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Novel mechanism for the angiogenesis in hepatocellular carcinoma

Research Project

Project/Area Number 20590780
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOkayama University

Principal Investigator

SHIRAHA Hidenori  Okayama University, 病院, 助教 (40379748)

Co-Investigator(Kenkyū-buntansha) KOBASHI Haruhiko  岡山大学, 病院, 講師 (00403486)
ONISHI Hideki  岡山大学, 大学院・医歯薬学総合研究科, 助教 (30595468)
NAKAMURA Shinichiro  岡山大学, 病院, 助教 (70514230)
YAMAMOTO Kazuhide  岡山大学, 大学院・医歯薬学総合研究科, 教授 (90140491)
KOBAYASHI Yoshiyuki  岡山大学, 病院, 助教 (20379746)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞増殖 / 肝細胞癌 / 血管新生
Research Abstract

Des-gamma carboxy prothrombin (DCP) stimulated KDR in human umbilical vein epithelial cell ; enhanced cell migration by 2.2-fold and enhanced cell proliferation by 1.5-fold. KDR inhibitor abrogated these effects. Sequence analysis revealed that exon 2 skipping splice variant gamma-glutamyl carboxylase (Δ2-GGCX) was expressed in DCP-positive hepatocellular carcinoma (HCC) cells. DCP-positive HCC cells expressed 69% of Δ2-GGCX, while DCP-negative HCC cells expressed 8% of Δ2-GGCX. The introduction of Δ2-GGCX converted DCP-negative HCC cells into DCP-positive HCC cells. On the other hand, the introduction of wild type (WT)-GGCX converted DCP-positive HCC cells into DCP-negative HCC cells. WT-GGCX and Δ2-GGCX expressing Hep3B cells were injected subcutaneously into nude mice. Δ2-GGCX-Hep3B formed more angiogenic tumors and 4.2-fold larger tumors than WT-GGCX-Hep3B. HCC tissue samples demonstrated a positive correlation between DCP production and angiogenesis determined by CD31 index. The serum DCP level of hypervascular HCC was significantly higher than that of hypovascular HCC. In toto, DCP expression is associated with tumor angiogenesis in HCC.

Report

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

    (31 results)

All 2011 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 16 results) Presentation (12 results) Remarks (1 results)

  • [Journal Article] Prognostic model for hepatocellular carcinoma with time-dependent factors.2011

    • Author(s)
      Kuwaki K, Kobayashi Y, Nakamura S, Onishi H, Shiraha H, Kobashi H, Yamamoto K, et.al.
    • Journal Title

      Acta Med Okayama 65(1)巻

      Pages: 11-19

    • NAID

      120002807407

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis.2011

    • Author(s)
      Nakanishi Y, Shiraha H, Ohnishi H, Nakamura S, Kobayashi Y, Yamamoto K, et.al.
    • Journal Title

      BMC Cancer 11巻

      Pages: 312-312

    • NAID

      120005053306

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of runt-related transcription factor 3 causes development and progression of hepatocellular carcinoma.2011

    • Author(s)
      Shiraha H, Nishina SI, Yamamoto K.
    • Journal Title

      J Cell Biochem. 112(3)巻

      Pages: 745-749

    • Related Report
      2010 Final Research Report
  • [Journal Article] Loss of runt-related transcription factor 3 causes development and progression of hepatocellular carcinoma.2011

    • Author(s)
      Shiraha H, Nishina SI, Yamamoto K.
    • Journal Title

      J Cell Biochem.

      Volume: 112(3) Pages: 745-749

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis.2011

    • Author(s)
      Nakanishi Y, Shiraha H, Ohnishi H, Nakamura S, Kobayashi Y, Yamamoto K, et.al.
    • Journal Title

      BMC Cancer

      Volume: 11 Pages: 3-12

    • NAID

      120005053306

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic model for hepatocellular carcinoma with time-dependent factors.2011

    • Author(s)
      Kuwaki K, Kobayashi Y, Nakamura S, Onishi H, Shiraha H, Kobashi H, Yamamoto K, et.al.
    • Journal Title

      Acta Med Okayama

      Volume: 65(1) Pages: 11-19

    • NAID

      120002807407

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time-dependent analysis of predisposing factors for the recurrence of hepatocellular carcinoma.2010

    • Author(s)
      Iwadou S, Kobayashi Y, Nakamura S, Ohnishi H, Shiraha H, Yamamoto K, et.al.
    • Journal Title

      Liver Int. 30(7)巻

      Pages: 1027-1032

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Application of radiofrequency ablation for the treatment of metastatic liver cancers.2010

    • Author(s)
      Nouso K, Kobayashi Y, Nakamura S, Shiraha H, Yamamoto K, et.al.
    • Journal Title

      Hepatogastroenterology. 57(97)巻

      Pages: 117-120

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of prognostic factors in hepatocellular carcinoma in Japan.2010

    • Author(s)
      Nouso K, Shiraha H, et.al.
    • Journal Title

      Aliment Pharmacol Ther 31(3)巻

      Pages: 407-414

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Application of radiofrequency ablation for the treatment of metastatic liver cancers.2010

    • Author(s)
      Nouso K, Kobayashi Y, Nakamura S, Shiraha H, Yamamoto K, et.al.
    • Journal Title

      Hepatogastroenterology.

      Volume: 57(97) Pages: 117-120

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time-dependent analysis of predisposing factors for the recurrence of hepatocellular carcinoma.2010

    • Author(s)
      Iwadou S, Kobayashi Y, Nakamura S, Ohnishi H, Shiraha H, Yamamoto K, et.al.
    • Journal Title

      Liver Int.

      Volume: 30(7) Pages: 1027-1032

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of prognostic factors in hepatocellular carcinoma in Japan.2010

    • Author(s)
      Nouso K, Shiraha H, et. al.
    • Journal Title

      Aliment Pharmacol Ther 31(3)

      Pages: 407-414

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Twist expression promotes migration and invasion in hepatocellular carcinoma.2009

    • Author(s)
      Matsuo N, Shiraha H, et.al.
    • Journal Title

      BMC Cancer 9巻

      Pages: 240-251

    • NAID

      120005053307

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of des-gamma-carboxy prothrombin production in hepatocellular carcinoma.2009

    • Author(s)
      Fujikawa T, Shiraha H, Yamamoto K.
    • Journal Title

      Acta Medica Okayama 63(6)巻

      Pages: 299-304

    • NAID

      120002312337

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of des-gamma-carboxy prothrombin production in hepatocellular carcinoma.2009

    • Author(s)
      Fujikawa T, Shiraha H, Yamamoto K.
    • Journal Title

      Acta Medica Okayama 63(6)

      Pages: 299-304

    • NAID

      120002312337

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Twist expression promotes migration and invasion in hepatocellular carcinoma.2009

    • Author(s)
      Matsuo N, Shiraha H, et. al.
    • Journal Title

      BMC Cancer 9

      Pages: 240-251

    • NAID

      120005053307

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines.2008

    • Author(s)
      Ueda N, Shiraha H, et.al.
    • Journal Title

      Molecular Oncology 2(3)巻

      Pages: 241-249

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Exon 2 deletion splice variant of γ-glutamyl carboxylase causes des-γ-carboxy prothrombin production in hepatocellular carcinoma cell lines.2008

    • Author(s)
      Ueda N, Shiraha H, et. al.
    • Journal Title

      Molecular Oncology 2(3)

      Pages: 241-249

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Des-gamma-carboxy prothrombin and angiogenesis in hepatocellular carcinoma.2010

    • Author(s)
      白羽英則
    • Organizer
      37th Congress of the International Society of Oncology and Biomarkers
    • Place of Presentation
      ミュンヘン
    • Year and Date
      2010-09-05
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝細胞癌の分子標的探索と臨床応用RUNX3欠損による肝癌のシグナル活性化2010

    • Author(s)
      白羽英則
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 異常プロトロンビンの血管新生促進効果の検討2010

    • Author(s)
      白羽英則
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 異常プロトロンビンと肝癌血管新生2010

    • Author(s)
      白羽英則
    • Organizer
      第13回Vitamin K & aging研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-02-20
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] カルボキシラーゼ活性によるEMT制御2010

    • Author(s)
      白羽英則
    • Organizer
      第14回Vitamin K & aging研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-02-19
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Des-gamma-carboxy prothrombin promotes growth and angiogenesis in hepatocellular carcinoma.2009

    • Author(s)
      白羽英則
    • Organizer
      37th Congress of the International Society of Oncology and Biomarkers
    • Place of Presentation
      アムステルダム
    • Year and Date
      2009-09-29
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 血管新生因子としての異常プロトロンビンin vivoにおける検討2009

    • Author(s)
      白羽英則
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2009-06-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 血管新生因子としての異常プロトロンビン in vivoにおける検討2009

    • Author(s)
      白羽英則
    • Organizer
      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] カルボキシラーゼ異常による肝癌血管新生誘導2009

    • Author(s)
      白羽英則
    • Organizer
      第12回Vitamin K & aging研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-02-14
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Gamma-Glutamyl-Carboxylase Regulates Development of Hepatocellular Carcinoma.2008

    • Author(s)
      白羽英則
    • Organizer
      36th Congress of the International Society of Oncology and Biomarkers
    • Place of Presentation
      東京
    • Year and Date
      2008-10-14
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 肝癌の分子標的治療2008

    • Author(s)
      白羽英則
    • Organizer
      カルボキシラーゼ異常による血管新生誘導DDW2008
    • Place of Presentation
      東京
    • Year and Date
      2008-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝癌の分子標的治療 カルボキシラーゼ異常による血管新生誘導2008

    • Author(s)
      白羽 英則
    • Organizer
      DDW2008
    • Place of Presentation
      東京
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.okayama-u.ac.jp/user/gastro/049kantansuikenkyu.html

    • Related Report
      2010 Final Research Report

URL: 

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

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