原发性肝癌复发转移防治的临床与基础研究

简述近年复旦大学肝癌研究所获“九五”国家科技攻关等基金的资助对防治原发性肝癌复发转移的临床与基础研究课题的一些进展。在临床研究方面，亚临床复发作再切除手术是进一步提高疗效的主要途径，但预防复发则甚为困难。术后栓塞化疗（TACE）、生物治疗、术中肝动脉插管、冷冻肝切除等，可能有助于降低术后复发率。在实验研究方面，建立了人肝癌转移动物模型和细胞株。在分子水平对肝癌侵袭性作了研究，初步发现CerbB2、p12、p21、p53、mdm-2、VEGF、TGFα、EGF受体、MMP－2、uPA、uPA－R、ICAM－1与肝癌侵袭性呈正相关；nm23-H1、TIMP－2、Integrinα、E－cadherin、Kai-1则呈负相关。在实验性干预治疗方面，反义H－ras、Suramin、Heparin、抗肿瘤血管生成TNP－470、抗CD3／抗HBx的双特异抗体合并LAK治疗、基质金属蛋白酶抑制剂BBP－94及我所自行设计的β肽等对肝癌转移模型均有抑制转移的作用。预期生物治疗、转移复发的预测指标、多模式的干预治疗对防治肝癌转移甚为重要，其中抗肿瘤血管途径尤为突出。

Recurrence and Metastasis of Hepatocellular Carcinoma:Clinical and Experimental Studies

This paper briefly reviewed the studies on prevention and treatment of recurrence and metastasis after the resection of hepatocellular carcinoma(HCC) in Liver Cancer Institute of Fudan University. In clinical aspect, re-resection has been proved to prolong survival in patients with subclinical recurrence,however,prevention of recurrence is difficult. Postoperative chemoembolization (TACE) ,biotherapy, hepatic artery cannulation during operation and cryohepatectomy might be helpful. In experimental aspect, a highly metastatic human HCC model in nude mice and metastatic human HCC cell line have been established. Invasiveness of HCC in molecular events has been tried. C-erb B2, p16, p21,p53, mdm-2, VEGF, TGFα, EGF receptor, MMP-2. μPA, μPA-R, PAI-l, ICAM-1 were positively related, and nm-23-H1, TIMP-2, Integrin α5,E-cadherin, Kai-1 were negatively related. Intervention with antisense H-ras. Suramin, Hepanin, TNF-470, anti CD3/HBx, BB94, β peptide, etc. has also been found to inhibit tumor invasion and metastasis in experimental study. It is expected that biotherapy, novel approach based on molecular findings, multidisciplinary interventions migbt be important, and anti-angiogenic approach will be of particular implication for HCC.