2021/12/18 更新

写真a

ナカムラ ケイイチロウ
中村 圭一郎
NAKAMURA Keiichiro
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 医学博士 ( 2000年3月   岡山大学 )

研究キーワード

  • 婦人科癌

  • 子宮頸癌

  • 子宮体癌

  • 卵巣癌

研究分野

  • ライフサイエンス / 産婦人科学

学歴

  • 岡山大学    

    1996年4月 - 2000年3月

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  • 川崎医科大学    

    - 1994年3月

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経歴

  • 岡山大学   産科・婦人科学   准教授

    2018年1月 - 現在

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    国名:日本国

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  • 岡山大学病院   産科・婦人科講座   講師

    2012年10月 - 2017年12月

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  • 岡山大学病院   産科・婦人科   助教

    2009年4月 - 2012年9月

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  • 岡山大学医学部・歯学部附属病院   産科・婦人科   助教

    2007年4月 - 2009年3月

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  • 岡山大学医学部・歯学部附属病院   産科・婦人科   助手

    2003年10月 - 2007年3月

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  • 岡山大学医学部附属病院   産科・婦人科   助手

    2002年10月 - 2003年9月

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  • 尾道市立市民病院   産婦人科

    2002年4月 - 2002年9月

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  • Uniformed Services University of the Health Science

    2000年5月 - 2002年3月

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  • 岡山大学医学部附属病院   産科婦人科   医員

    2000年4月

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▼全件表示

所属学協会

  • 日本産科婦人科遺伝診療学会

    2016年12月 - 現在

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  • 日本女性医学学会

    2016年10月 - 現在

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  • 日本腫瘍学会

    2016年7月 - 現在

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  • 日本産婦人科手術学会

    2011年10月 - 現在

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  • 日本婦人科腫瘍学会

    2004年7月 - 現在

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  • 日本癌学会

    1997年8月 - 現在

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  • 日本産科婦人科学会

    1994年4月 - 現在

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▼全件表示

委員歴

  • 日本産科婦人科学会   代議員  

    2019年4月 - 現在   

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  • 岡山県産婦人科医会   理事  

    2019年4月 - 現在   

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  • 日本婦人科腫瘍学会   代議員  

    2014年4月 - 現在   

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  • 日本産婦人科手術学会   日本産婦人科手術学会幹事  

    2012年4月 - 現在   

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論文

  • The Spiral Trial: A multicenter, randomized, controlled trial of Spiral thread sutures versus conventional thread sutures to prevent thinning of uterine scars following elective cesarean section. 国際誌

    Jota Maki, Hikari Nakatou, Kazumasa Tani, Eriko Eto, Kei Hayata, Dan Yamamoto, Kenji Kai, Takashi Tamada, Kazuyo Akamatsu, Kunihiro Kawanishi, Keiichiro Nakamura, Hisashi Masuyama

    Contemporary clinical trials   107   106449 - 106449   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)  

    BACKGROUND: The aim of this randomized controlled trial (RCT) is to investigate whether Spiral-thread sutures are superior to conventional sutures (0-Vicryl) for preventing uterine scar thinning following elective cesarean section. METHODS: This multicenter, parallel-group RCT will be conducted in four hospitals across three medical regions in Japan to assess 200 women (≥20 years old) with singleton pregnancies who are scheduled to undergo cesarean sections. Eligible women will be randomly assigned (1:1 ratio) to receive either the conventional uterine suture continuous absorption thread, which is most commonly used in Japan, or the Spiral thread. The primary endpoint is the degree of scar thinning, measured by transvaginal ultrasonography 6-7 months postoperatively, to evaluate the position of the uterus (anterior or posterior tilt) and myometrial wound thickness. The degree of thinning will be compared between the groups, and four measurements (mm) of the thinning area, including caudal distance, depth of the depression, remaining thickness of the myometrium on the serous side of the most depressed area, and width of the depression, will be recorded in the sagittal view on transvaginal ultrasound. Secondary endpoints will include total operative time, suture application time (from birth to the end of uterine suturing), operative blood loss, number of additional Z-sutures or continuous sutures required to stop bleeding, maternal abnormality frequency (surgical complications and postoperative infections), surgeon's years of experience, and clinical interpretation of individual subscale scores. DISCUSSION: This study shall provide important evidence on the optimal suture for preventing hysterotomy wound thinning after the first cesarean section. TRIAL REGISTRATION: National Institute of Public Health, Japan: jRCT1062200001 (May 7, 2020; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT1062200001) and Okayama University Certified Review Board: CRB6180001 (April 9, 2020, version 3.0).

    DOI: 10.1016/j.cct.2021.106449

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  • Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix: a phase II study.

    Muneaki Shimada, Shinya Sato, Tadahiro Shoji, Shoji Nagao, Hideki Tokunaga, Kotaro Sueoka, Kazuhiro Takehara, Keiichiro Nakamura, Satoshi Yamaguchi, Junzo Kigawa

    International journal of clinical oncology   26 ( 7 )   1314 - 1321   2021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)  

    BACKGROUND: This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. METHODS: A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events. Except for two patients, 48 were eligible for evaluation. Another patient withdrew consent before treatment; adverse events were evaluated in 47. RESULTS: The response rate was 47.9% with 5 patients achieving complete response, 18 partial response, 14 stable disease, and 6 progressive disease. The disease control rate was 77.1%. With a median follow-up duration of 368 days, the median progression-free survival and overall survival were 6.1 months (95% CI 5.5-8.6) and 15.8 months (95% CI 18.2-28.3), respectively. The most frequent grade 3 and grade 4 hematological toxicity was neutropenia, with 38 patients (81%) having grade 4 and 4 (9%) having grade 3 neutropenia. The non-hematological toxicities were mainly grade 1 or 2 in severity. CONCLUSION: Docetaxel/carboplatin chemotherapy was effective, with a higher disease control rate and well-tolerated chemotherapeutic regimen for patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix.

    DOI: 10.1007/s10147-021-01903-1

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  • Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix: a phase II study

    Muneaki Shimada, Shinya Sato, Tadahiro Shoji, Shoji Nagao, Hideki Tokunaga, Kotaro Sueoka, Kazuhiro Takehara, Keiichiro Nakamura, Satoshi Yamaguchi, Junzo Kigawa

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   26 ( 7 )   1314 - 1321   2021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:SPRINGER JAPAN KK  

    Background This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. Methods A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m(2), followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events. Except for two patients, 48 were eligible for evaluation. Another patient withdrew consent before treatment; adverse events were evaluated in 47. Results The response rate was 47.9% with 5 patients achieving complete response, 18 partial response, 14 stable disease, and 6 progressive disease. The disease control rate was 77.1%. With a median follow-up duration of 368 days, the median progression-free survival and overall survival were 6.1 months (95% CI 5.5-8.6) and 15.8 months (95% CI 18.2-28.3), respectively. The most frequent grade 3 and grade 4 hematological toxicity was neutropenia, with 38 patients (81%) having grade 4 and 4 (9%) having grade 3 neutropenia. The non-hematological toxicities were mainly grade 1 or 2 in severity. Conclusion Docetaxel/carboplatin chemotherapy was effective, with a higher disease control rate and well-tolerated chemotherapeutic regimen for patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix.

    DOI: 10.1007/s10147-021-01903-1

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  • Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide.

    Hiroyuki Sugiura, Hisakazu Nishimori, Hirofumi Matsuoka, Keiichiro Nakamura, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    Acta medica Okayama   75 ( 2 )   219 - 224   2021年4月

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    記述言語:英語  

    Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

    DOI: 10.18926/AMO/61904

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  • Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide

    Hiroyuki Sugiuraa, Hisakazu Nishimori, Hirofumi Matsuoka, Keiichiro Nakamura, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

    ACTA MEDICA OKAYAMA   75 ( 2 )   219 - 224   2021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:OKAYAMA UNIV MED SCHOOL  

    Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

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  • DNA mismatch repair deficiency and p53 abnormality are age-related events in mixed endometrial carcinoma with a clear cell component. 国際誌

    Naoyuki Ida, Keiichiro Nakamura, Masayuki Saijo, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

    Pathology, research and practice   220   153383 - 153383   2021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)  

    Mixed endometrial carcinoma (MEC) is defined as a tumor composed of two or more spatially distinct subtypes, at least one of which is serous or clear cell carcinoma. In this study, the clinicopathological features of 15 MEC cases containing a clear cell component (MEC-C) were investigated. The ages of patients ranged from 32 to 83 years (median, 61 years). The combinations of carcinoma components observed were endometrioid and clear cell in ten patients; endometrioid, clear cell and serous in three; and clear cell and serous in two. Immunohistochemically, nine had DNA mismatch repair (MMR) protein deficiency (MMR-d), nine had loss of ARID1A and three cases had aberrant p53 expression. MMR-d and loss of ARID1A showed a strong correlation. Only one case showed both MMR-d and aberrant p53 expression. The patients with MMR-d were younger than those without MMR-d (median; 58 years vs. 71 years). Loss of ARID1A also showed significant predilection for younger women than ARID1A intact cases. In conclusion, MMR-d was observed in 60 % of MEC-C, showed predilection for young women, and was associated with ARID1A loss. In contrast, non- MMR-d MEC-C occurred in elder women and some tumors may associate with TP53 mutation. These findings suggest that MEC-C develop via two different molecular mechanisms and they are age-related events.

    DOI: 10.1016/j.prp.2021.153383

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  • Molecular Characterization of Second Primary Endometrial Cancer. 国際誌

    Junko Haraga, Keiichiro Nakamura, Tomoko Haruma, Akihiro Nyuya, Takeshi Nagasaka, Hisashi Masuyama

    Anticancer research   40 ( 7 )   3811 - 3818   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)  

    BACKGROUND/AIM: The objective of this study was to determine the molecular and clinicopathological features, as well as the prognosis of patients with endometrial cancer (EC) having prior malignancy (second primary EC: SPEC) compared with those without a history of prior malignancy (first primary EC: FPEC). MATERIALS AND METHODS: We enrolled 294 FPEC patients and 32 SPEC patients who had undergone surgical resection with curative intent. EC was divided into four groups according to Cancer Genome Atlas Research Network (TCGA) classification. RESULTS: SPEC patients having greater than a 10-year interval from prior malignancy had risk factors including type II histology, deeper myometrial invasion, cervical invasion, and copy number high (CNH) phenotype compared with patients having less than a 10-year interval (p=0.007, p=0.002, p=0.015 and p=0.001). CONCLUSION: SPEC patients having greater than a 10-year interval from prior malignancy possessed numerous high-risk factors for EC.

    DOI: 10.21873/anticanres.14370

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  • Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

    Mamiko Onuki, Koji Matsumoto, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Shoji Maenohara, Naotake Tsuda, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Hideaki Yahata, Yuji Takei, Hisamori Kato, Takeshi Motohara, Keiichiro Nakamura, Mitsuya Ishikawa, Tatsuya Kato, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Nobuo Yaegashi, Hiroyuki Yoshikawa

    CANCER SCIENCE   111 ( 7 )   2546 - 2557   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)   出版者・発行元:WILEY  

    To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

    DOI: 10.1111/cas.14445

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  • Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan. 国際誌

    Mamiko Onuki, Koji Matsumoto, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Shoji Maenohara, Naotake Tsuda, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Hideaki Yahata, Yuji Takei, Yoichi Aoki, Hisamori Kato, Takeshi Motohara, Keiichiro Nakamura, Mitsuya Ishikawa, Tatsuya Kato, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Nobuo Yaegashi, Hiroyuki Yoshikawa

    Cancer science   111 ( 7 )   2546 - 2557   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)  

    To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

    DOI: 10.1111/cas.14445

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  • Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice. 国際誌

    Kosuke Kataoka, Andras Bilkei-Gorzo, Chihiro Nozaki, Akinobu Togo, Keiichiro Nakamura, Keisuke Ohta, Andreas Zimmer, Toru Asahi

    Brain research bulletin   160   40 - 49   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)  

    Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging. The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions. However, the underlying mechanisms that link CB1 activity and memory decline remain unknown. Mitochondrial activity profoundly influences neuronal function, and age-dependent mitochondrial activity change is one of the known hallmarks of brain aging. As CB1 receptor is expressed on mitochondria and may regulate neuronal energy metabolism in hippocampus, we hypothesized that CB1 receptors might influence mitochondria in hippocampal neurons. Here, we found that CB1 receptor significantly affected mitochondrial autophagy (mitophagy) and morphology in an age-dependent manner. Serine 65-phosphorylated ubiquitin, a key marker for mitophagy, was reduced in adult CB1-deficient mice (CB1-KO) compared to those in wild type controls, particularly in CA1 pyramidal cell layer. Transmission electron microscopy (TEM) analysis showed reduced mitophagy-like events in hippocampus of adult CB1-KO. TEM analysis also showed that mitochondrial morphology in adult CB1-KO mice was altered shown by an increase in thin and elongated mitochondria in hippocampal neurons. 3D reconstruction of mitochondrial morphology after scanning electron microscopy additionally revealed an enhanced density of interconnected mitochondria. Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging. These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory.

    DOI: 10.1016/j.brainresbull.2020.03.014

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  • Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan

    Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

    ACTA MEDICA OKAYAMA   74 ( 2 )   109 - 114   2020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:OKAYAMA UNIV MED SCHOOL  

    This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The X-2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31(10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

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  • The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan

    Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

    MOLECULAR AND CLINICAL ONCOLOGY   12 ( 4 )   336 - 342   2020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:SPANDIDOS PUBL LTD  

    The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged >= 70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

    DOI: 10.3892/mco.2020.1989

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  • The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan. 国際誌

    Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

    Molecular and clinical oncology   12 ( 4 )   336 - 342   2020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)  

    The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged ≥70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

    DOI: 10.3892/mco.2020.1989

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  • Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan.

    Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

    Acta medica Okayama   74 ( 2 )   109 - 114   2020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)  

    This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

    DOI: 10.18926/AMO/58268

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  • Reduction in HPV16/18 prevalence among young women with high-grade cervical lesions following the Japanese HPV vaccination program. 国際誌

    Koji Matsumoto, Nobuo Yaegashi, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Masao Okadome, Kimio Ushijima, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Kenzo Sonoda, Yuji Takei, Yoichi Aoki, Katsuyuki Konnai, Hidetaka Katabuchi, Keiichiro Nakamura, Mitsuya Ishikawa, Hidemichi Watari, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Hiroyuki Yoshikawa

    Cancer science   110 ( 12 )   3811 - 3820   2019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)  

    The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend  < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend  = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.

    DOI: 10.1111/cas.14212

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  • Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma Impact on Prognosis and Insights Into Tumorigenesis

    Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   43 ( 11 )   1493 - 1500   2019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:LIPPINCOTT WILLIAMS & WILKINS  

    Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

    DOI: 10.1097/PAS.0000000000001353

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  • Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis. 国際誌

    Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

    The American journal of surgical pathology   43 ( 11 )   1493 - 1500   2019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)  

    Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

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  • Pre-treatment psoas major volume is a predictor of poor prognosis for patients with epithelial ovarian cancer. 国際誌

    Yuko Matsubara, Keiichiro Nakamura, Hirofumi Matsuoka, Chikako Ogawa, Hisashi Masuyama

    Molecular and clinical oncology   11 ( 4 )   376 - 382   2019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)  

    Low skeletal muscle mass (sarcopenia) is an important prognostic risk factor for the outcome of a variety of cancer types. The current study investigated whether skeletal muscle area (SMA), psoas area (PA) and psoas major volume (PV) are associated with progression-free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (OC). A total of 92 OC patients were enrolled in the present study. Pre-treatment with SMA and PA was assessed using computed tomography (CT) and PV was calculated using a three-dimensional-CT (3D-CT). The clinical factors associated with sarcopenia and prognosis were retrospectively evaluated. For all patients, the median PFS and OS were 19 and 32 months, respectively. Patients exhibiting lower PV (<195.6 cm3) had significantly poorer PFS and OS compared with patients exhibiting higher PV (≥195.6 cm3; P=0.018 and P=0.006), while those with low SMA (<92.92 cm2) had significantly worse OS than patients with higher SMA (≥92.92 cm2; P=0.030). PV was also demonstrated to be superior to SMA and PA in prognosis prediction. PV by 3D-CT can serve as an indicator of poor prognosis in patients with OC.

    DOI: 10.3892/mco.2019.1912

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  • Assessment of glucose kinetics with real-time continuous glucose monitoring during labor. 国際誌

    Jota Maki, Eriko Eto, Shoko Tamada, Takashi Mitsui, Kei Hayata, Keiichiro Nakamura, Yuji Hiramatsu, Hisashi Masuyama

    The journal of obstetrics and gynaecology research   45 ( 9 )   1851 - 1859   2019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)  

    AIM: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT). METHODS: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h. RESULTS: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024). CONCLUSION: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT.

    DOI: 10.1111/jog.14058

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  • Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer. 国際誌

    Koji Matsuo, Muneaki Shimada, Keiichiro Nakamura, Yuji Takei, Kimio Ushijima, Toshiyuki Sumi, Tatsuru Ohara, Hideaki Yahata, Mikio Mikami, Toru Sugiyama

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology   45 ( 8 )   1417 - 1424   2019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)  

    OBJECTIVE: To examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. METHODS: This study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (n = 714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. RESULTS: Parametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4-59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0-87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. CONCLUSION: In clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.

    DOI: 10.1016/j.ejso.2019.02.019

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  • Sarcopenia Is Not a Prognostic Factor of Outcome in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy. 国際誌

    Hirofumi Matsuoka, Keiichiro Nakamura, Yuko Matsubara, Naoyuki Ida, Takeshi Nishida, Chikako Ogawa, Kuniaki Katsi, Susumu Kanazawa, Hisashi Masuyama

    Anticancer research   39 ( 2 )   933 - 939   2019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/AIM: The objective of this study was to determine if sarcopenia was a predictor of poor prognosis in patients with cervical cancer (CC) undergoing concurrent chemoradiation therapy (CCRT) or radiation therapy (RT). MATERIALS AND METHODS: A total of 236 patients with CC undergoing CCRT or RT were retrospectively examined. We determined if clinical characteristics and survival were correlated with pretreatment sarcopenia, measured as psoas muscle index (PI) or skeletal muscle index (SMI). RESULTS: Pretreatment PI and SMI were related to parametrial involvement with CC undergoing CCRT or RT (p=0.002, and, p=0.034, respectively). The median progression-free survival (PFS) and overall survival (OS) times in patients undergoing CCRT or RT were 29.0 and 34.5 months, respectively. Neither PI nor SMI were prognostic predictors in patients with CC undergoing CCRT or RT. CONCLUSION: Sarcopenia is not a predictive factor of outcome in patients with CC undergoing CCRT or RT.

    DOI: 10.21873/anticanres.13196

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  • The Influence of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life of Gynecologic Cancer Survivors. 国際誌

    Hirofumi Matsuoka, Keiichiro Nakamura, Yuko Matsubara, Naoyuki Ida, Masayuki Saijo, Chikako Ogawa, Hisashi Masuyama

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society   28 ( 7 )   1394 - 1402   2018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: The aim of this observational study was to investigate correlations between long-term chemotherapy-induced peripheral neurotoxicity (CIPN) and quality of life (physical well-being, social well-being, emotional well-being, and functional well-being [FWB]) among survivors of gynecologic cancer (GC). METHODS: We aimed to assess the correlation of quality of life and long-term CIPN with the temporal change in recurrence-free GC survival. Questionnaire responses and clinical data of 259 GC survivors were collected and assessed according to treatment received. The χ test was used to determine the significance of correlations. RESULTS: Of 165 evaluable patients treated by chemotherapy, 36 patients (21.8%) developed CIPN of Common Toxicity Criteria for Adverse Events grade 1 or higher during the study. Chemotherapy-induced peripheral neurotoxicity had significantly improved over time in the domain of FWB at 61 months or more after the end of chemotherapy (posttreatment 4) among GC survivors (P = 0.003). Furthermore, CIPN treated by more than 6 courses of the paclitaxel and carboplatin regimen among GC survivors showed significant improvement over time in the emotional well-being domain at 25 to 60 months and 61 months or more after the end of chemotherapy (posttreatments 3 and 4) (P = 0.037 and P = 0.023) and in FWB at posttreatment 4 (P < 0.001). CONCLUSIONS: Emotional and functional domains of CIPN improved over time among GC survivors treated by more than 6 courses of the paclitaxel and carboplatin regimen. Based on these results, further research is required to identify additional preventative or curative approaches.

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  • Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles. 国際誌

    Yoshiko Mori, Akihiro Nyuya, Kazuya Yasui, Toshiaki Toshima, Takashi Kawai, Fumitaka Taniguchi, Keisuke Kimura, Ryo Inada, Masahiko Nishizaki, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroyuki Kishimoto, Toshiyoshi Fujiwara, Yosuke Katata, Yoshiyuki Yamaguchi, Takeshi Nagasaka

    Oncotarget   9 ( 23 )   16477 - 16488   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)  

    We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25 months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

    DOI: 10.18632/oncotarget.24735

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  • Prognostic nutritional index as a predictor of survival in patients with recurrent cervical cancer. 国際誌

    Naoyuki Ida, Keiichiro Nakamura, Masayuki Saijo, Tomoyuki Kusumoto, Hisashi Masuyama

    Molecular and clinical oncology   8 ( 2 )   257 - 263   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)  

    Systemic inflammatory responses (SIRs) can help predict survival in various cancers. The present study investigated the accuracy of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI) in predicting survival for patients with recurrent cervical cancer. A retrospective review of prognoses examined the associations among NLR, PLR, and PNI, and clinical characteristics and survival in 79 patients with recurrent cervical cancer after undergoing concurrent chemoradiation therapy (CCRT) or radical hysterectomies with or without CCRT. The Mann-Whitney U-test was used for statistical analyses. In addition, 12-month, 24-month and overall survival were analyzed by the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. Median survival was 15.0 months over follow-up periods of 2-93 months. At the last follow-up point, 54 had succumbed to disease and 25 were alive with disease. In univariate analysis, NLR, PLR and PNI were significantly associated with 12-month, 24 month and overall survival (12 months: P=0.021, P=0.001 and P<0.001; 24 months: P=0.020, P=0.008 and P<0.001; overall; P=0.032, P=0.032 and P<0.001, respectively). In multivariate analyses, PNI was an independent prognostic factor for 12-month, 24-month and overall survival (P=0.001, P=0.001 and P<0.001, respectively). PNI is a useful predictor of survival of recurrent cervical cancer.

    DOI: 10.3892/mco.2017.1508

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  • Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors

    Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C. Richard Boland, Ajay Goel

    JOURNAL OF TRANSLATIONAL MEDICINE   16   2018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:BMC  

    Background: To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6.Methods: To improve the sensitivity for tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4 bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR [45 MutL homolog (MLH) 1-deficient, 45 MutS protein homolog (MSH)2-deficient, and 15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In addition, we analyzed a cohort of 138 endometrial cancers (EC) by immunohistochemistry to determine MMR protein expression and validation of our new MSI assay.Results: Using the criteria of >= 1 unstable markers as MSI-positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence interval (Cl) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% Cl = 91.5-97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a sensitivity of 92.7% (95% Cl = 80.6-97.5%) and a specificity of 97.9% (95% Cl = 92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC-validation set, Tetraplex detected | dMSH6 tumors with a sensitivity of 86.7% (13 of 15 dMSH6 CRCs), which was subsequently validated in the EC test set I as well (sensitivity, 75.0%; 6 of 8 dMSH6 ECs).Conclusions: Our newly optimized Tetraplex system will help offer a robust and highly sensitive assay for the identification of dMMR in solid tumors.

    DOI: 10.1186/s12967-017-1376-4

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  • Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability. 国際誌

    Tomoko Haruma, Takeshi Nagasaka, Keiichiro Nakamura, Junko Haraga, Akihiro Nyuya, Takeshi Nishida, Ajay Goel, Hisashi Masuyama, Yuji Hiramatsu

    PloS one   13 ( 4 )   e0195655   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). RESULTS: Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. CONCLUSIONS: This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

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  • The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer

    Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Naoyuki Ida, Masayuki Saijo, Takeshi Nishida, Tomoyuki Kusumoto, Hisashi Masuyama

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 ( 9 )   2014 - 2019   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:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physicalwell-being [PWB], socialwell-being, emotional well-being [EWB], and functionalwell-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patientswith gynecologic cancer (GC).Methods: From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The chi(2) test was used to determine the significance of correlations.Results: Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017).Conclusions: Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

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  • Gene expression profiles in BRAF V600E mutant colorectal cancer and association with SFRP2 methylation status

    Kazuya Yasui, Takeshi Nagasaka, Toshiaki Toshima, Takashi Kawai, Kunitoshi Shigeyasu, Yoshiko Mori, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara

    CANCER RESEARCH   77   2017年7月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2017-5711

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  • Glasgow prognostic score is a prognosis predictor for patients with endometrial cancer

    Masayuki Saijo, Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   210   355 - 359   2017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:ELSEVIER SCIENCE BV  

    Objective: This study investigated whether the inflammation-based Glasgow prognostic score (GPS) predicted the prognosis of patients with endometrial cancer (EC) in terms of progression-free survival (PFS) and overall survival (OS).Study design: Pretreatment GPS was examined to determine the correlations with recurrence and survival in 431 patients with EC. Statistical analyses were performed using the Mann-Whitney U test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results: Median PFS and OS were 49.7 and 52.7 months, respectively. The follow-up range was I to 140 months. Kaplan-Meier analysis revealed that patients with EC cancer and high GPS (GPS 2) had a shorter PFS and OS than those with lower GPS (GPS 0 + 1) (PFS: P < 0.001; OS; P < 0.001). On multivariate analysis, GPS (GPS 2) was an independent predictor of both recurrence (P < 0.001) and survival (P < 0.001) for all cases of EC.Conclusion: GPS can be useful as an indicator of poor prognosis in patients with EC. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ejogrb.2017.01.024

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  • Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer

    Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 ( 1 )   117 - 122   2017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  

    Objective: Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer.Methods: Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The chi(2) test was used to determine the significance of the correlations.Results: The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return towork in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than-6-month interval between treatment and return towork and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034).Conclusions: Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer.

    DOI: 10.1097/IGC.0000000000000840

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  • Glasgow prognostic score is an independent marker for poor prognosis with all cases of epithelial ovarian cancer

    Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Hisashi Masuyama, Yuji Hiramatsu

    CANCER MEDICINE   5 ( 6 )   1074 - 1080   2016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  

    Inflammatory markers are important prognostic factors in various cancers. This study investigated whether inflammatory markers of the Glasgow prognostic score (GPS) predicted progression-free survival (PFS) and overall survival (OS) for patients with all cases of epithelial ovarian cancer (OC). Pretreatment GPS was examined for the correlations with PFS and OS in 216 patients in all stages of epithelial OC. Statistical analyses were performed using the Mann-Whitney U-test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. For all patients, the median PFS was 35.1 months, and median OS was 46.7 months; follow-up range was 1-162 months. Kaplan-Meier analysis revealed that patients with high GPS (GPS 2) at pretreatment had a shorter PFS and OS than did patients with lower GPS (GPS 0 + 1) in for early, advanced, and all-stages of OC (PFS: P < 0.001 for early-, advanced- and all-stages; OS; P < 0.001 for early- and all-stage, P = 0.015 for advanced-stage). GPS (GPS 2) was also found to be an independent predictor of both recurrence (P = 0.002) and survival (P = 0.001) of all cases of epithelial OC by a multivariate analysis. GPS can serve as an indicator of poor prognosis in patients with all stages of epithelial OC, including early-stage disease and regardless of histology.

    DOI: 10.1002/cam4.681

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  • Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome

    Mari Sawada, Hisashi Masuyama, Kei Hayata, Yasuhiko Kamada, Keiichiro Nakamura, Yuji Hiramatsu

    ENDOCRINE JOURNAL   62 ( 11 )   1017 - 1023   2015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:JAPAN ENDOCRINE SOC  

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of beta-cell function (HOMA-beta) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-beta at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-beta, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of beta-cell function, such as HOMA-beta, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients.

    DOI: 10.1507/endocrj.EJ15-0364

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  • The Glasgow Prognostic Score Determined During Concurrent Chemoradiotherapy Is an Independent Predictor of Survival for Cervical Cancer

    Takeshi Nishida, Keiichiro Nakamura, Junko Haraga, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Norihisa Katayama, Susumu Kanazawa, Yuji Hiramatsu

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   25 ( 7 )   1306 - 1314   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:BMJ PUBLISHING GROUP  

    Objective The Glasgow prognostic score (GPS) determined at pretreatment is important in the prediction of prognosis in various cancers. We investigated if the GPS used both at pretreatment and during concurrent chemoradiotherapy (CCRT) could predict the prognosis of patients with cervical cancer.Methods We collected GPS and clinicopathological data from the medical records of 91 patients who underwent CCRT for cervical cancer; their GPSs at pretreatment and during CCRT were retrospectively analyzed for correlations with recurrence and survival. Statistical analyses were performed using the Mann-Whitney U test. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results The median follow-up for all patients who were alive at the time of last follow-up was 38.0 months (range, 1-108 months). The DFS and OS rates of patients with a high GPS during CCRT (GPS 1 + 2; 55 patients; 60.4%) were significantly shorter than those for patients with a low GPS (GPS 0; 36 patients; 39.6%) (DFS, P < 0.001; OS, P < 0.001). Furthermore, multivariate analyses showed that high GPS during CCRT was an independent prognostic factor of survival for OS (P = 0.008).Conclusions During CCRT, a high GPS was revealed to be an important predictor of survival for cervical cancer.

    DOI: 10.1097/IGC.0000000000000485

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  • Three Cases of Struma Ovarii Underwent Laparoscopic Surgery with Definite Preoperative Diagnosis

    Nurliza Binti Md Nor, Tomoyuki Kusumoto, Seiji Inoue, Keiichiro Nakamura, Noriko Seki, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

    ACTA MEDICA OKAYAMA   67 ( 3 )   191 - 195   2013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:OKAYAMA UNIV MED SCHOOL  

    Struma ovarii is a rare neoplasm that accounts for approximately 0.3% of ovarian tumors. Due to its ultrasound morphology, which is quite similar to that of malignant ovarian carcinoma, most struma ovarii cases are open operated with laparotomy rather than laparoscopy. We present 3 cases of struma ovarii, which were diagnosed preoperatively by imaging studies and removed by laparoscopic surgery. All patients were premenopausal women between ages 31-50. The magnetic resonance imaging (MRI) findings were complex masses composed of multiple cysts and solid components with T2-hypointense regions as well as multiple T1-hyperintense cystic areas, findings that are typical for struma ovarii. A combination of plain computed tomography (CT), positron emission tomography (PET)-CT, and scintigraphy was useful for diagnosis. Laboratory examination revealed elevated serum thyroglobulin, which led to the diagnosis of struma ovarii. Laparoscopic surgeries were performed without rupturing the tumors. Although it has been difficult to differentiate between struma ovarii and malignant tumors by conventional methods, recently MRI techniques appear make it possible to diagnose struma ovarii preoperatively from the abovementioned imaging characteristic, together with laboratory data. As for treatment, we think laparoscopy could be successful for struma ovarii, but the surgeon must be careful not to rupture the tumor intra-abdominally in order to prevent dissemination, which could lead to malignancy.

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  • Antitumor effects of novel shorter truncated insulin-like growth factor I receptors

    Yojiro Ojima, Atsushi Hongo, Yixuan Liu, Lisha Zhu, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Junichi Kodama, Yuji Hiramatsu

    CANCER BIOLOGY & THERAPY   13 ( 7 )   559 - 566   2012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:LANDES BIOSCIENCE  

    We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the antitumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.

    DOI: 10.4161/cbt.19609

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  • Hepsin inhibits the cell growth of endometrial cancer

    Keiichiro Nakamura, Norio Takamoto, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE   22 ( 3 )   389 - 397   2008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:SPANDIDOS PUBL LTD  

    Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the, family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3 sigma expression which leads to both cell cycle arrest at the G(2)/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

    DOI: 10.3892/ijmm_00000035

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  • Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer

    Keiichiro Nakamura, Norio Takamoto, Atsushi Hongo, Junichi Kodama, Fernando Abrzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

    ONCOLOGY REPORTS   19 ( 5 )   1085 - 1091   2008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:SPANDIDOS PUBL LTD  

    In light of the poor prognosis for ovarian cancer, research continues for innovative and efficacious treatment modalities. It is now widely accepted that new approaches for the treatment of ovarian cancers are pivotal in further improving prognosis of this disease. Secretory leukoprotease inhibitor (SLPI) is an 11.7-kDa non-glycosylated, serine protease inhibitor that has a broad inhibitory spectrum against serine protease. SLPI showed potential therapeutic inhibitory effects mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF-alpha, death receptor (DR)-4, DR-5 and TNF receptor (TNFR)-I expression which lead to an activation of apoptosis pathway through Caspase-2, Caspase-8 and Caspase-9. We examined whether levels of SLPI protein expression correlated with clinicopathological characteristics in 58 ovarian cancer samples, and investigated the role of SLPI and its biological functions. SLPI expression showed a significant correlation between low expression of SLPI and amount of ascites (p=0.021), lymph node metastasis (p=0.011). We propose that SLPI could be considered a therapeutic target for the treatment of ovarian cancer.

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書籍等出版物

  • やさしくわかる 産科婦人科検査マスターブック

    中村圭一郎、原賀順子、増山寿( 担当: 分担執筆 ,  範囲: (第2章)婦人科腫瘍分野 がん化学療法のQOL評価)

    科と婦人科 (0386-9792)87巻Suppl. Page195-199  2020年3月 

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  • 産婦人科手術スタンダード

    日本産婦人科手術学会( 担当: 分担執筆 ,  範囲: 付属器手術(1)開腹法)

    メジカルビュー社  2017年3月 

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  • OGS NOW23 覚えておきたい手術の工夫と周術期管理 さまざまな局面で役立つ手技と知識

    ( 担当: 分担執筆 ,  範囲: 周術期管理の必須知識 術前準備と術後管理の基本)

    メジカルビュー社  2015年8月 

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MISC

  • トラベクテジン血管外漏出による皮膚壊死2例の治療経験

    杉原 悟, 池田 賢太, 山崎 修, 森実 真, 下江 敬生, 中村 圭一郎

    西日本皮膚科   83 ( 5 )   417 - 422   2021年10月

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    記述言語:日本語   出版者・発行元:日本皮膚科学会-西部支部  

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  • 卵巣癌のSister Mary Joseph's nodule(SMJN)に対して臍切除を行った3例

    小川 麻理子, 依田 尚之, 入江 恭平, 岡本 和浩, 松岡 敬典, 小川 千加子, 中村 圭一郎, 増山 寿

    現代産婦人科   69 ( Suppl. )   S90 - S90   2021年9月

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    記述言語:日本語   出版者・発行元:中国四国産科婦人科学会  

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  • がんゲノム入門 がんゲノムプロファイリング検査を行うために必要な知識と実例

    小川 千加子, 入江 恭平, 岡本 和浩, 松岡 敬典, 依田 尚之, 中村 圭一郎, 増山 寿

    現代産婦人科   69 ( Suppl. )   S29 - S29   2021年9月

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    記述言語:日本語   出版者・発行元:中国四国産科婦人科学会  

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  • MSI-Highを有する再発子宮体癌に対してペムブロリズマブを使用し、髄膜脳炎を発症した一例

    長谷井 稜子, 松岡 敬典, 入江 恭平, 岡本 和浩, 依田 尚之, 小川 千加子, 中村 圭一郎, 増山 寿

    現代産婦人科   69 ( Suppl. )   S54 - S54   2021年9月

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    記述言語:日本語   出版者・発行元:中国四国産科婦人科学会  

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  • 高齢者に発症した排尿障害を伴う会陰癒着症の1例

    西田 康平, 岡本 和浩, 入江 恭平, 松岡 敬典, 依田 尚之, 小川 千加子, 中村 圭一郎, 増山 寿

    現代産婦人科   69 ( Suppl. )   S83 - S83   2021年9月

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    記述言語:日本語   出版者・発行元:中国四国産科婦人科学会  

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  • アルツハイマー病患者の行動心理症状と日常生活活動との関連についての研究

    韓 こう煕, 福原 竜治, 竹林 実, 丸田 道雄, 中村 篤, 宮田 浩紀, 下木原 俊, 徳田 圭一郎, 池田 由里子, 田平 隆行

    日本作業療法研究学会雑誌   24 ( 1 )   62 - 62   2021年5月

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    記述言語:日本語   出版者・発行元:日本作業療法研究学会  

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  • CVポート部より漏出したトラベクテジンによる広範囲壊死の2例

    杉原 悟, 池田 賢太, 山崎 修, 森実 真, 下江 敬生, 中村 圭一郎

    日本皮膚外科学会誌   25   54 - 55   2021年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本皮膚外科学会  

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  • Meckel憩室から小腸軸捻転をきたした1例

    昼間 楓, 宮本 和幸, 中村 元保, 井上 元, 柿 佑樹, 鈴木 恵輔, 池田 圭一郎, 加藤 晶人, 垂水 庸子, 森川 健太郎, 土肥 謙二

    日本臨床救急医学会雑誌   24 ( 2 )   232 - 232   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床救急医学会  

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  • 低出力経頭蓋集束超音波刺激に関する提言

    花島 律子, 寺尾 安生, 出江 紳一, 宇川 義一, 緒方 勝也, 金子 文成, 鬼頭 伸輔, 小林 正人, 中村 元昭, 西田 圭一郎, 野田 賀大, 細見 晃一, 松本 英之, 日本臨床神経生理学会脳刺激法に関する小委員会

    臨床神経生理学   49 ( 2 )   114 - 118   2021年4月

  • 重度口腔乾燥状態の症例における当院の口腔ケア術式 鼻呼吸を促進し口腔乾燥を軽減させるための鼻孔ケアの有用性

    五十嵐 史征, 輿 圭一郎, 中村 絵美, 赤松 博子, 金子 博子, 玉井 洋太郎

    日本口腔ケア学会雑誌   15 ( 3 )   195 - 195   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔ケア学会  

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  • 卵巣がんの破裂を契機に腹部コンパートメント症候群をきたした1症例

    谷 佳紀, 依田 尚之, 岡本 和浩, 松岡 敬典, 久保 光太郎, 春間 朋子, 小川 千加子, 中村 圭一郎, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 329   2021年3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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  • 高エストロゲン血症を伴う卵巣偽粘液腫の一例

    川口 優里香, 小川 千加子, 松岡 敬典, 岡本 和浩, 依田 尚之, 春間 朋子, 中村 圭一郎, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 331   2021年3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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  • 当院の子宮体癌に対する低侵襲手術の検討

    久保 光太郎, 依田 尚之, 岡本 和浩, 松岡 敬典, 春間 朋子, 小川 千加子, 中村 圭一郎, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 401   2021年3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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  • ABCP療法が奏効したSMARCA4-DTS or DTSTの3症例

    國政 啓, 河内 勇人, 中村 ハルミ, 久木田 洋児, 本間 圭一郎, 大阪国際がんセンター/病理ゲノムユニット

    日本病理学会会誌   110 ( 1 )   290 - 290   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • TC療法を受ける婦人科癌患者におけるSF36を活用したQOL調査

    春間 朋子, 岡本 和浩, 松岡 敬典, 依田 尚之, 久保 光太郎, 小川 千加子, 中村 圭一郎, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 280   2021年3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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  • 当院の子宮頸癌IB2期の検討

    依田 尚之, 岡本 和浩, 松岡 敬典, 春間 朋子, 小川 千加子, 中村 圭一郎, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 308   2021年3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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  • Shear Wave Elastographyは子宮頸癌に対する放射線治療の効果予測に有用である

    松岡 敬典, 中村 圭一郎, 岡本 和浩, 依田 尚之, 久保 光太郎, 春間 朋子, 小川 千加子, 増山 寿

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 312   2021年3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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  • エストロゲン症状を伴う巨大多房性嚢胞腫瘤として発見された輪状細管を伴う性索腫瘍の一例

    春間 朋子, 角南 華子, 松岡 敬典, 依田 尚之, 原賀 順子, 小川 千加子, 中村 圭一郎, 柳井 広之, 増山 寿

    日本婦人科腫瘍学会雑誌   39 ( 1 )   424 - 424   2021年1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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  • 肺癌切除例における術中捺印細胞診Group分類は肺胞腔内腫瘍散布像(STAS)の術中予測因子となり得るか?

    木村 亨, 大村 彰勲, 田中 諒, 寛島 隆史, 馬庭 知弘, 中村 ハルミ, 本間 圭一郎, 東山 聖彦, 岡見 次郎

    肺癌   60 ( 6 )   611 - 611   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 協力歯科医院との医科歯科連携体制で行っている湘南鎌倉総合病院血液内科病棟における周術期口腔機能管理について

    五十嵐 史征, 輿 圭一郎, 中村 絵美, 玉井 洋太郎

    日本口腔ケア学会雑誌   14 ( 3 )   150 - 150   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔ケア学会  

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講演・口頭発表等

  • 高齢者婦人科癌患者のCharlson Comorbidity Indexは 予後予測因子になる

    中村圭一郎, 入江恭平, 岡本和浩, 松岡敬典, 依田尚之, 久保光太郎, 春間朋子, 小川千加子, 増山 寿

    第63回日本婦人科腫瘍学会学術講演会  2021年7月17日 

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    開催年月日: 2021年7月16日 - 2021年7月18日

    会議種別:ポスター発表  

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  • チャールソン併存疾患指数とグラスゴー予後スコアの組み合わせは高齢婦人科がん患者における独立した予後因子になる

    第73回日本産科婦人科学会学術講演会  2021年4月24日 

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    開催年月日: 2021年4月22日 - 2021年4月25日

    会議種別:ポスター発表  

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受賞

  • がん研究奨励賞 (林原・山田賞)受賞

    2013年6月   岡山医学会  

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  • 八木賞

    2009年9月   日本産科婦人科学会中国四国合同地方部会  

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  • グットプレゼンテーション賞

    2008年4月   日本産科婦人科学会  

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共同研究・競争的資金等の研究

  • 子宮体部癌肉腫新規革新的新規治療戦略の構築

    研究課題/領域番号:19K09753  2019年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中村 圭一郎, 増山 寿, 小川 千加子, 松原 侑子, 松岡 敬典

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    子宮体癌はTCGAによる網羅的ゲノム解析から4つのサブタイプに分類でき,臨床病理学的特徴と遺伝子変異の照合を行い,遺伝子変異情報を基盤とした子宮体癌に対するゲノム解析を推進してきた。本研究では子宮体癌の最も予後不良で難治性の子宮体部癌肉腫に着目し,細分化を図り,革新的新規治療戦略の構築を試みる。

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  • 子宮内膜癌に対する革新的新規治療戦略の構築

    研究課題/領域番号:16K11141  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中村 圭一郎, 永坂 岳司, 春間 朋子, 平松 祐司

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    研究成果の概要(和文):我々は子宮内膜癌に対し以前から遺伝子解析を鋭意遂行し,その臨床病理学的特徴と遺伝子変異の照合を行ってきた。より細やかなPersonalized Medicineへ繋ぐためにもEpigenetic変異を加味する必要があり,Epigenetic変異を基盤とした革新的新規治療戦略の構築が重要であり,そこで大腸癌の予後や薬剤効果に寄与するO6-methylguanine-DNA methyltransferase(MGMT)やMSH2メチル化を子宮体癌で検討し,MGMT発現率は0.8%,MSH2メチル化は2.4%であった。

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  • MicroRNAを用いた新規大腸癌治療戦略の開発

    研究課題/領域番号:26462016  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    母里 淑子, 楳田 祐三, 永坂 岳司, 中村 圭一郎

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    予後不良なBRAF変異+Non-MSI大腸癌で発現増加するmiRNA群をGroup A、発現低下群をGroup Bと定義。Group A miRNA高発現、Group B miRNA低発現群は予後不良であることが67例のStage IV癌にて確認。また大腸癌細胞株にGroup B miRNA を導入し、それらmiRNA群の標的であるZEBs、ZEBsの標的であるE-Cadherinの発現量を確認。さらにscratch assay、migration assayを行い、Group B miRNAが腫瘍のmalignant potentialを下げ、大腸癌の新規治療になり得る可能性を示した。

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  • 遺伝子変異情報をバイオマーカーとした子宮体癌非侵襲的鑑別診断法の開発

    研究課題/領域番号:25462595  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中村 圭一郎, 永坂 岳司, 楳田 祐三, 須野 学, 平松 祐司

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    我々は1)ミスマッチ修復機構の異常を検出する指標であるマイクロサテライト不安定性検査(microsatellite instability; MSI; BAT26, NR27, NR21, CAT25), 2) 腫瘍組織のMLH1, MSH2,MSH6,PMS2に対する免疫組織化学的検討(immunohistochemistry; IHC) , 3) PCRを用いてのMLH1 promoter CpG island の解析を行い, 新規子宮体癌リンチ症候群(LS)スクリーニングの一助となる技術を開発した。

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  • 産婦人科疾患とインスリン抵抗性に関する研究

    研究課題/領域番号:23390390  2011年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    平松 祐司, 増山 寿, 鎌田 泰彦, 中村 圭一郎

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    配分額:18720000円 ( 直接経費:14400000円 、 間接経費:4320000円 )

    糖尿病は年々増加し,わが国の国民病といっても良い状況にある.血糖を下げるインスリンは妊娠,多嚢胞性卵巣症候群,子宮体癌などの産婦人科疾患では,効かなくなるインスリン抵抗性が出現している.今回はこのインスリン抵抗性がこれら疾患にどのように関係しているかを研究し,そのメカニズムを明らかにし,一部の疾患では予防法の開発を目指した.また胎児期の栄養と将来の糖尿病,肥満の発症についても検討した.

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  • ヘプシンにおける子宮頸癌の抗腫瘍抑制効果かつ分子作用機序の検討

    研究課題/領域番号:17791119  2005年 - 2006年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    中村 圭一郎

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    配分額:3600000円 ( 直接経費:3600000円 )

    ヘプシンはセリンプロテアーゼの1種類であり、正常肝臓・腎臓に多く存在し、前立腺、肺においても若干ではあるが含まれている1.85キロダルトンの蛋白である。我々専門分野である婦人科において、1997年谷本らはCancer researchで正常卵巣は発現せず、境界型悪性、卵巣癌に高発現することを発表し、その後2001年にもNatureにおいて、前立腺癌でも同様に癌化することでヘプシンが発現することが述べられる。しかしながらそのヘプシンにおける機能等のいまだ詳細はわかっておらず、そこで我々は卵巣癌細胞株を用いて、hepsin cDNAの遺伝子導入を行い、メカニズム解明を行った。その結果p53を介し、p53のdown-streamであるPuma,Noxa,p53AIP1,Bax,Bak,p53R2に作用し、アポトーシスに関連しているCaspase-3、6、7に働き、in vitroだけでなく、in vivoにおいても癌抑制することを突き止めた(Int.J.Oncol.28:393-398,2006.)。そこで今回、研究課題としてp53,RB癌抑制遺伝子に大いに関わっている子宮頚癌について研究を行なったが数個の子宮頚癌細胞株を用いるも、ヘプシン導入細胞株樹立できず、やむなく子宮頚癌細胞株から子宮体癌細胞株に変更を行い、実験を行った。
    子宮体癌は近年増加傾向である悪性腫瘍の1つであり、子宮体癌の代表株とされるIshikawa細胞株を用い、ヘプシンの遺伝子導入を試み、ヘプシン機能解明ならびに公腫瘍効果検討を待った。その結果、ヘプシン導入細胞株(Ishikawa/hepsin-10・Ishikawa/hepsin-12)はEmpty vectorと比較し、p53・14-3-3sigmaを介し、G2-M期でGrowth Arrestを認めるとともにCyclinA,Bを抑制し、Bak、Bcl-XL、Bcl-2、Caspase-3等のアポトーシスに機序し、in vitro、in vivoにおいても癌抑制が認められた。この事よりヘプシンは子宮体癌に有効な癌抑制遺伝子であり、現在Molecular Cancer TherapeuticsにIn press中である。

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  • 変異p53によるIGF-Iレセプター転写制御機構の解析と子宮頚癌における臨床応用

    研究課題/領域番号:16591661  2004年 - 2005年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    本郷 淳司, 中村 圭一郎, 児玉 順一, 平松 祐司

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    配分額:3600000円 ( 直接経費:3600000円 )

    まず野生型p53の子宮頸癌における役割をHPV陽性である子宮頸癌由来細胞を用いて検討した。SiHa細胞にHPVの初期転写蛋白であるE6を、HeLa S3細胞にE2を一過性に遺伝子導入したところ、SiHa細胞ではp53蛋白の減少とIGF-Iレセプター蛋白の増加を、そしてHeLa S3細胞ではp53蛋白の増加とIGF-Iレセプター蛋白の減少を認めた。それぞれの恒久的遺伝子発現クローンを作成して検討したところ同様の事象を確認できた。ルシフェラーゼアッセイにて、このIGF-Iレセプター蛋白発現量の変化は転写制御による事を確認した。またE6/E2遺伝子導入によるIGF-Iレセプター発現量の変化により軟寒天培地での足場非依存性増殖能やヌードマウス皮下移植での腫瘍形成能は大きく変化しており、生理的な範囲でのHPV感染によるIGF-Iレセプター発現量の変化が子宮頸癌細胞の前述の悪性度に関与していることが示唆された。
    次に子宮頸癌や異型上皮の臨床検体を用いて、IGF-Iレセプターの発現量とそのチロシンリン酸化を免疫組織染色にて検討した。IGF-Iレセプター発現量はCINIII以上で有意に亢進し、またそのリン酸化は病巣の進展と共に有意に亢進していた。また異型上皮病変において、その基底細胞や労基底細胞のIGF-Iレセプター発現はCINIIIでは明らかに亢進しており、HPVの染色体組み込みによるE6蛋白の異常発現を反映していると考えられた。
    そしてhot spot mutationを主とした様々な変異p53発現ベクターをsite directed mutagenesisにて作成し、そのIGF-1レセプター発現調整に及ぼす効果を比較検討した。内因性p53を有しない卵巣癌由来SKOV-3細胞と骨肉腫由来Saos-2細胞を用いて検討したところ、野生型p53やP72R、V143AはIGF-1レセプターの転写を強力に抑制した。一方、T123A, R175H, R248Q, R273Hには転写抑制効果は認められなかった。

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  • クルクミンの子宮体癌細胞に及ぼす抗腫瘍活性とその分子作用機序の解明

    研究課題/領域番号:15790891  2003年 - 2004年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    中村 圭一郎

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    配分額:3300000円 ( 直接経費:3300000円 )

    天然癌抑制物質の一種とされているカレー成分内のターメリック含有のクルクミン(Curcumin)に着目し、子宮体癌を対象に細胞株の1種類であるIshikawa細胞株を用い、研究を行なった。子宮体癌患者は年々増加傾向で、当院においてもこの10年間に約2倍の増加傾向を示している。子宮体癌は食生活に密接に関係し、肥満患者の頻度が高いことは良く知られている。しかしながら子宮体癌の予防医学においては皆無であり、そこで申請者は前立腺癌でもアンドロゲンレセプターに作用、形質転換能、抗腫瘍効果抑制を得ることが可能なクルクミンを用い、ホルモンレセプターの核内リガンド結合を介する子宮体癌をin vivoの実験も加え、研究を行なった。しかしながら子宮体癌ではクルクミン投与にも関わらず、エストロゲンレセプターを介さず、転写因子のEstrogen Response Element(ERE)のみ抑制を認めた。一方、分子作用因子として作用に影響されるとされるActivator Protein-1(AP-1)は、クルクミンに投与により蛋白量、転写因子ともに抑制され、共役転写抑制因子であるcAMP response element-binding protein(CREB)-binding protein(CBP)においても強く関与を示していた。そのことにより、クルクミン投与による子宮体癌はAP-1、CBP、EREを介し、in vitroでの形質転換能は約90%、クルクミン摂取でのin vivoの腫瘍抑制能においても約75%抑制効果を認められた。
    本研究でクルクミンは子宮体癌においても有効な天然癌抑制物質であり、経口により容易に抗腫瘍効果を得ることから、今後治療に貢献できることだけでなく、予防的なサップリメントとしても効果があることを示唆した。現在投稿中である。

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  • RNAinterferenceによる子宮頸癌に対する新しい遺伝子治療の基礎的検討

    研究課題/領域番号:15591749  2003年 - 2004年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    吉野内 光夫, 中村 圭一郎

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    配分額:2900000円 ( 直接経費:2900000円 )

    最近,標的遺伝子の発現を阻害する方法としてRNA interference (RNAi)が発見され,哺乳動物細胞での遺伝子発現抑制の成功が報告された。我々はRNAiが子宮頸癌遺伝子標的治療の戦略として応用可能か否かを探るため,HPV16型陽性子宮頚癌細胞株SiHaを材料にE6およびE7を標的としたRNAiを行い,これら癌遺伝子の発現とその生物学的効果を解析した。E6/E7 mRNAに相補的な21塩基二重短鎖RNA (siRNA)を合成し、SiHa細胞に導入した。72時間後、E6 siRNAはE6/E7 mRNAレベルをそれぞれ30%および40%に,E7 siRNは88%および20%にまで抑制した。これらのE6およびE7 siRNAはSiHa細胞の足場依存性増殖をそれぞれ29%および66%に,足場非依存性増殖を18%および87%に抑制した。E6 siRNによる増殖抑制は,p53の増加とp21の発現誘導,さらにはRbの低リン酸化を伴っていたが,E7 siRNAはこの効果をまったく示さなかった。また,E6 siRNAはNOD/SCIDマウスにおけるSiHa細胞の造腫瘍性を著明に抑制した。以上から,RNAiは、HPV陽性子宮頚癌に対する新たな治療戦略として期待しうると考えられた。

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担当授業科目

  • 産科・婦人科学I(演習・実習) (2021年度) 特別  - その他

  • 産科・婦人科学I(講義・演習) (2021年度) 特別  - その他

  • 産科・婦人科学II(演習・実習) (2021年度) 特別  - その他

  • 産科・婦人科学II(講義・演習) (2021年度) 特別  - その他

  • 臨床医歯科学概論 (2021年度) 集中  - その他

  • 産科・婦人科学I(演習・実習) (2020年度) 特別  - その他

  • 産科・婦人科学I(講義・演習) (2020年度) 特別  - その他

  • 産科・婦人科学II(演習・実習) (2020年度) 特別  - その他

  • 産科・婦人科学II(講義・演習) (2020年度) 特別  - その他

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学術貢献活動

  • 第43回岡山産科婦人科学会

    役割:企画立案・運営等, パネル司会・セッションチェア等, 監修, 学術調査立案・実施, 査読

    主催者:増山寿・責任者:中村圭一郎  2018年11月18日

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    種別:学会・研究会等 

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  • 第53回日本婦人科腫瘍学会

    役割:企画立案・運営等, 監修, 学術調査立案・実施, 保存・修復

    主催者:平松祐司・責任者:中村圭一郎  2012年11月23日 - 2012年11月24日

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    種別:学会・研究会等 

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