Investigation into multiple pathways involved in the malignant transformation of endometriosis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nara Medical University
• Principal Investigator: KAWAGUCHI Ryuji 奈良県立医科大学, 医学部, 助教 (50382289)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Hiroshi 奈良県立医科大学, 医学部, 教授 (40178330) ; YOSHIZAWA Yoriko 奈良県立医科大学, 医学部, 助教 (80526723)
• Project Period (FY): 2012
• Keywords: 卵巣明細胞腺癌 / HNF-1beta / マイクロアレイ / 細胞周期 / 卵巣子宮内膜症性嚢胞 / 癌化 / チェックポイント機構

Research Abstract

Among the ovarian cancers, clear cell adenocarcinoma (CCC) has been recognized as a distinct clinicopathological entity because of its frequent concurrence with endometriotic lesions and its high chemoresistance, resulting in a poor prognosis of high stage tumors. However, the mechanism of resistance in CCC has remained unclear. Hepatocyte nuclear factor-1beta (HNF-1beta) was significantly up-regulated in CCC. Cell cycle arrest induced by DNA damage was maintained by sustained activation of ATM-Chk1 pathway and suppression of cell death in HNF-1beta-overexpressing cells. Chemoresistance of CCC may be the result of aberrant retention of the G2 checkpoint through overexpression of HNF-1 beta. Anticancer agents combined with Chk1 inhibitors may improve the chemosensitivity of CCC.

Research Products

• [Journal Article] Redox-active iron-induced oxidative stress in the pathogenesis of clear cell carcinoma of the ovary (2011)
  • Author(s): Yamada Y, Shigetomi H, Onogi A, Haruta S, Kawaguchi R, Yoshida S, Furukawa N, Nagai A, Tanase Y, Tsunemi T, Oi H, Kobayashi H
  • Journal Title: Int J Gynecol Cancer Volume: 21(7) Pages: 1200-7
  • Peer Reviewed
• [Journal Article] 卵巣チョコレート嚢胞に合併する明細胞腺癌と類内膜腺癌の発生病理と、その遺伝子特性 (2011)
  • Author(s): 重富洋志、 吉澤順子、 山田嘉彦、 川口龍二、吉田昭三、古川直人、大井豪一、小林浩
  • Journal Title: 日本エンドメトリオーシス学会会誌 Volume: 32 Pages: 43-48
• [Journal Article] New insights into pattern recognition receptors and their ligands in gynecologic pathologies (2011)
  • Author(s): Yamada Y, Shigetomi H, Onogi A, Haruta S, Kawaguchi R, Yoshida S, Furukawa N, Nagai A, Tanase Y, Tsunemi T, Oi H, Kobayashi H
  • Journal Title: Human immunology Volume: 72(3) Pages: 213-218
  • Peer Reviewed
• [Journal Article] 卵巣明細胞腺癌における転写因子HNF-1beta のターゲット遺伝子の網羅的検索 (2010)
  • Author(s): 重富洋志、 吉澤順子、 山田嘉彦、 川口龍二、小林浩
  • Journal Title: 日本エンドメトリオーシス学会会誌 Volume: 31巻 Pages: 70-74
• [Presentation] Anticancer agents combined with Chk1 inhibitor sensitize HNF-1beta overexpressing clear cell adenocarcinoma of the ovary (2012)
  • Author(s): Hiroshi Shigetomi, Yoriko Yoshizawa, Seiji Kanayama, Ryuji Kawaguchi, Hiroshi Kobayashi, Tamotsu Sudo
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] Investigation into the biological functions of hepatocyte nuclear factor-1beta in clear sell adenocarcinoma of the ovary (2011)
  • Author(s): H. Shigetomi ,Y. Yoshizawa, Y. Yamada, R. Kawaguchi, S. Yoshida, N. Furukawa, H. Oi, H. Kobayashi, S. Kanayama, T. Sudo
  • Organizer: 17th International Meeting of the European Society of Gynaecological Oncology (ESGO) SEPTEMBER 14
  • Place of Presentation: Milano, Italy
  • Year and Date: 20110000
• [Presentation] 卵巣チョコレート嚢胞に合併する明細胞腺癌と類内膜腺癌の発生病理と、その遺伝子特性 (2011)
  • Author(s): 重富洋志、 吉澤順子、山田嘉彦、 川口龍二、小林浩
  • Organizer: 第32回日本エンドメトリオーシス学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-01-22