ENDOGENOUS PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN COMBINATION WITH HYPERTHERMIA FOR THE TREATMENT OF MICE BEARING EHRLICH ASCITES TUMOR

Multiple hyperthermia was found to exert an additive antitumor effect when combined with the in vivo production of tumor necrosis factor alp ha (TNF-alpha) in mice bearing Ehrlich ascites tumor (EAT). TNF-alpha was produced in EAT-bearing mice by priming the animals with zymosan a nd subsequently challenging with lipopolysaccharide (LPS). Mice were p retreated with sulindac and D-mannoheptulose to alleviate the toxic si de effects of LPS. While the ability of these tumor-bearing mice to pr oduce TNF-alpha remained unchanged under hyperthermia, the EAT cell nu mber was suppressed in the combined-treatment group compared with grou ps treated with TNF-alpha or hyperthermia alone. In the same compariso n, the life span of EAT-bearing mice in the combined-treatment group w as prolonged.