Gridley D S, Archambeau J O, Andres M A, Mao X W, Wright K, Slater J M
Department of Microbiology & Molecular Genetics, Loma Linda University School of Medicine and Medical Center, CA 92350, USA.
Oncol Res. 1997;9(5):217-27.
Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. The aim of this study was to determine if low doses of tumor necrosis factor-alpha (TNF-alpha) could augment the effects of radiation in a glioma xenograft model and to evaluate hematological and other parameters that might indicate treatment-related toxicity. Nude mice were injected subcutaneously with C6 rat glioma cells and randomized into groups. Two different time-dose protocols were employed using intravenous human recombinant TNF-alpha and radiation beginning within 24 h after tumor cell implantation. The administration of radiation as a single agent slowed tumor progression, whereas TNF-alpha alone had no effect. However, TNF-alpha, especially when given twice per week before radiation for a total of four doses each, significantly increased the efficacy of the radiation. Low leukocyte counts were associated with combination treatment, whereas transforming growth factor-beta 1 levels were depressed in all treated groups. TNF-alpha did not modulate radiation-induced inhibition of C6 cell proliferation in vitro. The data show that TNF-alpha at relatively nontoxic doses can significantly enhance the antitumor effects of radiation against a rapidly growing glioma. This effect was more than additive, because TNF-alpha alone did not slow tumor progression.
目前的治疗方案很少能实现对高级别脑肿瘤的长期控制。本研究的目的是确定低剂量的肿瘤坏死因子-α（TNF-α）是否能增强胶质瘤异种移植模型中放疗的效果，并评估可能表明治疗相关毒性的血液学和其他参数。将C6大鼠胶质瘤细胞皮下注射到裸鼠体内，并随机分组。在肿瘤细胞植入后24小时内开始，采用两种不同的时间-剂量方案，静脉注射人重组TNF-α和进行放疗。单独放疗可减缓肿瘤进展，而单独使用TNF-α则无效果。然而，TNF-α，尤其是在放疗前每周给药两次，共给药四剂时，可显著提高放疗的疗效。联合治疗与白细胞计数降低有关，而所有治疗组的转化生长因子-β1水平均降低。TNF-α在体外并未调节放疗诱导的C6细胞增殖抑制。数据表明，相对无毒剂量的TNF-α可显著增强放疗对快速生长的胶质瘤的抗肿瘤作用。这种作用不仅仅是相加的，因为单独使用TNF-α并不能减缓肿瘤进展。
