Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Cryobiology. 2012 Feb;64(1):43-9. doi: 10.1016/j.cryobiol.2011.09.137. Epub 2011 Sep 29.
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-α) arguments the anti-tumor effect of cryotherapy in breast and prostate cancers. To test the hypothesis that cryosurgery and rhTNF-α 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 rhTNF-α; and G4 group received combined treatment with cryosurgery and rhTNF-α. 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 G1 rats. Tumor sizes in each group were significantly decreased as compared with those in G1 rats. PCNA-positive cells were significantly decreased in G2, G3 and G4 rats as compared with G1 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-α may have a synergistic effect on glioma tumor therapy, enhancing the inhibition of proliferation and the induction of apoptosis.
脑胶质瘤是一种起源于神经胶质细胞的脑肿瘤，其侵袭性差异很大，会导致严重的症状，但治疗方法有限。研究表明，冷冻手术对肿瘤治疗有多种作用，而人肿瘤坏死因子-α（rhTNF-α）可以增强冷冻疗法在乳腺癌和前列腺癌中的抗肿瘤作用。为了验证冷冻手术和 rhTNF-α 对脑肿瘤具有协同作用的假设，我们在大鼠皮质区建立了脑胶质瘤模型，采用不同的治疗方法：G1 组为假手术组；G2 组采用冷冻手术治疗；G3 组采用 rhTNF-α 治疗；G4 组采用冷冻手术联合 rhTNF-α 治疗。采用磁共振成像测量肿瘤大小；采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL 检测）检测 DNA 片段化；采用免疫组织化学染色评分 P21(WAF1/CIP1)和增殖细胞核抗原（PCNA）的表达水平。G2 和 G4 组大鼠的存活时间明显长于 G1 组。与 G1 组相比，各组的肿瘤体积均明显减小。与 G1 组相比，G2、G3 和 G4 组的 PCNA 阳性细胞明显减少。相反，在每个治疗组中，DNA 片段化和 P21(WAF1/CIP1)阳性细胞均显著增加。重要的是，联合治疗增强了冷冻手术的效果。冷冻手术联合 rhTNF-α 可能对脑胶质瘤的治疗具有协同作用，增强对增殖的抑制和对细胞凋亡的诱导。
