Brunstein Flavia, Santos Ivan Dunshee de Abranches Oliveira, Ferreira Lydia Masako, van Tiel Sandra T, Eggermont Alexander M M, Ten Hagen Timo L M
Laboratory of Experimental Surgical Oncology, Daniel den Hoed Cancer Center, Erasmus MC, Rotterdam, The Netherlands.
Acta Cir Bras. 2005 Jul-Aug;20(4):275-9. doi: 10.1590/s0102-86502005000400003. Epub 2005 Jul 18.
To evaluate the potential benefit of histamine combined with melphalan in the isolated limb perfusion (ILP) as an alternative to TNF-alfa and melphalan combination, for the treatment of irresectable soft tissue sarcomas of the limbs in Brown Norway (BN) rats.
20 BN rats had small fragments of syngeneic BN-175 fibrosarcoma inserted on the right hind limb. In 7-10 days the tumor reached a median diameter of 12-15 mm and they were randomly divided in four groups (sham, melphalan, histamine and escalating doses of histamine combined to melphalan) being submitted to experimental ILP for 30 minutes. Tumors were measured daily with a caliper and the volume was calculated.
Response curves showed a significant effect of the combination of histamine 200 mg/mL with melphalan, with 66% overall response, including 33% complete responses (p< 0.01). There were no systemic collateral effects and locally only mild temporary edema was observed for some animals treated with histamine.
Histamine combined with melphalan had a promising effect in the ILP warranting future studies to better explore the mechanism of action as well as its potential use in organ perfusion.
评估组胺联合美法仑在离体肢体灌注（ILP）中作为肿瘤坏死因子-α与美法仑联合方案的替代方案，用于治疗棕色挪威（BN）大鼠肢体不可切除软组织肉瘤的潜在益处。
20只BN大鼠在右后肢植入同基因BN-175纤维肉瘤的小碎片。7-10天后，肿瘤中位直径达到12-15毫米，将它们随机分为四组（假手术组、美法仑组、组胺组以及组胺与美法仑递增剂量联合组），进行30分钟的实验性ILP。每天用卡尺测量肿瘤大小并计算体积。
反应曲线显示200毫克/毫升组胺与美法仑联合具有显著效果，总体反应率为66%，包括33%的完全缓解（p<0.01）。未观察到全身副作用，仅部分接受组胺治疗的动物局部出现轻度暂时水肿。
组胺联合美法仑在ILP中具有良好效果，值得进一步研究以更好地探索其作用机制及其在器官灌注中的潜在应用。
