Functional analysis of retinoic acid signaling in ovarian cancer

• Project/Area Number: 16K11130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Gunma University
• Principal Investigator: hirakawa Takashi 群馬大学, 大学院医学系研究科, 准教授 (80375534)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 卵巣癌 / シグナル伝達 / 治療標的 / 予後因子 / 化学療法 / 癌

Outline of Final Research Achievements

High expression of Pin1 in ovarian tumor tissues was correlated with histological type (serous cancer) and clinically advanced stage (II to IV stage). In a multivariate analysis of factors affecting progression-free survival in 45 non-serous cancers, clinical stage and high Pin expression were extracted as independent poor prognosis factors. The antitumor effect of Pin1 inhibitors was verified in cultured cell lines. The antitumor effect at low concentration was confirmed in SKOV3 and EGCG, OVSAHO and Juglone, respectively. These results suggest that Pin1 may be one of the target molecules for ovarian cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

上皮性卵巣癌においてPin1の高発現は予後不良因子となること、特に非漿液性癌においては独立した予後不良因子となることが示された。卵巣漿液性癌培養細胞系において低濃度でのPin1阻害剤で殺細胞効果が確認された。Pin1は卵巣癌治療の標的分子の1つになりうることが示唆された

Research Products

• [Journal Article] FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy (2019)
  • Author(s): Darwis, N. D. M. Nachankar, A. Sasaki, Y. Matsui, T. Noda, S. E. Murata, K. Tamaki, T. Ando, K. Okonogi, N. Shiba, S. Irie, D. Kaminuma, T. Kumazawa, T. Anakura, M. Yamashita, S. Hirakawa, T. Kakoti, S. Hirota, Y. Tokino, T. Iwase, A. Ohno, T. Shibata, A. Oike, T. Nakano, T.
  • Journal Title: Int J Mol Sci Volume: 20 Issue: 18 Pages: 4563-4563
  • DOI: 10.3390/ijms20184563
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An electrical scalpel conization versus Shimodaira-Taniguchi conization procedure for cervical intraepithelial neoplasia (2018)
  • Author(s): Nakamura K, Kigure K, Kitahara Y, Nakao K, Hirakawa T, Rokukawa S, Ito M, Nishimura T, Ito I, Kagami I, Itoga S.
  • Journal Title: Medicine. Volume: 97 Issue: 41 Pages: e12640-e12640
  • DOI: 10.1097/md.0000000000012640
  • Peer Reviewed
• [Journal Article] Phase I Study of Carbon Ion Radiotherapy and Image-Guided Brachytherapy for Locally Advanced Cervical Cancer (2018)
  • Author(s): Ohno T, Noda SE, Murata K, Yoshimoto Y, Okonogi N, Ando K, Tamaki T, Kato S, Hirakawa T, Kanuma T, Minegishi T, Nakano T
  • Journal Title: Cancers Volume: 10 Issue: 9 Pages: 338-338
  • DOI: 10.3390/cancers10090338
  • Peer Reviewed
• [Journal Article] High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients. (2018)
  • Author(s): Nakao K, Hirakawa T, Suwa H, Kogure K, Ikeda S, Yamashita S, Minegishi T, Kishi H.
  • Journal Title: Int J Gynecol Cancer. Volume: 28 Issue: 4 Pages: 675-683
  • DOI: 10.1097/igc.0000000000001201
  • Peer Reviewed
• [Journal Article] Retinoic acid enhances progesterone production via the cAMP/PKA signaling pathway in immmature rat granulosa cells (2016)
  • Author(s): Hiroto Suwa, Hiroshi Kishi, Fumiharu Imai,Kohshiro Nakao, Takashi Hirakawa, Takashi Minegishi
  • Journal Title: Biochemistry and Biophysics Reports Volume: ８ Pages: 6267-6267
  • DOI: 10.1016/j.bbrep.2016.08.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 上皮性卵巣癌におけるPin1阻害剤による抗腫瘍効果の検討 (2019)
  • Author(s): 平川 隆史, 池田 禎智, 小林 梓, 井上 直紀, 西村 俊夫, 小暮 佳代子, 岩瀬 明
  • Organizer: 第71回日本産科婦人科学会学術総会
• [Presentation] Expression of Pin1 is a predictive biomarker of prognosis in epithelial ovarian cancer. (2018)
  • Author(s): Hirakawa T
  • Organizer: 17TH BIENNIAL MEETING OF THE INTERNATIONAL GYNECOLOGIC CANCER SOCIETY
  • Int'l Joint Research
• [Presentation] 子宮体部類内膜腺癌における新規予後因子としてのUCH-L1の可能性について (2017)
  • Author(s): 中尾 光資郎, 平川 隆史, 小暮 佳代子, 池田 禎智, 山下 宗一, 峯岸 敬
  • Organizer: 日本産科婦人科学会
• [Presentation] レチノイン酸が顆粒膜細胞におけるプロゲステロン産生に及ぼす効果 (2016)
  • Author(s): 諏訪 裕人, 岸 裕司, 中尾 光資郎, 今井 文晴, 平川 隆史, 峯岸 敬
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21