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γ-secretase Inhibitor Enhances Antitumor Effect of Radiation in Notch Expressing Lung Cancer

Research Project

Project/Area Number 22790742
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionHokkaido University

Principal Investigator

SAKAKIBARA Jun (KONISHI Jun)  北海道大学, 北海道大学病院, 助教 (50374278)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺癌 / Notch / 放射線治療
Research Abstract

We discovered that the antitumor effect of combining GSI(-secretase inhibitor) and radiation was dependent on treatment schedule. GSI administration after radiation had the greatest growth inhibition of lung cancer in vitro and in vivo. We showed that the combination induced apoptosis of lung cancer cell lines through the regulation of MAPK and Bcl-2family proteins. Furthermore, activation of Notch after radiation was ameliorated by GSI administration, suggesting that treatment with GSI prevent Notch-induced radiation resistance.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (5 results)

All 2012 2011 2010

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results)

  • [Journal Article] γ-secretase Inhibitor enhances antitumoreffect of radiation in Notch expressing lungcancer2012

    • Author(s)
      Hidenori Mizugaki, Jun Sakakibara-Konishi, et al
    • Journal Title

      British Journal of Cancer

      Volume: 106(4) Pages: 1953-1959

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch3cooperates with the EGFR pathway to modulate apoptosis through the induction of bim2010

    • Author(s)
      Konishi J, Yi F, Chen X, Vo H, Carbone DP, Dang TP
    • Journal Title

      Oncogene

      Volume: 29(4) Pages: 589-596

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] γーセクレターゼインヒビターと放射線照射併用による肺癌細胞に対する航腫瘍効果の検討2011

    • Author(s)
      水柿秀紀
    • Organizer
      日本臨床腫瘍学会
    • Place of Presentation
      東京ビッグサイト(東京都)
    • Year and Date
      2011-03-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] γ-secretase inhibitorと放射線照射併用による肺癌細胞に対する抗腫瘍効果の検討2010

    • Author(s)
      水柿秀紀
    • Organizer
      北海道癌談話会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2010-10-23
    • Related Report
      2011 Final Research Report
  • [Presentation] γ-secretase inhibitorと放射線照射併用による肺癌細胞に対する抗腫瘍効果の検討2010

    • Author(s)
      水柿秀紀
    • Organizer
      に本臨床腫瘍学会
    • Place of Presentation
      東京ビッグサイト(東京)
    • Year and Date
      2010-03-18
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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