Angiogenesis inhibitor TNP-470 prevents implanted liver metastases after partial hepatectomy in an experimental model without impairing wound healing

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Abstract
The ability of the angiogenesis inhibitor TNP-470 to prevent liver metastasis after partial hepatectomy, and whether TNP-470 impairs liver regeneration or skin wound healing, was evaluated. Following the injection of VX2 carcinoma cells into the portal vein of rabbits, half of the animals underwent resection of the middle hepatic lobe (hepatectomized group) and half did not (non-hepatectomized group). TNP-470 (50 mg) was infused continuously into the portal vein in both groups for 7 days, while controls received only water. The hepatectomized TNP-470-treated group had significantly fewer tumours (mean(s.e.m.) 23·3(12·3)) than the hepatectomized control group (123·7(24·4)). There was no significant difference in the 5-bromo-2′-deoxyuridine labelling index of regenerated 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.