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横纹肌肉瘤和神经母细胞瘤肿瘤细胞中与治疗抗性相关蛋白质的表达

Expression of proteins associated with therapy resistance in rhabdomyosarcoma and neuroblastoma tumour cells.

作者信息

Pituch-Noworolska Anna, Zaremba Marcin, Wieczorek Agnieszka

机构信息

Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, ul. Wielicka 265, 30-663 Kraków.

出版信息

Pol J Pathol. 2009;60(4):168-73.

Abstract

The activity of multidrug resistance (MDR) proteins in tumour cells is associated with an increased resistance to therapy and in consequence with a decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) transporters. Neuroblastoma (NBL) and rhabdomyosarcoma (RMS) are common solid tumours of childhood. The response to therapy is better in NBL, worse in RMS, but still unsatisfactory despite surgery and aggressive chemotherapy. The immunohistochemical staining for p-gp (p-glycoprotein), MRP1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) expression was performed in primary tumour sections of NBL (10 cases) and RMS (10 cases). A different pattern of MDR expression in NBL and RMS were noted. In NBL, MRP1 was expressed in all studied tumours, p-gp, BCRP only in 3 out of 10 tumours, LRP, in 4 cases. The combination of more than one protein was noted in the majority of NBL tumours. In RMS, the expression of 3 or 4 MDR proteins was noted in 9 cases. The high expression of an MDR protein profile in RMS suggests various mechanisms acting simultaneously, which might explain chemotherapy resistance and a low percentage of long-time survival in this tumour.

摘要

肿瘤细胞中多药耐药(MDR)蛋白的活性与治疗抗性增加相关,进而与化疗效果降低相关。大多数MDR分子属于ABC(ATP结合盒)转运蛋白家族。神经母细胞瘤(NBL)和横纹肌肉瘤(RMS)是儿童常见的实体瘤。NBL对治疗的反应较好,RMS较差,但尽管进行了手术和积极化疗,效果仍不尽人意。对10例NBL和10例RMS的原发肿瘤切片进行了p-糖蛋白(p-gp)、多药耐药相关蛋白1(MRP1)、乳腺癌耐药蛋白(BCRP)和肺耐药蛋白(LRP)表达的免疫组化染色。在NBL和RMS中观察到不同的MDR表达模式。在NBL中,所有研究的肿瘤均表达MRP1,p-gp、BCRP仅在10个肿瘤中的3个中表达,LRP在4例中表达。大多数NBL肿瘤中观察到一种以上蛋白的组合。在RMS中,9例中观察到3种或4种MDR蛋白的表达。RMS中MDR蛋白谱的高表达提示多种机制同时起作用,这可能解释了该肿瘤的化疗抗性和低长期生存率。

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