Multidrug-resistant gene expression in small-cell lung cancer.
Multidrug-resistant gene expression in small-cell lung cancer.
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小细胞肺癌中的多重耐药基因表达。
DOI：
10.1097/00000421-199708000-00016
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
Feun,LG
中科院分区：
文献类型：
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作者：
Savaraj,N;Wu,CJ;Xu,R;Lampidis,T;Lai,S;Donnelly,E;Solomon,J;Feun,LG
耐药的发展可能导致小细胞肺癌（SCLC）治疗失败。在本报告中，我们研究了这些患者中p糖蛋白介导的多药耐药（MDR）。治疗前取肿瘤组织，复发时取肿瘤组织，进行短期培养，采用槽位印迹（slot blot）、逆转录聚合酶链反应（RT-PCR）和northern blot分析肿瘤细胞的MDR基因表达情况。通过短期培养也建立了3个细胞系。24例MDR（−）患者和7例MDR+(++)患者可用于生存分析。MDR（-）患者的中位生存期为10个月，而MDR+(++)患者的中位生存期为2个月。差异有统计学意义（p< 0.0007）。MDR1基因表达的存在也与对化疗缺乏反应相关（p< 0.001）。MDR1基因表达增加通常出现在初始诊断时肿瘤负荷较大的患者中。此外，内在MDR (+) SCLC细胞在无药培养基中多次传代后，MDR1基因表达的丢失可能发生。我们的结论是，在化疗前后，少量SCLC中都存在MDR1基因表达增加，这通常意味着生存不良和对化疗无反应。
The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short-term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from shortterm cultures. Twenty-four patients with MDR (−) and seven with MDR+(++) were available for survival analysis. Median survival for MDR (−) patients was 10 months, whereas for MDR+(++) patients it was 2 months. This was statistically significance (p< 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p< 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR (+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.