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A mechanism how mTOR inhibitor potentiate the effect of gemcitabine against pancreatic cancer

Research Project

Project/Area Number 15K18923
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionKyushu University

Principal Investigator

Murakami Yuichi  九州大学, 薬学研究院, 共同研究員 (60464385)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsmTOR / Gemcitabine
Outline of Final Research Achievements

Gemcitabine, a difluorinated deoxy cytidine analogue, shows clinical activity against various human solid tumors, including pancreas. Clinical application of the gemcitabine-base adjuvant therapy has improved progression-free survival of patients with pancreas cancer. Many clinical trials for gemcitabine-based chemotherapy with various drugs has been applied to patients with pancreas cancer. However, its benefit is modest.
In this study, we screened anticancer agents that can potentiate gemcitabine against human pancreatic cancer cells. We found that combination of mTOR inhibitor and GEM synergistically inhibit cell growth in pancreatic cancer cells. We also elucidated mechanism how mTOR inhibitors can augment the cytotoxic effect of gemcitabine. Inhibitor of mTOR induced CDA mRNA expression via stabilization of CDA mRNA.
Therefore, mTOR inhibitor might potentiate the therapeutic efficacy of gemcitabine through modification of nucleoside metabolism in pancreatic cancer cells.

Report

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

    (5 results)

All 2017 2016 2015 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Breast cancer resistance to antiestrogens is enhanced by increased ER degradation and ERBB2 expression2017

    • Author(s)
      Tomohiro Shibata, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Satoshi Hattori, Chihiro Fukumitsu, Yuichi Murakami, Ryuji Takahashi, Uhi Toh, Ken-ichi Ito, Shigehiro Ohdo, Maki Tanaka, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono
    • Journal Title

      Cancer Research

      Volume: 77 Issue: 2 Pages: 545-556

    • DOI

      10.1158/0008-5472.can-16-1593

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Overcoming drug resistance to receptor tyrosine kinase inhibitors: Learning from lung cancer.2016

    • Author(s)
      Kuwano M, Sonoda K, Murakami Y, Watari K, Ono M.
    • Journal Title

      Pharmacol Ther

      Volume: 161 Pages: 97-110

    • DOI

      10.1016/j.pharmthera.2016.03.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of mTOR Ser2481 is a key target limiting the efficacy of rapalogs for treating hepatocellular carcinoma.2016

    • Author(s)
      Watari K, Nishitani A, Shibata T, Noda M, Kawahara A, Akiba J, Murakami Y, Yano H, Kuwano M, Ono M.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 30 Pages: 47403-47417

    • DOI

      10.18632/oncotarget.10161

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] ゲムシタビンとmTOR阻害剤の併用による相乗的な膵癌の増殖抑制効果のメカニズム2015

    • Author(s)
      村上雄一, 渡公佑, 柴田智博, 河原明彦, 鹿毛政義, 桑野信彦, 小野眞弓
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://shuyo.phar.kyushu-u.ac.jp/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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