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Therapeutic strategy of advanced ovarian cancer by targeting carbonyl reductase 1

Research Project

Project/Area Number 20K09589
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 InstitutionHirosaki University

Principal Investigator

Yokoyama Yoshihito  弘前大学, 医学研究科, 教授 (90261453)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsCarbonyl reductase 1 / 卵巣癌 / エクソソーム / トランスジェニックマウス / プロテオーム解析 / パスウェイ解析 / eIF2シグナル / 質量分析解析 / 卵巣癌細胞増殖抑制 / 卵巣癌細胞 / シグナル伝達 / EIF2シグナル / 腫瘍制御 / 遺伝子治療 / 癌性腹膜炎
Outline of Research at the Start

本研究は3つの目的を達成するために計画されている。Carbonyl reductase 1 (CBR1)DNAを卵巣癌腹膜播種の遺伝子治療に応用するためエクソソームを新たなDrug delivery toolとして安全かつ効率的に行い得る遺伝子治療の条件を確立すること。CBR1の抗腫瘍作用が直接的なものか間接的なものか明確にするためCBR1が細胞内シグナル伝達系のどこに作用するのかメタボローム解析によってCBR1の作用機序を明らかにすること。血中のCBR1 DNA量が予後と相関するのか治療効果と相関があるのかを調べ予後予測マーカーとなり得るか検討すること。

Outline of Final Research Achievements

We created transgenic mice overexpressing mouse Cbr1 (mCbr1), and investigated the expression of mCbr1 in two strains of these mice. One strain showed overexpression of mCbr1 in various tissues, while the other strain exhibited overexpression specifically in the heart. Mass spectrometry analysis using the heart tissue identified 73 proteins that correlated with overexpression of mCbr1, including voltage-dependent anion channels. We believe that the mCbr1-Tg mouse will be useful for analyzing the physiological significance of CBR1 in various organs. Overexpression of CBR1 in ovarian cancer cells was found to significantly affect eIF2 signaling. This suggests that CBR1 may be involved in tumor suppression through multiple pathways.

Academic Significance and Societal Importance of the Research Achievements

Carbonyl reductase 1 (CBR1) の生理的意義を解明する一助として、マウスCbr1 (mCbr1) を過剰発現するトランスジェニックマウス (mCbr1-Tgマウス) の作製に成功した。mCbr1-Tgマウスは、各臓器におけるCBR1の生理的意義を解析するのに有用であると考える。CBR1が腫瘍抑制に複数の経路を介して関与している可能性が示唆され、新たな治療戦略の可能性を見出した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 2020

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (6 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Development of transgenic mice overexpressing mouse carbonyl reductase 12023

    • Author(s)
      Yokoyama M, Fujita T, Kadonosawa Y, Tatara Y, Motooka D, Ikawa M, Fujii H, Yokoyama Y.
    • Journal Title

      Mol Biol Rep

      Volume: 50 Issue: 1 Pages: 531-540

    • DOI

      10.1007/s11033-022-07994-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomal MicroRNA as Biomarkers for Diagnosing or Monitoring the Progression of Ovarian Clear Cell Carcinoma: A Pilot Study2022

    • Author(s)
      Horie Kayo、Nanashima Naoki、Yokoyama Yoshihito、Yoshioka Haruhiko、Watanabe Jun
    • Journal Title

      Molecules

      Volume: 27 Issue: 12 Pages: 3953-3953

    • DOI

      10.3390/molecules27123953

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of COVID-19 on gynecologic cancer treatment in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO).2022

    • Author(s)
      Nogami Y, Komatsu H, Makabe T, Hasegawa Y, Yokoyama Y, Kawana K, Okamoto A, Mikami M, Katabuchi H; COVID-19 Task Force of the Japan Society of Gynecologic Oncology.
    • Journal Title

      J Gynecol Oncol

      Volume: 33(1) Issue: 1

    • DOI

      10.3802/jgo.2022.33.e8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fertility awareness and subclinical infertility among women trying to get pregnant at home2022

    • Author(s)
      Iino K, Fukuhara R, Yokota M, Yokoyama Y
    • Journal Title

      BMC Womens Health

      Volume: 22 Issue: 1

    • DOI

      10.1186/s12905-022-01626-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Perioperative Heart Rate Variability Analysis to Evaluate Autonomic Activity in Gynecologic Patients2022

    • Author(s)
      Annells A, Futagami M, Osawa Y, Oishi M, Washima H, Sugimoto R, Tsushima R, Takenoko K, Kurotaki S, Taguchi T, Maeda J, Kadonosawa Y, Ebina A, Akaishi A, Miura R, Matsumura Y, Yokoyama Y
    • Journal Title

      Hirosaki Med J

      Volume: 72 Pages: 51-61

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.2021

    • Author(s)
      Tokunaga H, Mikami M, Nagase S, Kobayashi Y, Tabata T, Kaneuchi M, Satoh T, Hirashima Y, Matsumura N, Yokoyama Y, Kawana K, Kyo S, Aoki D, Katabuchi H.
    • Journal Title

      J Gynecol Oncol

      Volume: 32 Issue: 2

    • DOI

      10.3802/jgo.2021.32.e49

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment strategies for ovarian cancer focusing on prostaglandins.2021

    • Author(s)
      Shigeto T, Yokoyama Y
    • Journal Title

      Eur J Gynaecol Oncol

      Volume: 42 Issue: 5 Pages: 996-1000

    • DOI

      10.31083/j.ejgo4205148

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbonyl reductase 1-overexpressing exosomes inhibits proliferation of ovarian cancer cells2021

    • Author(s)
      Takabayashi-Eibina A, Yokoyama M, Horie K, Yokoyama Y
    • Journal Title

      Hirosaki Medical Journal

      Volume: 71 Pages: 120-130

    • NAID

      130007998259

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer2021

    • Author(s)
      Okamoto Aikou、Yanagida Satoshi、Hamanishi Junzo、Harano Kenichi、Hasegawa Kosei、Hirasawa Takeshi、Hori Kensukei、Nakai Hidekatsu、Sakata Jun、Tabata Tsutomu、Takehara Kazuhiro、Takekuma Munetaka、Yokoyama Yoshihito、Kase Yoichi、Sumino Shuuji、Soeda Junpei、Suri Ajit、Aoki Daisuke、Sugiyama Toru
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 32 Issue: 2

    • DOI

      10.3802/jgo.2021.32.e16

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer2021

    • Author(s)
      Takehara Kazuhiro、Matsumoto Takashi、Hamanishi Junzo、Hasegawa Kosei、Matsuura Motoki、Miura Kiyonori、Nagao Shoji、Nakai Hidekatsu、Tanaka Naotake、Tokunaga Hideki、Ushijima Kimio、Watari Hidemichi、Yokoyama Yoshihito、Kase Yoichi、Sumino Shuuji、Suri Ajit、Itamochi Hiroaki、Takeshima Nobuhiro
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 32 Issue: 2

    • DOI

      10.3802/jgo.2021.32.e21

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A semen-based stimulation method to analyze cytokine production by uterine CD56bright natural killer cells in women with recurrent pregnancy loss2020

    • Author(s)
      Taima Ayako、Fukui Atsushi、Yamaya Ayano、Yokota Megumi、Fukuhara Rie、Yokoyama Yoshihito
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 142 Pages: 103206-103206

    • DOI

      10.1016/j.jri.2020.103206

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological analysis of peritoneal dissemination of ovarian cancer based in levels of carbonyl reductase 1 expression.2020

    • Author(s)
      Oyama F, Asano Y, Shimoda H, Horie K, Watanabe J, Yokoyama Y.
    • Journal Title

      Eur J Gynaecol Oncol

      Volume: 41 Pages: 352-360

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Carbonyl reductase 1を過剰発現させたトランスジェニックマウスの作製および解析2022

    • Author(s)
      横山美奈子、藤田敏次、門ノ沢結花、多田羅洋太、藤井穂高、横山良仁
    • Organizer
      第159回弘前医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Carbonyl reductase 1はEIF2シグナルを介して卵巣癌細胞増殖を抑制する2022

    • Author(s)
      門ノ沢結花、横山美奈子、横山良仁
    • Organizer
      第64回日本婦人科腫瘍学会
    • Related Report
      2021 Research-status Report
  • [Presentation] カルボニルリダクターゼ1を過剰発現させたトランスジェニックマウスの作成および解析2022

    • Author(s)
      横山美奈子、門ノ沢結花、張賀冕、横山良仁
    • Organizer
      第64回日本婦人科腫瘍学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Carbonyl reductase 1安定発現卵巣癌細胞におけるプロテオーム解析2022

    • Author(s)
      門ノ沢結花、横山美奈子、横山良仁
    • Organizer
      第74回日本産科婦人科学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] カルボニル還元酵素1過剰発現エクソソームはが卵巣癌細胞の増殖を抑制する2021

    • Author(s)
      海老名杏奈、横山美奈子、堀江香代、横山良仁
    • Organizer
      第63回日本婦人科腫瘍学会
    • Related Report
      2021 Research-status Report
  • [Presentation] カルボニル還元酵素1過剰発現エクソソームは卵巣癌細胞の増殖を抑制する2021

    • Author(s)
      海老名杏奈、横山良仁
    • Organizer
      青森県糖鎖研究会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] トランスジェニック非ヒト動物2022

    • Inventor(s)
      横山良仁、横山美奈子
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-009381
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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