研究者詳細 - 平沢　晃

論文 - 平沢　晃

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CD63 as a potential biomarker for patients with ovarian cancer. 国際誌

Keiichiro Nakamura, Naoyuki Ida, Akira Hirasawa, Kazuhiro Okamoto, Thuy Ha Vu, Dao Thi Hai Ly, Hisashi Masuyama

European journal of obstetrics, gynecology, and reproductive biology 306 87 - 93 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Exosomes play an important role in regulating physiological processes and mediating the systemic dissemination of various types of cancer. We investigated the association of exosomal tetraspanins CD9, CD63, and CD81 in patients with ovarian cancer (OC). MATERIAL AND METHODS: We measured the plasma tetraspanins CD9, CD63, and CD81 by enzyme-linked immunosorbent assay in 91 patients who underwent treatment for OC between April 2018 and March 2024. Additionally, we analyzed clinical pathologic factors, chemotherapy response, and prognosis. RESULTS: In terms of stages, CD63 expression was significantly higher in patients with stage IV compared to those with stage I OC (p = 0.003). In terms of histological type, CD63 expression was significantly higher in high-grade serous carcinoma (HGSC) than in clear cell carcinoma (CCC) with OC (p = 0.009). Furthermore, CD63 levels were significantly higher in advanced-stage, HGSC than in patients with early-stage, non-HGSC and early-stage, HGSC OC (p = 0.045 and p = 0.002, respectively). In the Neoadjuvant chemotherapy (NAC) of 12 patients with OC assessed as having either a partial response (PR) or complete response (CR), CD63 was significantly decreased (p = 0.043), whereas perforin was significantly increased (p = 0.001). In the NAC of 16 patients with OC, CD63 of the response rate to chemotherapy tended to differ between the progressive disease (PD) and PR/CR groups (p = 0.056). A moderate inverse correlation was observed between CD63 and perforin levels (R = 0.638, R2 = 0.428, p = 0.008). CONCLUSIONS: CD63 could be a potential biomarker for all types of OC patients.

DOI： 10.1016/j.ejogrb.2025.01.011

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P143: Original protocol for presumed germline pathogenic variants in cancer genome profiling tests

Mashu Futagawa, Hideki Yamamoto, Fumino Kato, Chika Fukano, Risa Osumi, Yusaku Urakawa, Tetsuya Okazaki, Shuta Tomida, Daisuke Ennishi, Akira Hirasawa

Genetics in Medicine Open 3 102987 - 102987 2025年

Molecular and functional profiling of primary normal ovarian cells defines insights into cancer development and drug responses. 国際誌

Emilia Piki, Alice Dini, Frida Rantanen, Franziska Bentz, Lassi Paavolainen, Harlan Barker, Juuli Raivola, Akira Hirasawa, Olli Kallioniemi, Astrid Murumägi, Daniela Ungureanu

Molecular therapy. Oncology 32 ( 4 ) 200903 - 200903 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with ovarian cancer, especially the high-grade serous ovarian cancer (HGSOC) subtype, face poor prognosis due to late diagnosis and treatment resistance. Owing to the high heterogeneity of HGSOC, identifying the origin of the disease and optimal treatments is difficult. Here, we characterized two primary immortalized human ovarian cell lines, human ovarian surface epithelium (HOSE)1C and HOSE2C, comparing their molecular profiling with representative HGSOC cells. We identified molecular features associated with normal and malignant phenotype of ovarian cells by applying single-cell transcriptomics, high-content image-based cell painting, and high-throughput drug testing. Our findings reveal distinct transcriptomic and morphological profiles for the two HOSEs, with a stromal phenotype. Moreover, their responses to the tumor microenvironment differ, exemplified by STAT1 and GREM1 upregulation in HOSE1C and HOSE2C, respectively. We identified selective activation of ERK/MEK targeted inhibitors in cancer cells compared to HOSEs. This study offers insights into the normal and malignant ovarian cells, shedding light on cancer development and drug responses.

DOI： 10.1016/j.omton.2024.200903

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Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study. 国際誌

Mashu Futagawa, Tetsuya Okazaki, Eiji Nakata, Chika Fukano, Risa Osumi, Fumino Kato, Yusaku Urakawa, Hideki Yamamoto, Toshifumi Ozaki, Akira Hirasawa

Human genome variation 11 ( 1 ) 42 - 42 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care.

DOI： 10.1038/s41439-024-00299-4

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Knowledge and Awareness of Cancer Genome Profiling Tests among Japanese Patients with Cancer. 国際誌

Yuko Kawasaki, Tamotsu Sudo, Kazuo Tamura, Saki Hinoshita, Kayoko Hasuoka, Satoko Miyawaki, Nao Matsutani, Akira Hirasawa, Atsuko Uchinuno

Clinics and practice 14 ( 5 ) 2105 - 2115 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

(1) Background: The number of patients with cancer undergoing cancer genome profiling is increasing; however, it remains unclear how accurately they understand the details of the tests and treatments. This study aimed to clarify the awareness of cancer genome profiling tests among patients with cancer who visited cancer genome medical clinics. (2) Methods: A questionnaire survey was conducted on awareness, anxiety, sources of information, and psychological states concerning cancer genome profiling tests. (3) Results: In total, 265 patients with cancer (117 men, 142 women, 6 no response, average age of 58.29 ± 11.9 years) were included in the study, of which 218 (82.3%) were aware of the term "cancer genomic medicine" and 90 (34.0%) were aware of its details. Thus, only a few respondents understood that cancer genome profiling tests facilitate the discovery of secondary findings and of genes associated with hereditary tumors. Regarding their psychological state when visiting the cancer genome clinic, the respondents were anxious about standard treatment and prognosis limits. (4) Conclusions: From the viewpoint of advance care planning, we suggest that medical professionals build a support system that links palliative care and cancer treatment and coordinates genetic counseling at an early stage.

DOI： 10.3390/clinpract14050166

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Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy. 国際誌

Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, 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 70 ( 1 ) 33 - 40 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.

DOI： 10.1038/s10038-024-01294-x

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多遺伝子パネル検査(MGPT)を用いた遺伝性腫瘍の診断-国内外における現状と課題-

平沢晃

癌と化学療法 51 ( 7 ) 677 - 680 2024年7月

神経線維腫症1型を中心とした遺伝性骨・軟部腫瘍に対する専門外来の有用性

中田英二, 二川摩周, 平沢晃, 山本英喜, 国定俊之, 板野拓人, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1614 - S1614 2024年6月

多職種から見た骨・軟部腫瘍治療の現状と課題肉腫発生ハイリスク患者に対する遺伝性骨・軟部腫瘍外来の取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1579 - S1579 2024年6月

加速する骨・軟部腫瘍に対するゲノム医療: 現状と課題肉腫におけるゲノム医療の現状と課題

中田英二, 遠西大輔, 二宮貴一朗, 山本英喜, 冨田秀太, 藤原智洋, 国定俊之, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1457 - S1457 2024年6月

Assessing the efficacy of target adaptive sampling long-read sequencing through hereditary cancer patient genomes. 国際誌

Wataru Nakamura, Makoto Hirata, Satoyo Oda, Kenichi Chiba, Ai Okada, Raúl Nicolás Mateos, Masahiro Sugawa, Naoko Iida, Mineko Ushiama, Noriko Tanabe, Hiromi Sakamoto, Shigeki Sekine, Akira Hirasawa, Yosuke Kawai, Katsushi Tokunaga, Shin-Ichi Tsujimoto, Norio Shiba, Shuichi Ito, Teruhiko Yoshida, Yuichi Shiraishi

NPJ genomic medicine 9 ( 1 ) 11 - 11 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read sequencing technologies are expected to significantly improve the diagnostic rate by overcoming the limitations of short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers adaptive sampling and computationally driven target enrichment technology. This enables more affordable intensive analysis of target gene regions compared to standard non-selective long-read sequencing. In this study, we developed an efficient computational workflow for target adaptive sampling long-read sequencing (TAS-LRS) and evaluated it through application to 33 genomes collected from suspected hereditary cancer patients. Our workflow can identify single nucleotide variants with nearly the same accuracy as the short-read platform and elucidate complex forms of structural variations. We also newly identified several SINE-R/VNTR/Alu (SVA) elements affecting the APC gene in two patients with familial adenomatous polyposis, as well as their sites of origin. In addition, we demonstrated that off-target reads from adaptive sampling, which is typically discarded, can be effectively used to accurately genotype common single-nucleotide polymorphisms (SNPs) across the entire genome, enabling the calculation of a polygenic risk score. Furthermore, we identified allele-specific MLH1 promoter hypermethylation in a Lynch syndrome patient. In summary, our workflow with TAS-LRS can simultaneously capture monogenic risk variants including complex structural variations, polygenic background as well as epigenetic alterations, and will be an efficient platform for genetic disease research and diagnosis.

DOI： 10.1038/s41525-024-00394-z

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神経線維腫症1型患者由来ヒトiPS細胞株の樹立

大澤太郎, 中田英二, 岡本真幸, 山田大祐, 二川摩周, 高尾知佳, 平沢晃, 尾崎敏文, 宝田剛志

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 24 - 24 2024年2月

HBOCに対するリスク低減卵管卵巣摘出術及び乳腺外科手術の合同実施に関する当院での取り組み

花谷智美, 原賀順子, 小川千加子, 長尾昌二, 杉原花子, 谷佳紀, 白河伸介, 依田尚之, 松岡敬典, 中村圭一郎, 平沢晃, 増山寿

日本産科婦人科学会雑誌 76 ( 臨増 ) S - 500 2024年2月

Patient survey on cancer genomic medicine in Japan under the national health insurance system. 国際誌

Hidenori Kage, Nana Akiyama, Hyangri Chang, Aya Shinozaki-Ushiku, Mirei Ka, Junichi Kawata, Manabu Muto, Yusuke Okuma, Natsuko Okita, Katsuya Tsuchihara, Junko Kikuchi, Hidekazu Shirota, Hideyuki Hayashi, Toshio Kokuryo, Shinichi Yachida, Akira Hirasawa, Makoto Kubo, Hirotsugu Kenmotsu, Masahiko Tanabe, Tetsuo Ushiku, Kaori Muto, Yasuyuki Seto, Katsutoshi Oda

Cancer science 115 ( 3 ) 954 - 962 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

In Japan, comprehensive genomic profiling (CGP) tests have been reimbursed under the national health care system for solid cancer patients who have finished standard treatment. More than 50,000 patients have taken the test since June 2019. We performed a nation-wide questionnaire survey between March 2021 and July 2022. Questionnaires were sent to 80 designated Cancer Genomic Medicine Hospitals. Of the 933 responses received, 370 (39.7%) were web based and 563 (60.3%) were paper based. Most patients (784, 84%) first learned about CGP tests from healthcare professionals, and 775 (83.1%) gave informed consent to their treating physician. At the time of informed consent, they were most worried about test results not leading to novel treatment (536, 57.4%). On a scale of 0-10, 702 respondents (75.2%) felt that the explanations of the test result were easy to understand (7 or higher). Ninety-one patients (9.8%) started their recommended treatment. Many patients could not receive recommended treatment because no approved drugs or clinical trials were available (102/177, 57.6%). Ninety-eight patients (10.5%) did not wish their findings to be disclosed. Overall satisfaction with the CGP test process was high, with 602 respondents (64.5%) giving a score of 7-10. The major reason for choosing 0-6 was that the CGP test result did not lead to new treatment (217/277, 78.3%). In conclusion, satisfaction with the CGP test process was high. Patients and family members need better access to information. More patients need to be treated with genomically matched therapy.

DOI： 10.1111/cas.16065

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Ligneous periodontitis exacerbated by Behçet's disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report. 国際誌

Yuki Shinoda-Ito, Anna Hirai, Kazuhiro Omori, Hidetaka Ideguchi, Hideki Yamamoto, Fumino Kato, Kyoichi Obata, Tatsuo Ogawa, Keisuke Nakano, Takato Nakadoi, Eri Katsuyama, Soichiro Ibaragi, Tadashi Yamamoto, Hitoshi Nagatsuka, Akira Hirasawa, Shogo Takashiba

BMC oral health 23 ( 1 ) 843 - 843 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

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多遺伝子パネル検査を用いて治療方針を決定した若年の非浸潤性乳管癌患者の一例

鈴木陽子, 岩谷胤生, 仁科卓也, 吉本皓一, 宇野摩耶, 中本翔伍, 高橋侑子, 突沖貴宏, 岩本高行, 伊波茂道, 平沢晃, 枝園忠彦

日本臨床外科学会雑誌 84 ( 11 ) 1830 - 1830 2023年11月