Synergistic cytotoxic and antitumor effects of recombinant human tumor necrosis factor and hyperthermia.
A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of rH-TNF against L-M cells in incubation for 12 h at 38.5 and 40 degrees C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37 degrees C. As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i.v. administration of rH-TNF at 1000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40 degrees C), whereas rH-TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i.v. administration of rH-TNF three times at 100 or 300 units/mouse together with hyperthermia (40 degrees C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth. The results suggest that combination therapy including rH-TNF and hyperthermia may be of value in the treatment of malignancy in human patients.
Watanabe
N
N
Department of Internal Medicine, Sapporo Medical College, Japan.
Niitsu
Y
Y
Umeno
H
H
Sone
H
H
Neda
H
H
Yamauchi
N
N
Maeda
M
M
Urushizaki
I
I
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004334:Drug Administration Schedule; D006979:Hyperthermia, Induced; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000628:therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha