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Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary

Research Project

Project/Area Number 25462615
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionJikei University School of Medicine

Principal Investigator

Yanaihara Nozomu  東京慈恵会医科大学, 医学部, 講師 (20349624)

Co-Investigator(Kenkyū-buntansha) YAMADA KYOSUKE  東京慈恵会医科大学, 医学部, 准教授 (30230452)
TAKAKURA SATOSHI  東京慈恵会医科大学, 医学部, 講師 (60256401)
OCHIAI KAZUNORI  東京慈恵会医科大学, 医学部, 教授 (20152514)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsIL-6/STAT3シグナル / IL-6受容体 / 卵巣明細胞腺癌 / 卵巣癌 / 明細胞腺癌 / 1IL-6/STAT3シグナル
Outline of Final Research Achievements

Clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics. Recently, CCC was characterized by upregulation of the IL-6/IL-6R-Stat3 signal. In this study, we aim to clarify whether IL-6/IL-6R mediated signal pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases were evaluated by the immunohistochemical analysis for IL-6R and we found that high IL-6R expression correlated with poor patient survival. We further investigated the effects of IL-6/IL-6R signal inhibition either by IL-6R siRNA or humanized anti-human IL-6R antibody in CCC. Inhibition of endogenous IL-6R in CCC did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signal could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

Report

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

    (2 results)

All 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Antitumor Effects of Interleukin-6 (IL-6)/Interleukin-6 Receptor (IL-6R) Signaling Pathway Inhibition in Clear Cell Carcinoma of the Ovary2016

    • Author(s)
      Nozomu Yanaihara, Yukihiro Hirata, Noriko Yamaguchi, Yukiko Noguchi, Misato Saito,1 Chie Nagata, Satoshi Takakura, Kyosuke Yamada, and Aikou Okamoto
    • Journal Title

      MOLECULAR CARCINOGENESIS

      Volume: 55 Issue: 5 Pages: 832-41

    • DOI

      10.1002/mc.22325

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 卵巣明細胞腺癌におけるゲノムコピー数・遺伝子発現解析による分子生物学的機構の解明2015

    • Author(s)
      矢内原臨,岡本愛光
    • Organizer
      第53回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
    • Invited

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

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