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Development of novel molecular targeted therapy for pancreatic cancer with Notch / Sox9 signal inhibitor

Research Project

Project/Area Number 15K18439
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionChiba University

Principal Investigator

Kagawa Shingo  千葉大学, 医学部附属病院, 助教 (90507302)

Research Collaborator Higashihara Taku  千葉大学, 大学院医学研究院
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords膵臓癌 / Sox9 / 癌幹細胞 / Pancreatic cancer / Chemoresistance / Notch signal / Sox9と癌幹細胞
Outline of Final Research Achievements

Pancreatic cancer is aggressive disease and in many patients it recur even after curative resection. It is also known that it will become chemo-resistance after treatment. We focused on the transcription factor Sox9, which is thought to regulate differentiation at the developmental stage of the pancreas, and found that the intensity of Sox9 expression was associated with the prognosis after surgery. We analyzed the characteristics of pancreatic cancer cell line and showed the strength of Sox 9 is associated with chemo resistance and such cells have cancer stem cell properties. Furthermore, in a mouse subcutaneous tumor model, Sox9 was associated with tumorigenicity, indicating that Sox9 could be a target for treatment of pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

癌の悪性度や治療抵抗性を特徴とする癌幹細胞の概念に近年注目が集まっており、このような癌幹細胞を治療標的とすることが必要と考えられている。一方、このような癌幹細胞を生体内で特徴づけるマーカーを見出すことや、如何にこのような細胞を除去するかは、膵癌を克服するための重要な課題である。今回我々は、Sox9が膵癌幹細胞の維持に貢献しており、治療対象となり得ることを示した。未だSox9をターゲットとした治療方法の開発は研究段階であるが、難治性癌である膵臓癌治療への糸口を示すことができたと考える

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis.2017

    • Author(s)
      Higashihara T, Yoshitomi H, Nakata Y, Kagawa S, Takano S, Shimizu H, Kato A, Furukawa K, Ohtsuka M, Miyazaki M.
    • Journal Title

      Pancreas

      Volume: 46 Pages: 1296-1304

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] SOX9 induces chemo-resistance in pancreatic cancer cells and its high expression predicts poor prognosis2016

    • Author(s)
      S Kagawa, T Higashihara, H Yoshitomi, S Takano, H Shimizu, M Ohtsuka, A Kato, K Furukawa and M Miyazaki
    • Organizer
      AACR Special Conference on Pancreatic Cancer
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] SOX9 induces chemo-resistance in pancreatic cancer cells and its high expression predicts poor prognosis2016

    • Author(s)
      shingo kagawa, taku higasihara, hideyuki yoshitomi, shigetsugu takano, hiroaki shimizu, masayuki ohtsuka, atsushi kato, katsunori furukawa, masaru miyazaki
    • Organizer
      AACR Special Conference on Pancreatic Cancer
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2016-05-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵癌におけるSox9による抗癌剤耐性メカニズムの解明2016

    • Author(s)
      東原琢、吉富秀幸、賀川真吾、高野重紹、清水宏明、大塚将之、加藤厚、古川勝規、高屋敷吏、久保木知、鈴木大亮、酒井望、野島広之、宮崎勝
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場 (大阪府大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 膵癌におけるSox9による 抗癌剤耐性メカニズムの解明2016

    • Author(s)
      東原琢、吉富秀幸、賀川真吾、高野重紹、清水宏明、大塚将之、加藤厚、古川勝規、高屋敷吏、久保木知、鈴木大亮、酒井望、野島広之、宮崎勝
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵癌におけるSox9による抗癌剤耐性メカニズムの解明2015

    • Author(s)
      東原 琢、賀川真吾、吉富秀幸、高野重紹、清水宏明、大塚将之、加藤 厚、 古川勝規、高屋敷 吏、久保木 知、岡村大樹、鈴木大亮、酒井 望、宮崎 勝
    • Organizer
      第46回日本膵臓学会大会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-06-19
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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