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癌幹細胞の発生分化制御機構の解析

Research Project

Project/Area Number 18659209
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

坂井田 功  Yamaguchi University, 大学院・医学系研究科, 教授 (80263763)

Co-Investigator(Kenkyū-buntansha) 寺井 崇二  山口大学, 大学院・医学系研究科, 講師 (00332809)
内田 耕一  山口大学, 大学院・医学系研究科, 助教 (80397992)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2007: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords癌 / 再生医学 / 応用動物 / 発生・分化 / 癌幹細胞 / メダカ / ゼブラフィッシュ / TG / HHM
Research Abstract

我々の今までの解析よりHLH型転写制御分子HHMがヒト前癌性病変におけるマーカー蛋白になる可能性があり、HHM蛋白の発現制御、その機能解析を行っていくことで肝発癌における"肝幹細胞"と"癌幹細胞"の違いについて明らかにできると考え研究を進めてきた。また新規化合物の化学構造の解析だけでは生体内における薬物動態、効果の評価は困難であり新たな薬物スクリーニングシステムの開発が必要であると考えた。マウス、ラットの系は個体が大きく、多種の新規化合物を用いた大規模な抗癌物質のスクリーニングには不向きである。その問題点を解決するため、我々はヒトと同じ小型の脊椎動物であるメダカモデルを用いて肝発癌モデルを作成することで新たなスクリーニングシステムを構築したいと考え研究を行なった。今年度は研究成果として、HHMと同じHLH型転写制御分子のId2の肝星細胞の増殖・制御機構の解析を行なうとともに、メダカモデルを用いて肝硬変モデル、肝線維化モデルを確立し、その成果をアジア太平洋肝臓会議、アメリカ肝臓学会で報告した。これらのモデルは肝発癌を誘導する周辺環境の誘導モデルになると考える。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007 2006 Other

All Journal Article (18 results) (of which Peer Reviewed: 8 results) Presentation (2 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Serum S100b(astrocyte-specific protein)is a useful marker of hepatic encephalopathy in patients with fulminant hepatitis2008

    • Author(s)
      Isobe-Harima Y,
    • Journal Title

      Liver International 28(1)

      Pages: 146-7

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anew hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behavior disorder2008

    • Author(s)
      Isobe-Harima Y,
    • Journal Title

      Liver International 28(1)

      Pages: 117-25

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Continuous high expression of XBP1 and GRP78 is important for the survival of bone marrow cells in CCl_4-treated cirrhotic liver2008

    • Author(s)
      Marumoto Y,
    • Journal Title

      BBRC 367(3)

      Pages: 546-552

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Importance of inhibitor of DNA binding/differentiation 2 in hepatic stellatecell differentiation and proliferation.2007

    • Author(s)
      Tajima K.
    • Journal Title

      Hepatol Res. 37(8)

      Pages: 647-55

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circulating cell-free DNA as a predictive marker fbr distant metastasis of hepatitis C virus-related hepatocellular carcinoma.2007

    • Author(s)
      Tokuhisa Y.
    • Journal Title

      Br J Cancer. 97(10)

      Pages: 1399-403

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis.2007

    • Author(s)
      Jin H,
    • Journal Title

      J Gastroenterol. 42

      Pages: 475-84

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Telmisartan prevents hepatic fibro sis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-aminoacid-defined2007

    • Author(s)
      Jin H,
    • Journal Title

      BBRC 364(4)

      Pages: 801-7

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice2007

    • Author(s)
      Ishikawa T,
    • Journal Title

      Cell Tissue Res. 327

      Pages: 463-70

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a new NASH model using medaka fish2007

    • Author(s)
      Matsumoto T
    • Journal Title

      Hep Intl 1

      Pages: 226-226

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes.2006

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 323・2

      Pages: 221-231

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protein level of apolipoprotein E increased in human hepatocellular carcinoma.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Int J Oncol. 28・3

      Pages: 625-631

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics. 6・8

      Pages: 2564-2570

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Improved liver function in liver cirrhosis patients after autologous bone marrow cell infusion therapy2006

    • Author(s)
      Terai S
    • Journal Title

      Stem Cells 24・10

      Pages: 2292-2298

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon tetrachloride-induced liver fibrosis in mice.2006

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 327・3

      Pages: 463-470

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical application of bone marrow cell transplantation for liver diseases.2006

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol 41

      Pages: 93-93

    • NAID

      10017328609

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma.2006

    • Author(s)
      Iizuka N
    • Journal Title

      Anticancer Res. 26・6c

      Pages: 4713-4719

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 多施設臨床研究 : 肝硬変症に対するABMI療法の開発2006

    • Author(s)
      寺井 崇二
    • Journal Title

      日本再生医療学会誌、再生医療 5

      Pages: 79-87

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Development of a new NASH model using medaka fish.2006

    • Author(s)
      Matsumoto T
    • Journal Title

      Hepatology 44・suppl. 1

    • Related Report
      2006 Annual Research Report
  • [Presentation] The development of new drug screening system using steatohepatitis Medaka fish model induced by high fat diet2007

    • Author(s)
      Matsumoto T
    • Organizer
      The liver meeting
    • Place of Presentation
      Boston,U.S.A
    • Year and Date
      2007-11-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Analysis for the mechanism of NASH using medaka high fat diet model.Oral presentation2007

    • Author(s)
      Terai S.
    • Organizer
      APDW
    • Place of Presentation
      Kobe,Japan
    • Year and Date
      2007-10-17
    • Related Report
      2007 Annual Research Report
  • [Book] Surgery Frontier2007

    • Author(s)
      寺井 崇二
    • Publisher
      肝幹細胞の分化を制御するhuman homologue of Maid(HHM)の視点から考えた肝発癌制御機構について
    • Related Report
      2007 Annual Research Report
  • [Book] 肝幹細胞の分化を制御するhuman homologue of Maid (HHM)の視点から考えた肝発癌制御機構についてSurgery Frontier2007

    • Author(s)
      寺井 崇二
    • Publisher
      メデイカルレビュー 社
    • Related Report
      2006 Annual Research Report
  • [Book] 自己骨髄細胞を用いた肝臓再生療法の開発-基礎研究から臨床研究へ 実験医学2006

    • Author(s)
      石川 剛
    • Publisher
      羊土社
    • Related Report
      2006 Annual Research Report
  • [Remarks]

    • URL

      http://www.ichinai-yamaguchi.jp/contents4/?categoryId=8

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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