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The carcinogenesis of ovarian endometrioma due to redox environmentt

Research Project

Project/Area Number 18K09269
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNara Medical University

Principal Investigator

Yuki Yamada  奈良県立医科大学, 医学部, 助教 (20588537)

Co-Investigator(Kenkyū-buntansha) 棚瀬 康仁  奈良県立医科大学, 医学部, 助教 (20423915)
小林 浩  奈良県立医科大学, 医学部, 研究員 (40178330)
川口 龍二  奈良県立医科大学, 医学部, 准教授 (50382289)
松原 翔  奈良県立医科大学, 医学部附属病院, 研究員 (20825236)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords卵巣がん / 酸化ストレス / 癌化 / 卵巣癌
Outline of Final Research Achievements

In this study, we found that oxidative stress was high in endometriotic cysts in tumor content fluid and tumor tissue, and antioxidant-dominated environment in the case of cancer. Using immortalized epithelial cells from endometriosis and stromal cells extracted from endometriosis, we reproduced the microenvironment of endometriosis. Since HO-1 was found to be expressed in macrophages, immortalized epithelial cells and stromal cells were co-cultured with macrophages and subjected to oxidative stress by adding H2O2. As a result, we found that HO-1 expressing macrophages were strongly expressed in macrophages.

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症は酸化ストレスが強く癌化しやすい環境にある。実際これまでの研究で、内膜症患者では、自然発生卵巣がんに比べ8倍以上の高率で癌化が起こることがわかっている。このように高い酸化ストレス環境にあるにもかかわらず、ほとんどの内膜症では卵巣癌が発生しない。今回の研究結果から推察すると、M2マクロファージが内膜症上皮に浸潤し、マクロファージにHO-1が高発現することで、内膜症細胞を酸化ストレスから保護している可能性が考えられた。癌化した組織でHO-1が低下していることから、HO-1の発現低下が癌化に一因となっている可能性がある。

Report

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

    (7 results)

All 2021 2020 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] A delicate redox balance between iron and heme oxygenase-1 as an essential biological feature of endometriosis2021

    • Author(s)
      Imanaka Shogo、Yamada Yuki、Kawahara Naoki、Kobayashi Hiroshi
    • Journal Title

      Archives of Medical Research

      Volume: 1 Issue: 6 Pages: 641-647

    • DOI

      10.1016/j.arcmed.2021.03.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 酸化還元反応のバランス変化に基づく発癌仮説2021

    • Author(s)
      山田有紀,松原 翔,竹田善紀,河原直紀,川口龍二,岩渕拓也,小林 浩
    • Organizer
      第42回日本エンドメトリオーシス学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 子宮内膜症の癌化におけるマクロファージの役割2020

    • Author(s)
      山田有紀,内山智子,竹田善紀,松原 翔,河原直紀,新納恵美子,川口龍二,小林 浩
    • Organizer
      第41回日本エンドメトリオーシス学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 子宮内膜症に類似した微小環境でのヘムオキシゲナーゼ1(HO-1)の発現機序2019

    • Author(s)
      小川憲二, 河原直紀, 山田有紀, 吉元千陽, 川口龍二, 佐道俊幸, 小林 浩
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Discrimination of malignant transformation from benign endometriosis using near-infrared approach2018

    • Author(s)
      Yamada Y, Yoshimoto C, Ogawa K, Kawahara N, Kawaguchi R, Sado T, Kobayashi H
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮内膜症の癌化におけるヘムオキシゲナーゼ1(HO-1)の抗酸化作用2018

    • Author(s)
      小川憲二, 山田有紀,河原直紀,吉元千陽,川口龍二,佐道俊幸,小林 浩
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Role of heme oxygenase 1(ho-1) in malignant transformation of ovarian endometriosis.2018

    • Author(s)
      Ogawa K, Yamada Y, Kawahara N, Yoshimoto C, Kawaguchi R, Sado T, Kobayashi H
    • Organizer
      The 17th Biennial Meeting of the International Gynecologic Cancer Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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