Creasey A A, Reynolds M T, Laird W
Cancer Res. 1986 Nov;46(11):5687-90.
We tested the effect of recombinant human tumor necrosis factor (TNF) on the growth of the murine methylcholanthrene induced fibrosarcoma and the human ovarian carcinoma (NIH:OVCAR-3) in mice. The mice received multiple doses (25-250 micrograms/kg) of TNF starting 7-10 days after s.c. transplantation of tumors when they were easily palpable. TNF was administered i.v. every other day for a total of 6 injections per mouse, or i.p. daily for 7 days. Complete tumor regression was observed in the methylcholanthrene induced tumor bearing mice in 90% of the mice treated with TNF (100 micrograms/kg), 67% treated with TNF (50 micrograms/kg), and 34% treated with TNF (25 micrograms/kg). Tumors which did not completely regress were growth retarded during the course of TNF treatment. All mice given the highest TNF dose are still alive and tumor free (currently over 400 days), whereas the median survival of control mice was 28-39 days. Partial regression was observed in 100% of mice bearing the ovarian carcinoma treated i.p. with 250 micrograms/kg. Injections of TNF i.v. resulted in higher percentage of cures than i.p. injections at similar dose levels. These results suggest that tumor necrosis factor represents a likely potent drug against solid tumors and that the method of administration is critical in optimizing its use in cancer.
我们测试了重组人肿瘤坏死因子（TNF）对小鼠甲基胆蒽诱导的纤维肉瘤以及人卵巢癌（NIH:OVCAR-3）在小鼠体内生长的影响。在皮下移植肿瘤7 - 10天后，当肿瘤易于触及时，小鼠接受多剂量（25 - 250微克/千克）的TNF。TNF通过静脉注射给药，每只小鼠每隔一天注射一次，共注射6次；或者通过腹腔注射给药，每天注射一次，持续7天。在接受TNF（100微克/千克）治疗的甲基胆蒽诱导的荷瘤小鼠中，90%观察到肿瘤完全消退；接受TNF（50微克/千克）治疗的小鼠中，67%肿瘤完全消退；接受TNF（25微克/千克）治疗的小鼠中，34%肿瘤完全消退。未完全消退的肿瘤在TNF治疗过程中生长受到抑制。所有接受最高剂量TNF的小鼠仍然存活且无肿瘤（目前已超过400天），而对照小鼠的中位生存期为28 - 39天。在腹腔注射250微克/千克TNF治疗的荷卵巢癌小鼠中，100%观察到部分消退。在相似剂量水平下，静脉注射TNF比腹腔注射导致更高的治愈率。这些结果表明肿瘤坏死因子可能是一种有效的抗实体瘤药物，并且给药方式对于优化其在癌症治疗中的应用至关重要。
