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Molecular biological analysis of angiogenetic process of hepatocellular carcinoma, from the view point of standardization of diagnosis and treatment

Research Project

Project/Area Number 14570530
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOkinaka Memorial Institute for Medical Research (OMIMR)

Principal Investigator

IKEDA Kenji  OMIMR, Research worker, 研究員 (80211027)

Co-Investigator(Kenkyū-buntansha) KUMADA Hiromitsu  OMIMR, Research worker, 研究員 (20124307)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsHepatocellular carcinoma / alpha-smooth muscle actin / angiogenesis / VEGF / immunohistochemistry / non-triadal vessel / 血管新生 / 早期肝細胞癌 / 新生血管 / non-triadal vessel / alpha-smooth muscle actin
Research Abstract

To elucidate the relationship between angiographic features and histological findings, an immunohistological study of alpha-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography, and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich, and slender-shaped vessels (Type II), 8 (11.0%) had thin-walled, nuclei-poor, and oval-shaped vessels. (Type I), and the remaining 8 had a mixed type of II and Type I. Conversely among 33 patients without hypervascularity, 5 (15.2%) had a Type II, 21 (63.6%) had a Type I, 5 had a mixed type, and 2 had no positive vessel. Tumor size, histological classification, and amount of non-triadal vessels were also associated with the angiographic appearance of the … More tumors. Among varied aspects of the cancer including tumor size, tumor multiplicity, microscopic portal invasion, histological classification, amount of alpha-smooth muscle actin-positive vessels, and shape of alpha-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of alpha-smooth muscle actin positive vessels was solely associated with angiographic hypervascularity independently. Although the existence of non-triadal vessel characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the Type II vessel. A morphological change of non-triadal vessel from Type I to Type II was considered to occur in an early stage of hepatocellular carcinoma.
Eleven surgically resected specimens of well-differentiated hepatocellular carcinoma were analyzed for neovascular structure using monoclonal alpha-smooth muscle actin antibody. Each paraffin specimen was serially sliced with a thickness of 3 micrometers for immunohistochemistry. All of the eleven liver cancers had thin-walled, round-or oval-shaped non-triadal vessels in their well-differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non-triadal vessels were connected to portal veins in portal triads in well-differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well-differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All eleven tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed "negative enhancement" on intra-arterial carbon dioxide-enhanced ultrasonography or computerized tomographic hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular carcinoma."J Gastroenterol Hepatol. 13. 1264-1271 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of hepatocellular carcinogenesis with precore mutant virus and serum hepatitis B virus DNA concentration --- A longitudinal analysis of patients with cirrhosis"Hepatology Research. 10. 142-155 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Effect of arterial administration of a high molecular weight antitumor agent, styrene maleic acid neocarzinostatin, in embolization-resistant liver cancer"Int J Clin Oncol. 4. 148-155 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Saitoh S, et al.: "Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C --- A long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis"Hepatology. 31. 1124-1130 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Saitoh S, et al.: "Interferon Beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor --- A prospective randomized study of hepatitis C virus --- Related liver cancer"Hepatology. 32. 229-232 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Kobayashi M, et al.: "Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis"Intervirology. 43. 96-104 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular carcinoma."J Gastroenterol Hepatol. 13. 1266-1273 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of hepatocellular carcinogenesis with precore mutant virus and ser um hepatitis B virus DNA concentration --------A longitudinal analysis of patients with cirrhosis."Hepatology Research. 10. 142-155 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Saitoh S, Suzuki Y, et al.: "Effect of arterial administration of a high molecular weight antitumor agent, styrene maleic acid neocarzinostatin, in embolization-resistant liver cancer."Int J Clin Oncol. 4. 148-155 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Saitoh S, et al.: "Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C ------A long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis."Hepatology. 31. 1124-1130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Saitoh S, et al.: "Interferon Beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor ----A prospective randomized study of hepatitis C virus ---Related liver cancer"Hepatology. 32(2). 229-232 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Arase Y, Kobayashi M, et al.: "Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV related cirrhosis."Intervirology. 43. 96-104 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda K, Kobayashi M, Someya T et al.: "Influence of hepatitis C virus subtype on hepatocellular carcinogenesis : A multivariate analysis of a retrospective cohort of 593 patients with cirrhosis."Intervirology. 45. 71-78 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikeda K, Arase Y, Kobayashi M, et al.: "Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis"Intervirology. 46. 96-104 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikeda K, Kobayashi M, Saitoh S, et al.: "Recurrence rate and prognosis of patients with hepatocellular carcinoma that developed after elimination of hepatitis C virus-RNA by interferon therapy. ---- A closed cohort study using matched control patients."Oncology. 65. 204-210 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikeda K, Arase Y, Kobayashi M, et al.: "Significance of multicentric cancer recurrence after potentially curative ablation of hepatocellular carcinoma ---- A long-term cohort study of 892 patients with viral cirrhosis"J Gastroenterol. 38. 865-876 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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