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卵巣癌の薬剤獲得耐性における「進化」を標的とした治療法の開発

Research Project

Project/Area Number 22659301
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

鈴木 彩子  京都大学, 医学(系)研究科(研究院), 助教 (90378696)

Co-Investigator(Kenkyū-buntansha) 松村 謙臣  京都大学, 医学研究科, 助教 (20452336)
小阪 謙三  京都大学, 医学研究科, 講師 (90359828)
小西 郁生  京都大学, 医学研究科, 教授 (90192062)
Project Period (FY) 2010-04-01 – 2013-03-31
Project Status Declined (Fiscal Year 2012)
Budget Amount *help
¥3,430,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥630,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥700,000 (Direct Cost: ¥700,000)
Keywords卵巣癌 / 化学療法耐性 / 化学療法 / 獲得耐性 / バイオインフォマティックス
Research Abstract

1)化学療法耐性の卵巣明細胞腺癌に高発現しているHNF1βは、酸化ストレス耐性をもたらしていることが明らかになった。シスプラチンをはじめとする化学療法剤は癌細胞内の酸化ストレスを惹起するため、HNF1βによる酸化ストレス耐性が卵巣明細胞腺癌の化学療法耐性に寄与している可能性が示唆された。
2)卵巣漿液性腺癌の発現マイクロアレイ解析によって、化学療法に耐性で予後不良の癌では、免疫反応が乏しく、その背景にはMHC class1分子の欠如があることが明らかになった。
3)卵巣癌に対して化学療法を行う前と後のマイクロアレイデータの比較によって、化学療法によって免疫反応が生じることは、化学療法への感受性と関連していることが明らかとなった。
4)卵巣癌において、CD1,CD4,CD8,CD57,FOXP3,PD1がそれぞれ陽性のリンパ球数、さらに、腫瘍細胞由来の免疫抑制分子であるPD-L1,PD-L2,COX-1,COX-2,TGF-β1の発現を免療組織染色で調べて、hierarchical clusteringで分類したところ、CD4陽性リンパ球および、CD8陽性リンパ球が腫瘍内に浸潤している卵巣癌では、もっとも予後がよく、化学療法に感受性を示し、その他のタイプでは免疫抑制分子のいずれかの高発現を認めた。したがって、卵巣癌において、腫瘍細胞由来の免疫抑制分子が化学療法耐性をもたらしており、同シグナルをブロックすることで予後が改善すると期待される。

Report

(2 results)
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (12 results)

All 2012 2011 2010

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (3 results)

  • [Journal Article] Phase II study of oral et oposide and intravenous irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer : Japan Clinical Oncology Group Study 05032012

    • Author(s)
      Matsumoto K, Katsumata N, Saito I, Shibata T, Konishi I, Fukuda H, Kamura T.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 42(3) Issue: 3 Pages: 222-5

    • DOI

      10.1111/j.1447-0756.2011.01752.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors2011

    • Author(s)
      Hamanishi J, Mandai M, Abiko K, Matsumura N, Baba T, Yoshioka Y, Kosaka K, Konishi I.
    • Journal Title

      Clin Immunol

      Volume: 141(3) Issue: 3 Pages: 338-47

    • DOI

      10.1016/j.clim.2011.08.013

    • NAID

      120003610113

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ovarian clear cell carcinoma as a stress-responsive cancer : influence of the microenvironment on the carcinogenesis and cancer phenotype2011

    • Author(s)
      Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Konishi I.
    • Journal Title

      Cancer Lett

      Volume: 310(2) Issue: 2 Pages: 129-33

    • DOI

      10.1016/j.canlet.2011.06.039

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinguishing primary from secondary mucinous ovarian tumors : an algorithm using the novel marker DPEP1.2011

    • Author(s)
      Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I.
    • Journal Title

      Modern Pathology

      Volume: 24 Pages: 267-276

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation.2011

    • Author(s)
      Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I.
    • Journal Title

      American Journal of Surgical Pathology

      Volume: 34 Pages: 1842-1848

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer.2011

    • Author(s)
      Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, Iversen ES, Berchuck A, Murphy SK.
    • Journal Title

      Genome Research

      Volume: 21 Pages: 74-82

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GPR54 Is a Target for Suppression of Metastasis in Endometrial Cancer.2011

    • Author(s)
      Kang HS, Baba T, Mandai M, Matsumura N, Hamanishi J, Kharma B, Kondoh E, Yoshioka Y, Oishi S, Fujii N, Murphy SK, Konishi I.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 10 Pages: 580-590

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.2011

    • Author(s)
      Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I.
    • Journal Title

      International Journal of Cancer

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling.2010

    • Author(s)
      Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, Baba T, Hamanishi J, Kang HS, Matsui S, Mori S, Murphy SK, Konishi I.
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 2658-2663

    • NAID

      10027834982

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 卵巣癌に対する抗がん剤治療は腫瘍局所の免疫を変化させる"The immunologic change in ovarian cancer patients after chemotherapy"2011

    • Author(s)
      濱西潤三、万代昌紀、小西郁生
    • Organizer
      第15回日本がん免疫学会
    • Place of Presentation
      大阪市
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Genome-wide methylation analyses reveal a prominent role of HNF1 network genes, via hypomethylation, in ovarian clear cell carcinoma.2011

    • Author(s)
      Yamaguchi K, Baba T, Matsumura N, Mandai M, Konishi I, Berchuck A, Murphy SK
    • Organizer
      The 42nd Annual Meeting on Women's Cancer
    • Place of Presentation
      Orland, FL, USA
    • Year and Date
      2011-03-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] A study on Long Term Survival after Recurrence of Epithelial Ovarian Cancer2011

    • Author(s)
      Yumiko Yoshioka, Megumi Onaka, Noriomi Matsumura, Akihiko Ueda, Tsukasa Baba, Ayako Suzuki, Kenzo Kosaka, Masaki Mandai, Ikuo Konishi
    • Organizer
      2nd Biennial Meeting of Asian Society of Gynecologic Oncology (ASGO)
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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