肝癌复发转移的研究

Studies on postoperative recurrence and metastasis of hepatocellular carcinoma

目的 通过实验和临床研究为肝癌根治性切除后复发转移提供预测指标和预防方法。方法 用组织块肝原位移植建立高转移人肝癌裸鼠模型 ,用该模型建立高转移潜能人肝癌细胞系 ,用分子生物学方法研究肝癌侵袭性有关变化 ,并由此设计实验性干预治疗。开展预防复发转移的临床实验。结果 (1)建成在肺、肝和淋巴结高转移的人肝癌裸鼠模型LCI D2 0 ,建成高转移潜能人肝癌细胞系MHCC97。 (2 )初步摸清与肝癌侵袭性呈正、负相关的分子水平变化。 (3)发现染色体 8p缺失与肝癌转移有关。 (4 )验血提示血栓调节蛋白与肝内播散呈负相关 ,细胞间粘附分子 1、纤溶酶原激活物受体的抑制剂 (PAI 1)和血管内皮生长因子 (VEGF)水平与肝癌侵袭转移呈正相关。 (5 )用LCI D2 0模型 ,证实TNP470、苏拉明、反义VEGF、突变型flk 1基因转染、羧基胺基咪唑、Endostain、干扰素α等抗血管生成剂有抑制肝癌生长和转移作用。反义H ras、BB94或肝素也有类似作用。 (6 )根治性切除后经动脉化学药物治疗 (化疗 ) ,化学药物栓塞合并干扰素或LAK细胞治疗使 3年复发率有所降低。结论 肝癌侵袭性相关的分子水平变化与其他实体瘤相仿 ,小肝癌的生物学特性比大肝癌略好 ,这些研究为复发转移的预测和预防提供了有潜在意义的线索。

Objective[WT5”BZ] To provide predictive markers of and prevent the recurrence and metastasis after curative resection of hepatocellular carcinoma (HCC) based on experimental and clinical studies.[WT5”HZ]Methods [WT5”BZ]We established metastatic human HCC model in nude mice using orthotopic transplantation of intact tissue and human HCC cell line with high metastatic potential. We studied the HCC invasiveness-related alterations and conducted experimental intervention, clinical trials for prevention of recurrence and metastasis.[WT5”HZ]Results [WT5”BZ](1) Human HCC model in nude mice with high metastatic rate in lung, liver and lymph node (LCI-D20) and human HCC cell line with high metastatic potential (MHCC97) were established.(2) The molecular mechanism related with HCC invasiveness was delineated.(3) Chromosome 8p deletion was found to be associated with HCC metastasis.(4) Thrombomodulin was negatively related to intrahepatic spreading.Whereas PAI-1 and VEGF level were positively related to HCC invasiveness.(5) Anti-angiogenic agents TNP 470, suramin, antisense VEGF, gene transfer of flk-1 mutant, carboxyamido-triazole, endostatin, interferon α inhibit tumor growth and metastasis. (6) Curative resection, postoperative TAE with interferon, or LAK cell therapy decreased the 3-year recurrent rate.[WT5”HZ]Conclusion [WT5”BZ]Molecular mechanism of HCC invasiveness was similar to that of other solid tumors. The biological characteristics of small HCC was better than that of large HCC. These results will help in predicting and preventing recurrence and metastasis of HCC. [WT5”HZ]