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Targeting strategy to inhibit liver metastasis for pancreatic cancer

Research Project

Project/Area Number 15K10183
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

HORI YUICHI  神戸大学, 保健学研究科, 教授 (80248004)

Co-Investigator(Kenkyū-buntansha) 清水 一也  神戸大学, 保健学研究科, 保健学研究員 (50335353)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膵臓がん / がん幹細胞 / 肝臓転移 / エクソソーム / 膵がん / 肝転移 / 抗がん剤耐性 / 膵臓外科学 / 癌幹細胞 / 膵臓癌
Outline of Final Research Achievements

Pancreatic cancer shows an aggressive phenotype with a dismal prognosis despite of multimodal therapy. Notably, remote organ metastasis such as liver metastasis is a life-threatening problem. Previously, we have already established several human pancreatic cancer cell line (Shimizu, Hori et al.,PLoS One, 2013).In this study, we aimed to reconstruct early stage of liver metastasis by 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. We found that micro-vesicles called as “exosome” from both mouse and human pancreatic cancer stem cells had a pivotal role in early stage of liver metastasis in vivo. These results indicate that this system might be potent strategy to inhibit liver metastasis for pancreatic cancer.

Report

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

    (20 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 9 results) Book (2 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
      2017 Annual Research Report 2016 Research-status 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
  • [Presentation] Establishment of novel gemcitabine-resistant mouse pancreatic cancer cell line2017

    • Author(s)
      Yusuke Kadoi, Kazuya Simizu, Yukie Takegaki, Ayano Nishimura, Makoto Miyoshi, Tsuyoshi Akagi, Ken Sasai, Yuichi Hori
    • Organizer
      アメリカ膵臓学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gemcitabine Enhances Kras-MEK-induced Matrix Metalloproteinase-10 Expression in Gemcitabine-resistant Pancreatic Tumor-initiating Cells2017

    • Author(s)
      Ayano Nishimura, Kazuya Shimizu, Yusuke Kadoi, Yukie Takegaki,Makoto Miyoshi,Yuichi Hori
    • Organizer
      アメリカ膵臓学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oncogene transduced mouse pancreatic stem/progenitor cells show phenotypes similar to tumor-initiating cells2017

    • Author(s)
      Yukie Takegaki, Kazuya Shimizu, Yusuke Kadoi, Ayano Nishimura, Makoto Miyoshi, Tsuyoshi Akagi, Ken Sasai, Yuichi Hori
    • Organizer
      アメリカ膵臓学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗がん剤Gemcitabine耐性マウス膵癌細胞の樹立と解析2017

    • Author(s)
      角井祐介、清水一也、竹垣普惠、西村綾乃、三好真琴、赤城剛、笹井研、 堀裕一
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗がん剤耐性膵癌細胞ではヒストンアセチル化を介したKras-MEK-Matrix Metalloproteinase-10シグナルがGemcitabine投与で増強する2017

    • Author(s)
      西村綾乃、清水一也、角井祐介、竹垣普惠、三好真琴、堀裕一
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] がん遺伝子を導入したマウス膵臓組織幹細胞はがん幹細胞様の表現型を示す2017

    • Author(s)
      竹垣普惠、清水一也、角井祐介、西村綾乃、三好真琴、赤城剛、笹井研、 堀裕一
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [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 Research-status Report
  • [Presentation] Oncogene-mediated Mouse Pancreatic Progenitor Cells Show Cancer Stem Cell Phenotype2016

    • Author(s)
      Ise1 Y, Shimizu K, Uenoyama K, Nishiyama S, Tsuchida, Y, HoriY
    • Organizer
      第20回 International Association of Pancreatology
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [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 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gemcitabine Enhances Kras-MEK-induced Matrix Metalloproteinase-10 Expression in Gemcitabine-resistant Pancreatic Tumor-initiating Cells2016

    • 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 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel therapeutic approach for gemcitabine-resistant human pancreatic cancer2015

    • Author(s)
      Tsuchida Y, Nishiyama T, Nishiyama S, Hori Y
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      愛知・名古屋
    • Year and Date
      2015-10-07
    • Related Report
      2015 Research-status Report
  • [Presentation] Interaction between laminin and Notch pathway in the microenvironment of pancreatic cancer cells2015

    • Author(s)
      Nishiyama S, Nishiyama T, Tsuchida Y, Hori Y
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      愛知・名古屋
    • Year and Date
      2015-10-07
    • Related Report
      2015 Research-status 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] Uenoyama K, Shimizu K, Nishiyama T, Yamasaki C, Hori Y2015

    • Author(s)
      Pancreatic Ductal Adenocarcinoma Primes the Adjacent Normal Ducts for a Precancerous Phenotype
    • 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] nsulin-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
  • [Book] 新膵臓病学2016

    • Author(s)
      下瀬川編 堀裕一
    • Total Pages
      515
    • Publisher
      南江堂
    • Related Report
      2016 Research-status Report
  • [Book] 新膵臓病学2016

    • Author(s)
      堀裕一
    • Publisher
      南江堂
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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