• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the control mechanism by Fbxw7 / Notch1 / chemokine in perineural invasion of pancreatic cancer

Research Project

Project/Area Number 16K19910
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionTohoku University

Principal Investigator

Masuda Kunihiro  東北大学, 大学病院, 助教 (30569645)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsFbxw7 / 胆道癌 / 膵癌 / FBXW7 / 神経周囲浸潤
Outline of Final Research Achievements

I examined to elucidate the influence of Fbxw7 and the substrates accumulation in pancreatic cancer nerve infiltration. However, there was no association between Fbxw7 downregulation and pathological factors in pancreatic cancer pathological specimens. For that reason, I analyzed the relationship between the expression of Fbxw7 and clinicopathological factors in cholangiocarcinoma, which had Fbxw7 mutation.
FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. FBXW7 was the most important independent prognostic factor. I also demonstrate that the two FBXW7 substrates, NOTCH1 and MCL1), regulate cholangiocarcinoma progression. FBXW7 modulates the malignant potential of cholangiocarcinoma via independent regulation of NOTCH1 and MCL1.

Academic Significance and Societal Importance of the Research Achievements

膵癌神経浸潤でのFbxw7と基質の蓄積による影響を解明すべく実験を行ったが,膵癌病理検体Fbxw7 発現低下と病理学的因子の関連はなく,細胞株では基質の蓄積を確認できなかった.そのため、Fbxw7に変異を有する胆道癌で研究を行った.
胆道癌においてFbxw7の発現低下は臨床病理学的予後が不良であることを初めて確認した.また,それらのメカニズムとしてNotch1とMcl-1の蓄積の関与を明らかにした.
胆道癌において Fbxw7 と基質タンパク質の分子メカニズムを明らかにし、それらを標的とする新規治療を確立することは個別化治療へと繋がる研究であり,更なる治療成績向上への第一歩となると考えられる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL12018

    • Author(s)
      Mori Akiko、Masuda Kunihiro、Ohtsuka Hideo、Shijo Masahiro、Ariake Kyohei、Fukase Koji、Sakata Naoaki、Mizuma Masamichi、Morikawa Takanori、Hayashi Hiroki、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Fujishima Fumiyoshi、Unno Michiaki
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 12 Pages: 3883-3895

    • DOI

      10.1111/cas.13829

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 胆管癌におけるFBXW7発現の意義と基質MCL1を介した分子メカニズム2018

    • Author(s)
      盛 彬子, 益田 邦洋, 有明 恭平, 深瀬 耕二, 大塚 英郎, 中川 圭, 元井 冬彦, 亀井 尚, 内藤 剛, 海野 倫明
    • Organizer
      日本消化器外科学会総会 73回
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胆管癌における予後予測因子としてのFBXW7発現の意義と分子メカニズム2018

    • Author(s)
      盛 彬子, 益田 邦洋, 四條 正浩, 有明 恭平, 深瀬 耕二, 大塚 英郎, 水間 正道, 森川 孝則, 林 洋毅, 中川 圭, 元井 冬彦, 藤島 史喜, 内藤 剛, 石田 孝宣, 亀井 尚, 海野 倫明
    • Organizer
      日本外科学会定期学術集会抄録集 118回
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi