2004 Fiscal Year Final Research Report Summary
The role of hepatitis C infection and proliferators-activated receptor alpha protects (PPA α) in occurrence of hepatocellular carcinoma
| Project/Area Number |
15590633
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
KIYOSAWA Kendo Shinshu University School of Medicine, Department of Internal Medicine (Gastroenterology), Professor, 医学部, 教授 (30020829)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Toshihumi Shinshu University Graduate School of Medicine, Department of Metabolic Regulation, Institute on Aging and Adaptation, Professor, 医学研究科, 教授 (50231105)
TANAKA Eiji Shinshu University School of Medicine, Department of Internal Medicine (Gastroenterology), Associate Professor, 医学部, 助教授 (50163506)
YOSHIZAWA Kaname Shinshu University School of Medicine, Department of Internal Medicine (Gastroenterology), Assistant Professor, 医学部, 講師 (90220615)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hepatitis C virus (HCV) / HCV core protein / PPARα / steatosis / hepatocellular carcinoma (HCC) |
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| Research Abstract |
Persistent infection of hepatitis C virus (HCV) can lead to a high risk for hepatocellular carcinoma (HCC). Hepatitis C virus core protein (HVB core protein) plays important roles in HCV-related hepatocarcinogenesis, because its expression in mice causes hepatic steatosis and HCC without accompanuing hepatitis. To clarify whether the HCV core protein alters the expression of the factors associated with hepatic steatosis and HCC in vivo, expression of the proteins including oncogene products, sell cycle regulators and fatty acid-metabolizing enzymes, was investigated. The expression of numerous proteins, which is induced by the activation of peroxisome proliferators-activated receptor α (PPAR α), increased simultaneously and age-dependently in HCV core protein transgenic mouse. In these mice, stabilization and activation of nuclear PPAR α occurred, probably due to increased nuclear free fatty acids, endogenous PPAR actovators, and due to the interaction with HCV core protein. Persistent and heterogenous activation of PPAR a seemed to disturb the homeostasis in hepatocytes proliferation/removal, resulting in casing age-dependent appearance of aberrant hepatocytes, overexpression PPAR α or cycline D1, in scattered areas of the liver. These aberrant hepatocytes proliferated and tend to form multicentric clusters. These phenomena were entirely different from those observed in the rodents treated with nongenotoxic carcinogens such as fibrates. These results offer the first suggestion that persistent and heterogenous activation of PPAR α can contribute to age-dependent and multicentric hepatocarcinogenesis caused by HCV infection.
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Research Products
(13 results)
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[Journal Article] Interferon therapy for aged patients with chronic hepatitis C : improved survival in patients exhibiting a biochemical response.2004
Author(s)
Imai Y, Kasahara A, Tanaka H, Okanoue T, Hiramatsu N, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E, Hino K, Hayashi K, Tamura S, Itoh Y, Sasaki Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N.
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Journal Title
J Gastroenterol 39
Pages: 1069-1077
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characteritics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy.2004
Author(s)
Makiyama A, Itoh Y, Kasahara A, Imai Y, Kawata S, Yoshioka K, Tsubouchi H, Kiyosawa K, Kakumu S, Okita K, Hayashi N, Okanoue T.
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Journal Title
Cancer 101
Pages: 1616-1622
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Long-term follow-up of hepatitis C virus Infection : HLA class II loci influences the natural history of the disease.2003
Author(s)
Yoshizawa K, Ota M, Saito S, Maruyama A, Yamaura T, Rokuhara A, Orii K, Ichijo T, Matsumoto A, Tanaka E, Kiyosawa K.
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Journal Title
Tissue Antigens 61
Pages: 159-165
Description
「研究成果報告書概要(欧文)」より
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