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The development of novel therapy for hepatocellular carcinoma using RXR-alpha genetically modified mice

Research Project

Project/Area Number 15K19320
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionGifu University

Principal Investigator

Sakai Hiroyasu  岐阜大学, 医学部附属病院, 助教 (40738259)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝細胞癌 / レチノイド / RXRα / 核内受容体 / 肝化学発癌
Outline of Final Research Achievements

The role of phosphorylated-RXRa (p-RXRa) on the development of liver tumorigenesis was investigated by using RXRa genetically modified mice. The transgenic mice were more susceptible to the treatment of diethylnitrosamine (DEN), and developed more liver tumors compared to the control mice. In addition, liver tumors observed in the transgenic mice had more PCNA positive cells, indicating that those tumors had high proliferative capacity. Besides, increased mRNA and protein expressions of cyclin D1 were observed in transgenic liver tumors, and the protein expressions of either p-Rb or PCNA, both of which are the downstream targets of cyclin D1, were also increased in those liver tumors. Interestingly, the transgenic liver tumors had more b-catenin protein expression, which regulates the expression of cyclin D1. Thus, these results indicate that the p-RXRa is associated with the development of DEN-induced liver tumorigenesis by promoting b-catenin/cyclin D1 signaling pathway.

Report

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

    (13 results)

All 2017 2016 2015

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Preventative Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice2017

    • Author(s)
      Fukuta K, Shirakami Y, Maruta A, Obara K, Iritani S, Nakamura N, Kochi T, Kubota M, Sakai H, Tanaka T, Shimizu M
    • Journal Title

      Int J Mol Sci

      Volume: 18(2) Issue: 2 Pages: 413-413

    • DOI

      10.3390/ijms18020413

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Catechins and Its Role in Chronic Disease2016

    • Author(s)
      Shirakami Y, Sakai H, Kochi T, Seishima M, Shimizu M
    • Journal Title

      Adv Exp Med Biol

      Volume: 929 Pages: 67-90

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.2016

    • Author(s)
      Miyazaki T, Shirakami Y, Kubota M, Ideta T, Kochi T, Sakai H, Tanaka T, Moriwaki H, Shimizu M.
    • Journal Title

      Oncotarget

      Volume: - Issue: 9 Pages: 10448-10458

    • DOI

      10.18632/oncotarget.7249

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chemoprevention of obesity-related liver carcinogenesis by using pharmaceutical and nutraceutical agents.2016

    • Author(s)
      Sakai H, Shirakami Y, Shimizu M.
    • Journal Title

      World J Gastroenterol

      Volume: 22(1) Issue: 1 Pages: 394-406

    • DOI

      10.3748/wjg.v22.i1.394

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preventive effects of astaxanthin on diethylnitrosamine-induced liver tumorigenesis in C57/BL/KsJ-db/db obese mice.2016

    • Author(s)
      Ohno T, Shimizu M, Shirakami Y, Miyazaki T, Ideta T, Kochi T, Kubota M, Sakai H, Tanaka T, Moriwaki H.
    • Journal Title

      Hepatol Res.

      Volume: 46(3) Issue: 3 Pages: 201-209

    • DOI

      10.1111/hepr.12550

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice.2015

    • Author(s)
      Ideta T, Shirakami Y, Miyazaki T, Kochi T, Sakai H, Moriwaki H, Shimizu M.
    • Journal Title

      Int J Mol Sci.

      Volume: 16(12) Issue: 12 Pages: 29207-29218

    • DOI

      10.3390/ijms161226156

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Retinoid roles in blocking hepatocellular carcinoma.2015

    • Author(s)
      Shirakami Y, Sakai H, Shimizu M.
    • Journal Title

      Hepatobiliary Surg Nutr.

      Volume: 4(4) Pages: 222-228

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemopreventive potential of green tea catechins in hepatocellular carcinoma.2015

    • Author(s)
      Shimizu M, Shirakami Y, Sakai H, Kubota M, Kochi T, Ideta T, Miyazaki T, Moriwaki H.
    • Journal Title

      Int J Mol Sci.

      Volume: 16(3) Issue: 3 Pages: 6124-6139

    • DOI

      10.3390/ijms16036124

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The role of the phosphorylated RXR-alpha on cellular proliferation and liver tumorigenesis2016

    • Author(s)
      Hiroyasu Sakai, Yohei Shirakami, Masahito Shimizu
    • Organizer
      AACR annual meeting 2016
    • Place of Presentation
      ニューオーリンズ(アメリカ合衆国)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of the phosphorylated RXRα on Diethylnitrosamine-induced liver tumorigenesis in mice2016

    • Author(s)
      Hiroyasu Sakai, Yasuhiro Yamada, Yohei Shirakami, Akira Hara, and Masahito Shimizu
    • Organizer
      APASL 2016 in Tokyo
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of the phosphorylated RXRα on Diethylnitrosamine-induced liver tumorigenesis in mice2015

    • Author(s)
      Hiroyasu Sakai, Yasuhiro Yamada, Yohei Shirakami, Akira Hara, and Masahito Shimizu
    • Organizer
      第3回国際レチノイド研究会
    • Place of Presentation
      岐阜グランドホテル(岐阜)
    • Year and Date
      2015-10-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of the phosphorylated RXRα on Diethylnitrosamine-induced liver tumorigenesis in mice2015

    • Author(s)
      Hiroyasu Sakai, Yasuhiro Yamada, Yohei Shirakami, Akira Hara, and Masahito Shimizu
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] The role of the phosphorylated RXRα on cellular proliferation and liver tumorigenesis in mice2015

    • Author(s)
      Hiroyasu Sakai, Yohei Shirakami, and Masahito Shimizu
    • Organizer
      2015 AACR annual meeting
    • Place of Presentation
      フィラデルフィア(アメリカ合衆国)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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

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