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Characterization of circulating tumor cells and its application of the treatment selection for hepatocellular carcinoma

Research Project

Project/Area Number 24592008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

BEPPU toru  熊本大学, 医学部附属病院, 特任教授 (70301372)

Co-Investigator(Kenkyū-buntansha) OKABE Hirohisa  熊本大学, 医学部附属病院, 診療助手 (40573621)
ANDO Yukio  熊本大学, 大学院生命科学研究部, 教授 (20253742)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血中癌細胞 / 上皮間葉形質転換 (EMT) / 肝細胞癌 / CD44 / Anoikis / CD45-CD44+CD90+細胞 / 血中癌幹細胞 / 血中癌細胞(CTC) / CD44+CD90+細胞 / 上皮間葉形質転換
Outline of Final Research Achievements

As the characteristics of hepatocellular carcinoma (HCC), CD44 is correlated with mesenchymal characteristics of HCC and is present downstream of TGF-β signals. After hepatic resection, CD44-positive HCC patients showed poor prognosis (Mima K, Beppu T, et al. Cancer Res 2012). Furthermore we demonstrated that sphere forming ability was very high in CD44 + cells compared to CD44- cells. These characteristics are regulated by Twist1 controlling the mesenchymal characteristics and we confirmed the co-localization of the expression of CD44, Vimentin, Twist1 in human HCC primary tumors (Okabe H, Beppu T, et al. Br J Cancer 2014). As compared with the CD45-CD44 + CD90 + HCC cells in the tissue, the expression of the CD44, and Vimentin in the CD45-CD44 + CD90 + HCC cells in the blood rose markedly, and expression of E-cadherin was dramatically declined. Finally it was confirmed that CD44 is useful as EMT marker for HCC (Okabe H, Beppu T, et al. Br J Cancer 2014).

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (5 results)

  • [Journal Article] LINE-1 Methylation Level and Patient Prognosis in a Database of 208 Hepatocellular Carcinomas2015

    • Author(s)
      Harada K, Baba Y, Ishimoto T, Chikamoto A, Kosumi K, Hayashi H, Nitta H, Hashimoto D, Beppu T, Baba H
    • Journal Title

      Ann Surg Oncol

      Volume: 22(4) Issue: 4 Pages: 1280-7

    • DOI

      10.1245/s10434-014-4134-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma2014

    • Author(s)
      Okabe H, Delgado E, Lee JM, Yang J, Kinoshita H, Hayashi H, Tsung A, Behari J, Beppu T, Baba H, Monga SP
    • Journal Title

      PLOS ONE

      Volume: 9(6) Issue: 6 Pages: e98817-e98817

    • DOI

      10.1371/journal.pone.0098817

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma.2014

    • Author(s)
      Okabe H, Ishimoto T, Mima K, Nakagawa S, Hayashi H, Kuroki H, Imai K, Nitta H, Saito S, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Nagano O, Beppu T, Saya H and Baba H
    • Journal Title

      Br J Cancer

      Volume: 印刷中 Issue: 4 Pages: 958-66

    • DOI

      10.1038/bjc.2013.759

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CYLD down-regulation might berelated to tumor development in HCCpatients.2013

    • Author(s)
      Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Yokoyama N, Ishiko T,Shinriki S, Jono H, Ando Y, Baba H
    • Journal Title

      Mol Clin Oncol 1

      Volume: 1 Issue: 2 Pages: 309-314

    • DOI

      10.3892/mco.2013.68

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancer of Zeste Homolog 2 (EZH2) Promotes Progression of Cholangiocarcinoma Cells by Regulating Cell Cycle and Apoptosis.2013

    • Author(s)
      Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H.
    • Journal Title

      Ann Surg Oncol

      Volume: 3 Issue: S3 Pages: 667-675

    • DOI

      10.1245/s10434-013-3135-y

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epithelial-mesenchymal transition expression profiles as prognostic factor for disease-free survival in hepatocellular carcinoma: clinical significance of transforming growth factor-β signaling.2013

    • Author(s)
      Mima K, Hayashi H, Kuroki H, Nakagawa S, Okabe H, Chikamoto A, Watanabe M, Beppu T, Baba H.
    • Journal Title

      Oncol Lett

      Volume: 5 Pages: 149-154

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] High CD44s expression is associatedwith the EMT expression profile andintrahepatic dissemination ofhepatocellular carcinoma after localablation therapy.2013

    • Author(s)
      Mima K, Hayashi H,Imai K, Kuroki H,Shigaki N, Nakagawa S, Okabe H,Chikamoto A, Watanabe M, Beppu T, BabaH
    • Journal Title

      J Hepatobiliary Pancreatic Surg

      Volume: 20 Issue: 4 Pages: 429-34

    • DOI

      10.1007/s00534-012-0580-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with2012

    • Author(s)
      Mima K, Beppu T, et al.
    • Journal Title

      Cancer Research

      Volume: 72 Pages: 3414-3423

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The expression levels of CD44v6 arecorrelated with the invasiveness ofhepatocellular carcinoma in vitro,but do not appear to be clinicallysignificant.2012

    • Author(s)
      Mima K, Okabe H, Ishimoto T, HayashiH, Nakagawa S, Kuroki H, Miyake K,Takamori H
    • Journal Title

      Oncol Lett

      Volume: 5 Issue: 5 Pages: 1047-1051

    • DOI

      10.3892/ol.2012.611

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba2012

    • Author(s)
      Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba
    • Journal Title

      Oncol Rep

      Volume: 29 Issue: 2 Pages: 685-9

    • DOI

      10.3892/or.2012.2162

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver hanging maneuver decrease blood loss and operative2012

    • Author(s)
      Beppu T, et al.
    • Journal Title

      Hepatogastroenterology

      Volume: 59 Pages: 542-545

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝細胞癌における予後因子であるTAZを制御するmicroRNAの同定2014

    • Author(s)
      東 孝暁
    • Organizer
      第25回日本消化器癌発生学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-13 – 2014-11-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝細胞癌におけるLINE-1メチル化レベルの網羅的解析 -Marker for epigenetic field defect and prognosis-2014

    • Author(s)
      馬場 祥史
    • Organizer
      第22回日本消化器関連学会週間(第12回日本消化器外科学会大会)
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] The relationship between LINE-1 hypomethylation and fibrosis status in noncancerous liver tissues of hepatocellular carcinoma patients2014

    • Author(s)
      Yoshifumi Baba
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      San Diego, California
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 切除不能肝細胞癌follow up中の門脈侵襲出現に関する検討2014

    • Author(s)
      岡部 和利
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-04-03 – 2014-04-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝細胞癌における系統的切除の意義―Propensity Score Matchingを用いた検討2013

    • Author(s)
      別府 透
    • Organizer
      第25回日本肝胆膵外科学会・学術集会
    • Place of Presentation
      ホテル東日本宇都宮
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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