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Development of new anti-fibrotic therapeutic drug for targeting Wnt signal

Research Project

Project/Area Number 15K09037
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Metropolitan Komagome Hospital (Clinical research laboratory)

Principal Investigator

Kimura Kiminori  東京都立駒込病院(臨床研究室), 肝臓内科, 部長 (70397339)

Co-Investigator(Kenkyū-buntansha) 大澤 陽介  国立研究開発法人国立国際医療研究センター, その他部局等, 第三肝疾患室医長 (60447787)
Co-Investigator(Renkei-kenkyūsha) KOHARA Michinori  東京都医学総合研究所, シニア研究員 (10250218)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords線維化 / 肝硬変 / Wnt阻害剤 / PRI-724 / MMP / wnt シグナル / HCV
Outline of Final Research Achievements

Liver cirrhosis is a condition caused by accumulation of excessive fibers in tissues, and when fibrosis occurs, various essential functions for life maintenance are deteriorated, leading to a dysfunction state. In the case of the liver, hepatic failure occurs and synthesis of proteins, which is an important function of liver function, and detoxification of harmful substances are reduced. A therapeutic drug that improves the liver function that has liver failure due to fibrosis at present is not put to practical use. Based on this situation, it is urgent to develop therapeutic drugs to improve liver fibrosis. In this study, we focused on Wnt signal and administered PRI-724 in mouse hepatic fibrosis model using Wnt inhibitor PRI-724. We showed that PRI-724 has anti-fibrotic treatment effect.

Report

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

    (5 results)

All 2018 2017 2015

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

  • [Journal Article] Tumor Necrosis Factor-a-Mediated Hepatocyte Apoptosis Stimulates Fibrosis in the Steatotic Liver in Mice2018

    • Author(s)
      Yosuke Osawa,1,2 Ekumi Kojika,1 Yukiko Hayashi,1 Masamichi Kimura,1 Koji Nishikawa,1 Sachiyo Yoshio,2 Hiroyoshi Doi,2 Tatsuya Kanto,2 and Kiminori Kimura1
    • Journal Title

      HEPATOLOGY COMMUNICATIONS

      Volume: 2 Issue: 4 Pages: 407-420

    • DOI

      10.1002/hep4.1158

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial.2017

    • Author(s)
      2.Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, Imamura J, Osawa Y, Kimura M, Nishikawa K, Okusaka T, Morita S, Inoue K, Kanto T, Todaka K, Nakanishi Y, Kohara M, Mizokami M.
    • Journal Title

      EBioMedicine

      Volume: 23 Pages: 79-87

    • DOI

      10.1016/j.ebiom.2017.08.016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] M2 macrophages play critical roles in progression of inflammatory liver disease in hepatitis C virus transgenic mice.2015

    • Author(s)
      1.Ohtsuki T, Kimura K, Tokunaga Y, Tsukiyama-Kohara K, Tateno C, Hayashi Y, Hishima T, Kohara M
    • Journal Title

      J Virol

      Volume: Oct 14;90(1) Issue: 1 Pages: 300-7

    • DOI

      10.1128/jvi.02293-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of Cyclic Adenosine Monophosphate (cAMP)-response Element-binding Protein (CREB)- binding Protein (CBP)/β-Catenin Reduces Liver Fibrosis in Mice.2015

    • Author(s)
      Osawa Y, Oboki K, Imamura J, Kojika E, Hayashi Y, Hishima T, Saibara T, Shibasaki F, Kohara M, Kimura K
    • Journal Title

      EBioMedicine

      Volume: 2 Issue: 11 Pages: 1751-8

    • DOI

      10.1016/j.ebiom.2015.10.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C.2015

    • Author(s)
      Ezzikouri S, Kimura K, Sunagozaka H, Kaneko S, Inoue K, Nishimura T, Hishima T, Kohara M, Tsukiyama-Kohara K.
    • Journal Title

      EBioMedicine

      Volume: Apr 13;2(6) Issue: 6 Pages: 604-12

    • DOI

      10.1016/j.ebiom.2015.04.007

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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

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