Cryosurgery and rhTNF-α play synergistic effects on a rat cortex C6 glioma model

Glioma, a type of brain tumor originating from glioma cells, varies widely in aggressiveness and causes serious symptoms, but the treatments are limited. Studies have shown that cryosurgery has multiple effects on tumor treatments, and administration of human tumor necrosis factor-alpha (rhTNF-alpha) arguments the anti-tumor effect of cryotherapy in breast and prostate cancers. To test the hypothesis that cryosurgery and rhTNF-alpha play synergistic effects against brain tumors, we established a brain glioma model on rat cortex regions following different treatments: the G1 group was sham-operated; the G2 group was treated with cryosurgery; the G3 group was treated with rhINF-alpha; and G4 group received combined treatment with cryosurgery and rhTNF-alpha. Tumor sizes were measured by magnetic resonance imaging; DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay); P21 (WAF1/CIP1) and proliferating cell nuclear antigen (PCNA) expression levels were scored using immunohistochemical staining. G2 and G4 rats had significantly longer survival time than did GI rats. Tumor sizes in each group were significantly decreased as compared with those in GI rats. PCNA-positive cells were significantly decreased in G2, G3 and G4 rats as compared with GI rats. In contrast, DNA fragmentation and P21 (WAF1/CIP1) -positive cells were significantly increased in each treatment group. Importantly, a combined treatment enhanced the effects of cryosurgery. Combined treatment with cryosurgery and rhTNF-alpha may have a synergistic effect on glioma tumor therapy, enhancing the inhibition of proliferation and the induction of apoptosis. (C) 2011 Elsevier Inc. All rights reserved.