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Development of cancer treatment targeting morphogen and cancer stem cell

Research Project

Project/Area Number 24592043
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKawasaki Medical School

Principal Investigator

NAKAMURA Masafumi  川崎医科大学, 医学部, 教授 (30372741)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Hiroshi  川崎医科大学, 医学部, 講師 (60623048)
TSUTSUMI Kosuke  川崎医科大学, 医学部, 助教 (00467937)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords膵癌 / 癌微小環境 / 形態形成シグナル / Hedgehog signaling / Sonic Hedgehog / metformin / AMPK / Hedgehogシグナル / Sonic Hedgehog (Shh) / 自己抗体 / 癌性幹細胞 / 微小環境 / 線維芽細胞
Outline of Final Research Achievements

[Aim] The aim of this study is to explore the relationship between metformin and Hh signaling pathway, and to clarify the mechanism by which metformin prevents cancers. [Materials and methods] Expression of Shh was examined at protein and mRNA level with or without metformin by real-time PCR, immunoblotting and immunestaining. Phosphorylation of AMPK was detected by immunoblotting. [Results] Shh expression was decreased at protein and mRNA level by addition of metformin in BxPC3 cells. Phosphorylation of AMPK was increased by metformin and decreased by dorsomorphin. Interestingly, Shh expression was increased by dorsomorphin. This effect was further confirmed by siRNA of AMPK. [Conclusion] Metformin inhibits production of Shh in BxPC3 through phosphorylation of AMPK. Activation of AMPK might be one of the routes to link metformin and suppression of Shh.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Metformin suppresses Sonic Hedgehog expression in pancreatic cancer cells2014

    • Author(s)
      Masafumi Nakamura, Ayako Ogo, Masahiro Yamamura, Yoshiyuki Yamaguchi and Hiroshi Nakashima
    • Journal Title

      Anticancer Research

      Volume: 34 Pages: 1765-1770

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients2014

    • Author(s)
      Yosuke Nagayoshi, Masafumi Nakamura, Kazuhiro Matsuoka, Takao Ohtsuka, Yasuhisa Mori, Hiroshi Kono, Teppei Aso, Noboru Ideno, Shunichi Takahata, Akihide Ryo, Hiroyuki Takeda, Tetsuhide Ito, Yoshinao Oda, Yaeta Endo, Tatsuya Sawasaki, Masao Tanaka
    • Journal Title

      Annals of surgical oncology

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] High expression of microRNA-155 is associated with the aggressive malignant behavior of gallbladder carcinoma2013

    • Author(s)
      Hiroshi Kono, Masafumi Nakamura, Takao Ohtsuka, Yosuke Nagayoshi, Yasuhisa Mori, Shunich Takahata, Shinich Aishima, Masao Tanaka
    • Journal Title

      ONCOLOGY REPORTS

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 膵・胆管合流異常と胆嚢癌におけるmicroRNA発現解析2013

    • Author(s)
      河野博、中村雅史、大塚隆生、藤野稔、田村公二、井手野昇、安蘇鉄平、永吉洋介、上田純二、高畑俊一、小田義直、田中雅夫
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ビオチン化タンパク質ライブラリーを用いた膵癌患者血中自己抗体プロファイリング

    • Author(s)
      永吉洋介, 中村雅史, 松岡和弘, 安蘇鉄平, 井手野昇, 河野博, 大塚隆生, 高畑俊一, 澤崎達也, 田中雅夫
    • Organizer
      第68回日本消化器外科学会総会
    • Place of Presentation
      宮崎市(シーガイアコンベンションセンター)
    • Related Report
      2013 Research-status Report
  • [Remarks] 川崎医科大学消化器外科ホームページ

    • URL

      http://www.kawasaki-m.ac.jp/dig-surg/index.html

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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