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头颈部鳞状细胞癌和正常黏膜中耐药相关基因的表达

Expression of drug resistance-related genes in head and neck squamous cell carcinomas and normal mucosa.

作者信息

Hirata S, Katoh O, Oguri T, Watanabe H, Yajin K

机构信息

Department of Otorhinolaryngology, Hiroshima University Faculty of Medicine.

出版信息

Jpn J Cancer Res. 2000 Jan;91(1):84-90. doi: 10.1111/j.1349-7006.2000.tb00863.x.

Abstract

We examined the expression levels of mRNA for multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT), lung resistance-related protein (LRP), topoisomerase IIalpha, beta (Topo IIalpha, beta) and topoisomerase I (Topo I) genes in human head and neck squamous cell carcinoma (HNSCC) specimens and mucosa (HNM) specimens, to elucidate their roles in relation to the biological characteristics and drug resistance in vivo. Fifty-eight samples (45 head and neck carcinomas and 13 head and neck mucosa) obtained during surgical resection or biopsy from 38 patients were analyzed using the quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. MDR1, MRP, LRP, Topo IIalpha, Topo IIbeta, and Topo I gene transcripts were detected in all the samples tested, but cMOAT mRNA was not detected in them. Comparisons of the expression levels in HNSCC with those in HNM showed that the Topo IIalpha gene expression level was higher in HNSCC than in HNM (P=0.0298). Moreover, the Topo IIalpha mRNA level was significantly higher in metastatic lymph node samples of HNSCC than in HNM samples (P=0.0205). There were no significant differences in the six genes' expression levels between samples exposed to platinum drugs and those not exposed to platinum drugs. These results suggest that it may be effective in anticancer therapy to use topoisomerase-targetting drugs against HNSCC, especially metastatic neck tumors, and that the expression of these genes in HNSCC is not associated with platinum drug exposure.

摘要

我们检测了人头颈鳞状细胞癌(HNSCC)标本和黏膜(HNM)标本中多药耐药1(MDR1)、多药耐药相关蛋白(MRP)、人胆小管多特异性有机阴离子转运体(cMOAT)、肺耐药相关蛋白(LRP)、拓扑异构酶IIα、β(Topo IIα、β)和拓扑异构酶I(Topo I)基因的mRNA表达水平,以阐明它们在体内与生物学特性和耐药性的关系。使用定量逆转录聚合酶链反应(RT-PCR)方法分析了从38例患者手术切除或活检时获得的58个样本(45例头颈癌和13例头颈黏膜)。在所有检测样本中均检测到MDR1、MRP、LRP、Topo IIα、Topo IIβ和Topo I基因转录本,但未检测到cMOAT mRNA。HNSCC与HNM中表达水平的比较表明,HNSCC中Topo IIα基因表达水平高于HNM(P = 0.0298)。此外,HNSCC转移淋巴结样本中Topo IIα mRNA水平显著高于HNM样本(P = 0.0205)。暴露于铂类药物的样本与未暴露于铂类药物的样本之间,这六个基因的表达水平没有显著差异。这些结果表明,使用拓扑异构酶靶向药物治疗HNSCC,尤其是转移性颈部肿瘤,可能在抗癌治疗中有效,并且这些基因在HNSCC中的表达与铂类药物暴露无关。

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