Jones A L, Millar J L, Millar B C, Powell B, Selby P, Winkley A, Lakhani S, Gore M E, McElwain T J
Section of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK.
Br J Cancer. 1990 Nov;62(5):776-80. doi: 10.1038/bjc.1990.378.
The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation.
研究了重组人肿瘤坏死因子α（rhTNFα）与卡莫司汀（BCNU）联合应用对实验性黑色素瘤的体内外作用。在体外，单独使用BCNU对小鼠B16黑色素瘤细胞具有细胞毒性，并且在所有BCNU浓度下，添加TNF均可增强这种毒性。在体内，单独给予BCNU和TNF可导致免疫缺陷小鼠体内B16黑色素瘤和人黑色素瘤异种移植物的肿瘤生长延迟。低剂量TNF（2.5×10⁵U kg⁻¹ = 122 ng kg⁻¹）与BCNU（35 mg kg⁻¹）联合使用可使B16黑色素瘤的生长显著延迟（与单独使用任一药物相比，P = 0.005）。通过体重减轻和外周血细胞计数评估，毒性没有显著增加。用人黑色素瘤异种移植物进行的实验也得到了类似结果（P = 0.001），但仅在较高剂量的TNF（1×10⁶U kg⁻¹ = 489 ng kg⁻¹）时出现。如果TNF对BCNU细胞毒性的增强作用能够应用于黑色素瘤患者，可能具有重要意义。目前正在进行一项随机研究，以调查这一观察结果的临床潜力。
