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Analysis of effect and resistance of molecular-targeted therapy in renal cell carcinoma

Research Project

Project/Area Number 25460422
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKeio University

Principal Investigator

Mikami Shuji  慶應義塾大学, 医学部, 講師 (20338180)

Co-Investigator(Kenkyū-buntansha) KOSAKA TAKEO  慶應義塾大学, 医学部, 講師 (30445407)
MIZUNO RYUICHI  慶應義塾大学, 医学部, 講師 (60383824)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腎細胞癌 / 浸潤 / 転移 / 分子標的治療 / 癌幹細胞 / 上皮-間葉転換 / 上皮ー間葉転換 / 予後 / 分子標的薬 / 治療耐性
Outline of Final Research Achievements

This study was performed to clarify the significance of TNF-α and CD44 in clear cell renal cell carcinomas (ccRCCs). Co-upregulation of TNF-α and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-α enhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix MMP9 and CD44 expression. Among ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-α plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-α may be involved in the resistance to the sunitinib treatment.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2016 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer.2016

    • Author(s)
      Hashimoto, S,. Mikami, S., Sugino, H., Yoshikawa, A., Hashimoto, A., Onodera, Y., Furukawa, S., Handa, H., Oikawa, T., Okada, Y., Oya, M. and Sabe, H.
    • Journal Title

      Nat. Commun.

      Volume: 7 Issue: 1 Pages: 10656-10656

    • DOI

      10.1038/ncomms10656

    • NAID

      120005743066

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of TNF-α and CD44 is implicated in poor prognosis, cancer cell invasion, metastasis and resistance to the sunitinib treatment in clear cell renal cell carcinomas.2014

    • Author(s)
      Mikami S, Mizuno R, Kosaka T, Saya H, Oya M and Okada Y
    • Journal Title

      Int J Cancer

      Volume: 136 Issue: 7 Pages: 1504-1514

    • DOI

      10.1002/ijc.29137

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Invasion and metastasis of renal cell carcinoma2014

    • Author(s)
      Mikami S, Oya M, Mizuno R, Kosaka T, Katsube K, Okada Y.
    • Journal Title

      Medical Molecular Morphology

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 尿路上皮癌の総合診断学のup to date 病理2016

    • Author(s)
      三上修治
    • Organizer
      日本画像医学会
    • Place of Presentation
      ステーションコンファレンス東京(東京都千代田区)
    • Year and Date
      2016-02-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腎細胞癌の増殖・進展機構に関する研究2014

    • Author(s)
      三上 修治
    • Organizer
      第60回日本病理学会秋季特別総会
    • Place of Presentation
      沖縄
    • Year and Date
      2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] 「腎癌up to date 個別化医療をめざして」 腎細胞癌における上皮-間葉転換と分子標的治療2013

    • Author(s)
      三上 修治, 水野 隆一, 小坂 威男, 大家 基嗣, 岡田 保典
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 腫瘍病理鑑別診断アトラス 腎癌2013

    • Author(s)
      三上 修治、黒田 直人、長嶋 洋治他
    • Total Pages
      264
    • Publisher
      文光堂
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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