A combined therapy of hyperthermia and tumor necrosis factor for nude mice bearing KK-47 bladder cancer

Abstract

A combined therapy of hyperthermia (43.5 C) and tumor necrosis factor (10(3) and 10(4) units) for the treatment of experimental bladder carcinoma KK-47 in athymic mice was studied. Briefly, mice were injected subcutaneously with 10(7) disaggregated cells. When the tumors were 250 mm3 in size, tumor necrosis factor was administered, either intravenously or by intratumor injection. Intravenous injection was 10(3) to 10(4) units tumor necrosis factor in the tail vein and intratumor was 10(3) to 10(4) units injected directly into the center of the tumor. Immediately following injection, the tumor bearing leg was placed in a 43.5 C water bath for 20 minutes. Tumor size was monitored once a week for seven weeks and the animals were divided into control, hyperthermia alone, tumor necrosis factor alone and combined therapy. Results of the study showed no significant difference in 10(3) units of tumor necrosis factor intravenously versus control but a significant regression in hyperthermia alone. Anti-tumor effects significantly increased in hyperthermia plus 10(3) units tumor necrosis factor versus hyperthermia alone. Similar results were seen with 10(4) units tumor necrosis factor intravenously though in the combination group of hyperthermia and tumor necrosis factor, eight mice of eight died one to three days following treatment. In those receiving intratumor injections, there was no difference between tumor necrosis factor or control. Tumor necrosis factor with hyperthermia had the approximate same characteristics as hyperthermia alone and therefore there was no synergistic finding. These results reflect on the suggestion that the combination therapy of hyperthermia and systemic administration of the proper dosage of tumor necrosis factor may produce synergistic anti-cancer effects in bladder cancer patients.