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Applying Wnt/beta-catenin pathway inhibitors for the treatment of endometriosis

Research Project

Project/Area Number 18K16774
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionOita University

Principal Investigator

Tomoko Hirakawa  大分大学, 医学部, 客員研究員 (20516132)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords子宮内膜症 / β-catenin / 線維化 / β-カテニン / Wnt/β-catenin
Outline of Final Research Achievements

We investigated whether ICG-001 and C-82, which are inhibitors of CREB-binding protein (CBP) / β-catenin, could be therapeutic agents for endometriosis. For endometriotic stromal cells, the binding of β-catenin to CBP / P300 was confirmed by immunoprecipitation. Administration of ICG-001 and C-82 significantly suppressed collagen gel contraction and suppressed cicatrization. ICG-001 and C-82 suppressed cell proliferation, induced apoptosis, and suppressed cell migration. The expression of α-SMA involved in fibrosis was suppressed by administration of ICG-001 and C-82. ICG-001 reduced endometriotic lesions in model mice.

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症は生殖可能年齢女性において罹患頻度が高く、月経困難症や不妊の原因となる。また日本人に多いとされる卵巣明細胞癌の発生母地となることも知られている。本研究成果はCREB-binding protein (CBP) / β-catenin阻害剤であるICG-001とC-82が子宮内膜症治療の有望な選択肢であることを示した。女性のヘルスケアの観点からも、婦人科腫瘍の観点からも臨床的に応用可能な治療選択肢を示すことができた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] Vulvar neuroendocrine carcinoma that is independent of merkel cell polyomavirus and human papillomavirus suggests endometrial cancer recurrence: a case report2022

    • Author(s)
      Hirakawa Tomoko、Yano Mitsutake、Nishida Haruto、Sato Shimpei、Nasu Kaei
    • Journal Title

      BMC Endocrine Disorders

      Volume: 22 Issue: 1 Pages: 81-81

    • DOI

      10.1186/s12902-022-00987-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] hsa-miR-199a-3p Inhibits Motility, Invasiveness, and Contractility of Ovarian Endometriotic Stromal Cells2021

    • Author(s)
      Zhu Ruofei、Nasu Kaei、Hijiya Naoki、Yoshihashi Masato、Hirakawa Tomoko、Aoyagi Yoko、Narahara Hisashi
    • Journal Title

      Reproductive Sciences

      Volume: 28 Issue: 12 Pages: 3498-3507

    • DOI

      10.1007/s43032-021-00604-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis2019

    • Author(s)
      Hirakawa T, Nasu K, Miyabe S, Kouji H, Katoh A, Uemura N, Narahara H.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20056-20056

    • DOI

      10.1038/s41598-019-56302-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 子宮内膜症の線維化治療薬としてのCBP/β-catenin阻害剤の効果2018

    • Author(s)
      平川 東望子
    • Organizer
      日本分子形態学会
    • Related Report
      2018 Research-status Report
  • [Presentation] CBP/β-catenin阻害剤は子宮内膜症の線維化を改善する2018

    • Author(s)
      平川 東望子
    • Organizer
      日本生殖医学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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