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A novel therapeutic strategy for endometriosis focusing on angiogenesis and the hypoxia-inducible factor:HIF-1

Research Project

Project/Area Number 15K20169
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionKansai Medical University

Principal Investigator

TSUZUKI Tomoko  関西医科大学, 医学部, 嘱託医員 (00465642)

Project Period (FY) 2015-04-01 – 2020-03-31
Project Status Discontinued (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords異所性子宮内膜 / VEGF / HIF-1 / エキノマイシン / アポトーシス / 子宮内膜症細胞 / SDF-1 / 低酸素刺激 / 異所性子宮内膜症
Outline of Final Research Achievements

Recent evidence points to a possible role for HIF-1 in the development of endometriosis. The objectives of this study were to investigate the critical role of HIF-1 in endometriosis and the effect of the HIF-1 inhibitor echinomycin on human ectopic endometriotic stromal cells (eESCs). Hypoxic stress induced expression of HIF-1a protein and VEGF production in eESCs, and VEGF production was significantly suppressed by treatment of echinomycin without causing cell toxicity. Synthetic progestins, including MPA and DNG, are used to treat endometriosis. In the present study, we were unable to demonstrate the inhibitory effects of MPA and DNG on VEGF production in eESCs. Therefore, echinomycin might be more useful than progestins as an inhibitor of VEGF production to regulate the angiogenesis of endometriosis. Moreover, echinomycin inhibited cell proliferation and induced apoptotic cell death of the eESCs, and significantly inhibited expression of the anti-apoptotic proteins.

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症病変の進展に重要と思われる血管新生因子の発現とその調節機構の一部を解明することができた。またHIF-1阻害剤のEMはこれまでのホルモン製剤とは全く異なる機序で異所性子宮内膜細胞の増殖を抑制し、子宮内膜症の治療薬となる可能性を持っている。またEMは子宮内膜症への作用として血管新生因子の阻害のみならずアポトーシス効果も期待できる薬剤であることがわかった。本研究により子宮内膜症における血管新生の新たな制御機構を解明し、さらに血管新生因子やHIF-1をターゲットとした新規治療戦略として、実地診療への応用が期待される。

Report

(5 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Effects of the hypoxia-inducible factor-1 inhibitor echinomycin on vascular endothelial growth factor production and apoptosis in human ectopic endometriotic stromal cells.2016

    • Author(s)
      Tsuzuki T, *Okada H, Shindoh H, Shimoi K, Nishigaki A, Kanzaki H.
    • Journal Title

      Gynecol Endocrinol.

      Volume: 32 Issue: 4 Pages: 323-328

    • DOI

      10.3109/09513590.2015.1121225

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of the hypoxia-inducible factor-1 inhibitor echinomycin on vascular endothelial growth factor production in human ectopic endometriotic stromal cells2016

    • Author(s)
      Tomoko Tsuzuki
    • Organizer
      Asian Conference on Endometriosis
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
  • [Presentation] 妊孕性温存の受精卵凍結から妊娠・分娩まで管理できた乳癌の1症例2015

    • Author(s)
      都築朋子 高畑暁 村田紘未 小野淑子 岡田園子  吉村智雄 好村正博 下井華代 岡田英孝
    • Organizer
      第33回日本受精着床学会学術講演会
    • Place of Presentation
      TFTホール(東京都江東区有明)
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Book] 不妊・不育症診療パーフェクトガイド2016

    • Author(s)
      都築朋子、吉村智雄、岡田英孝
    • Total Pages
      390
    • Publisher
      医学書院
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2021-02-19  

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