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Development of an innovative, simple system to detect the critical gene mutations of skin cancers

Research Project

Project/Area Number 26670522
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionUniversity of Yamanashi

Principal Investigator

SHIMADA Shinji  山梨大学, その他部局等, その他 (10114505)

Co-Investigator(Kenkyū-buntansha) INOZUME Takashi  山梨大学, 総合研究部, 講師 (80334853)
OKAMOTO Takashi  山梨大学, 総合研究部, 助教 (30402043)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsAID / メラノーマ / Nupr1 / Timp3 / 免疫療法 / 治療抵抗性
Outline of Final Research Achievements

We have developed simple system to identify the genetic changes that induced treatment resistances of skin cancers. We transduced AID gene, that is known to induce random mutations in the transduced cells, into B16 murine melanoma cells. Then, we treated mice bearing the tumor with anticancer drugs and a cancer vaccine. Grown tumors were collected, and the status of gene mutation and gene expression profiles were compared with pre-treatment tumor cells. In the result, we could identify many genetic changes as candidates for the factors of treatment resistance. For example, resistance to anticancer drugs was mediated by upregulation of Nupr1, and resistance to a cancer vaccine was mediated by downregulation of Timp3. These findings suggested usefulness of our system to identify the important factors that induce treatment resistances of skin cancers.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2016 2015 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Melanoma cells control anti-melanoma CTL responses via interaction between TIGIT and CD155 in the effector phase.2016

    • Author(s)
      Inozume T, Yaguchi T, Furuta F, Harada K, Kawakami Y, Shimada S.
    • Journal Title

      J Invest Dermatol.

      Volume: 136 Issue: 1 Pages: 255-263

    • DOI

      10.1038/jid.2015.404

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Co-blockade of TIGIT and PD-1 signals in tumor-infiltrating cytotoxic T lymphocytes is an effective anti-melanoma therapy2015

    • Author(s)
      Takashi Inozume, Tomonori Yaguchi, Yutaka Kawakami, Shinji Shimada
    • Organizer
      The 40th annual meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      岡山コンベンションセンター, 岡山県、北区
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高頻度遺伝子変異導入システムを利用したメラノーマ治療の成否を左右する重要因子の検索2015

    • Author(s)
      猪爪隆史、原田和俊、島田眞路
    • Organizer
      第114回日本皮膚科学会総会
    • Place of Presentation
      パシフィコ横浜、神奈川県、横浜市
    • Year and Date
      2015-05-29 – 2015-05-31
    • Related Report
      2014 Research-status Report
  • [Presentation] Blockade for CD155-TIGIT interaction is an effective therapy for melanoma2015

    • Author(s)
      Takashi Inozume, Tomonori Yaguchi, Yutaka Kawakami, Shinji Shimada
    • Organizer
      Society for Investigative Dermatology, 2015, annual meeting
    • Place of Presentation
      Hilton Atlanta, Atlanta, Georgia
    • Year and Date
      2015-05-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 皮膚の免疫学-山梨大学からの発信-皮膚科よもやま話2015

    • Author(s)
      島田眞路
    • Organizer
      第20回茨城皮膚・アレルギー懇話会
    • Place of Presentation
      つくば国際会議場, 茨城県、つくば市
    • Year and Date
      2015-02-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Book] 癌と免疫  第2部 15,がん免疫における共刺激分子、共抑制分子と免疫チェックポイント2015

    • Author(s)
      猪爪隆史、島田眞路
    • Total Pages
      9
    • Publisher
      南山堂
    • Related Report
      2015 Annual Research Report
  • [Remarks] 山梨大皮膚科HP

    • URL

      http://www.med.yamanashi.ac.jp/clinical/dermatol/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 山梨大学皮膚科学教室ホームページ

    • URL

      http://www.med.yamanashi.ac.jp/clinical/dermatol/index.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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