Postoperative recurrence of human hepatocellular carcinoma (HCC) is the major issue that must be addressed to further improve prognosis. This study was undertaken to investigate the effects of interferon-alfa-1b (IFN-a-1b) on recurrent tumor and metastasis after curative resection in nude mice bearing an HCC xenograft with high metastatic potential. Tumor tissues from LCI-D20, a metastatic model of HCC in nude mice, were orthotopically implanted in 105 nude mice. Eleven days later, 64 mice underwent curative resection of liver tumors. IFN-a at different doses was administered subcutaneously to mice with or without resection. In mice without resection, when comparison was made among control, IFN 7.5 3 106 U/kg/day, 1.5 3 107 U/kg/day for treated groups, and 3 3 107 U/kg/day; tumor volume was 8,475 mm3 6 2,636 mm3, 7,963 mm3 6 3,214 mm3, 769 mm3 6 287 mm3, and 13 mm3 6 9 mm3; incidence of lung metastasis being 100%, 80%, 40%, and 0%; life span was 45 6 4 days, 53 6 8 days, 81 6 6 days, and 105 6 24 days, respectively. In mice with curative resection, when comparison was made among control, IFN 5 3 105 U/kg/day, 1 3 106 U/kg/day, 4 3 106 U/kg/day, 7.5 3 106 U/kg/day, 1.5 3 107 U/kg/day, and 3 3 107 U/kg/day for treated groups; incidence of recurrent tumor was 100%, 100%, 87.5%, 100%, 87.5%, 62.5%, and 12.5%; lung metastasis being 100%, 75%, 87.5%, 50%, 62.5%, 0%, and 0%, respectively. IFN-a inhibited neovascularization induced by LCI-D20 tumor specimens implanted into the micropocket of nude mice corneas. In conclusion, high-dose and longterm therapy with IFN-a dose-dependently inhibits tumor growth and recurrence after resection of HCC. The effect of IFN-a may be attributed to antiangiogenesis in this experiment. These results provide potential clinical implication, particularly for the prevention of recurrence after curative resection of HCC.

A highly metastatic LCI•D20 model of human hepatocellular carcinoma (HCC) was obtained via orthotopic implantation of a histologically preserved metastatic tumour selected from I of 30 surgical specimens, and has been maintained for 18 passages in nude mice. All mice with transplanted tumours exhibited 100% transplantability and metastatic ability, as well as various manifestations reminiscent of tumour behaviour in HCC pa-tients. These included: local growth, regional invasion, spontane-ous metastasis to liver, lymph nodes and lungs, and peritoneal seeding, Histological characteristics of the LCI-D20 tumour were similar to those of the original tumour. Karyotypic analysis revealed heteroploid cells. Immunohistochemically, expression of AFP and HBXAG was shown, Our nude mouse model with its high metastatic rate and short latency period could be an interesting tool for the study of human HCC.