Effects of tumor necrosis factor-a on tumor blood flow and hyperthermic treatment

Author(s): Moehle, R., Schaefer, C., Vaupel, P.

Journal/Book: Onkologie. 1989; 12: 131-135.

Abstract: The impact of recombinant human tumor necrosis factor-a (rhTNF-a), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-a-sensitive rat tumor (DS-carcinosarcoma) was investigated. DS-carcinosarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Tumor blood flow (TBF) was measured with the krypton-85 clearance technique. Treatment with either tumor necrosis factor-a (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3°C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-a injection and lasted for at least 4 h. The application of local hyperthermia (T> 42°C) 3h after rhTNF-? administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-a (0.2 and 1.0mg/kg i.v.) combined with hyperthermia (43.3 and 44.3°C, 40 min, starting 3 h after rhTNF-a injection) were given every third day from the fifth to the 20th day after tumor implantation. Monotherapies retarded tumor growth in a dose-dependent manner. Combined treatment was superior to either monotherapy leading to local tumor control in 40-50% of the animals treated. It is concluded that local hyperthermia can enhance the efficacy of rhTNF-a treatment by further reducing tumor perfusion.

Keyword(s): Tumor-Nekrose-Factor-?

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