AUGMENTED ANTITUMOR EFFECTS OF COMBINED TREATMENT WITH HYPERTHERMIA AND TUMOR-NECROSIS-FACTOR ON HUMAN GASTRIC-CANCER XENOTRANSPLANTED INTO NUDE-MICE

Hyperthermia combined with recombinant human tumour necrosis factor (rH-TNF) was evaluated for antitumour efficacy in vivo. Use was made of human gastric cancer tissues xenografted into nude mice. When 100, 300, 600, and 1200 units of rH-TNF (2.4 x 10(6) units/mg protein) were given twice intraperitoneally, tumour regression did not occur in any animal. In contrast, a remarkable suppression of tumour growth was observed when 600 and 1200 units of rH-TNF was given in combination with hyperthermia at 43.5 +/- 0.1-degrees-C. No effects were evident with the regimen of 100 and 300 units of rH-TNF plus hyperthermia at the same temperature, as compared with evidence obtained with hyperthermia alone. The tumoral blood flow, determined by the hydrogen diffusion method, decreased immediately after hyperthermia alone or hyperthermia plus 1200 units of rH-TNF, whereas a slight decrease was seen after rH-TNF alone. When hyperthermia plus 1200 units of rH-TNF were given, there was a remarkable delay in reversion to pretreatment values of tumoral blood flow, as compared to findings with rH-TNF only or heat only. These results are discussed in relation to the antitumour and side-effects of rH-TNF.