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The Elucidation of Mechanisms Underlying Resistance to Molecular Targeted Therapy in Malignant Gliomas and Development of Novel Therapeutic Strategy.

Research Project

Project/Area Number 20591706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

MUKASA Akitake  The University of Tokyo, 医学部附属病院, 特任講師 (90463869)

Co-Investigator(Kenkyū-buntansha) TANAKA Minoru  東京大学, 医学部附属病院, 助教 (50332581)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords悪性神経膠腫 / 上皮性増殖因子受容体 / 分子標的治療 / 薬剤耐性 / 腫瘍幹細胞
Research Abstract

The aim of this project was to identify key molecules among genes named as Substitute for EGFR* Expression (SE*Es) which are presumed to contribute to the resistance against therapy for malignant glioma, and to clarify their functions. First we categorized clinical specimens of malignant gliomas into basic subclasses based on genetic analyses and established several cell lines of brain tumor stem-like cells. Then to detect whether expressions of SE*E genes are elevated in human malignant gliomas and brain tumor stem-like cells, we investigated genomic amplification and gene expression in these tumor samples and consequently could pick up potentially important candidate genes which are subjected to further analyses.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (21 results)

All 2010 2009 2008 Other

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (13 results) Remarks (2 results)

  • [Journal Article] Mutant EGFR is required for maintenance of glioma growth in vivo, and its ablation leads to escape from receptor dependence.2010

    • Author(s)
      Mukasa A, Wykosky J, Ligon KL, Chin L, Cavenee WK, Furnari F
    • Journal Title

      Proc Natl Acad Sci U S A. 107巻

      Pages: 2616-2621

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Escape from targeted inhibition : the dark side of kinase inhibitor therapy.2010

    • Author(s)
      Wykosky J, Mukasa A, Furnari F, Cavenee WK
    • Journal Title

      Cell Cycle. 9巻

      Pages: 1611-1662

    • Related Report
      2010 Final Research Report
  • [Journal Article] Tumor Heterogeneity is an Active Process Maintained by a Mutant EGFR-induced Cytokine Circuit in Glioblastoma.2010

    • Author(s)
      Inda MM, Bonavia R, Mukasa A, Narita Y, Sah DW, Vandenberg S, Brennan C, Johns TG, Bachoo R, Hadwiger P, Tan P, Depinho RA, Cavenee W, Furnari F
    • Journal Title

      Genes & Development. 24巻

      Pages: 1731-1745

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Escape from targeted inhibition : the dark side of kinase inhibitor therapy.2010

    • Author(s)
      Wykosky J, Mukasa A, Furnari F, Cavenee WK
    • Journal Title

      Cell Cycle

      Volume: 9巻 Pages: 1661-1662

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Tumor Heterogeneity is an Active Process Maintained by a Mutant EGFR-induced Cytokine Circuit in Glioblastoma.2010

    • Author(s)
      Inda MM, Bonavia R, Mukasa A, Narita Y, Sah DW, Vandenberg S, Brennan C, Johns TG, Bachoo R, Hadwiger P, Tan P, Depinho RA, Cavenee W, Furnari F
    • Journal Title

      Genes & Development

      Volume: 24巻 Pages: 1731-1745

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant EGFR is required for maintenance of glioma growth in vivo, and its ablation leads to escape from receptor dependence.2010

    • Author(s)
      Mukasa A, Wykosky J, Ligon KL, Chin L, Cavenee WK, Furnari F.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 107巻 Pages: 2616-2621

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 悪性神経膠腫における変異型EGF受容体に対する分子標的療法とその治療耐性獲得機構2010

    • Author(s)
      武笠晃丈、他
    • Organizer
      第28回日本脳腫瘍学会
    • Place of Presentation
      軽井沢プリンスホテル ウエスト(長野県)
    • Year and Date
      2010-11-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 悪性神経膠腫における変異型EGF受容体に対する分子標的療法とその治療耐性獲得機構2010

    • Author(s)
      武笠晃丈, 他
    • Organizer
      第28回日本脳腫瘍学会
    • Place of Presentation
      軽井沢プリンスホテルウエスト(長野県)
    • Year and Date
      2010-11-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 悪性グリオーマにおけるIDH遺伝子変異と染色体1p19qLOHおよびp53変異の関連とその意義2010

    • Author(s)
      武笠晃丈、他
    • Organizer
      第68回日本脳神経外科学会総会
    • Place of Presentation
      福岡国際会議場(福岡県)(シンポジウム)
    • Year and Date
      2010-10-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 悪性グリオーマにおけるIDH遺伝子変異と染色体1p19qLOHおよびp53変異の関連とその意義(シンポジウム)2010

    • Author(s)
      武笠晃丈, 他
    • Organizer
      第68回日本脳神経外科学会総会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2010-10-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mutant EGFR Signaling is Required for Maintenance of Enhanced In Vivo Glioblastoma Growth and Its Ablation Leads to Escape by Emergence of Receptor-Independent Mechanisms2010

    • Author(s)
      武笠晃丈, et al
    • Organizer
      The 18th International Conference on Brain Tumor Research & Therapy
    • Place of Presentation
      Travemunde(Germany).
    • Year and Date
      2010-05-18
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutant EGFR Signaling is Required for Maintenance of Enhanced In Vivo Glioblastoma Growth and Its Ablation Leads to Escape by Emergence of Receptor-Independent Mechanisms2010

    • Author(s)
      Akitake Mukasa, et al
    • Organizer
      The 18th International Conference on Brain Tumor Research & Therapy
    • Place of Presentation
      Travemunde(Germany)
    • Year and Date
      2010-05-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 悪性グリオーマにおけるIDH遺伝子異常の検討2009

    • Author(s)
      武笠晃丈、他
    • Organizer
      第27回 日本脳腫瘍学会
    • Place of Presentation
      全日本ゲートタワーホテル大阪(大阪)
    • Year and Date
      2009-11-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 悪性グリオーマにおけるIDH遺伝子異常の検討2009

    • Author(s)
      武笠晃丈, 他
    • Organizer
      第27回日本脳腫瘍学会
    • Place of Presentation
      全日本ゲートタワーホテル大阪(大阪)
    • Year and Date
      2009-11-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] 悪性神経膠腫における変異型EGF受容体に対する分子標的療法とその治療耐性獲得メカニズムの基礎研究2009

    • Author(s)
      武笠晃丈、他
    • Organizer
      第68回 日本脳神経外科学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2009-10-15
    • Related Report
      2010 Final Research Report
  • [Presentation] 悪性神経膠腫における変異型EGF受容体に対する分子標的療法とその治療耐性獲得メカニズムの基礎研究2009

    • Author(s)
      武笠晃丈, 他
    • Organizer
      第68回日本脳神経外科学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2009-10-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] 神経細胞関連遺伝子群の染色体1p欠失を有するオリゴデンドログリオーマにおける発現2008

    • Author(s)
      武笠晃丈
    • Organizer
      第67回 日本脳神経外科学会総会
    • Place of Presentation
      岩手県盛岡市
    • Year and Date
      2008-10-02
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] The Role of EGFR* Signaling Pathway for Tumor Maintenance and Alternative Pathways in Glioblastoma which Enhance Tumor Growth2008

    • Author(s)
      武笠晃丈
    • Organizer
      The 17th International Conference on Brain Tumor Research & Therapy
    • Place of Presentation
      Hakodate, Japan.
    • Year and Date
      2008-06-10
    • Related Report
      2010 Final Research Report
  • [Presentation] The Role of EGFR^<*> Signaling Pathway for Tumor Maintenance and Alternative Pathways in Glioblastoma which Enhance Tumor Growth2008

    • Author(s)
      武笠晃丈
    • Organizer
      The 17th International Conference on Brain Tumor Research & Therapy
    • Place of Presentation
      Hakodate, Japan
    • Year and Date
      2008-06-10
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks] 東京大学医学部脳神経外科 研究内容

    • URL

      http://www.h.u-tokyo.ac.jp/neurosurg/kenkyu/kenkyu.html

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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