ANGIOGENESIS INHIBITOR TNP-470 AUGMENTS THE EFFECT OF REPEATED ARTERIAL ISCHEMIA ON GROWTH BUT DOES NOT AFFECT TAKE IN A RAT-LIVER TUMOR-MODEL

Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes p lace from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (th erapeutic model). Wistar rats with a dimethylhydrazine-induced adenoca rcinoma implanted into the liver received one of the following treatme nts: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP -470 decreases the risk of tumor take in the liver after intraportal i njection of viable tumor cells (adjuvant study. Transient hepatic isch emia combined with TNP-470 gave a smaller increase in tumor volume tha n transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls ( p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retarda tion of tumor growth (p < 0.02 as compared to controls) but did not af fect tumor number. It is concluded that TNP-470 suppressed tumor growt h, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor.