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Hyperthermia alone had a lethal effect on V-79 cells. Temporary exposure to hyperthermia resulted in substantial decreases in cell growth, in a time (20-120 min)- and temperature (39-44 degrees C)-dependent manner. A precipitous fall in cell growth occurred when cells were incubated at temperatures between 42 and 43 degrees C. Concomitant application of hyperthermia, bleomycin and irradiation (hyperthermochemoradiotherapy) led to a maximal effect, compared with findings in cells treated with a single or two modalities, in vitro as well as in vivo and in clinical cases. To produce a similar situation of tumor cell growth in vivo, multicellular tumor spheroids (MTS) were developed by culturing tumor cells on soft agar. The effect of various treatments on the cells was then determined. Hyperthermia had a greater effect on the inner layer (hypoxic state) of MTS than on the outer layer, while radiotherapy was more effective on the outer layer (aerobic state). The synergistic effect of the combination with hyperthermia and irradiation was exhibited in all layers of MTS. Hyperthermochemoradiotherapy may prove to be an effective and safe form of adjuvant therapy for treating clinical carcinoma.
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