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Analysis of CTL targeted on hepatoma transfected with HIV gene Innovation of vaccine against hepatitis C virus.

Analysis of CTL targeted on hepatoma transfected with HIV gene Innovation of vaccine against hepatitis C virus.
HIV基因转染肝癌靶向CTL分析丙型肝炎病毒疫苗创新
批准号:
14570473
负责人:
KUROKOHCHI Kazutaka
金额:
$2.11万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003

项目摘要

项目成果

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中文摘要
翻译
HCV感染引起肝细胞损伤的致病机制尚不清楚。采用流式细胞术对hcv感染患者外周血单核细胞(PBMCs)和肝浸润单核细胞(LIMCs)进行抗体检测。与健康对照组相比,hcv感染患者中表达CD8、CD28、CD80或CD154的pbmc显著减少。患者CD28(+)CD8(+)PBMCs与ALT水平呈负相关。相反,CD28(-)CD8(+)LIMCs水平与ALT水平相关。抗cb8抗体可阻断hcv特异性CTL活性,而抗cd4或抗cd28抗体则不能。免疫组织化学分析显示慢性活动性丙型肝炎患者肝脏门静脉区周围CD28(+)细胞的积累。这些结果表明,CD28(+)CD8(+) T细胞离开循环,移动到肝脏,并在门静脉区被激活,与肝脏疾病的程度成比例。CD28(-)CD8(+) T细胞可能最终作为效应T细胞在HCV感染中引起肝细胞损伤。射频消融(RFA)目前用于治疗肝细胞癌(HCC)。本研究的目的是评价经皮乙醇注射(PEI)与RFA (PEI-RFA)联合治疗的有效性。活检证实的HCC和肝硬化患者在肝细胞癌内大量注射乙醇(PEI-RFA)后接受RFA。估计凝固坏死的体积,并与单独RFA组进行比较。与单独接受RFA治疗的患者相比,接受PEI-RFA治疗的患者观察到更大的凝固坏死区域。在PEI-RFA组中,凝固坏死的体积与肝细胞癌内注射乙醇的量显著相关。在PEIRFA治疗期间和之后未观察到重大并发症。
英文摘要
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.
期刊论文(102)
专著(0)
科研奖励(0)
会议论文
Kurokohchi K, Masaki T, Arima K, 8 Others.: "CD28-negative CD8-positive cytotoxic T lymphocytes mediate Hepatocellular damage in hepatitis C virus infection."J Clin Immunol. 23. 518-527 (2003)
Kurokohchi K、Masaki T、Arima K、8 其他人:“CD28 阴性 CD8 阳性细胞毒性 T 淋巴细胞介导丙型肝炎病毒感染中的肝细胞损伤。”J Clin Nutrition。
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通讯作者:
Kuriyama S, Yoshiji H, Masaki T, 12 Others(2^<nd>): "ARCHMEDIA (Tokyo) Induction of hepatoma specific gene expression using the chimera regulatory factor including AFP promoter."Arcmedium Tokyo. 93-99 (2003)
Kuriyama S、Yoshiji H、Masaki T、12 其他(2^<nd>):“ARCHMEDIA(东京)使用包括 AFP 启动子的嵌合调节因子诱导肝癌特异性基因表达。”Arcmedium 东京。
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Watanabe S, Sasahara K, Kinekawa F, 8 Others (6th): "Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer"Oncol Rep. 9. 1063-1068 (2002)
Watanabe S、Sasahara K、Kinekawa F、8 其他(第 6 篇):“日本食道癌患者中的醛脱氢酶 2 基因型和 HLA 单倍型”Oncol Rep. 9. 1063-1068 (2002)
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黒河内和貴, 栗山茂樹: "抗結核剤リファンピシンのチトクロームP450に与える影響"消化器科. 35. 655-659 (2002)
Kazuki Kurokochi、Shigeki Kuriyama:“抗结核药物利福平对细胞色素 P450 的影响”胃肠病学 35. 655-659 (2002)。
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