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Synergistic Effects of Recombinant Human Tumor Necrosis Factor and Hyperthermia on in Vitro Cytotoxicity and Artificial Metastasis

Department of Internal Medicine (Section 4), Sapporo Medical College, South-1, South-1, West-16, Chu-ku, Sapporo, Japan

Synergy in cytotoxic effect between recombinant human tumor necrosis factor and hyperthermia (incubation at 38.5°C or 40°C) was observed to occur against L-M (mouse tumorigenic fibroblast) cells and shown to be related to an accelerated turnover rate of recombinant human tumor necrosis factor-receptor complex under elevated temperatures rather than to changes in number of cell receptors or binding strength. However, no synergy in cytotoxic effect was observed to occur against human embryonic lung (HEL) cells.

A clearly synergistic inhibition of metastatic tumor growth by combined administration of recombinant human tumor necrosis factor (300 units) and whole-body hyperthermia (40°C, 30 min) was also observed in BALB/c mice previously given injections of 1 x 10⁶ Meth-A (MH) cells/mouse via tail vein, neither of which alone resulted in significant inhibition.

Received 6/26/87. Revised 10/ 1/87. Accepted 10/27/87.

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