| Project/Area Number |
07307009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | University of Tokyo |
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Principal Investigator |
OMATA Masao University of Tokyo, Second Department of Internal carcinoma, 医学部附属病院, 教授 (90125914)
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| Co-Investigator(Kenkyū-buntansha) |
TANIKAWA Kyuichi Kurume University, Second Department of Internal Madicine Professor., 医学部, 教授 (10080649)
SATO Chifumi Tokyo Medical and Dental University, Internal carcinoma Pofessor, 教授 (60154069)
KAKUMU Shinichi Aichi Medical University Internal carcinoma Pofessor, 教授 (10115545)
YOKOSUKA Osamu Chiba University, First Department of Internal carcinoma Medicine, Professor, 医学部, 講師 (90182691)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1995: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | hepatitis Cvirus / NS5A / interferon / transactivation / GBV-C / hepatocellular carcinoma / 肝発癌 / 肝硬変 / 腫瘍マーカー / ウイルスとの結合蛋白 / two laybrid system / C型ウイルス肝炎 / 発癌抑止 |
|---|
| Research Abstract |
Present study was conducted to clarify the mechanisms for inhibition of progression of chronic hepatitis C and for suppression of hepatocellular carcinoma from the clinical and molecular points of views. The molecular analysis on the HCV revealed that NS5A region have transactivating function, where hepatocyte proteins of Rac-1, ribosomal protein, Rab4 and MIF have been found to bind. Efficacy of interferon (IFN) was related to the number of mutation of this NS5A region, especially ranging from nt 2209 to nt 2248. In addition, mutation of amino acid sequence was accumulated in the region of E2/NS1 and NS5B in association with the aggravation of chronic hepatitis after IFN therapy. In addition, although an analysis on GBV-C has been developed recently, a minus strand of GBV-C was scarcely detected in hepatocytes. These data suggested that this GBV-C have little effect on the progression of liver disease leading to HCC from the clinical point of view.
Multicentered studies on analysis of role of IFN on suppression of HCC were performed, indicating that HCV viral load and subtypes are important factors for predicting the efficacy of IFN therapy, and that not only the eradication of HCV RNA by IFN but biochemical response were found to reduce the incidence of HCC,especially precirrhotic patients of stage F3. Among these patients, histological improvement was also demonstrated several years later. For earlier detection of HCC,serial measurement of AFP fraction, DCP and MAGE-4 may provide clue in addition to periodical check up using ultrasonography.
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