Antitumor effects of intraarterial infusion of tumor necrosis factor/lipiodol emulsion on hepatic tumor in rabbits.

Human recombinant tumor necrosis factor (TNF) suspended in lipiodol (TNF/lipiodol emulsion) was injected via the hepatic artery, and its antitumor effects on VX2 tumor inoculated into the liver were evaluated. In TNF/lipiodol-treated rabbits, soft-X-ray study revealed an accumulation of lipiodol in the liver tumor and the TNF concentration in the tumors was significantly higher than in rabbits treated with free TNF. 7 days after the various treatments, the tumor growth ratio evaluated macroscopically was found to be significantly lower in TNF/lipiodol emulsion-treated rabbits compared to rabbits treated with either free TNF or lipiodol (p < 0.05). Microscopically, the necrotic-area ratio of the tumors in the TNF/lipiodol emulsion-treated group was also significantly greater than in any other group (p < 0.01). Pathohistologically, liver tumors treated with TNF/lipiodol emulsion revealed massive necrosis associated with occlusive thromboangitis in the tumor vessels and fibrous capsule formation around the tumor. In these rabbits, the elevation of serum transaminase after the treatment was transient and tissue damage in the surrounding noncancerous liver tissue was minimal. These findings therefore suggest that the intraarterial infusion of TNF/lipiodol emulsion may produce prominent antitumor effects, possibly due to the retention of TNF in the tumors, which causes damage to the endothelium of the tumor vessels.