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Targeted therapy for cancer stem-like cells of non-small cell lung cancers with inhibition of the cJun transcription factor

Research Project

Project/Area Number 23591132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHokkaido University

Principal Investigator

KINOSHITA Ichiro  北海道大学, 医学(系)研究科(研究院), 准教授 (40343008)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Yasushi  北海道大学, 大学病院, 助教 (10374513)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺癌 / 癌幹細胞 / cJun / EZH2 / 幹細胞 / cJun / HDAC / エピジェネティクス / 分子標的薬
Research Abstract

Sphere forming capacity under serum-free culture, indicative of cancer stem cells, were decreased by cJun inhibition in non-small lung cancer (NSCLC) cells, while sphere forming cells did not show enhanced tumorigenicity in SCID mice.
Meanwhile, an inhibitor of histone methyltransferase EZH2 involved in stem cell maintenance via epigenetic regulation suppressed growth of NSCLC cells. An inhibitor of histone deacetylase (HDAC), another epigenetic regulator, showed a synergistic growth suppressive effect with the EZH2 inhibitor. Combined epigenetic therapy with an EZH2 inhibitor and an HDAC inhibitor may represent an effective approach for NSCLCs.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] CD133 expression: a potential prognostic marker for non-small cell lung cancers2014

    • Author(s)
      Mizugaki H, Sakakibara-Konishi J, Kikuchi J, Moriya J, Hatanaka KC, Kikuchi E, Kinoshita I, Oizumi S, Dosaka-Akita H, Matsuno Y and Nishimura M
    • Journal Title

      Int J Clin Oncol

      Volume: 19 Issue: 2 Pages: 254-259

    • DOI

      10.1007/s10147-013-0541-x

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells.2014

    • Author(s)
      Yamashina T, Baghdadi M, Yoneda A, Kinoshita I, Suzu S, Dosaka-Akita H, Jinushi M.
    • Journal Title

      Cancer Research

      Volume: 74 Issue: 10 Pages: 2698-2709

    • DOI

      10.1158/0008-5472.can-13-2169

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads to reduced antigen presentation and increased immune tolerance.2013

    • Author(s)
      Baghdadi M, Yoneda A, Yamashina T, Nagao H, Komohara Y, Nagai S, Akiba H, Foretz M, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Takeya M, Viollet B, Yagita H, Jinushi M
    • Journal Title

      Immunity

      Volume: 39 Issue: 6 Pages: 1070-1081

    • DOI

      10.1016/j.immuni.2013.09.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Updated Overall Survival Results from A Randomized Phase III Trial Comparing Gefitinib with Carboplatin-Paclitaxel for Chemo-Naive Non-Small Cell Lung Cancer with Sensitive EGFR Gene Mutations (NEJ002)2013

    • Author(s)
      Inoue A, Kobayashi K, Maemondo M, et al
    • Journal Title

      Ann Oncol

      Volume: 24 Issue: 1 Pages: 54-9

    • DOI

      10.1093/annonc/mds214

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells2012

    • Author(s)
      Kikuchi J, Takashina T, Kinoshita I, Kikuchi E, Shimizu Y, Sakakibara-Konishi J, Oizumi S, Marquez VE, Nishimura M, Dosaka-Akita H
    • Journal Title

      Lung Cancer

      Volume: 78 Issue: 2 Pages: 138-143

    • DOI

      10.1016/j.lungcan.2012.08.003

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. S.2012

    • Author(s)
      Chiba, M. Baghdadi, H. Akiba, H. Yoshiyama, I. Kinoshita, H. Dosaka-Akita, Y. Fujioka, Y. Ohba, J. V. Gorman, J. D. Colgan, M. Hirashima, T. Uede, A. Takaoka, H. Yagita and M. Jinushi.
    • Journal Title

      Nat. Immunol.

      Volume: 13 Issue: 9 Pages: 832-842

    • DOI

      10.1038/ni.2376

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ATM-mediated DNA damage signals mediate immune escape through integrin αvβ3-dependent mechanisms.2012

    • Author(s)
      Jinushi M
    • Journal Title

      Cancer Res

      Volume: 72 Issue: 1 Pages: 56-65

    • DOI

      10.1158/0008-5472.can-11-2028

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer2011

    • Author(s)
      Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Takeda K, Aburatani H, Oizumi S, Konishi J, Kaga K, Matsuno Y, Birrer MJ, Nishimura M and Dosaka-Akita H
    • Journal Title

      Lung Cancer

      Volume: 72 Issue: 2 Pages: 229-237

    • DOI

      10.1016/j.lungcan.2010.08.020

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis2011

    • Author(s)
      Takeda K, Kinoshita I, Shimizu Y, Matsuno Y, Shichinohe T and Dosaka-Akita H
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 263-270

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells2011

    • Author(s)
      Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, Yagita H, Takaoka A, Tahara H.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108巻 Issue: 30 Pages: 12425-30

    • DOI

      10.1073/pnas.1106645108

    • NAID

      10030575946

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Pharmacologic disruption of polycomb group protein EZH2 via 3-Deazaneplanocin A inhibits growth of non-small cell lung cancer cells2012

    • Author(s)
      Kinoshita I
    • Organizer
      5th Asia Pacific Lung Cancer Conference
    • Place of Presentation
      Hilton Fukuoka Sea Hawk, Fukuoka
    • Year and Date
      2012-11-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of polycomb group protein EZH2 in lung cancer2012

    • Author(s)
      Kinoshita I
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      教育文化会館, 札幌市
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Growth inhibition of non-small cell lung cancer cells by the histone methyltransferase ezh2 inhibitor 3-deazaneplanocin2011

    • Author(s)
      Kinoshita I
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場, 名古屋市
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Growth inhibition of non-small cell lung cancer cells by the histone methyltransferase ezh2 inhibitor 3-deazaneplanocin2011

    • Author(s)
      Kinoshita I
    • Organizer
      9th International Symposium for Future Drug Discovery and Medical Care
    • Place of Presentation
      Hokkaido University, Sapporo
    • Year and Date
      2011-09-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Growth inhibition of non-small cell lung cancer cells by the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin2011

    • Author(s)
      木下一郎,菊地順子,菊地英毅, 清水康, 榊原純, 大泉聡史, 西村正治, 秋田弘俊
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Related Report
      2011 Research-status Report
  • [Presentation] Growth inhibition of non-small cell lung cancer cells by the histone methyltransferase ezh2 inhibitor 3-deazaneplanocin2011

    • Author(s)
      Kinoshita I, Kikuchi J, Shimizu Y, Sakakibara-Konishi J, Oizumi S, Nishimura M, Dosaka-Akita H
    • Organizer
      9th International Symposium for Future Drug Discovery and Medical Care
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Effects of combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin and the histone deacetylase inhibitor SAHA on non-small cell lung cancer cells

    • Author(s)
      Takashina T, Kinoshita I, Kikuchi J, Shimizu Y, Konishi JS, Oizumi S, Nishimura M and Dosaka-Akita H
    • Organizer
      the 105th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      San Diego Conventon Center (San Diego)
    • Related Report
      2013 Annual Research Report
  • [Presentation] EZH2阻害薬とヒストン脱アセチル化酵素阻害薬の併用療法の非小細胞肺癌細胞に対する抗腫瘍効果の検討

    • Author(s)
      高階太一、木下一郎、菊地順子、池澤靖元、榊原純、大泉聡史、西村正治、秋田弘俊
    • Organizer
      第54回日本肺癌学会総会
    • Place of Presentation
      ホテルニューオータニ(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Effects of combined epigenetic therapy with EZH2 and HDAC inhibitors on NSCLC cells

    • Author(s)
      Takashina T, Kinoshita I, Kikuchi J, Kikuchi E, Shimizu Y, Sakakibara-Konishi J, Oizumi S, Nishimura M and Dosaka-Akita H
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of polycomb group protein EZH2 in lung cancer

    • Author(s)
      Kinoshita I
    • Organizer
      第71会日本癌学会学術総会
    • Place of Presentation
      教育文化会館(札幌市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Pharmacologic disruption of polycomb group protein EZH2 via 3-Deazaneplanocin A inhibits growth of non-small cell lung cancer cells

    • Author(s)
      Kinoshita I
    • Organizer
      5th Asia Pacific Lung Cancer Conference
    • Place of Presentation
      Hilton Fukuoka Sea Hawk (Fukuoka)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒストンメチル化酵素EZH2阻害剤3-deazaneplanocin Aによる非小細胞肺癌細胞株に対する増殖抑制効果の検討

    • Author(s)
      高階太一、木下一郎、菊地順子、菊地英毅、清水康、榊原純、大泉聡史、西村正治、秋田弘俊
    • Organizer
      第53回日本肺癌学会総会
    • Place of Presentation
      岡山コンベンションセンター(岡山市)
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://medicaloncology.med.hokudai.ac.jp/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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