ANGIOGENESIS INHIBITOR TNP-470 PREVENTS IMPLANTED LIVER METASTASES AFTER PARTIAL-HEPATECTOMY IN AN EXPERIMENTAL-MODEL WITHOUT IMPAIRING WOUND-HEALING

The ability of the angiogenesis inhibitor TNP-470 to prevent liver met astasis after partial hepatectomy, and whether TNP-470 impairs liver r egeneration or skin wound healing, was evaluated. Following the inject ion of VX2 carcinoma cells into the portal vein of rabbits, half of th e animals underwent resection of the middle hepatic lobe (hepatectomiz ed group) and half did not (non-hepatectomized group). TNP-470 (50 mg) was infused continuously into the portal vein in both groups for 7 da ys, while controls received only water. The hepatectomized TNP-470-tre ated group had significantly fewer tumours (mean(s.e.m.) 23.3(12.3)) t han the hepatectomized control group (123.7(24.4)). There was no signi ficant difference in the 5-bromo-2'-deoxyuridine labelling index of re generated hepatocytes between the TNP-470-treated and control groups. Wound healing in TNP-470-treated animals was not impaired. Intraportal infusion of TNP-470 prevents the recurrence of liver metastasis after partial hepatectomy without impairing healing or liver regeneration.