱萸湯エキス顆粒7.5g/日を1クールとして治療を開始した。その結果、症例1は1クール目で頭痛発作により寝込まなくなり、結果的に非ステロイド抗炎症薬とトリプタン系薬を1錠ずつ服用するだけで月経を終了した。症例2は1クール目よりトリプタン系薬を服用しなくても済むようになったが、その後月経が2ヵ月発来しなかったことと偏頭痛発作を数回認めたため、呉茱萸湯の服用方法を連続投与に変更した。その後の月経時に手足の浮腫が著明になったことからフロセミドと五苓散も併用しながら経過観察中である。今回の検討では症例1で効果が得られたと考えられる。

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  • ファーマコゲノミクスの臨床応用を目指した簡易迅速な遺伝子多型診断システムの開発.

    平沢 晃

    臨床薬理   41 ( 3 )   109-110 - 110S   2010年

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    記述言語:日本語   出版者・発行元:(一社)日本臨床薬理学会  

    DOI: 10.3999/jscpt.41.109S

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  • 両側卵巣摘出術施行例における骨代謝関連遺伝子多型の探索-性ホルモン代謝関連酵素遺伝子におけるコピー数多型の検索を中心として-

    平沢 晃, 赤羽智子, 牧田和也, 青木大輔

    Osteoporosis Japan   18 ( 3 )   406-408 - 408   2010年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    子宮体癌の診断で両側卵巣摘出に伴う標準療法を施行し、研究に同意が得られた145例を対象に、骨粗鬆症高危険群に対する早期介入を最終的な目標に、骨量変化における遺伝子コピー多型(CNV)の関与について検討した。骨密度(DXA)で測定した腰椎BMDの結果を日本骨代謝学会の原発性骨粗鬆症診断基準で診断し、骨粗鬆症および骨量減少群(A群)58例、骨量正常群(B群)87例に分類した。エストロゲンレセプター1(ESR1)のCNVに関する検討で、A群全例、B群の85例が解析可能で、共に全例で2コピー数であった。ウリジンジホスフェートグリコシルトランスフェラーゼ2ファミリーナンバーB17(UGT2B17)のCNVに関する検討で、A群全例、B群の86解析可能であった。A群は0コピー49例、2コピー9例、B群は0コピー63例、2コピー21例、4コピー2例であった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J03021&link_issn=&doc_id=20100816080010&doc_link_id=%2Fai6ostoe%2F2010%2F001803%2F010%2F0406-0408%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2010%2F001803%2F010%2F0406-0408%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 閉経前両側卵巣摘出例における骨密度とFRAXの特徴に関する検討.

    堀場裕子, 平沢 晃, 牧田和也, 松村聡子, 小川真里子, 岩田 卓, 弟子丸亮太, 柳本茂久, 青木大輔

    Osteoporosis Japan   18 ( 3 )   461-465 - 465   2010年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    1979年〜2009年に大学病院産婦人科で44歳以下で両側卵巣摘出術を受けた51例(卵摘群)、健康維持外来受診中で、有経、自然閉経後卵巣摘出を含めた323例(対照群)を対象に2008年に開発したFRAXを用い、骨折リスクを算出し、閉経前両側卵巣摘出という因子がFRAXに与える影響について検討した。卵摘群では骨量正常が45例、骨量減少が6例、骨粗鬆症例は認めなかった。一方、対照群では骨量正常が238例、骨量減少が59例、骨粗鬆症が26例であった。卵摘群と対照群の骨密度を比較すると、卵摘群においてYAM値90%未満の例が31.8%に認められ、両群間に有意差を認めず、平均値の比較でも対照群と有意差を認めなかった。卵摘群における骨量減少6例は共に低BMIで、うち2例ではBMIが16以下であった。61歳例のFRAX値は9.7で他の5例に比べ高値であった。卵摘群における骨正常例ではL2-4YAMと大腿骨骨密度が骨量減少例と比べ有意に高値であった。

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  • ゲノム薬理学の最近の親展とUGT1A1遺伝子多型診断について

    平沢 晃, 青木大輔

    産婦人科の実際   58 ( 12 )   2005-2011 - 2011   2009年11月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • 私はこうしている:私の主張 週1回のビスフォスフォネート製剤の投与

    牧田和也, 平沢 晃, 高松 潔, 青木大輔

    産婦人科治療   99 ( 5 )   509-511 - 511   2009年11月

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    記述言語:日本語   出版者・発行元:(株)永井書店  

    ビスフォスフォネート製剤のうち第2世代のアレンドロネートと第3世代のリセドロネートは、今日の骨粗鬆症の薬物治療の根幹を成す薬剤であり、従来からの連日服用するタイプだけでなく、近年週1回の服用で良いタイプも登場し、それによる服薬継続率の向上が期待されている。しかしながら、どちらの剤型を選択するかは、服用者の年齢層、合併症の有無、服用者の嗜好なども踏まえたうえで決定すべきである。(著者抄録)

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  • Analysis of candidate target genes for mononucleotide repeat mutation in microsatellite instability-high (MSI-H) endometrial cancer

    Makiko Kawaguchi, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Arisa Kishimi, Seiji Ogawa, Iori Kisu, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   35 ( 5 )   977 - 982   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Microsatellite instability (MSI) is an indicator of DNA instability and is caused by abnormalities in DNA mismatch repair (MMR) genes such as hMLH1, hMSH2 and hMSH6. MSI occurs frequently in endometrial cancer (in approximately 30% of cases), and accumulation of gene mutations due to MSI may therefore have a major role in the mechanism of malignant transformation. However, a responsible target gene has not been identified in endometrial cancer. In this study, we analyzed mutations in 11 cancer-related genes with mononucleotide repeats susceptible to MST in a coding region [hMSH3 (A8), hMSH6 (C8), TGF-beta RII (A10), MBD4 (A10), BAX (G8), PTEN (A6 in exon 7), HDAC2 (A9), EPHB2 (A9), Caspase-5 (A10), TCF-4 (A9) and Axin2 (G7)] in 22 patients with MSI-H sporadic endometrial cancer. Mutations in hMSH6 (C8) and TGF-beta RII (A10) were found most frequently, at rates of 36.3% (8/22) each. Mutations of BAX (G8) and TCF-4 (A9), which are common in MSI-positive colorectal cancer, occurred at rates of 22.7 and 0%, respectively, which suggests that the MSI target gene may differ between endometrial and colorectal cancers. Mutations in hMSH6 (C8) were correlated with reduced protein expression (p=0.042) and patients with these mutations had significantly more mutations in mononucleotide repeats in other cancer-related genes compared to patients without hMSH6 (C8) mutations (p=0.042). This suggests the possibility of a novel cascade in carcinogenesis of endometrial cancer in which MST mutates hMSH6 (C8), increases gene instability, and leads to accumulation of mutations in other cancer-related genes. To our knowledge, this is the first report to show that hMSH6 (C8) has an important role as an MSI target gene in sporadic endometrial cancer.

    DOI: 10.3892/ijo_00000411

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  • Epigenetic DNA hypermethylation: clinical applications in endometrial cancer (Review). 国際誌

    Yuriko Muraki, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Oncology reports   22 ( 5 )   967 - 72   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA repair. An epigenetic analysis of DNA hypermethylation in type I endometrial cancer has led to a proposed mechanism for endometrial carcinogenesis. Reduced DNA mismatch repair due to loss of hMLH1 expression is thought to have a major role in carcinogenesis and these findings open up approaches to prevention, diagnosis, risk assessment, and treatment of type I endometrial cancer. Aberrant DNA hypermethylation can be detected with high sensitivity for identification of cancer cells in sputum, blood and other biopsy materials, including in endometrial cancer specimens. There have been many attempts to use methylation inhibitors as anticancer agents, and epigenetic abnormalities may be useful as biomarkers of anticancer drug sensitivity and to identify biological characteristics of tumor cells for determination of treatment options based on hypermethylation. For example, aberrant hypermethylation of the CHFR gene is correlated with cellular sensitivity to microtubule inhibitors, and this may be useful in treatment of type I endometrial cancer. An ultimate objective of epigenetics is to identify the type of hereditary methylation responsible for cancer, with the goal of improved diagnosis and treatment based on control of methylation.

    DOI: 10.3892/or_00000523

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  • Epigenetic DNA hypermethylation: Clinical applications in endometrial cancer (Review) 査読

    Yuriko Muraki, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    ONCOLOGY REPORTS   22 ( 5 )   967 - 972   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA repair. An epigenetic analysis of DNA hypermethylation in type I endometrial cancer has led to a proposed mechanism for endometrial carcinogenesis. Reduced DNA mismatch repair due to loss of hMLH1expression is thought to have a major role in carcinogenesis and these findings open up approaches to prevention, diagnosis, risk assessment, and treatment of type I endometrial cancer. Aberrant DNA hypermethylation can be detected with high sensitivity for identification of cancer cells in sputum, blood and other biopsy materials, including in endometrial cancer specimens. There have been many attempts to use methylation inhibitors as anticancer agents, and epigenetic abnormalities may be useful as biomarkers of anticancer drug sensitivity and to identify biological characteristics of tumor cells for determination of treatment options based on hypermethylation. For example, aberrant hypermethylation of the CHFR gene is correlated with cellular sensitivity to microtubule inhibitors, and this may be useful in treatment of type I endometrial cancer. An ultimate objective of epigenetics is to identify the type of hereditary methylation responsible for cancer, with the goal of improved diagnosis and treatment based on control of methylation.

    DOI: 10.3892/or_00000523

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  • Analysis of candidate target genes for mononucleotide repeat mutation in microsatellite instability-high (MSI-H) endometrial cancer 査読

    Makiko Kawaguchi, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Arisa Kishimi, Seiji Ogawa, Iori Kisu, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   35 ( 5 )   977 - 982   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Microsatellite instability (MSI) is an indicator of DNA instability and is caused by abnormalities in DNA mismatch repair (MMR) genes such as hMLH1, hMSH2 and hMSH6. MSI occurs frequently in endometrial cancer (in approximately 30% of cases), and accumulation of gene mutations due to MSI may therefore have a major role in the mechanism of malignant transformation. However, a responsible target gene has not been identified in endometrial cancer. In this study, we analyzed mutations in 11 cancer-related genes with mononucleotide repeats susceptible to MST in a coding region [hMSH3 (A8), hMSH6 (C8), TGF-beta RII (A10), MBD4 (A10), BAX (G8), PTEN (A6 in exon 7), HDAC2 (A9), EPHB2 (A9), Caspase-5 (A10), TCF-4 (A9) and Axin2 (G7)] in 22 patients with MSI-H sporadic endometrial cancer. Mutations in hMSH6 (C8) and TGF-beta RII (A10) were found most frequently, at rates of 36.3% (8/22) each. Mutations of BAX (G8) and TCF-4 (A9), which are common in MSI-positive colorectal cancer, occurred at rates of 22.7 and 0%, respectively, which suggests that the MSI target gene may differ between endometrial and colorectal cancers. Mutations in hMSH6 (C8) were correlated with reduced protein expression (p=0.042) and patients with these mutations had significantly more mutations in mononucleotide repeats in other cancer-related genes compared to patients without hMSH6 (C8) mutations (p=0.042). This suggests the possibility of a novel cascade in carcinogenesis of endometrial cancer in which MST mutates hMSH6 (C8), increases gene instability, and leads to accumulation of mutations in other cancer-related genes. To our knowledge, this is the first report to show that hMSH6 (C8) has an important role as an MSI target gene in sporadic endometrial cancer.

    DOI: 10.3892/ijo_00000411

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  • Analysis of candidate target genes for mononucleotide repeat mutation in microsatellite instability-high (MSI-H) endometrial cancer. 国際誌

    Makiko Kawaguchi, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Arisa Kishimi, Seiji Ogawa, Iori Kisu, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    International journal of oncology   35 ( 5 )   977 - 82   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Microsatellite instability (MSI) is an indicator of DNA instability and is caused by abnormalities in DNA mismatch repair (MMR) genes such as hMLH1, hMSH2 and hMSH6. MSI occurs frequently in endometrial cancer (in approximately 30% of cases), and accumulation of gene mutations due to MSI may therefore have a major role in the mechanism of malignant transformation. However, a responsible target gene has not been identified in endometrial cancer. In this study, we analyzed mutations in 11 cancer-related genes with mononucleotide repeats susceptible to MSI in a coding region [hMSH3 (A8), hMSH6 (C8), TGF-beta RII (A10), MBD4 (A10), BAX (G8), PTEN (A6 in exon 7), HDAC2 (A9), EPHB2 (A9), Caspase-5 (A10), TCF-4 (A9) and Axin2 (G7)] in 22 patients with MSI-H sporadic endometrial cancer. Mutations in hMSH6 (C8) and TGF-beta RII (A10) were found most frequently, at rates of 36.3% (8/22) each. Mutations of BAX (G8) and TCF-4 (A9), which are common in MSI-positive colorectal cancer, occurred at rates of 22.7 and 0%, respectively, which suggests that the MSI target gene may differ between endometrial and colorectal cancers. Mutations in hMSH6 (C8) were correlated with reduced protein expression (p=0.042) and patients with these mutations had significantly more mutations in mononucleotide repeats in other cancer-related genes compared to patients without hMSH6 (C8) mutations (p=0.042). This suggests the possibility of a novel cascade in carcinogenesis of endometrial cancer in which MSI mutates hMSH6 (C8), increases gene instability, and leads to accumulation of mutations in other cancer-related genes. To our knowledge, this is the first report to show that hMSH6 (C8) has an important role as an MSI target gene in sporadic endometrial cancer.

    DOI: 10.3892/ijo_00000411

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  • Epigenetic DNA hypermethylation: Clinical applications in endometrial cancer (Review)

    Yuriko Muraki, Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    ONCOLOGY REPORTS   22 ( 5 )   967 - 972   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA repair. An epigenetic analysis of DNA hypermethylation in type I endometrial cancer has led to a proposed mechanism for endometrial carcinogenesis. Reduced DNA mismatch repair due to loss of hMLH1expression is thought to have a major role in carcinogenesis and these findings open up approaches to prevention, diagnosis, risk assessment, and treatment of type I endometrial cancer. Aberrant DNA hypermethylation can be detected with high sensitivity for identification of cancer cells in sputum, blood and other biopsy materials, including in endometrial cancer specimens. There have been many attempts to use methylation inhibitors as anticancer agents, and epigenetic abnormalities may be useful as biomarkers of anticancer drug sensitivity and to identify biological characteristics of tumor cells for determination of treatment options based on hypermethylation. For example, aberrant hypermethylation of the CHFR gene is correlated with cellular sensitivity to microtubule inhibitors, and this may be useful in treatment of type I endometrial cancer. An ultimate objective of epigenetics is to identify the type of hereditary methylation responsible for cancer, with the goal of improved diagnosis and treatment based on control of methylation.

    DOI: 10.3892/or_00000523

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  • ファーマコゲノミクスの現状と課題 ファーマコゲノミクスの臨床応用を目指した簡易迅速な遺伝子多型診断システムの開発

    平沢 晃, 松村 聡子, 鶴田 智彦, 赤羽 智子, 野村 弘行, 青木 大輔, 谷川原 祐介, 杉田 哲佳, 緒方 是嗣, 花房 信博

    臨床薬理   40 ( Suppl. )   S138 - S138   2009年11月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床薬理学会  

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  • 当科更年期外来受診患者における動脈硬化性疾患の危険因子に関する検討

    柳本 茂久, 牧田 和也, 堀場 裕子, 平沢 晃, 田島 博人, 金田 佳史, 伊藤 仁彦, 高松 潔, 青木 大輔

    日本更年期医学会雑誌   17 ( Suppl. )   113 - 113   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

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  • 子宮傍結合織炎

    進 伸幸, 平沢 晃, 青木大輔

    日本臨床(子宮疾患・子宮内膜症の臨床-基礎・臨床研究のアップデート)   67 ( 増刊号5 )   327-330   2009年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • イリノテカン

    平沢 晃, 鶴田智彦, 進 伸幸, 青木大輔

    小児科   50 ( 7 )   1227-1232   2009年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 中高年女性と片頭痛

    牧田和也, 平沢 晃, 青木大輔

    産婦人科治療   98 ( 6 )   971-975 - 975   2009年6月

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    記述言語:日本語   出版者・発行元:(株)永井書店  

    片頭痛は、周期的に襲ってくる激しい頭痛発作により著しいquality of lifeの低下を招く一次性頭痛の1つであり、女性の場合月経周期・妊娠・出産・授乳・閉経といった各ライフステージに伴う女性ホルモンの変動との関連性が高い。中高年女性の場合、閉経に伴うエストロゲンの低下により一時的に症状が増悪したり、またホルモン補充療法を行う際にも症状の増悪が認められることがあり、注意が必要である。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J00534&link_issn=&doc_id=20090612170008&doc_link_id=%2Faf2sftye%2F2009%2F009806%2F008%2F0971-0975%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faf2sftye%2F2009%2F009806%2F008%2F0971-0975%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer. 国際誌

    Makiko Kawaguchi, Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Yoshiko Kuwabara, Maya Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    International journal of oncology   34 ( 6 )   1541 - 7   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endo-metrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.

    DOI: 10.3892/ijo_00000283

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  • Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer

    Makiko Kawaguchi, Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Yoshiko Kuwabara, Maya Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Datsuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   34 ( 6 )   1541 - 1547   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endometrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.

    DOI: 10.3892/ijo_00000283

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  • Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer

    Makiko Kawaguchi, Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Yoshiko Kuwabara, Maya Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Datsuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   34 ( 6 )   1541 - 1547   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endometrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.

    DOI: 10.3892/ijo_00000283

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  • Endometrial cancer as HNPCC associated tumor

    青木 大輔

    家族性腫瘍   9 ( 2 )   64-68   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis (Review) 査読

    Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    CURRENT GENOMICS   10 ( 2 )   127 - 132   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.

    DOI: 10.2174/138920209787847069

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  • Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis (Review) 査読

    Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    CURRENT GENOMICS   10 ( 2 )   127 - 132   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.

    DOI: 10.2174/138920209787847069

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  • 結合型エストロゲン製剤を用いたホルモン補充療法の腰椎骨密度に対する長期的な効果の検討 ~当科更年期外来における継続投与10年例の結果から~

    牧田和也, 堀場裕子, 平沢 晃, 岩田 卓, 冨永英一郎, 堀口 文, 青木大輔

    Osteoporosis Japan   17 ( 2 )   329-330 - 330   2009年4月

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

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  • Endometrial cancer as a familial tumor: pathology and molecular carcinogenesis (review). 国際誌

    Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Current genomics   10 ( 2 )   127 - 32   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.

    DOI: 10.2174/138920209787847069

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  • 当科更年期外来における更年期不定愁訴に対する漢方薬の使用状況について-8年前の調査結果との比較検討-.

    牧田和也, 堀場 裕子, 平沢 晃, 岩田卓, 片岡史夫, 冨永英一郎, 堀口文, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   26 ( 26 )   44-47 - 47   2009年

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    2006年1月〜2007年12月に更年期外来を3ヵ月以上継続通院した671例を抽出し、治療内容について外来カルテを中心に追跡調査し、2000年外来で行った同様調査結果と比較検討した。125例(18.6%)は特に継続的な薬物治療は行わず、血液検査や骨密度測定を定期的に施行している経過観察例、残り546例(81.4%)は継続的な薬物治療が行われていた。ホルモン補充療法(HRT)継続施行例は128例(19.1%)、漢方薬のみ使用例は54例(8.5%)であった。漢方薬の内訳は8年前の調査では桂枝茯苓丸の使用頻度が最も高く、加味逍遙散、牛車腎気丸、芍薬甘草湯の順であったが、今回調査でも使用頻度は桂枝茯苓丸が最も高く、以下加味逍遙散と共に慢性頭痛に対する呉茱萸湯、釣藤散使用例が急増していた。8年前調査では使用漢方薬の種類は10種類程度であったが今回調査では23種類に及んでいた。

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  • 更年期外来受診患者における動脈硬化性疾患の危険因子に関する検討.

    柳本茂久, 牧田和也, 堀場裕子, 平沢 晃, 高松 潔, 堀口 文, 青木大輔

    日本更年期医学会雑誌   17 ( 2 )   171-178 - 178   2009年

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    日本動脈硬化学会の「動脈硬化性疾患の予防と治療に関するガイドライン」が5年ぶりに改定され、その中で「高脂血症」の疾患名は「脂質異常症」に改められている。2007年10月〜2008年12月に更年期外来に受診した初診患者199例(平均54.7歳)を対象として、新しいガイドラインに基づく動脈硬化性疾患の一次予防に関連する危険因子について検証した。199例中87例(43.7%)が「脂質異常症」の診断基準を満たし、79例(39.7%)は評価対象となる危険因子を認めず、1項目該当が76例(38.2%)、2項目該当が24例(12.1%)、3項目以上該当が20例(10.1%)であった。危険因子別では年齢が最も多く該当し、次いで両親の心筋梗塞/狭心症の既往と高血圧が多く認められた。更年期外来受診者においては、動脈硬化性疾患の危険因子として55歳以上という年齢因子を有する者が最も多く、保有因子数が0〜1個の低〜中リスク群に分類される者が主であることが判明した。

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  • Endometrial cancer as a familial tumor: Pathology and molecular carcinogenesis (review)

    Kouji Banno, Megumi Yanokura, Yusuke Kobayashi, Makiko Kawaguchi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

    Current Genomics   10 ( 2 )   127 - 132   2009年

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    記述言語:英語  

    Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor. © 2009 Bentham Science Publishers Ltd.

    DOI: 10.2174/138920209787847069

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  • 閉経後骨粗鬆症に対する予防的治療を行う際の薬剤選択に関する再検証.

    牧田和也, 平沢 晃, 堀場 裕子, 弟子丸亮太, 柳本茂久, 堀口 文, 青木大輔

    Osteoporosis Japan   17 ( 3 )   447-449 - 449   2009年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    過去10年間に更年期外来で腰椎骨密度値から「原発性骨粗鬆症」と診断された106症例、「骨量減少」と診断された183症例、および少なくとも1年以上骨粗鬆症に対する治療を施行している塩酸ラロキシフェン(RLX)投与群35症例と各種ビスフォスフォネート(BIS)投与群43症例を対象に、薬剤選択について再検証した。その結果、1)骨粗鬆症例では骨量減少例や骨密度正常範囲例と比べて、診断時の年齢が有意に高く、閉経ないし卵巣全摘出後期間が有意に長い傾向にあった。2)骨量減少例は骨粗鬆症例と比較して、閉経後5年未満ないし周閉経期が多く、血管運動神経症状を合併した症例も少なくなかった。3)RLX群はBIS群と比べて薬剤開始年齢が有意に高いが、その施行期間が発売開始時期の差異を反映して有意に短い傾向にあった。3)RLXが初回治療薬となっていたのは35例中10例で、21例は2種類以上の薬剤治療歴が認められた。尚、ホルモン補充療法からの直接の切替えは4例であった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J03021&link_issn=&doc_id=20090813170015&doc_link_id=%2Fai6ostoe%2F2009%2F001703%2F016%2F0447-0449%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2009%2F001703%2F016%2F0447-0449%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 子宮体がん例におけるFRAXを用いた骨折リスク評価.

    平沢 晃, 牧田和也, 堀場 裕子, 弟子丸亮太, 柳本茂久, 阪埜浩司, 進 伸幸, 青木大輔

    Osteoporosis Japan   17 ( 3 )   492-495 - 495   2009年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    FRAX(fracture risk assessment tool)は将来的な大腿骨近位部骨折リスクを判定するスコアとして汎用されているが、閉経前の卵巣摘出が骨粗鬆症の危険因子であるにもかかわらず、その調査項目に含まれていない。そこで、子宮体癌例におけるFRAXを用いた骨折リスク評価の特徴を検討した。対象は両側卵巣摘出術を伴う手術療法を施行した子宮体癌症例112例(平均年齢58歳)で、健康維持外来通院中の非子宮体癌132例(平均年齢53歳)を対照とした。その結果、1)子宮体癌群ではBMI高値例が有意に多く、子宮体癌の罹患の有無にかかわらず、10年以内の大腿骨近位部骨折の発生リスクが10%以上の高危険例は高齢者に多かった。2)本検討により、大腿骨近位部骨折のリスクに影響を及ぼす因子として、FRAXに含まれる危険因子よりもそれ以外の環境因子や遺伝的因子等が関与する可能性も示唆された。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J03021&link_issn=&doc_id=20090813170027&doc_link_id=%2Fai6ostoe%2F2009%2F001703%2F028%2F0492-0495%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2009%2F001703%2F028%2F0492-0495%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 当科更年期外来における塩酸ラロキシフェン治療の現況-子宮体癌術後症例を中心に-.

    牧田和也, 堀場裕子, 岩田 卓, 平沢 晃, 片岡史夫, 富永英一郎, 堀口 文, 青木大輔

    SERM   7   106-107   2009年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Can ABCF2 protein expression predict the prognosis of uterine cancer? 査読

    S. Nishimura, H. Tsuda, Y. Miyagi, A. Hirasawa, A. Suzuki, F. Kataoka, H. Nomura, T. Chiyoda, K. Banno, T. Fujii, N. Susumu, D. Aoki

    BRITISH JOURNAL OF CANCER   99 ( 10 )   1651 - 1655   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity ( risk ratio (rr) = 1.437), old age (rr = 1.550) and advanced stage (rr = 2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

    DOI: 10.1038/sj.bjc.6604734

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  • Can ABCF2 protein expression predict the prognosis of uterine cancer?

    S. Nishimura, H. Tsuda, Y. Miyagi, A. Hirasawa, A. Suzuki, F. Kataoka, H. Nomura, T. Chiyoda, K. Banno, T. Fujii, N. Susumu, D. Aoki

    BRITISH JOURNAL OF CANCER   99 ( 10 )   1651 - 1655   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity ( risk ratio (rr) = 1.437), old age (rr = 1.550) and advanced stage (rr = 2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

    DOI: 10.1038/sj.bjc.6604734

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  • Can ABCF2 protein expression predict the prognosis of uterine cancer?

    S. Nishimura, H. Tsuda, Y. Miyagi, A. Hirasawa, A. Suzuki, F. Kataoka, H. Nomura, T. Chiyoda, K. Banno, T. Fujii, N. Susumu, D. Aoki

    BRITISH JOURNAL OF CANCER   99 ( 10 )   1651 - 1655   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity ( risk ratio (rr) = 1.437), old age (rr = 1.550) and advanced stage (rr = 2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

    DOI: 10.1038/sj.bjc.6604734

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  • 子宮がん患者へのインフォームドコンセント(IC)

    進 伸幸, 平沢 晃, 阪埜浩司, 藤井多久磨, 青木大輔

    臨床腫瘍プラクティス   4 ( 4 )   313-319 - 319   2008年11月

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    記述言語:日本語   出版者・発行元:(株)ヴァンメディカル  

    <View Points>がん告知は十分な組織学的根拠が得られてから慎重に行う。がん告知は患者と家族が同席する場で行い、診療録にその説明内容を記載する。特に妊孕性温存の可否、妊娠中の子宮頸がん発症時の妊娠継続の可否、卵巣機能温存の可否などの説明には、詳細なevidenceの説明、選択決定のための反復説明も必要となる場合がある。病態説明や治療法選択に関しては、口頭だけでなく書面でも情報提供を行いinformed consentを得ることが望ましい。(著者抄録)

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  • Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. 査読 国際誌

    Kokichi Sugano, Seigo Nakamura, Jiro Ando, Shin Takayama, Hiroyuki Kamata, Isao Sekiguchi, Megumi Ubukata, Tetsuro Kodama, Masami Arai, Fujio Kasumi, Yasuo Hirai, Tadashi Ikeda, Hiromitsu Jinno, Masaki Kitajima, Daisuke Aoki, Akira Hirasawa, Yuko Takeda, Kumiko Yazaki, Takashi Fukutomi, Takayuki Kinoshita, Ryuichiro Tsunematsu, Teruhiko Yoshida, Masako Izumi, Shino Umezawa, Hiroshi Yagata, Hiroko Komatsu, Naoko Arimori, Noriko Matoba, Nobuhisa Gondo, Shiro Yokoyama, Yoshio Miki

    Cancer science   99 ( 10 )   1967 - 76   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).

    DOI: 10.1111/j.1349-7006.2008.00944.x

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  • Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer

    Kokichi Sugano, Seigo Nakamura, Jiro Ando, Shin Takayama, Hiroyuki Kamata, Isao Sekiguchi, Megumi Ubukata, Tetsuro Kodama, Masami Arai, Fujio Kasumi, Yasuo Hirai, Tadashi Ikeda, Hiromitsu Jinno, Masaki Kitajima, Daisuke Aoki, Akira Hirasawa, Yuko Takeda, Kumiko Yazaki, Takashi Fukutomi, Takayuki Kinoshita, Ryuichiro Tsunematsu, Teruhiko Yoshida, Masako Izumi, Shino Umezawa, Hiroshi Yagata, Hiroko Komatsu, Naoko Arimori, Noriko Matoba, Nobuhisa Gondo, Shiro Yokoyama, Yoshio Miki

    CANCER SCIENCE   99 ( 10 )   1967 - 1976   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64). (Cancer Sci 2008; 99: 1967-1976).

    DOI: 10.1111/j.1349-7006.2008.00944.x

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  • 子宮体がん術後患者における骨密度の特徴に関する検討.

    平沢 晃, 牧田和也, 堀場 裕子, 弟子丸亮太, 柳本茂久, 野村弘行, 片岡史夫, 岩田卓, 冨永英一郎, 阪埜浩司, 進 伸幸, 堀口 文, 青木大輔

    Osteoporosis Japan   16 ( 3 )   429-431   2008年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 子宮体がん術後患者における骨密度の特徴に関する検討

    平沢 晃, 牧田和也, 堀場 裕子, 弟子丸亮太, 柳本茂久, 野村弘行, 片岡史夫, 岩田卓, 冨永英一郎, 阪埜浩司, 進 伸幸, 堀口 文, 青木大輔

    Osteoporosis Japan   16 ( 3 )   429-431 - 431   2008年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    産婦人科で初回治療として両側卵巣摘出術を伴う手術療法を施行した子宮体癌(体癌群)132例、健康維持外来を受診した非担癌自然閉経症例(対照群)224例、計356例を対象に、子宮体癌術後患者における骨代謝の特徴について自然閉経例と比較検討した。体癌群においては骨粗鬆症/骨量減少と診断できた症例は132例中35例(27%)で、対照群では224例中90例(40%)で、体癌群では骨量正常例が有意に多かった。また卵巣摘出時の閉経の有無によって骨粗鬆症/骨量減少の発生頻度に有意差を認めなかった。検討結果から、子宮体癌例は卵巣摘出を施行しているにも拘わらず、骨粗鬆症/骨量減少の高危険群とはいいがたいことが判明した。しかし、近年、若年発症例が増加していることから長期的フォローアップが必要と思われた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J03021&link_issn=&doc_id=20080812230011&doc_link_id=%2Fai6ostoe%2F2008%2F001603%2F011%2F0429-0431%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2008%2F001603%2F011%2F0429-0431%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 当科更年期外来にて診断し得た骨粗鬆症/骨量減少症における低エストロゲン血症以外の危険因子の検討

    牧田和也, 冨永英一郎, 平沢 晃, 堀口 文, 青木大輔

    Osteoporosis Japan   16 ( 2 )   308   2008年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 更年期外来でのアンケート調査結果からみた本邦中高年婦人の「night sweats」の実態とホルモン療法の有用性に関する一考察.

    牧田和也, 柳本茂久, 張簡珮怡, 平沢 晃, 冨永英一郎, 高松 潔, 堀口 文, 青木大輔

    日本更年期医学会雑誌   16 ( 2 )   246-251 - 251   2008年

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    記述言語:日本語   出版者・発行元:(一社)日本女性医学学会  

    中等度以上のホットフラッシュや発汗を主な適応としてホルモン療法(HRT)を施行中の50例(平均年齢54.8歳)を対象として、「night sweats」の有無およびその出現時期と重症度、「night sweats」に対するHRTの効果の印象などを自己記入式アンケートにて調査した。23例に「night sweats」を認め、そのうち65.2%はホットフラッシュや発汗が出現した時期と同時期より「night sweats」も認めていた。程度は中等度が最も多く、69.6%はHRTが「night sweats」にも有効であると回答した。

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  • 季節による漢方製剤の切り替えが片頭痛発作の軽減に有効であった1例

    牧田和也, 平沢 晃, 冨永英一郎, 堀口 文, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   25   115-118   2008年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 季節による漢方製剤の切り替えが片頭痛発作の軽減に有効であった1例.

    牧田和也, 平沢 晃, 冨永英一郎, 堀口 文, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   25 ( 25 )   115-118 - 118   2008年

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    症例は初診時48歳で、閉経に伴い片頭痛発作が再燃・増悪した。季節によって東洋医学的病態が異なることに着目し、使用する漢方製剤の切り替えを行った。すなわち、「水毒」の徴候がみられる春〜夏季には五苓散、「冷え」がみられる秋〜冬季には当帰四逆加呉茱萸生姜湯を使用し、良好な経過が得られている。

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  • 当科更年期外来にて診断し得た骨粗鬆症/骨量減少症における低エストロゲン血症以外の危険因子の検討.

    牧田和也, 冨永英一郎, 平沢 晃, 堀口 文, 青木大輔

    Osteoporosis Japan   16 ( 2 )   308 - 308   2008年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

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  • 当科更年期外来受診者におけるアレンドロネート製剤のweekly投与への切り替えの現状.

    牧田和也, 平沢 晃, 冨永英一郎, 堀口 文, 青木大輔

    Osteoporosis Japan   16 ( 3 )   268-269 - 469   2008年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    更年期外来で閉経後骨粗鬆症又は骨量減少と診断され、薬物治療を1年以上継続し、2006年度アンケートに協力した57例(平均61.3歳)を対象にアレンドロネート製剤の2007年10月以降の外来受診者切替えの現状について報告した。07年10月以降15例中13例が移行したが、2例は従来からの連日服用のままで大きな問題はないとして移行しなかった。リセドロネート製剤の07年10月の服用状況は12例中3例が1年以内に脱落・移行し、7例は従来通り連日服用を継続した。エチドロネート製剤の07年10月の服用状況は18例中2例が1年以内に脱落、1例が上腹部痛の副作用のためビタミンD3(VD3)製剤に2例が骨密度に対する治療効果不良でアレンドロネート製剤へ移行、残り10例がその後も継続服用した。ラロキシフェンの07年10月の服用状況は12例中1例が副作用でVD3製剤に、1例がアレンドロネート製剤に、残り10例が継続した。

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  • Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes

    Kouji Banno, Megumi Yanokura, Makiko Kawaguchi, Yoshiko Kuwabara, Jyunko Akiyoshi, Yusuke Kobayashi, Takashi Iwata, Akira Hirasawa, Takuma Fujii, Nobuyuki Susumu, Kastumi Tsukazaki, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   31 ( 4 )   713 - 720   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

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  • Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes 査読

    Kouji Banno, Megumi Yanokura, Makiko Kawaguchi, Yoshiko Kuwabara, Jyunko Akiyoshi, Yusuke Kobayashi, Takashi Iwata, Akira Hirasawa, Takuma Fujii, Nobuyuki Susumu, Kastumi Tsukazaki, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   31 ( 4 )   713 - 720   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

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  • Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes 査読

    Kouji Banno, Megumi Yanokura, Makiko Kawaguchi, Yoshiko Kuwabara, Jyunko Akiyoshi, Yusuke Kobayashi, Takashi Iwata, Akira Hirasawa, Takuma Fujii, Nobuyuki Susumu, Kastumi Tsukazaki, Daisuke Aoki

    INTERNATIONAL JOURNAL OF ONCOLOGY   31 ( 4 )   713 - 720   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

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  • Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. 国際誌

    Kouji Banno, Megumi Yanokura, Makiko Kawaguchi, Yoshiko Kuwabara, Jyunko Akiyoshi, Yusuke Kobayashi, Takashi Iwata, Akira Hirasawa, Takuma Fujii, Nobuyuki Susumu, Kastumi Tsukazaki, Daisuke Aoki

    International journal of oncology   31 ( 4 )   713 - 20   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

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  • 進行子宮体癌の再発・予後因子としてのCOX-2とCD8陽性リンパ球についての検討

    末盛 友浩, 進 伸幸, 鶴田 智彦, 市川 義一, 野村 弘行, 片岡 史夫, 平澤 晃, 冨永 英一郎, 阪埜 浩司, 鈴木 淳, 青木 大輔

    日本癌治療学会誌   42 ( 2 )   508 - 508   2007年9月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • ヒトモノクローナル抗体HMMC-1の子宮体癌細胞に対する増殖抑制効果の検討

    笈川 文子, 鈴木 淳, 冨永 英一郎, 末盛 友浩, 市川 義一, 野村 弘行, 片岡 史夫, 平澤 晃, 進 伸幸, 青木 大輔

    日本臨床細胞学会雑誌   46 ( Suppl.2 )   448 - 448   2007年9月

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    記述言語:日本語   出版者・発行元:(公社)日本臨床細胞学会  

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  • 卵巣明細胞腺癌におけるシアリダーゼ発現の多寡が腹膜播種形成に及ぼす影響の検討

    野村弘行, 玉田 裕, 鈴木 淳, 平沢 晃, 進 伸幸, 宮城妙子, 入村達郎, 青木大輔

    日本分子腫瘍マーカー研究会誌   22   39429 - 13   2007年4月

  • 卵巣癌の各組織型特異的バイオマーカーに基づく診断用マイクロアレイDNAチップ作成

    鈴木 淳, 杉田 哲佳, 東口 敦史, 末盛 友浩, 市川 義一, 野村 弘行, 平澤 晃, 玉田 裕, 進 伸幸, 佐藤 孝明, 青木 大輔, 吉村 泰典

    日本産科婦人科学会雑誌   59 ( 2 )   409 - 409   2007年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer 査読

    Megumi Yanokura, Kouji Banno, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Nobuyuki Susumu, Katsumi Tsukazaki, Daisuke Aoki

    ONCOLOGY REPORTS   17 ( 1 )   41 - 48   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p &lt; 0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.

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  • Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer

    Megumi Yanokura, Kouji Banno, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Nobuyuki Susumu, Katsumi Tsukazaki, Daisuke Aoki

    ONCOLOGY REPORTS   17 ( 1 )   41 - 48   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p < 0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.

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  • Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer. 国際誌

    Megumi Yanokura, Kouji Banno, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Nobuyuki Susumu, Katsumi Tsukazaki, Daisuke Aoki

    Oncology reports   17 ( 1 )   41 - 8   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p<0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.

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  • 妊娠に伴い増悪した片頭痛に対して呉茱萸湯が著効した1例―妊娠期間中の片頭痛治療に関する考察も含めて―

    牧田和也, 小久保靖子, 張簡珮怡, 平沢 晃, 堀口文, 青木大輔, 吉村泰典

    産婦人科漢方研究のあゆみ   24 ( 24 )   98-101 - 101   2007年

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    記述言語:日本語   出版者・発行元:産婦人科漢方研究会  

    26歳女。10歳頃より片頭痛によるエピソディックな発作を認めていた。妊娠が成立し、発作回数が妊娠前の2倍に増悪したため、薬物療法によるコントロールを希望した。妊娠4ヵ月目に入っており、急性期の片頭痛薬の多くは服用が制限されていたため、「習慣性偏頭痛」や「習慣性頭痛」に適応がある呉茱萸湯エキス顆粒に着目した。本剤の添付文書では妊婦の投与に関し、「治療上の有益性が危険性を上回ると判断された場合にのみ投与」と記載されており、本人の同意を得た上で7.5g/日の服用を開始した。開始後2週間目で、週4〜5回発生していたエピソディックな頭痛は1回に減少した。その後、片頭痛発作は完全に消失し、開始2ヵ月後より5g/日に減量した。妊娠41週1日目に女児を経腟分娩で出産したが、分娩後も本人の希望により同剤を2.5g/日で継続し、激しい片頭痛発作は生じていない。

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  • 当院更年期外来にて診断された閉経後骨粗鬆症/骨量減少症における血清脂質動態の検討

    牧田和也, 冨永英一郎, 平沢 晃, 堀口文, 青木大輔

    Osteoporosis Japan   15 ( 2 )   158   2007年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 骨粗鬆症治療薬の服薬コンプライアンス向上に必要な要因の検討

    牧田和也, 平沢 晃, 張簡珮怡, 堀口文, 青木大輔

    Osteoporosis Japan   15 ( 3 )   142-144 - 486   2007年

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    記述言語:日本語   出版者・発行元:ライフサイエンス出版(株)  

    当科更年期外来で閉経後骨粗鬆症ないし骨量減少と診断され1年以上服薬している57例(平均年齢60.5歳)を対象に、薬物治療に関するアンケート調査を行い、骨粗鬆症治療薬の服薬コンプライアンス向上に必要な要因を検証した。使用薬剤は塩酸ラロキシフェン 14例、エチドロネート 16例、アレンドロネートとリセドロネート 27例であった。その結果、約8割が骨粗鬆症に対するイメージとして骨折による寝たきり、身長低下、亀背に対する恐れがあった。服薬開始時ではその服薬方法に多少とまどったことはあったがすぐに慣れ、現在は全例で特に問題はなかった。週1回内服の薬剤について多くが支持したことから、服薬コンプライアンスの向上には服薬方法の単純化が重要な要因の一つであり、週1回服薬タイプの薬剤や服薬時期を問わない薬剤のアピールが有用であると考えられた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J03021&link_issn=&doc_id=20070808110032&doc_link_id=%2Fai6ostoe%2F2007%2F001503%2F033%2F0484-0486%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2007%2F001503%2F033%2F0484-0486%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 家族内癌集積性を有する子宮体癌症例におけるMMR遺伝子の生殖細胞変異解析

    阪埜浩司, 進 伸幸, 矢野倉恵, 平沢 晃, 塚崎克己, 青木大輔, 三木義男, 野澤志朗

    家族性腫瘍   7 ( 1 )   15-18 - 18   2007年

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    記述言語:日本語   出版者・発行元:(一社)日本遺伝性腫瘍学会  

    遺伝的素因の強い、家系内癌集積性を有する、または重複癌を認めた子宮体癌36例を対象として、3種のMMR遺伝子(hMLH1、hMSH2、hMSH6遺伝子)の生殖細胞変異を解析した。すべて類内膜腺癌で、2例に明細胞腺癌の混在を認めた。子宮体癌36例中6例でMMR遺伝子の生殖細胞変異を認めた。この6例は家系内癌集積性を示すA群症例で、重複癌を示すB群症例12例には遺伝子変異は認めなかった。A群に限定すれば、24例中6例と高率にMMR遺伝子の生殖細胞変異が存在した。A群において遺伝子変異を有する6例の子宮体癌発症年齢、変異を有さない症例に比べ7歳ほど若年であった。MMR遺伝子の中ではhMSH6遺伝子の変異が3例と最も高頻度で、次いでhMSH2遺伝子が2例、hMLH1遺伝子が1例であった。3例のhMSH6遺伝子の変異はすべてexon4〜5に集中し、変異型もフレームシフト変異と共通していた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J03931&link_issn=&doc_id=20080620410004&doc_link_id=%2Fcg3kazok%2F2007%2F000701%2F005%2F0015-0018%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2007%2F000701%2F005%2F0015-0018%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 明細胞腺癌

    平沢 晃, 進 伸幸, 青木大輔

    産婦人科の実際   55 ( 13 )   2185-2193   2006年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer

    Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

    ONCOLOGY REPORTS   16 ( 6 )   1189 - 1196   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the. hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

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  • Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer. 査読 国際誌

    Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

    Oncology reports   16 ( 6 )   1189 - 96   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

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  • Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer

    Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

    ONCOLOGY REPORTS   16 ( 6 )   1189 - 1196   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the. hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

    Web of Science

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  • Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer 査読

    Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

    ONCOLOGY REPORTS   16 ( 6 )   1189 - 1196   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the. hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

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  • 卵巣明細胞腺癌におけるシアリダーゼ発現の多寡が腹膜播種形成に及ぼす影響の検討

    野村 弘行, 玉田 裕, 鈴木 淳, 平沢 晃, 進 伸幸, 宮城 妙子, 入村 達郎, 青木 大輔

    日本分子腫瘍マーカー研究会プログラム・講演抄録   26回   28 - 29   2006年9月

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    記述言語:日本語   出版者・発行元:日本分子腫瘍マーカー研究会  

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  • 子宮体癌における腫瘍マーカーの意義

    進 伸幸, 平沢 晃, 玉田 裕, 阪埜浩司, 鈴木 淳, 塚崎克己, 青木大輔

    産婦人科の実際   55 ( 5 )   753-762 - 762   2006年5月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

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  • コルポスコピー、コルポ下狙い生検

    平沢 晃, 片岡史夫, 青木大輔

    臨床婦人科産科   60 ( 4 )   369-375 - 375   2006年4月

  • Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer. 国際誌

    Wataru Yamagami, Nobuyuki Susumu, Kouji Banno, Takeshi Hirao, Fumio Kataoka, Akira Hirasawa, Nao Suzuki, Daisuke Aoki, Shiro Nozawa

    The journal of obstetrics and gynaecology research   31 ( 5 )   444 - 51   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    AIM: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed. METHODS: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent. RESULTS: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P < 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%). CONCLUSION: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

    DOI: 10.1111/j.1447-0756.2005.00318.x

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  • 実地臨床応用が期待される新たな腫瘍マーカー−バイオマーカーとしてのゲノム変化を中心に−

    平沢 晃, 進 伸幸, 青木大輔

    臨床婦人科産科   59 ( 10 )   1383-1387 - 1387   2005年10月

  • [Diagnostic significance of tumor markers for gynecologic malignancies].

    Daisuke Aoki, Akira Hirasawa, Nobuyuki Susumu

    Gan to kagaku ryoho. Cancer & chemotherapy   32 ( 3 )   411 - 6   2005年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms. With ovarian tumors, due to their location within the abdominal cavity, it is difficult to make a preoperative pathological diagnosis of cancer without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA 125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, there are no useful tumor markers for endometrial cancer that exhibit both high sensitivity and specificity, although CA 125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of post-molar disease as well as with the overall decrease in the number of pregnancies.

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  • 婦人科腫瘍

    青木大輔, 平沢 晃, 進 伸幸, 野澤志朗

    癌と化学療法   32 ( 33 )   411-416   2005年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Diagnostic significance of tumor markers for gynecologic malignancies

    Aoki Daisuke, Hirasawa Akira, Susumu Nobuyuki

    Gan to kagaku ryoho. Cancer & chemotherapy   32 ( 3 )   411 - 416   2005年3月

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    記述言語:英語  

    &lt;p&gt;Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms. With ovarian tumors, due to their location within the abdominal cavity, it is difficult to make a preoperative pathological diagnosis of cancer without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA 125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, there are no useful tumor markers for endometrial cancer that exhibit both high sensitivity and specificity, although CA 125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of post-molar disease as well as with the overall decrease in the number of pregnancies.&lt;/p&gt;

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  • 子宮体癌手術症例における傍大動脈リンパ節廓清の検討.

    山本阿紀子, 田中 淳, 上野和典, 石谷 健, 平沢 晃, 山下 博, 新井宏治

    日本産科婦人科学会東京地方部会会誌   54 ( 2 )   219-222 - 222   2005年

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    子宮体癌は近年増加傾向にあるが,本邦において手術術式は統一されていない.今回,当院にて子宮体癌に対し初回手術を施行した症例のうち,傍大動脈リンパ節郭清を施行した症例について検討したので報告する.対象は2000年1月から2004年12月までに手術を施行した90例中,骨盤内リンパ節郭清(PLN)のみ施行した21例と,傍大動脈リンパ節郭清(PAN)まで施行した41例の計62例を比較検討した.リンパ節転移は62例中8例に認め,うち,PLN転移例7例(11.3%),PAN転移例3例(7.3%)であった.PLNに転移を認めず,PANのみ転移陽性症例を1例(2.4%)に認めた.またPLNのみと比較し,PANを追加することにより手術時間の延長と出血量の増加を認め,合併症の頻度は増加したが,入院日数には有意差がなかった.今後さらに症例数をかさね,リンパ節郭清の適応について検討する必要があると考えられた(著者抄録)

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  • Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer

    W Yamagami, N Susumu, K Banno, T Hirao, F Kataoka, A Hirasawa, N Suzuki, D Aoki, S Nozawa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   31 ( 5 )   444 - 451   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Aim: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed.
    Methods: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent.
    Results: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P &lt; 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%).
    Conclusion: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

    DOI: 10.1111/j.1447-0756.2005.00318.x

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  • Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer 査読

    W Yamagami, N Susumu, K Banno, T Hirao, F Kataoka, A Hirasawa, N Suzuki, D Aoki, S Nozawa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   31 ( 5 )   444 - 451   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Aim: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed.
    Methods: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent.
    Results: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P &lt; 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%).
    Conclusion: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

    DOI: 10.1111/j.1447-0756.2005.00318.x

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  • Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines. 査読 国際誌

    Hideaki Tanami, Issei Imoto, Akira Hirasawa, Yasuhiro Yuki, Itaru Sonoda, Jun Inoue, Kohichiro Yasui, Akiko Misawa-Furihata, Yutaka Kawakami, Johji Inazawa

    Oncogene   23 ( 54 )   8796 - 804   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

    DOI: 10.1038/sj.onc.1208152

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  • Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines

    H Tanami, Imoto, I, A Hirasawa, Y Yuki, Sonoda, I, J Inoue, K Yasui, A Misawa-Furihata, Y Kawakami, J Inazawa

    ONCOGENE   23 ( 54 )   8796 - 8804   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

    DOI: 10.1038/sj.onc.1208152

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  • Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines

    H Tanami, Imoto, I, A Hirasawa, Y Yuki, Sonoda, I, J Inoue, K Yasui, A Misawa-Furihata, Y Kawakami, J Inazawa

    ONCOGENE   23 ( 54 )   8796 - 8804   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

    DOI: 10.1038/sj.onc.1208152

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  • [Outline of treatment for endometrial cancer].

    Daisuke Aoki, Akira Hirasawa, Nobuyuki Susumu, Shiro Nozawa

    Nihon rinsho. Japanese journal of clinical medicine   62 Suppl 10   324 - 8   2004年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 子宮体癌の治療 治療概論

    青木大輔, 平沢 晃, 進 伸幸, 野澤志朗

    日本臨床   62 ( 増刊 )   324-328 - 328   2004年10月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary non-polyposis colorectal cancer (HNPCC), Amsterdam Criteria II 査読

    K Banno, N Susumu, T Hirao, M Yanokura, A Hirasawa, D Aoki, Y Udagawa, K Sugano, S Nozawa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   30 ( 4 )   287 - 292   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominantly inherited disorder of cancer susceptibility. Patients with HNPCC exhibit an increased risk for HNPCC-associated extracolonic tumors such as cancer of the endometrium. HNPCC is associated with germline mutations in DNA mismatch repair (MMR) genes: hMLH1, hMSH2 and hMSH6.
    Here, we describe two Japanese kindreds (0.5%) who met the new clinical criteria for HNPCC, Amsterdam criteria II, from among 375 endometrial cancer patients treated at Keio University Hospital from 1990 to 2002. From these results, it was found that female HNPCC patients comprised approximately 0.5% of all endometrial cancer patients. Decreased expression of two MMR gene protein products (hMLH1 and hMSH6) was confirmed immunohistochemically in these two endometrial tumors in HNPCC kindreds. This case report provides important information on Japanese HNPCC patients occurring endometrial cancer.

    DOI: 10.1111/j.1447-0756.2004.00195.x

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  • Association of HNPCC and endometrial cancers.

    Kouji Banno, Nobuyuki Susumu, Megumi Yanokura, Takeshi Hirao, Takashi Iwata, Akira Hirasawa, Daisuke Aoki, Kokichi Sugano, Shiro Nozawa

    International journal of clinical oncology   9 ( 4 )   262 - 9   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

    DOI: 10.1007/s10147-004-0402-8

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  • Association of HNPCC and endometrial cancers

    Kouji Banno, Nobuyuld Susumu, Megumi Yanokura, Takeshi Hirao, Takashi Iwata, Akira Hirasawa, Daisuke Aoki, Kokichi Sugano, Shiro Nozawa

    International Journal of Clinical Oncology   9 ( 4 )   262 - 269   2004年8月

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    記述言語:英語  

    Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

    DOI: 10.1007/s10147-004-0402-8

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  • Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary non-polyposis colorectal cancer (HNPCC), Amsterdam Criteria II. 国際誌

    Kouji Banno, Nobuyuki Susumu, Takeshi Hirao, Megumi Yanokura, Akira Hirasawa, Daisuke Aoki, Yasuhiro Udagawa, Kokichi Sugano, Shiro Nozawa

    The journal of obstetrics and gynaecology research   30 ( 4 )   287 - 92   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominantly inherited disorder of cancer susceptibility. Patients with HNPCC exhibit an increased risk for HNPCC-associated extracolonic tumors such as cancer of the endometrium. HNPCC is associated with germline mutations in DNA mismatch repair (MMR) genes: hMLH1, hMSH2 and hMSH6. Here, we describe two Japanese kindreds (0.5%) who met the new clinical criteria for HNPCC, Amsterdam criteria II, from among 375 endometrial cancer patients treated at Keio University Hospital from 1990 to 2002. From these results, it was found that female HNPCC patients comprised approximately 0.5% of all endometrial cancer patients. Decreased expression of two MMR gene protein products (hMLH1 and hMSH6) was confirmed immunohistochemically in these two endometrial tumors in HNPCC kindreds. This case report provides important information on Japanese HNPCC patients occurring endometrial cancer.

    DOI: 10.1111/j.1447-0756.2004.00195.x

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  • Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary non-polyposis colorectal cancer (HNPCC), Amsterdam Criteria II

    K Banno, N Susumu, T Hirao, M Yanokura, A Hirasawa, D Aoki, Y Udagawa, K Sugano, S Nozawa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   30 ( 4 )   287 - 292   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominantly inherited disorder of cancer susceptibility. Patients with HNPCC exhibit an increased risk for HNPCC-associated extracolonic tumors such as cancer of the endometrium. HNPCC is associated with germline mutations in DNA mismatch repair (MMR) genes: hMLH1, hMSH2 and hMSH6.
    Here, we describe two Japanese kindreds (0.5%) who met the new clinical criteria for HNPCC, Amsterdam criteria II, from among 375 endometrial cancer patients treated at Keio University Hospital from 1990 to 2002. From these results, it was found that female HNPCC patients comprised approximately 0.5% of all endometrial cancer patients. Decreased expression of two MMR gene protein products (hMLH1 and hMSH6) was confirmed immunohistochemically in these two endometrial tumors in HNPCC kindreds. This case report provides important information on Japanese HNPCC patients occurring endometrial cancer.

    DOI: 10.1111/j.1447-0756.2004.00195.x

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  • Association of HNPCC and endometrial cancers 査読

    Kouji Banno, Nobuyuld Susumu, Megumi Yanokura, Takeshi Hirao, Takashi Iwata, Akira Hirasawa, Daisuke Aoki, Kokichi Sugano, Shiro Nozawa

    International Journal of Clinical Oncology   9 ( 4 )   262 - 269   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

    DOI: 10.1007/s10147-004-0402-8

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  • Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug resistance phenotype in multiple myeloma

    J Inoue, T Otsuki, A Hirasawa, Imoto, I, Y Matsuo, S Shimizu, M Taniwaki, J Inazawa

    AMERICAN JOURNAL OF PATHOLOGY   165 ( 1 )   71 - 81   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC INVESTIGATIVE PATHOLOGY, INC  

    We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.7%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.

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  • Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug resistance phenotype in multiple myeloma

    J Inoue, T Otsuki, A Hirasawa, Imoto, I, Y Matsuo, S Shimizu, M Taniwaki, J Inazawa

    AMERICAN JOURNAL OF PATHOLOGY   165 ( 1 )   71 - 81   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC INVESTIGATIVE PATHOLOGY, INC  

    We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.7%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.

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  • Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug-resistance phenotype in multiple myeloma. 査読 国際誌

    Jun Inoue, Takemi Otsuki, Akira Hirasawa, Issei Imoto, Yoshinobu Matsuo, Shiroh Shimizu, Masafumi Taniwaki, Johji Inazawa

    The American journal of pathology   165 ( 1 )   71 - 81   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC INVESTIGATIVE PATHOLOGY, INC  

    We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.7%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.

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  • 子宮体癌に対する新たな治療戦略

    平沢 晃, 青木大輔, 野澤志朗

    産科と婦人科   71 ( 2 )   201-207 - 207   2004年2月

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    記述言語:日本語   出版者・発行元:(株)診断と治療社  

    子宮体癌の治療法として,我が国では化学療法としてCAP療法(シクロフォスファミド,アドリアマイシン,シスプラチン)が一般的であったが,最近の実地臨床ではタキサン系薬剤を用いた治療が導入されている.今後はrandomized controlled trialによる至適治療法の確立が求められる.一方,近年のゲノム医学をはじめとした悪性腫瘍に関する基礎科学の進歩により,癌分子標的治療や遺伝子治療などの新しい治療戦略も実現可能になっている

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  • 術前細胞診にて癌腫成分のみを示した子宮体部異所性癌肉腫の一例

    石谷 健, 平沢 晃, 山下 博, 田中 淳, 新井宏治, 前島新史

    日本婦人科腫瘍学会雑誌   22 ( 4 )   393-398   2004年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Outline of treatment for endometrial cancer

    Aoki Daisuke, Hirasawa Akira, Susumu Nobuyuki, Nozawa Shiro

    Nippon rinsho. Japanese journal of clinical medicine   62 Suppl 10   324 - 328   2004年

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    記述言語:英語  

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  • 腹腔内出血を繰り返した卵巣顆粒細胞腫晩期再発の一例.

    山田満稔, 田中 淳, 山本阿紀子, 上野和典, 石谷 健, 平沢 晃, 山下 博, 板倉紘一, 新井宏治, 倉持 茂

    日本産科婦人科学会東京地方部会会誌   53 ( 3 )   362-366 - 366   2004年

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    記述言語:日本語   出版者・発行元:(一社)東京産科婦人科学会  

    55歳(2経妊2経産).10年前に卵巣腫瘍と診断され,腹式単純子宮全摘術および両側付属器切除術が施行された.術後病理診断は卵巣顆粒膜細胞腫であり,臨床進行期はIb期であった.今回,腹部膨満感を主訴に受診,卵巣顆粒膜細胞腫再発と診断され,化学療法にて経過観察中,出血性ショックを起こし,腹腔内腫瘍性出血が疑われた.直ちにTJ療法を2コース施行したが,全く効果なく,施行後も出血性ショックを繰り返すため,原因検索および除去目的にて緊急試験開腹術を施行した.開腹時所見で大網を中心に5ヶ所の易出血性腫瘍と約2000mlの腹腔内出血が認められたため,手術は止血目的で可及的摘出術とした.術後の病理組織学的検査で卵巣顆粒膜細胞腫再発と診断された.その後腹腔内出血は完全に消失し,術後6ヵ月再発再燃の徴候は認めていない

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  • Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer. 国際誌

    Akira Hirasawa, Daisuke Aoki, Jun Inoue, Issei Imoto, Nobuyuki Susumu, Kokichi Sugano, Shiro Nozawa, Johji Inazawa

    Clinical cancer research : an official journal of the American Association for Cancer Research   9 ( 15 )   5675 - 82   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    PURPOSE: Although many articles have been published regarding chromosomal instability (CI) and microsatellite instability (MI) in endometrial adenocarcinoma, the relationship between prognostic factors and the biological mechanisms accounting for genetic instability in these tumors has not yet been precisely defined. To do that, it will be necessary to clarify the molecular mechanisms involved in endometrial carcinogenesis. EXPERIMENTAL DESIGN: Tissue samples from 43 human primary endometrioid endometrial adenocarcinomas (EACs) were analyzed for CI and MI status using comparative genomic hybridization and 11 microsatellite loci, respectively. Methylation status of the promoter of MLH1 was also determined. We analyzed all three of these parameters in relation to each other and to clinicopathological factors. RESULTS: Sixty-five percent of the EACs we examined had detectable CI. Frequent copy number gains were seen at 1q25-41 (23%), 8q11.1-q21.1 (23%), 8q21.3-qter (21%); 28% of these tumors exhibited high-frequency MI (MSI-H); Methylation of the MLH1 promoter was observed in 92% of EACs with MSI-H. Southern blotting showed amplification of MYCN in one tumor, which has been documented for the first time in a primary human EAC. CONCLUSIONS: MSI-H was correlated with histological grade, International Federation of Gynecologists and Obstetricians (FIGO) stage, myometrial invasion, and lymphonode metastasis. Our comparative genomic hybridization results demonstrated that the number of chromosomes involved in genomic alterations in EACs was distinctively fewer than those in other types of tumor. The carcinogenetic process leading to EAC appears to be highly complex; for example, MI and CI may act synergistically, whereas CI and/or MI are likely to be linked with tumor heterogeneity.

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  • Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer 査読

    A Hirasawa, D Aoki, J Inoue, Imoto, I, N Susumu, K Sugano, S Nozawa, J Inazawa

    CLINICAL CANCER RESEARCH   9 ( 15 )   5675 - 5682   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Purpose: Although many articles have been published regarding chromosomal instability (CI) and microsatellite instability (MI) in endometrial adenocarcinoma, the relationship between prognostic factors and the biological mechanisms accounting for genetic instability in these tumors has not yet been precisely defined. To do that, it will be necessary to clarify the molecular mechanisms involved in endometrial carcinogenesis.
    Experimental Design: Tissue samples from 43 human primary endometrioid endometrial adenocarcinomas (EACs) were analyzed for CI and MI status using comparative genomic hybridization And It microsatellite loci, respectively. Methylation status of the promoter of MLH1 was also determined. We analyzed all three of these parameters in relation to each other and to clinicopathological factors.
    Results: Sixty-five percent of the EACs we examined had detectable CI. Frequent copy number gains were seen at 1q25-41 (23%), 8q11.1-q21.1 (23%), 8q21.3-qter (21%); 28% of these tumors exhibited high-frequency MI (MSI-H); Methylation of the MLH1 promoter was observed in 92% of EACs with MSI-H. Southern blotting showed amplification of MYCN in one tumor, which has been documented for the first time in a primary human EAC.
    Conclusions: MSI-H was correlated with histological grade, International Federation of Gynecologists and Obstetricians (FIGO) stage, myometrial invasion, and lymphonode metastasis. Our comparative genomic hybridization results demonstrated that the number of chromosomes involved in genomic alterations in EACs was distinctively fewer than those in other types of tumor. The carcinogenetic process leading to EAC appears to be highly complex; for example, MI and CI may act synergistically, whereas CI and/or MI are likely to be linked with tumor heterogeneity.

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  • Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer

    A Hirasawa, D Aoki, J Inoue, Imoto, I, N Susumu, K Sugano, S Nozawa, J Inazawa

    CLINICAL CANCER RESEARCH   9 ( 15 )   5675 - 5682   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Purpose: Although many articles have been published regarding chromosomal instability (CI) and microsatellite instability (MI) in endometrial adenocarcinoma, the relationship between prognostic factors and the biological mechanisms accounting for genetic instability in these tumors has not yet been precisely defined. To do that, it will be necessary to clarify the molecular mechanisms involved in endometrial carcinogenesis.
    Experimental Design: Tissue samples from 43 human primary endometrioid endometrial adenocarcinomas (EACs) were analyzed for CI and MI status using comparative genomic hybridization And It microsatellite loci, respectively. Methylation status of the promoter of MLH1 was also determined. We analyzed all three of these parameters in relation to each other and to clinicopathological factors.
    Results: Sixty-five percent of the EACs we examined had detectable CI. Frequent copy number gains were seen at 1q25-41 (23%), 8q11.1-q21.1 (23%), 8q21.3-qter (21%); 28% of these tumors exhibited high-frequency MI (MSI-H); Methylation of the MLH1 promoter was observed in 92% of EACs with MSI-H. Southern blotting showed amplification of MYCN in one tumor, which has been documented for the first time in a primary human EAC.
    Conclusions: MSI-H was correlated with histological grade, International Federation of Gynecologists and Obstetricians (FIGO) stage, myometrial invasion, and lymphonode metastasis. Our comparative genomic hybridization results demonstrated that the number of chromosomes involved in genomic alterations in EACs was distinctively fewer than those in other types of tumor. The carcinogenetic process leading to EAC appears to be highly complex; for example, MI and CI may act synergistically, whereas CI and/or MI are likely to be linked with tumor heterogeneity.

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  • Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer 査読

    A Hirasawa, D Aoki, J Inoue, Imoto, I, N Susumu, K Sugano, S Nozawa, J Inazawa

    CLINICAL CANCER RESEARCH   9 ( 15 )   5675 - 5682   2003年11月

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    記述言語:英語