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Mechanism of PIVKA-II production in hepatocellular carcinoma

Research Project

Project/Area Number 20590795
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJichi Medical University

Principal Investigator

KAZUMOTO Murata  Jichi Medical University, 第四肝疾患室, 医長 (40345971)

Co-Investigator(Kenkyū-buntansha) 鈴木 秀人  自治医科大学, 地域医療学センター, 助教 (00508749)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords肝癌 / PIVKA-II / EMT / 転移 / Cytoskeletal rearrangement / Cttoskeletal rearrangement
Research Abstract

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an established tumor marker for hepatocellular carcinoma (HCC), but precise mechanism of its production is unknown. We recently demonstrated that cytoskeletal rearrangement during phenotypic changes involved in epithelial mesenchymal transition (EMT) plays a crucial role in PIVKA-II production through impairment of vitamin K uptake. In addition, we demonstrated that hypoxic stimulation induced HCC cells to produce PIVKA-II in the same way. We also demonstrated that further phenotypic changes by hypoxia with malnutrition attenuated protein synthesis in HCC cells through mTOR pathway, resulting in decrease of PIVKA-II production. Thus, our serial findings indicate that PIVKA-II could be a phenotypic marker of HCC as well as a tumor marker.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2010 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 7 results) Presentation (12 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Hypoxia-induced des-γ-carboxy prothrombin production in hepatocellular carcinoma.2010

    • Author(s)
      Murata K, Suzuki H, et al
    • Journal Title

      Int J Oncol 36

      Pages: 161-170

    • Related Report
      2010 Final Research Report
  • [Journal Article] Hypoxia-induced des-γ-carboxy prothrombin production in hepatocellular carcinoma2010

    • Author(s)
      Murata K, et al
    • Journal Title

      Int J Oncol

      Volume: 36 Pages: 161-170

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th rs8099917 polymorphism, determined by a suitable genotyping method, is a better predictor for response to pegylated interferon-α/ribavirin therapy in Japanese patients than other SNPs associated with IL28B2010

    • Author(s)
      Ito K, Murata K, et al
    • Journal Title

      J Clin Microbiol

      Volume: 49 Pages: 1853-1860

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Letter to the Editor.2009

    • Author(s)
      村田一素、他
    • Journal Title

      日本消化器病学会雑誌 106(4)

      Pages: 98-98

    • NAID

      10025177938

    • Related Report
      2010 Final Research Report
  • [Journal Article] Fulminant sepsis due to anaerobic bacterial infection in immuno-compromised state.2009

    • Author(s)
      Suzuki H, Murata K, Sakamoto A
    • Journal Title

      Leg Med (Tokyo) 11

      Pages: 237-240

    • Related Report
      2010 Final Research Report
  • [Journal Article] Primary malignant lymphoma of the ileum presenting as intussusception.2009

    • Author(s)
      村田一素, et al
    • Journal Title

      Intern Med 48

      Pages: 1559-1560

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cytoskeletal changes during epithelial-to-fibroblastoid conversion as a crucial mechanism of des-γ-carboxy prothrombin production in hepatocellular carcinoma.2009

    • Author(s)
      Murata K, Suzuki H, et al
    • Journal Title

      Int J Oncol 35

      Pages: 1005-1014

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cytoskeletal changes during epithelial-to-fibroblastoid conversion as a crucial mechanism of des-γ-carboxy prothrombin production in hepatocellular carcinoma.2009

    • Author(s)
      Murata K, et al
    • Journal Title

      Int J Oncol

      Volume: 35 Pages: 1559-1560

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoskeletal changes during epithelial-to-fibroblastoid conversion as a crucial mechanism of des-γ-carboxy prothrombin production in hepatocellular carcinoma2009

    • Author(s)
      Murata K, et al.
    • Journal Title

      Int J Oncol 35

      Pages: 1005-1014

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Splenectomy improves liver function in patients with liver cirrhosis.2008

    • Author(s)
      村田一素, et al
    • Journal Title

      Hepato-Gastroenterology 55

      Pages: 1407-1411

    • Related Report
      2010 Final Research Report
  • [Journal Article] Protective role of interleukin-18 against Fas-mediated liver injury.2008

    • Author(s)
      Yamamoto N, Murata K, et al
    • Journal Title

      Int J Mol Med 22

      Pages: 43-48

    • Related Report
      2010 Final Research Report
  • [Journal Article] Impairment of clathrin-mediated endocytosis via cytoskeletal change by epithelial to fibroblastoid conversion in HepG2 cells : A possible mechanism of des-γ-carboxy prothrombin production in hepatocellular carcinoma.2008

    • Author(s)
      Murata K, Sakamoto A
    • Journal Title

      Int J Oncol 33

      Pages: 1149-1155

    • Related Report
      2010 Final Research Report
  • [Journal Article] Immunohistochemical observation of Co-expression of E- and N-cadherin in rat.2008

    • Author(s)
      Atsushi S, Murata K, Suzuki H, et al
    • Journal Title

      Acta Histochem Cytoc 41

      Pages: 143-147

    • Related Report
      2010 Final Research Report
  • [Journal Article] Splenectomy improves liver function in patients with liver cirrhosis2008

    • Author(s)
      Murata K
    • Journal Title

      Hepato-Gastroenterology 55

      Pages: 1407-1411

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of interleukin-18 against Fas-mediated liver injury2008

    • Author(s)
      Yamamoto N
    • Journal Title

      Int J Mol Med 22

      Pages: 43-48

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of clathrin-mediated endocytosis via cytoske letal change by epithelial to fibroblastoid conversion in HepG2 cells : A possible mechanism of des-γ-carboxy prothrombin production in hepatocellular carcinoma2008

    • Author(s)
      Murata K
    • Journal Title

      Int J Oncol 33

      Pages: 1149-1155

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th rs8099917 polymorphism, determined by a suitable genotyping method, is a better predictor for response to pegylated interferon-α/ribavirin therapy in Japanese patients than other SNPs associated with IL28B.

    • Author(s)
      Ito K, Murata K, et al
    • Journal Title

      J Clin Microbiol (in press)

    • Related Report
      2010 Final Research Report
  • [Presentation] 肝癌におけるphenotype依存性PIVKA-IIの産生2010

    • Author(s)
      村田一素
    • Organizer
      第28回犬山シンポジウム
    • Place of Presentation
      犬山 独立行政法人国立国際医療研究センター国府台病院
    • Year and Date
      2010-08-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝癌におけるphenotype依存性PIVKA-IIの産生2010

    • Author(s)
      村田一素
    • Organizer
      第28回犬山シンポジウム
    • Place of Presentation
      犬山、愛知
    • Year and Date
      2010-08-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] Phenotype-dependent production of des-?-carboxy prothrombin in hepatocellular carcinoma.2010

    • Author(s)
      村田一素
    • Organizer
      The 4^<th> annual meeting of International Liver Cancer Association (ILCA)
    • Place of Presentation
      Montreal The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine
    • Related Report
      2010 Final Research Report
  • [Presentation] Phenotype-dependent production of des-γ-carboxy prothrombin in hepatocellular carcinoma2010

    • Author(s)
      Murata K
    • Organizer
      The 4^<th> annual meeting of International Liver Cancer Association (ILCA)
    • Place of Presentation
      Montreal, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] Microsomal triglyceride transfer protein regulates CD1d-restricted antigen presentation of hepatocytes and controls NKT cell homeostasis via CD1d-mediated apoptosis2009

    • Author(s)
      Zeissig S, Murata K, et al
    • Organizer
      The 60^<th> annual meeting of the American association for the study of liver diseases
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2009-11-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Hypoxia-induced des-γ-carboxy prothrombin production in hepatocellular carcinoma2009

    • Author(s)
      村田一素, 他
    • Organizer
      The 60^<th> annual meeting of the American association for the study of liver diseases
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2009-11-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Epithelial-to-fibroblastoid conversion誘導肝細胞癌株におけるPIVKA-IIの産生機序2009

    • Author(s)
      村田一素、岡野宏、坂本敦司
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸 自治医科大学・地域医療学センター、鈴鹿中央総合病院
    • Year and Date
      2009-06-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Epithelial-to-fibroblastoid conversion 誘導肝細胞癌株におけるPIVKA-IIの産生機序2009

    • Author(s)
      村田一素, 他
    • Organizer
      第45回 日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Hypoxia-induced des-γ-carboxy prothrombin production in hepatocellular carcinoma2009

    • Author(s)
      村田一素
    • Organizer
      The 60^<th> annual meeting of the American association for the study of liver diseases
    • Place of Presentation
      Boston Center for Community Medicine, Jichi Medical University, Shimotsuke, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Epithelial-mesencymal transition誘導肝細胞株におけるPIVKA-IIの産生機序2008

    • Author(s)
      村田一素、坂本敦司
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山 自治医科大学・地域医療学センター
    • Year and Date
      2008-06-05
    • Related Report
      2010 Final Research Report
  • [Presentation] A possible mechanism of des-g-carboxyprothrombin production in hepatocellular carcinoma.2008

    • Author(s)
      Murata K, Atsushi Sakamoto
    • Organizer
      The 59th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      San Franscisco Center for Community Medicine, Jichi Medical University, Shimotsuke, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] A possible mechanism of des-g-carboxy prothrombin in hepatocellular carcinoma2008

    • Author(s)
      Murata K
    • Organizer
      Annual Meeting of the American Association for the study of Liver Diseases
    • Place of Presentation
      San Franscisco
    • Related Report
      2008 Annual Research Report
  • [Book] ウィルスマーカーの選択と解釈(急性肝障害の診断:急性肝障害時の生化学・血液検査 25(11))2010

    • Author(s)
      村田一素、他
    • Publisher
      臨床消化器内科
    • Related Report
      2010 Final Research Report
  • [Book] 強力ミノファーゲンシー・グリチロン(肝胆膵薬物治療学の進歩-この30年- 61(6))2010

    • Author(s)
      村田一素、他
    • Publisher
      肝胆膵
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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