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Molecular targets and specific preventive therapy of anticancer drug-induced ovarian failure

Research Project

Project/Area Number 18591808
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionWakayama Medical University

Principal Investigator

MINAMI Sawako  Wakayama Medical University, 医学部, Assistant Professor (90219692)

Co-Investigator(Kenkyū-buntansha) KOKAWA Katsuji  Wakayama Medical University, 医学部, Assistant Professor (80254548)
UTSUNOMIYA Hirotoshi  Wakayama Medical University, 医学部, Assistant Professor (60264876)
TANAKA Tetsuji  Wakayama Medical University, 医学部, Associated Professor (80275255)
UMESAKI Naohiko  Wakayama Medical University, 医学部, Professor (20106339)
田中 和東  和歌山県立医科大学, 医学部, 助手 (00372863)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsAnticancer drug / Granulosa cell / apoptosis / CPT-11 / GnRH agonist / GnRH agonist
Research Abstract

The animal center of our university had been contaminated with mouse hepatitis virus from 2006 to 2007. Therefore, all the experimental animals including our mice were killed at first, and then the center was disinfected. However, 6 months after the disinfection, virus was found out again in the animal center. We changed experimental plans to try more in vitro experiments. In the end of 2007, animal experiments were restarted and we are now performing knockout mice experiments.
(1) Clinical histopathological study of the ovarian tissues from the cancer patients treated with anticancer drugs preoperatively : We have found several differences between histopathological damages in the ovaries and administered anticancer drugs.
(2) Molecular mechanisms of anticancer drug-induced granulosa cell damages in mouse experiments: (1) We have identified 2 candidate molecules that played an important roles in CPT-11-induced granulosa cell apoptosis. (2) Roles of Bcl-2 family and p53 in several anticancer drag induced ovarian damages were evaluated (these data are preparing in publication). (3) Possible key molecules in granulosa cell damages induced by the other anticancer drugs but CPT-11 were identified The molecules are confirming now. (4) A certain knockout mouse was found to be insensitive to CPT-11-induced granulosa cell apoptosis. The data will be published in 2008.
(3) Establishment of preventive therapy for anticancer drug induced granulosa cell apoptosis : Optimal protocols of GnRHa therapy to prevent anticancer drug-induced granulosa cell apoptosis were established Moreover, the preventive mechanisms were also identified. The data will be published in 2008.
(4) The mouse ovary organ culture was established to assay to evaluate direct ovarian damages by various drugs.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (14 results)

All 2008 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 4 results) Presentation (2 results)

  • [Journal Article] A novel molecular mechanism for anticancer drug-induced ovarian failure2008

    • Author(s)
      Utsunomiya T, et. al.
    • Journal Title

      International Journal of Oncology 32

      Pages: 991-1000

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Topoisomerase I inhibitor誘発卵巣顆粒騰細胞アポトーシスにおけるBCL-2familyの意義2007

    • Author(s)
      宇都宮 智子, ほか
    • Journal Title

      日本受精着床学会雑誌 24(1)

      Pages: 38-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 抗癌剤誘発卵巣障害を予防するためのGnRH agonist療法とGnRH agonist感受性の個人差2007

    • Author(s)
      田中 哲二, ほか
    • Journal Title

      日本受精着床学会雑誌 24(1)

      Pages: 54-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of BCL-2 and BAX products in the apoptotic large ovarian follicular granulosa cells treated with topoisomerase I inhibitor, irinotecan HCl2007

    • Author(s)
      Utsunomiya T, et. al.
    • Journal Title

      Journal of Fertlizarion and Implantation 24

      Pages: 38-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Preventive GnRH agonist therapy to inhibit anticancer drug- induced ovarian failure2007

    • Author(s)
      Tanaka T, et. al.
    • Journal Title

      Journal of Fertlizarion and Implantation 24

      Pages: 54-58

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Topoisomerase I inhibitor誘発卵巣顆粒膜細胞アポトーシスにおけるBCL-2 familyの意義2007

    • Author(s)
      宇都宮 智子, ほか
    • Journal Title

      日本受精着床学会雑誌 24(1)

      Pages: 38-42

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term personalized GnRH agonist therapy without estrogen supplementation for recurrent endometriotic catamenial pneumothorax,2007

    • Author(s)
      Tanaka T
    • Journal Title

      clinical & Experimental Obstetrics and Gynaecology (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Topoisomerase I inhibitor誘発卵巣顆粒膜細胞アポートーシスにおけるBCL-2 familyの意義2007

    • Author(s)
      宇都宮智子 ほか
    • Journal Title

      日本受精着床学会雑誌 24(1)(印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 存続hCG血症に対する子宮卵巣機能障害を回避するための選択的化学療法2006

    • Author(s)
      宇都宮智子 ほか
    • Journal Title

      日本受精着床学会雑誌 23(1)

      Pages: 239-245

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 抗がん剤の卵巣毒性とその予防法2006

    • Author(s)
      田中哲二, ほか
    • Journal Title

      日本臨床 64

      Pages: 101-111

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 婦人科領域における悪性腫瘍治療の現況と将来への展望2006

    • Author(s)
      梅咲直彦, 粉川克司
    • Journal Title

      FOCUS on ONCOLOGY 5

      Pages: 13-16

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 抗癌剤誘発卵巣障害を予防するためのGnRH agonist療法とGnRH agonist感受性の個人差2006

    • Author(s)
      田中哲二 ほか
    • Journal Title

      日本受精着床学会雑誌 24(1)(印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] 抗癌剤治療に伴う性腺機能障害の分子機序と予防療法2008

    • Author(s)
      田中 哲二, ほか
    • Organizer
      第58回和歌山内分泌代謝研究会・講演会
    • Place of Presentation
      和歌山県立医科大学
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Molecular mechanisms and preventive therapy of anticancer drug-induced gonadal dysfunction2008

    • Author(s)
      Tanaka T, et. al.
    • Organizer
      The 58th Conference of Wakayama Endocrinology & Metabolism
    • Place of Presentation
      Wakayama Medical University
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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