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Elucidation of the mechanism of occurrence and progression of ovarian dedifferentiated cancer using organoid culture

Research Project

Project/Area Number 21K16793
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNagoya City University (2023)
Shimane University (2021-2022)

Principal Investigator

Ishibashi Tomoka  名古屋市立大学, 医薬学総合研究院(医学), 助教 (40643648)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsオルガノイド / 卵巣脱分化癌 / オルガノイド培養
Outline of Research at the Start

卵巣脱分化癌(Ovarian dedifferentiated carcinoma: ODC)は高分化癌と未分化癌が混在する腫瘍で進行が早く、アグレッシブな経過をたどる非常に予後不良な疾患である。卵巣脱分化癌の症例報告はあるが、認知度は低く、その頻度や実態は不明である。本研究では、卵巣癌における脱分化癌の頻度や臨床経過を後方視的解析にて明らかにする。さらに卵巣脱分化癌の高分化部分、未分化部分でそれぞれ網羅的遺伝子解析を行い、卵巣脱分化癌の発生、進展の各段階に関わる遺伝子異常の特徴を明らかにする。また、卵巣脱分化癌のオルガノイドモデルを作成し、マウスゼノグラフと併用し、個別化医療を探索する。

Outline of Final Research Achievements

Ovarian dedifferentiated cancer is a disease with aggressive and very poor prognosis. Regarding uterine dedifferentiated endometrioid cancer, we reported that the combination of immune checkpoint inhibitors in addition to conventional chemotherapy may have a therapeutic effect (Ono R, Ishibashi T et al., Int J Mol Sci. 2019).
In recent years, 3D cell culture has attracted attention, and we have succeeded in creating spheroid derived from normal endometrial glands and single glands (Sato S, Ishibashi T et al., Cancer Sci. 2023). However, ovarian dedifferentiated cancer is rare, and the next goal is to create an organoid model and research it in detail.

Academic Significance and Societal Importance of the Research Achievements

卵巣脱分化癌に関しては症例報告が散見されるのみで、網羅的遺伝子解析やオルガノイドに成功したという報告はない。子宮脱分化型類内膜癌での免疫チェックポイント阻害薬の効果について報告しており、婦人科がんにおける脱分化癌の研究に関しては、本邦では当研究室がリードしている。
また近年in vivo の生理学的環境により近い3次元細胞培養が注目を集めている。3次元細胞培養下での発現プロファイルは2次元培養環境の場合と比較して、生理学的な重要性が高いと考えられている。オルガノイドモデルを用いた卵巣脱分化癌発生機構の検討は世界でも報告されておらず、今後の卵巣脱分化癌の研究基盤とな

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (29 results)

All 2024 2023 2022 2021

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (16 results)

  • [Journal Article] Current concept of low-grade serous ovarian carcinoma2024

    • Author(s)
      Nakayama Kentaro、Razia Sultana、Ishibashi Tomoka、Kyo Satoru
    • Journal Title

      Translational Cancer Research

      Volume: 13 Issue: 1 Pages: 6-10

    • DOI

      10.21037/tcr-23-1161

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Case of an Endometrial Cancer Patient with Breast Cancer Who Has Achieved Long-Term Survival via Letrozole Monotherapy2023

    • Author(s)
      Ishikawa Masako、Nakayama Kentaro、Razia Sultana、Yamashita Hitomi、Ishibashi Tomoka、Haraga Hikaru、Kanno Kosuke、Ishikawa Noriyoshi、Kyo Satoru
    • Journal Title

      Current Issues in Molecular Biology

      Volume: 45 Issue: 4 Pages: 2908-2916

    • DOI

      10.3390/cimb45040190

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histological and Genetic Diversity in Ovarian Mucinous Carcinomas:A Pilot Study.2023

    • Author(s)
      Razia S, Nakayama K, Yamashita H, Ishibashi T, Ishikawa M, Kanno K, Sato S, Kyo S.
    • Journal Title

      Curr Oncol.

      Volume: 30 Issue: 4 Pages: 4052-4059

    • DOI

      10.3390/curroncol30040307

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promising Therapeutic Impact of Immune Checkpoint Inhibitors in TypeⅡ Endometrial Cancer Patients with Deficient Mismatch Repair Status.2023

    • Author(s)
      Sawada K, Nakayama K, Razia S, Yamashita H, Ishibashi T, Ishikawa M, Kanno K, Sato S, Nakayama S, Otsuki Y, Kyo S.
    • Journal Title

      Healthcare (Basel).

      Volume: 11 Issue: 8 Pages: 1073-1073

    • DOI

      10.3390/healthcare11081073

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis2023

    • Author(s)
      Yamashita Hitomi、Nakayama Kentaro、Kanno Kosuke、Ishibashi Tomoka、Ishikawa Masako、Sato Seiya、Iida Koji、Razia Sultana、Kyo Satoru
    • Journal Title

      Current Issues in Molecular Biology

      Volume: 45 Issue: 3 Pages: 1843-1851

    • DOI

      10.3390/cimb45030118

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Frequent PIK3CA mutation in normal endometrial gland drives spheroid formation and may be involved in stem cell propagation2023

    • Author(s)
      Sato Seiya、Nakayama Kentaro、Kanno Kosuke、Sultana Razia、Ishikawa Masako、Ishibashi Tomoka、Yamashita Hitomi、Kyo Satoru
    • Journal Title

      Cancer Science

      Volume: - Issue: 6 Pages: 2335-2344

    • DOI

      10.1111/cas.15767

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Landscape of PARP Inhibitors in Ovarian Cancer: Molecular Mechanisms and Clues to Overcome Resistance2022

    • Author(s)
      Kyo Satoru、Kanno Kosuke、Takakura Masahiro、Yamashita Hitomi、Ishikawa Masako、Ishibashi Tomoka、Sato Seiya、Nakayama Kentaro
    • Journal Title

      Cancers

      Volume: 14 Issue: 10 Pages: 2504-2504

    • DOI

      10.3390/cancers14102504

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutation Profiles of Ovarian Seromucinous Borderline Tumors in Japanese Patients2022

    • Author(s)
      Sasamori Hiroki、Nakayama Kentaro、Razia Sultana、Yamashita Hitomi、Ishibashi Tomoka、Ishikawa Masako、Sato Seiya、Nakayama Satoru、Otsuki Yoshiro、Fujiwaki Ritsuto、Ishikawa Noriyoshi、Kyo Satoru
    • Journal Title

      Current Oncology

      Volume: 29 Issue: 5 Pages: 3658-3667

    • DOI

      10.3390/curroncol29050294

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Muscle Loss but Not Fat Loss during Primary Debulking Surgery and Chemotherapy on Prognosis of Patients with Ovarian Cancer2022

    • Author(s)
      Nakayama Naomi、Nakayama Kentaro、Ishibashi Tomoka、Katayama Satoru、Kyo Satoru
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 11 Pages: 3184-3184

    • DOI

      10.3390/jcm11113184

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines2022

    • Author(s)
      Shanta Kamrunnahar、Nakayama Kentaro、Hossain Mohammad Mahmud、Razia Sultana、Ishibashi Tomoka、Ishikawa Masako、Yamashita Hitomi、Kanno Kosuke、Sato Seiya、Nakayama Satoru、Otsuki Yoshiro、Kyo Satoru
    • Journal Title

      Current Oncology

      Volume: 29 Issue: 6 Pages: 4020-4033

    • DOI

      10.3390/curroncol29060321

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Low-Grade Serous Ovarian Carcinoma from Benign Ovarian Serous Cystadenoma Cells2022

    • Author(s)
      Dey Puja、Nakayama Kentaro、Razia Sultana、Ishikawa Masako、Ishibashi Tomoka、Yamashita Hitomi、Kanno Kosuke、Sato Seiya、Kiyono Tohru、Kyo Satoru
    • Journal Title

      Cancers

      Volume: 14 Issue: 6 Pages: 1506-1506

    • DOI

      10.3390/cancers14061506

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Outcomes of Genotype-Matched Therapy for Recurrent Gynecological Cancers: A Single Institutional Experience2021

    • Author(s)
      Sawada Kiyoka、Nakayama Kentaro、Nakamura Kohei、Yoshimura Yuki、Razia Sultana、Ishikawa Masako、Yamashita Hitomi、Ishibashi Tomoka、Sato Seiya、Kyo Satoru
    • Journal Title

      Healthcare

      Volume: 9 Issue: 10 Pages: 1395-1395

    • DOI

      10.3390/healthcare9101395

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] P16INK4A expression might be associated with a favorable prognosis for cervical adenocarcinoma via dysregulation of the RB pathway2021

    • Author(s)
      Ishikawa Masako、Nakayama Kentaro、Nakamura Kohei、Yamashita Hitomi、Ishibashi Tomoka、Minamoto Toshiko、Sawada Kiyoka、Yoshimura Yuki、Iida Kouji、Razia Sultana、Ishikawa Noriyoshi、Nakayama Satoru、Otsuki Yoshiro、Kyo Satoru
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-021-97703-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 急速な転帰をたどった若年性HPV非関連癌の2症例2023

    • Author(s)
      石川 雅子, 中山 健太郎, 山下 瞳, 石橋 朋佳, 菅野 晃輔, 原賀 光, 京 哲
    • Organizer
      第61回日本癌治療学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] in vitro発癌モデルを駆使した卵巣癌発生機構の再検証2023

    • Author(s)
      中山 健太郎 石橋 朋佳 石川 雅子 山下 瞳 菅野 晃輔 島田 愛里香 中川 恭子 原賀 光 スルタナ・ラジア ソヘル・ハシブル・イスラム 清野 透 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Investigating the Mechanism of Resistance to PARP Inhibitors: Genetic Analysis of an Ovarian Cancer Patient with Germline BRCA1 Variant2023

    • Author(s)
      Yamashita Hitomi , Kentaro Nakayama, Tomoka Ishibashi , Masako Ishikawa, Koji Iida , Razia Surutana , Satoru Kyo
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 子宮内膜症上皮細胞におけるがん遺伝子変異の臨床・生物学的意義の検討2023

    • Author(s)
      菅野 晃輔 中山 健太郎 島田 愛里香 原賀 光 中川 恭子 石川 雅子 石橋 朋佳 山下 瞳 スルタナ・ラジア 佐藤 誠也 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 極めて急速な経過をたどった,若年発症HPV非依存性扁平上皮癌の2例2023

    • Author(s)
      石川 雅子 , 中山 健太郎 , 山下 瞳 , 石橋 朋佳、京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 病理診断に苦慮した若年性卵巣癌の1例2023

    • Author(s)
      中川 恭子, 中山 健太郎, 石川 雅子, 山下 瞳, 石橋 朋佳, 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 境界悪性腫瘍,悪性腫瘍の診断に難渋した若年性巨大卵巣腫瘍の1例2023

    • Author(s)
      石川 雅子, 中山 健太郎, 澤田 希代加, 山下 瞳, 石橋 朋佳, 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 当科におけるレンバチニブ,ペムブロリズマブ治療の現状2023

    • Author(s)
      原賀 光, 石川 雅子, 山下 瞳, 石橋 朋佳, 中山 健太郎, 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 当院でのPARP阻害薬使用状況について2023

    • Author(s)
      島田 愛里香, 中山 健太郎, 石川 雅子, 山下 瞳, 石橋 朋佳, 京 哲
    • Organizer
      第65回日本婦人科腫瘍学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 妊娠初期に発見された子宮頸部細胞診異常の臨床的転帰2023

    • Author(s)
      石川 雅子, 中山 健太郎, 山下 瞳, 石橋 朋佳, 佐藤 誠也, 皆本 敏子, 菅野 晃輔, 中川 恭子, 原賀 光, 飯田 幸司, 京 哲
    • Organizer
      第75回日本産科婦人科学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Investigating the mechanism of resistance to PARP inhibitors:Genetic analysis of an ovarian cancer patient with germline BRCA1 variant who became resistant to PARP inhibitors2023

    • Author(s)
      Hitomi Yamashita, Kentaro Nakayama, Hikaru Haraga, Tomoka Ishibashi, Masako Ishikawa, Seiya Sato, Koji Iida, Satoru Kyo
    • Organizer
      第75回日本産科婦人科学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 婦人科良性疾患におけるロボット支援手術と腹腔鏡手術の治療成績2022

    • Author(s)
      石橋朋佳、中山健太郎、佐藤誠也、石川雅子、山下 瞳、管野晃輔、京 哲
    • Organizer
      第62回日本産科婦人科内視鏡学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients2022

    • Author(s)
      Tomoka Ishibashi, Kentaro Nakayama, Naomi Nakayama, Seiya Sato, Masako Ishikawa, Hitomi Yamashita, Ruriko Fukushima, Kiyoka Sawada, Yuki Nonomura, Kan Makihara, Kosuke Kanno, and Satoru Kyo
    • Organizer
      第74回日本産科婦人科学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients2022

    • Author(s)
      Tomoka Ishibashi, Kentaro Nakayama, Seiya Sato, Masako Ishikawa, Hitomi Yamashita, Ruriko Fukushima, Kiyoka Sawada, Yuki Nonomura, Kosuke Kanno, and Satoru Kyo
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Clinicopathological analysis of uterine dedifferentiated endometrioid adenocarcinoma2021

    • Author(s)
      Ishibashi Tomoka
    • Organizer
      第73回日本産科婦人科学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] Clinicopathological Investigation of Uterine Dedifferentiated Endometrioid Adenocarcinoma2021

    • Author(s)
      石橋 朋佳
    • Organizer
      第63回日本婦人科腫瘍学会学術講演会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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