2003 Fiscal Year Final Research Report Summary
Analysis of CTL targeted on hepatoma transfected with HIV gene Innovation of vaccine against hepatitis C virus.
| Project/Area Number |
14570473
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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 | Kagawa University(Faculty of Medicine) |
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Principal Investigator |
KUROKOHCHI Kazutaka Kagawa University, school of Medicine, Research Assistant, 医学部, 助手 (10294753)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Seishiro Kagawa University, school of Medicine, Assistant Professor, 医学部, 助教授 (00158635)
MASAKI Tsutomu Kagawa University, school of Medicine, Research Assistant, 医学部, 助手 (30335848)
KURIYAMA Shigeki Kagawa University, school of Medicine, Professor, 医学部, 教授 (50244710)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Hepatitis C / Hepatitis C virus / Cytotoxic T lymphocytes / Immunology / Costimulatory molecule / Hepatocellular carcinoma / Radiofrequency ablation (RFA) |
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| Research Abstract |
The pathogenic mechanism for hepatocellular damage in HCV infection has not been clearly understood. Peripheral blood mononuclear cells (PBMCs) and liver infiltrating mononuclear cells (LIMCs) isolated from the HCV-infected patients were analyzed with antibodies directed against a variety of co-stimulatory molecules by flow cytometry. PBMCs expressing CD8,CD28,CD80 or CD154 were significantly reduced in HCV-infected patients compared with the healthy controls. CD28(+)CD8(+)PBMCs in the patients inversely correlated with ALT levels. Conversely, levels of CD28(-)CD8(+)LIMCs correlated with ALT levels. HCV-specific CTL activity was blocked by the treatment with anti-CB8 antibody, but not with anti-CD4 or anti-CD28 antibody. Immunohistochemical analysis revealed the accumulation of CD28(+) cells around the portal area in the liver of a patient with chronic active hepatitis C. These results suggest that CD28(+)CD8(+) T cells leave the circulation, move to the livers and are activated in the portal area in proportion to the extent of liver diseases. CD28(-)CD8(+) T cells may finally function as effector T cells causing the hepatocellular damage in HCV infection.
Radiofrequency ablation (RFA) is currently used for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the usefullness of combination therapy of percutaneous ethanol injection (PEI) and RFA (PEI-RFA). Patients with biopsy-proven HCC and liver cirrhosis underwent RFA after a bolus injection of ethanol into HCC (PEI-RFA). The volume of coagulated necrosis was estimated and compared with that in the group treated with RFA alone. Significantly larger coagulated necrosis areas were observed in patients treated with PEI-RFA compared with those treated with RFA alone. In the PEI-RFA group, the volume of coagulated necrosis was significantly correlated with the amounts of ethanol injected into HCC. No major complications were observed during and after the PEIRFA treatment.
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