| Project/Area Number |
08670585
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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 | Osaka University |
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Principal Investigator |
KASAHARA Akinori Osaka University Hospital, Associate Professor, 医学部・附属病院, 助教授 (70214286)
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| Co-Investigator(Kenkyū-buntansha) |
MITA Eiji Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
KATAYAMA Kazuhiro Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
SASAKI Yutaka Osaka University Medical School, Assistant Professor, 医学部, 助手 (70235282)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Hepatitis C Virus / B7-1 / Fas Antigen / Apoptosis / Interferon / Ribozyme / Gene Therapy / テロメラーゼ / 肝細胞癌 |
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| Research Abstract |
In hepatitis C virus (HCV)-infected liver, B7/BB-1 was strongly expressed in the cytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infiltrating lymphocytes and were detected near HCV core antigen- and HLA class I-positive cells. B7/BB-1 expression was closely correlated with the activity of viral hepatitis. These findings suggest that B7/BB-1 expression by hepatocytes may be induced by HCV infection and may trigger generation and activation of CTL,which may cause damage to HCV-infected HLA class i-expressing hepatocytes. To elucidate the risk factors for liver carcinogenesis and to examine the incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1022 chronic hepatitis C patients treated with interferon were followed by ultrasonography for 13-97 months. The cumulative incidence of HCC in transient responders was almost equal to that in sustained responders, and it was significantly higher in non-responders than in sustained and transient responders. The
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seventh-year cumulative incidence rates of HCC in sustained responders, transient responders and non-responders were estimated to be 4.3%, 4.7% and 26.1%, respectively. Cox regression analysis showed that patients in the high risk gropu of HCC after interferon therapy were those showing no response, who were older and who were male.
The hammer-head ribozymes directed against HCV RNA cleaved the target HCV RNA and showed a significant inhibitory effect on viral translation, suggesting that ribozyme-mediated HCV RNA cleavage may serve as a new strategy in the treatment of HCV infection. Human B7-1 transfected HCC 'Is could induce cytolitic activity in vitro compared with B7-1 non-transfected HCC cells, suggesting that human HCC cells with strong expression of B7-1 by ex vivo or in vivo transfection could be used to induce antitumor immunity against human HCC.Tumor growth of B7-1 transfected HCC cells in syngenetic BALB/c nu/nu mouse was as fast as that of wild HCC cells. However, tumor growth of B7-1 transfected HCC cells in syngenetic BALB/c mouse was significantly inhibited compared with that of wild HCC cells, suggesting that antitumor immunity against HCC cells was induced by B7-1 transfected HCC cells in vivo. Thus, B7-1 gene transfer into HCC cells may be one of the candidates for human HCC gene therapy.
These findings may lead to clarify the mechanism of liver damage and to improve the efficacy of the treatment for patients with chronic HCV infection. Less
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