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.