美法仑与肿瘤坏死因子隔离肺灌注治疗转移性肺腺癌

Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma.

作者信息

Hendriks J M, Van Schil P E, De Boeck G, Lauwers P R, Van Oosterom A A, Van Marck E A, Eyskens E J

机构信息

Laboratory for Experimental Surgery, University of Antwerp, Belgium.

出版信息

Ann Thorac Surg. 1998 Nov;66(5):1719-25. doi: 10.1016/s0003-4975(98)00990-4.

DOI:10.1016/s0003-4975(98)00990-4

PMID:9875778

Abstract

BACKGROUND

Isolated left lung perfusion with melphalan and human tumor necrosis factor-alpha for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied.

METHODS

Survival was determined for melphalan, human tumor necrosis-alpha. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 x 10(6) CC531S cells intravenously. On day 7, rats underwent sham thoracotomy, received melphalan intravenously, or underwent isolated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted.

RESULTS

For the doses of 400 microg tumor necrosis factor, 1,000 microg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 microg), survival rates after contralateral pneumonectomy were 33%, 17%, and 80%, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to intravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28+/-17) compared to isolated administration (200+/-0) (p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16+/-10) compared to controls (171+/-65) (p = 0.00047). Tumor necrosis factor showed no significant effect.

CONCLUSIONS

Isolated lung perfusion with melphalan is an effective treatment for pulmonary metastases from adenocarcinoma in the rat.

摘要

背景

研究了在WAG/Rij大鼠中使用美法仑和人肿瘤坏死因子-α进行孤立性左肺灌注治疗肺转移性腺癌的情况。

方法

测定美法仑、人肿瘤坏死因子-α的生存率。在孤立性肺灌注或静脉注射后，通过色谱法分析肺、肺流出液和美法仑血清。在第0天，大鼠静脉注射2.0×10(6)个CC531S细胞。在第7天，大鼠接受假开胸手术、静脉注射美法仑，或用生理盐水、美法仑、肿瘤坏死因子以及后两者的组合进行孤立性左肺灌注。在第14天，对肿瘤结节进行计数。

结果

对于400微克肿瘤坏死因子、1000微克肿瘤坏死因子或美法仑与肿瘤坏死因子两者联合使用（2毫克 + 200微克）的剂量，对侧肺切除术后的生存率分别为33%、17%和80%。所有其他组的生存率为100%。与静脉给药相比，孤立性肺灌注后左肺美法仑水平显著更高。与孤立给药（200±0）相比，0.5毫克美法仑孤立性肺灌注时左肺结节明显更少（28±17）（p = 0.001），与对照组（171±65）相比，1.0毫克美法仑静脉肺灌注时左肺结节明显更少（16±10）（p = 0.00047）。肿瘤坏死因子未显示出显著效果。