Effects of tumor necrosis factor-alpha on tumor blood flow and hyperthermic treatment.
The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-alpha-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-alpha (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3 degrees C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-alpha injection and lasted for at least 4 h. The application of local hyperthermia (T greater than 42 degrees C) 3 h after rhTNF-alpha administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-alpha (0.2 and 1.0 mg/kg i.v.) combined with hyperthermia (43.3 and 44.3 degrees C, 40 min, starting 3 h after rhTNF-alpha 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-alpha treatment by further reducing tumor perfusion.
Kallinowski
F
F
Institute of Physiology and Pathophysiology, University of Mainz, FRG.
Moehle
R
R
Schaefer
C
C
Vaupel
P
P
D000818:Animals; D002296:Carcinosarcoma / Q000098:blood supply* / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D006979:Hyperthermia, Induced; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D012983:Soft Tissue Neoplasms / Q000098:blood supply* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha