| Project/Area Number |
04454243
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
HAYASHI Norio Osaka Univ, Medical School, Lecturer, 医学部, 講師 (00144478)
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| Co-Investigator(Kenkyū-buntansha) |
MITA Eiji Osaka Univ.Hospital, Research Fellow, 医学部・附属病院, 医員
TAKEHARA Tetsuo Osaka Univ.Hospital, Research Fellow, 医学部・附属病院, 医員
KATAYAMA Kazuhiro Osaka Univ.Hospital, Research Fellow, 医学部・附属病院, 医員
KASAHARA Akinori Osaka Univ, Medical School, Assist.Prof., 医学部, 助手 (70214286)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1992: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | hepatitis C virus / hepatocarcinogenesis / genotype / c-met / bcl-2 / apoptosis / Fas antigen / HGF / HCV / C型肝炎ウイルス / モノクローナル抗体 / "in situ"hybridization / C型慢性肝炎 / 肝癌 / HCV抗原 / RT-PCR法 |
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| Research Abstract |
1) Using a competitive assay that combined reverse transcription and polymerase chain reaction, we tested serum samples of HCV carriers. The replicative level of HCV is higher in advanced liver desease and the elevation of viral replication may play an important role in progression of liver disease and hepatocarcinogenesis.
2) There was no significant difference in the serum HCV RNA levels among each genotype at every stage of chronic liver desease, and genotype seems to have little influence on the progression of liver disease and hepatocarcinogenesis.
3) We examined the presence of the minus strand of HCV RNA in liver specimens of patients with HCC.The plus- and minus-strand RNA were detected in both HCC and surrounding liver, suggesting that HCV replicates even in tumor cells.
4) C-met mRNA and protein expression were elevated in HCC compared in HCC compared with surrounding normal liver. C-met protein expression was related with poor defferentiation of the cancer. Moreover, elevated proliferative activity was observed in some c-met positive cases. These data suggest the possible involvement of c-met hepatocarcinogenesis.
5) Expression of Bcl-2 oncoprotein, which inhibits apoptosis induced by a variety of circumstances, was elevated in HCC compared with surrounding normal liver, suggesting the possible involvement of Bcl-2 in the development of HCC.Also, expression of Fas antigen, which induces apoptosis, was supposed to play an important role of the inflammation in the HCV-infected liver.
6) Using sucrose equilibrium density gradient centrifugation, we demonstrated that HCV particle populations consist of low-density virions and high-density immune complexes and/or nucleocapsids, and the dominant HCV populations shifted from virion on immune complex and/or nucleocapsid with progression of liver disease, especially the development of HCC.
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