Increased expression of multidrug resistance-associated genes after chemotherapy in pediatric solid malignancies
Increased expression of multidrug resistance-associated genes after chemotherapy in pediatric solid malignancies
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DOI：
10.1016/j.jpedsurg.2008.10.088
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发表时间：
2009-02-01
影响因子：
2.4
通讯作者：
Fukuzawa, Masahiro
中科院分区：
文献类型：
--
作者：
Oue, Takaharu;Yoneda, Akihiro;Fukuzawa, Masahiro
背景/目的：多药耐药（MDR）相关基因在未经治疗的原发性肿瘤中的过度表达已被证实与多种儿科恶性肿瘤预后较差相关。本研究比较了3个耐多药相关基因MDR1、耐多药相关蛋白1 （MRP1）和肺耐药相关蛋白（LRP）在儿科肿瘤化疗前后的表达情况，以阐明化疗期间耐多药发生的机制。方法：选取24例小儿恶性肿瘤（神经母细胞瘤[NB] 8例；肝母细胞瘤[HB] 8例；肾母细胞瘤[WT] 4例；横纹肌肉瘤[RB] 4例）的原发和化疗肿瘤的手术标本。免疫组化染色检测MDR1、MRP1、LRP的表达。结果：在原发肿瘤中，MDR1在6个NBs、9个HBs、3个WTs和3个RBs中表达。MRP1在3个nb和1个HB中表达。LRP在原发肿瘤中未见表达。化疗后，5例NBs、4例HBs、2例WTs、3例RBs的MDR1表达升高。在7个nb、4个hb和3个RBs中新观察到或增加了MRP1表达。LRP在3例HBs和2例WTs中有新表达。结论：这些结果表明，这3种耐多药相关基因在各种儿科恶性肿瘤化疗后表达上调。这些发现可能有助于了解儿童恶性肿瘤的耐药机制。(C) 2009爱思唯尔公司版权所有。
Background/Purpose: The overexpression of multidrug resistance (MDR) associated genes in primary untreated tumors has been proven to be associated with worse prognosis in various pediatric malignancies. This Study compared the expression of 3 MDR-associated genes, MDR1, MDR-associated protein 1 (MRP1), and lung resistance related protein (LRP), in pediatric tumors before and after chemotherapy to elucidate the mechanism of MDR during chemotherapy.Methods: Surgical specimens of both primary and chemotherapy-treated tumors were obtained from 24 patients with pediatric malignancies (neuroblastoma [NB] 8; hepatoblastoma [HB] 8; Wilms tumor [WT] 4; rhabdomyosarcoma [RB] 4). The expression of MDR1, MRP1, and LRP was evaluated using the immunohistochemical staining.Results: In primary tumors, MDR1 expression was observed in 6 NBs, 9 HBs, 3 WTs, and 3 RBs. MRP1 expression was observed in 3 NBs and I HB. LRP expression was not detected in,my of the primary tumors. After chemotherapy, MDR1 expression was observed to increase in 5 NBs, 4 HBs, 2 WTs, and 3 RBs. MRP1 expression was newly observed or increased in 7 NBs, 4 HBs, and 3 RBs. LRP expression was newly observed in 3 HBs and 2 WTs.Conclusions: These results indicate that these 3 MDR-associated genes were upregulated after chemotherapy in various pediatric malignancies. These findings may be useful to Understand the mechanism of drug resistance in pediatric malignancies. (C) 2009 Elsevier Inc. All rights reserved.