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Establishment of Pancreatic Stellate Cell Inactivation by Cell Stromal Regulation to Conquer Pancreatic Cancer

Research Project

Project/Area Number 18K08695
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionHirosaki University

Principal Investigator

Ishido Keinosuke  弘前大学, 医学研究科, 准教授 (00436023)

Co-Investigator(Kenkyū-buntansha) 工藤 大輔  弘前大学, 医学研究科, 客員研究員 (00587024)
袴田 健一  弘前大学, 医学研究科, 教授 (30271802)
脇屋 太一  弘前大学, 医学部附属病院, 講師 (50571246)
木村 憲央  弘前大学, 医学研究科, 講師 (60436029)
柿崎 育子  弘前大学, 医学研究科, 准教授 (80302024)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords膵癌 / 間質制御 / 膵癌間質 / 化学療法 / 膵臓癌 / 膵星細胞 / gemcitabine / nab-paclitaxel / 膵癌間質制御
Outline of Final Research Achievements

The purpose of this study was to establish a model for the treatment of pancreatic cancer through the regulation of pancreatic cancer cell stroma. The following four experiments have been conducted so far. (1) Experiments on the antitumor effects of gemcitabine and nab-paclitaxel (GnP), pancreatic cancer chemotherapeutic agents; (2) Experiments on the effects of GnP on cancer-assosited fibroblasts (CAF) in the pancreatic cancer stroma; (3) Correlation between the duration of GnP administration and CAF suppression rate; (4) Experiments on the effects of GnP on the lymphocyte distribution in the pancreatic cancer stroma. (4) Experiments on the effect of GnP on lymphocyte distribution in the pancreatic cancer stroma. These results support the hypothesis that GnP efficiently induces cytotoxic lymphocytes into the stroma by regulating CAFs in the pancreatic cancer stroma and making the stroma sparse, and that tumor cell damage by regulatory lymphocytes is further suppressed.

Academic Significance and Societal Importance of the Research Achievements

膵癌の5年生存率は5%程度とされ、難治性癌の一つとされています。膵癌が難治性である理由の一つに、膵癌細胞間質の厚い線維性組織であるdesmoplasiaがあげられます。Desmoplasiaは、膵癌の悪性度を担っているとされ、膵癌の新たな治療ターゲットとして注目されています。今回の成果は、この間質desmoplasiaを攻略する糸口を明らかにしたこと、および膵癌に対する新たな治療開発のきっかけとなり得る点において、学術的意義を持つと思われます。また、難治性膵癌の克服を一刻も早く達成しなくてはならない現代社会において、この成果は大きな社会的意義を持つとも思われました。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Development of a Biomarker-Based Scoring System Predicting Early Recurrence of Resectable Pancreatic Duct Adenocarcinoma.2022

    • Author(s)
      Ishido K, Kimura N, Wakiya T, Nagase H, Hara Y, Kanda T, Fujita H, Hakamada K.
    • Journal Title

      Ann Surg Oncol

      Volume: 29 Issue: 2 Pages: 1281-1293

    • DOI

      10.1245/s10434-021-10866-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterogeneity of metabolic adaptive capacity affects the prognosis among pancreatic ductal adenocarcinomas2022

    • Author(s)
      Kanda T, Wakiya T, Ishido K, Kimura N, Fujita H, Yoshizawa T, Goto S, Tatara Y, Kijima H, Hakamada K.
    • Journal Title

      J Gastroenterol

      Volume: 57 Issue: 10 Pages: 798-811

    • DOI

      10.1007/s00535-022-01898-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential updates 2018/2019: Current topics in the surgical treatment of pancreatic ductal adenocarcinoma2020

    • Author(s)
      Ishido K, Hakamada K, Kimura N, Miura T, Wakiya T.
    • Journal Title

      Ann Gastroenterol Surg

      Volume: 5 Issue: 1 Pages: 7-23

    • DOI

      10.1002/ags3.12379

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] What are the most optimal conditions for meaningful conversion surgery in unresectable pancreatic cancer?2023

    • Author(s)
      Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Yusuke Wakasa, Kenichi Hakamada
    • Organizer
      第35回日本肝胆膵外科学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Effect of preoperative nab-paclitaxel and gemcitabine on pancreatic cancer stroma2019

    • Author(s)
      Keinosuke Ishido
    • Organizer
      50th American Pancreatic Association
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impact of chemotherapy with gemcitabine and nab-paclitaxel in conversion surgery for UR-LA pancreatic cance2019

    • Author(s)
      Keinosuke Ishido
    • Organizer
      第31回肝胆膵外科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HISTOPATHOLOGICAL IMPACT IN PANCREATIC CANCER STROMA INDUCED BY NAB-PACLITAXEL2018

    • Author(s)
      石戸圭之輔、工藤大輔、木村憲央、脇屋太一、櫻庭真悟、内田知顕、袴田健一
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] HISTOPATHOLOGICAL IMPACT IN PANCREATIC CANCER STROMA INDUCED BY NAB-PACLITAXEL2018

    • Author(s)
      石戸圭之輔、工藤大輔、木村憲央、脇屋太一、袴田健一
    • Organizer
      49th American Pancreatic Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 切除不能局所進行膵癌におけるConversion surgeryをゴールとした治療戦略2018

    • Author(s)
      石戸圭之輔、工藤大輔、木村憲央、脇屋太一、櫻庭真悟、袴田健一
    • Organizer
      第118回日本外科学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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