ANTITUMOR-ACTIVITY OF NATURAL-TYPE HUMAN TUMOR-NECROSIS-FACTOR ON EXPERIMENTAL BRAIN-TUMORS IN RATS

The effects of intralesional injection of newly synthesized natural-ty pe human tumor necrosis factor (nh-TNF) on experimental brain tumors i n rats were investigated. The repeated injection of 5,000 U of nh-TNF into the tumor resulted in tile prolongation of the survival time of t he rats. More than half of the nh-TNF treated tumors were red, and wer e characterized by histopathological features of marked congestion of tumor vessels. Fibrin formations were also found in the tumor vessels. These histological findings were not observed in the control tumors. Furthermore, coagulative necrosis was observed in the center of some r eddish tumors. Leukocytes adhering to vascular endothelium and infiltr ation of the leukocytes were also observed in the tumors of nh-TNF tre ated rats. In the immunohistochemical examination, these infiltrated c ells were primarily polymorphonuclear leukocytes and macrophages. Expr ession of intercellular adhesion molecule-1 (ICAM-1) increased on the tumor endothelial cells after the administration of nh-TNF. These resu lts suggest that repeated injection of nh-TNF has a therapeutic effect on brain tumors through its extensive influences on tumor vasculature .