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Different etiologic mechanisms underlying HFS depending on the classes of anti-cancer agents

Research Project

Project/Area Number 15K15002
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionKyoto University

Principal Investigator

Matsubara Kazuo  京都大学, 医学研究科, 教授 (20127533)

Co-Investigator(Kenkyū-buntansha) 中川 貴之  京都大学, 医学研究科, 准教授 (30303845)
今井 哲司  京都大学, 医学研究科, 講師 (80468579)
大村 友博  京都大学, 医学研究科, 助教 (00439035)
中川 俊作  京都大学, 医学研究科, 特定職員 (50721916)
金子 周司  京都大学, 薬学研究科, 教授 (60177516)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords抗がん剤副作用 / 手足症候群 / 分子標的薬 / ヒト皮膚ケラチノサイト / マウスモデル
Outline of Final Research Achievements

The present study is designed to investigate mechanisms underlying epidermal growth factor receptor inhibitors (EGFRIs)- or multikinase inhibitors (MKIs)-induced Hand-Foot Syndrome (HFS) using a human keratinocyte cell line, HaCaT cell. We evaluated the effects of EGFRIs (gefitinib and erlotinib) or MKIs (sunitinib and sorafenib) on the viability of HaCaT cells using MTT assay. Each of the anti-cancer agents reduced the viability of Schwann cells in a concentration-dependent manner after either 24 or 48 h of treatment. The treatment with gefitinib and erlotinib significantly increased the expression of apoptosis marker caspase3, and reduced phospholylated Akt (p-Akt) levels, which involves in cell survival, suggesting that EGFRIs might induce HFS via cell apoptosis mechanisms. In contrary, sunitinib and sorafenib failed to affect caspase3 and p-Akt levels. These findings clearly suggest the different etiologic mechanisms underlying HFS depending on the classes of anti-cancer agents.

Report

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

    (2 results)

All 2016 2015

All Presentation (2 results)

  • [Presentation] シュワン細胞に着目したタキサン系あるいは白金系抗がん剤誘発末梢神経障害の発症機序の相違2016

    • Author(s)
      小柳円花
    • Organizer
      2016神経科学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 分子標的薬による皮膚障害の発症機序解明2015

    • Author(s)
      小島奈津美、大村友博、今井哲司、中川俊作、米澤淳、中川貴之、松原和夫
    • Organizer
      第65回日本薬学会近畿支部総会
    • Place of Presentation
      大阪大谷大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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