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Drug screening and identification of biomarkers using sensitivity assay with a panel of primary cultured cancer spheroids derived from endometrial cancer

Research Project

Project/Area Number 26462522
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

Yoshino Kiyoshi  大阪大学, 医学系研究科, 准教授 (90362730)

Co-Investigator(Kenkyū-buntansha) 松崎 慎哉  大阪大学, 医学部附属病院, 助教 (00467565)
上田 豊  大阪大学, 医学系研究科, 助教 (10346215)
高田 友美  大阪大学, 医学系研究科, 助教 (30437420)
小林 栄仁  大阪大学, 医学系研究科, 助教 (50614773)
藤田 征巳  大阪大学, 医学系研究科, 招へい准教授 (60303963)
木村 敏啓  大阪大学, 医学系研究科, 招へい教員 (90584524)
Co-Investigator(Renkei-kenkyūsha) INOUE Masahiro  大阪府立成人病センター研究所, 生化学部門, 部長 (10342990)
NAKA Tetsuji  医薬基盤研究所, 免疫シグナルプロジェクト, プロジェクトリーダー (30303936)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords婦人科腫瘍 / 子宮体癌 / CTOS / 播種 / バイオマーカー / YM155
Outline of Final Research Achievements

We successfully prepared and cultured cancer tissue-originated spheroids
(CTOS) from endometrial cancers. Then, we screened 79 molecular targeting drugs using two CTOSs. Among several hits, we focused on everolimus and YM155, a survivin inhibitor. When sensitivity to everolimus or YM155 was assessed in 12 CTOSs, the sensitivity varied substantially. The phosphorylation status of the mammalian target of rapamycin complex 1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. In contrast, the CTOS sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Thus, sensitivity assays using cancer tissue-originated spheroids from endometrial cancers may be useful for screening drugs and finding biomarkers.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results)

  • [Journal Article] Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer2016

    • Author(s)
      Kiyohara Y, Yoshino K, Kubota S, Okuyama H, Endo H, Ueda Y, Kimura T, Kimura T, Kamiura S, Inoue M.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 4 Pages: 452-460

    • DOI

      10.1111/cas.12898

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Annexin A4 is a promising therapeutic target for the treatment of platinum-resistant cancers2014

    • Author(s)
      Matsuzaki, S. Serada, S. Morimoto, A. Ueda, Y. Yoshino, K. Kimura, T. Naka, T.
    • Journal Title

      Expert Opin Ther Tar

      Volume: 18(4) Issue: 4 Pages: 403-14

    • DOI

      10.1517/14728222.2014.882323

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CTOS法による子宮頚部小細胞がん・腺がん混合腫瘍の解析2015

    • Author(s)
      久保田哲 中嶋綾 清原裕美子 遠藤洋子 奥山裕照 吉野潔 木村正 井上正宏
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] CTOS法による子宮頸部小細胞がん・腺がん混合腫瘍のクロナリティーの解析2015

    • Author(s)
      久保田哲 清原裕美子 上田豊 吉野潔 井上正宏 木村正
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Screening of molecular targeting drugs and exploring biomarkers for uterine corpus carcinoma using CTOS method2014

    • Author(s)
      Takata, T. Kiyohara, Y. Endo, H. Okuyama, H. Yoshino, K. Kimura, T. Inoue, M.
    • Organizer
      The 19th Japan-Korea Cancer Research Workshop
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Research-status Report
  • [Presentation] A proteomic analysis demonstrates similar expression pattern between ovarian and endometrial high-grade serous carcinoma beyond an organ2014

    • Author(s)
      Hiramatsu, K. Enomoto, T. Serada, S. Yoshihara, K. Hori, Y. Fujimoto, M. Ueda, Y. Yoshino, K. Fujita, M. Morii, E. Naka, T.
    • Organizer
      The 15th Biennial Meeting of the International Gynecologic Cancer Society
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2014-11-06 – 2014-11-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Preparation of primary culture cells from a LCNEC of uterine corpus using CTOS (Cancer Tissue-Originated Spheroid) method2014

    • Author(s)
      Kiyohara, Y. Yoshino, K. Hiramatsu, K. Takata, T. Matsuzaki, S. Kimura, K. Kobayashi, E. Ueda, Y. Inoue, M. Kimura, T.
    • Organizer
      The 15th Biennial Meeting of the International Gynecologic Cancer Society
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2014-11-06 – 2014-11-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 子宮体がんの新規三次元培養CTOS法におけるmTOR阻害剤感受性の多様性2014

    • Author(s)
      清原裕美子 遠藤洋子 吉野潔 木村敏啓 上田豊 藤田征巳 木村正 井上正宏
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 子宮体部漿液性腺癌32例における子宮頸部細胞診と臨床所見の検討2014

    • Author(s)
      松崎聖子 吉野潔 堀由美子 高田友美 上田豊 和田直樹 池田純一郎 藤田征巳 森井英一
    • Organizer
      第52回日本臨床細胞学会春期大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規3次元癌細胞初代培養(CTOS)法を用いた子宮体癌に対するmTOR阻害剤感受性試験2014

    • Author(s)
      清原裕美子 吉野潔 木村正 井上正宏
    • Organizer
      化学療法基盤支援活動第3回シンポジウム
    • Place of Presentation
      沖縄
    • Year and Date
      2014-05-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 子宮体癌に対するオーダーメイド分子標的治療のためのCTOSを用いた基礎的研究2014

    • Author(s)
      清原裕美子 藤田征巳 吉野潔 上田豊 木村敏啓 松崎慎哉 木村正
    • Organizer
      第66回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-18 – 2014-04-20
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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