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Reconstruction of pancreatic cancer microenvironment

Research Project

Project/Area Number 26462059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKobe University

Principal Investigator

SHIMIZU KAZUYA  神戸大学, 保健学研究科, 保健学研究員 (50335353)

Co-Investigator(Kenkyū-buntansha) 堀 裕一  神戸大学, 保健学研究科, 教授 (80248004)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膵臓がん / がん幹細胞 / 胚性幹細胞 / 膵臓外科学 / 微小環境 / 膵臓癌 / 癌微小環境 / iPS / がん微小環境
Outline of Final Research Achievements

Pancreatic cancer shows an aggressive phenotype with a dismal prognosis despite of multimodal therapy. Notably, neural invasion is a life-threatening problem. In this study, we aimed to reconstruct microenvironment around pancreatic cancer cells. First, we developed novel mouse pancreatic cancer stem cells by introducing mutated KRAS, mutated p53, and CDK4 oncogenes common in human pancreatic cancer to mouse pancreatic stem/progenitor cells. Then, we established co-culture system between multipotent stem cells and pancreatic cancer cells. We found that both mouse embryonic stem cells and human induced pluripotent stem cells could differentiate into neural cells such as neuron or glia cells in vitro and in vivo. These results indicate that this system might be potent tool to develop novel treatment strategy for pancreatic cancer.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Journal Article] Gemcitabine enhances Kras-MEK-induced matrix metalloproteinase-10 expression via histone acetylation in gemcitabine-resistant pancreatic tumor-initiating cells.2017

    • Author(s)
      Shimizu K, Nishiyama T, Hori Y
    • Journal Title

      Pancreas

      Volume: 46 Issue: 2 Pages: 268-275

    • DOI

      10.1097/mpa.0000000000000744

    • NAID

      120005970750

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gemcitabine Enhances Kras-MEK-induced Matrix Metalloproteinase-10 Expression via Histone Acetylation in Gemcitabine-resistant Pancreatic Tumor-initiating Cells2016

    • Author(s)
      Shimizu K, Nishiyama T, Hori Y
    • Journal Title

      Pancreas

      Volume: 未定

    • NAID

      120005970750

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Novel cell line and animal model for human biliary tract cancer2016

    • Author(s)
      Shinozaki K, Ajiki T, Murakami S, Matsumoto T, Akita M, Shimizu K, Hori Y
    • Journal Title

      Medical Research Archieves

      Volume: 未定

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a novel cell line from intraductal papillary neoplasm of the bile duct.2014

    • Author(s)
      Murakami S, Ajiki T, Hori Y, Okazaki T, Fukumoto T, Ku Y
    • Journal Title

      Anticancer Res

      Volume: 34 Pages: 2203-2210

    • NAID

      120005970749

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵腫瘍は隣接する正常膵管に異型性を誘導する2016

    • Author(s)
      堀裕一
    • Organizer
      第116回日本外科学会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
  • [Presentation] Oncogene-mediated Mouse Pancreatic Progenitor Cells Show Cancer Stem Cell Phenotype2016

    • Author(s)
      Ise Y, Shimizu K, Uenoyama K,Nishiyama S, Tsuchida Y, Hori Y
    • Organizer
      第20回 International Association of Pancreatology
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] Co-culture with Pancreatic Ductal Adenocarcinoma Cells Converts Acinar Cells to Ductal Phenotype2016

    • Author(s)
      Nishiyama S, Shimizu K, Uenoyama K, Ise Y, Tsuchida Y, Hori Y
    • Organizer
      第20回 International Association of Pancreatology
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] Gemcitabine enhances Kras-MEK-induced matrix metalloproteinase-10 expression via histone acetylation in gemcitabine-resistant pancreatic tumor-initiating cells.2016

    • Author(s)
      Tsuchida Y, Shimizu K, Uenoyama K ,Ise Y, Nishiyama S, Hori Y
    • Organizer
      第20回 International Association of Pancreatology
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] Oncogene-mediated Mouse Pancreatic Stem Cell Shows Pancreatic Cancer Stem Cell Phenotype2015

    • Author(s)
      Nishiyama T, Shimizu K, Uenoyama K, Yamasaki C, Hori Y
    • Organizer
      第19回国際膵臓学会
    • Place of Presentation
      中国・上海
    • Year and Date
      2015-08-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pancreatic Ductal Adenocarcinoma Primes the Adjacent Normal Ducts for a Precancerous Phenotype2015

    • Author(s)
      Uenoyama K, Shimizu K, Nishiyama T, Yamasaki C, Hori Y
    • Organizer
      第19回国際膵臓学会
    • Place of Presentation
      中国・上海
    • Year and Date
      2015-08-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Insulin-Producing Cells Derived from the Immortalized Pancreatic Stem Cells2015

    • Author(s)
      Yamasaki C, Shimizu K, Uenoyama K, Nishiyama T, Hori Y
    • Organizer
      第19回国際膵臓学会
    • Place of Presentation
      中国・上海
    • Year and Date
      2015-08-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 幹細胞マーカーラベルマウスを用いた膵再生医療研究2014

    • Author(s)
      片山南詩、堀裕一
    • Organizer
      第61回日本臨床検査医学会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡)
    • Year and Date
      2014-11-22 – 2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Possible involvement of Notch pathway of stromal cells in the maintenance of pancreatic cancer cells2014

    • Author(s)
      Takuma Miura, Takaaki Nishiyama, Yuichi Hori
    • Organizer
      第73回日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Oncogene-mediated mouse pancreatic stem/progenitor cells produce pancreatic ductal adenocarcinoma phenotypes in vivo2014

    • Author(s)
      Takaaki Nishiyama, Takuma Miura, Yuichi Hori
    • Organizer
      第73回日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖尿病の再生医療を目指した不死化膵臓組織幹細胞の可能性2014

    • Author(s)
      山崎千寛、平井里奈、堀裕一
    • Organizer
      第45回日本膵臓学会
    • Place of Presentation
      北九州国際会議場(福岡県・小倉)
    • Year and Date
      2014-04-10 – 2014-04-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 抗がん剤耐性膵癌細胞の樹立とその解析2014

    • Author(s)
      平井里奈、山崎千寛、堀裕一
    • Organizer
      第45回日本膵臓学会
    • Place of Presentation
      北九州国際会議場(福岡県・小倉)
    • Year and Date
      2014-04-10 – 2014-04-11
    • Related Report
      2014 Research-status Report
  • [Book] 南江堂2016

    • Author(s)
      下瀬川徹編 堀裕一
    • Total Pages
      515
    • Publisher
      新膵臓病学
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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