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The role of nuclear receptor CAR in the pathogenesis of intrahepatic cholangiocellular carcinoma

Research Project

Project/Area Number 17K08387
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionGunma University

Principal Investigator

Kakizaki Satoru  群馬大学, 大学院医学系研究科, 講師 (80344935)

Co-Investigator(Kenkyū-buntansha) 山崎 勇一  群馬大学, 医学部附属病院, 助教 (00582404)
堀口 昇男  群馬大学, 大学院医学系研究科, 助教 (10550022)
井上 裕介  群馬大学, 大学院理工学府, 准教授 (90304302)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords核内受容体 / CAR / 胆管癌 / 化学発癌 / CAR / 肝内胆管癌
Outline of Final Research Achievements

The aim of this study was to investigate the role of nuclear receptor CAR (constitutive androstane receptor) in the pathogenesis of intrahepatic cholangiocarcinoma. Thioacetamide (TAA) was administered to CAR knockout and wild-type mice to create a chemical carcinogenic model of cholangiocarcinoma. Cholangiocarcinoma developed after 24-weeks TAA administration. However, there were no significant differences between the two groups. In the chemical carcinogenesis model of hepatocellular carcinoma, it has been reported that carcinogenesis is significantly suppressed in CAR knockout mice. However, it is not suppressed in the TAA-induced cholangiocarcinoma model used in this study.

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌(肝細胞由来)の化学発癌モデルでは、核内レセプターCARの発癌への関与が報告されている。同様に肝臓に発生し、胆管細胞由来の肝内胆管癌においてCARの関与の有無を検討した。Thioacetamide (TAA) による胆管癌モデルで検討したが、CARの関与は明らかでなかった。胆管癌モデルにおいてCARの関与の有無を検討したことは、胆管癌及びCARの病態生理を考える上で意義があったと考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The influence of the long‐term chemical activation of the nuclear receptor pregnane X receptor (PXR) on liver carcinogenesis in mice2021

    • Author(s)
      Ryota Shizu, Mai Ishimura, Sumihito Nobusawa, Takuomi Hosaka, Takamitsu Sasaki, Satoru Kakizaki, Kouichi Yoshinari
    • Journal Title

      Archives of Toxicology

      Volume: 95 Issue: 3 Pages: 1089-1102

    • DOI

      10.1007/s00204-020-02955-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lenvatinib for Hepatocellular Carcinoma: A Literature Review2021

    • Author(s)
      Hatanaka Takeshi、Naganuma Atsushi、Kakizaki Satoru
    • Journal Title

      Pharmaceuticals

      Volume: 14 Issue: 1 Pages: 36-36

    • DOI

      10.3390/ph14010036

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study.2020

    • Author(s)
      Hatanaka T, Kakizaki S, Nagashima T, Namikawa M, Tojima H, Shimada Y, Takizawa D, Naganuma A, Arai H, Sato K, Harimoto N, Shirabe K, Uraoka T.
    • Journal Title

      Hepatol Res.

      Volume: 50 Issue: 3 Pages: 382-395

    • DOI

      10.1111/hepr.13460

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Constitutive androstane receptor and pregnane X receptor cooperatively ameliorate DSS-induced colitis.2019

    • Author(s)
      Uehara D, Tojima H, Kakizaki S, Yamazaki Y, Horiguchi N, Takizawa D, Sato K, Yamada M, Uraoka T.
    • Journal Title

      Dig Liver Dis.

      Volume: Feb;51(2) Issue: 2 Pages: 226-235

    • DOI

      10.1016/j.dld.2018.10.008

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A feasibility study of high-dose hypofractionated carbon ion radiation therapy using four fractions for localized hepatocellular carcinoma measuring 3cm or larger.2019

    • Author(s)
      Shibuya K, Ohno T, Katoh H, Okamoto M, Shiba S, Koyama Y, Kakizaki S, Shirabe K, Nakano T.
    • Journal Title

      Radiother Oncol.

      Volume: 132 Pages: 230-235

    • DOI

      10.1016/j.radonc.2018.10.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indirect activation of pregnane X receptor in the induction of hepatic CYP3A11 by high-dose rifampicin in mice.2017

    • Author(s)
      Yamasaki Y, Kobayashi K, Inaba A, Uehara D, Tojima H, Kakizaki S, Chiba K.
    • Journal Title

      Xenobiotica.

      Volume: 11 Issue: 11 Pages: 1-8

    • DOI

      10.1080/00498254.2017.1400128

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Induction of hepatocyte-specific gene expression by a novel nuclear receptor.2017

    • Author(s)
      Sasaki S, Urabe M, Maeda T, Suzuki J, Irie R, Kakizaki S, Gonzalez FJ, Inoue Y.
    • Organizer
      4th International Symposium of Gunma University Medical Innovation
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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