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目的探讨肿瘤多药耐药蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)、肺耐药相关蛋白(LRP)、谷胱甘肽-S-转移酶(GST-π)及DNA拓扑异构酶Ⅱα(TopoⅡα)在儿童颅内肿瘤的表达特点,为其临床化疗方案的选择提供实验依据。方法分析本院2000年1月-2004年12月收治的临床资料完整、手术切除并经病理检查证实为儿童颅内肿瘤的石蜡标本38例,应用免疫组织化学S-P法检测38例颅内肿瘤儿童中多药耐药蛋白P-gp、MRP1、LRP、GST-π及TopoⅡα的表达;以10例非肿瘤患儿脑组织作为对照。结果1.颅内肿瘤患儿脑组织P-gp、GST-π、TopoⅡα、MRP1和LRP阳性表达率分别为65.8%、60.5%、47.4%、44.7%和44.7%,非肿瘤患儿脑组织P-gp阳性表达率为10%,其他4种多药耐药蛋白均为阴性。二组阳性表达率有显著性差异(P<0.01)。2.同一病理类型5种多药耐药蛋白的表达及同一耐药蛋白在不同病理类型间的表达均无显著性差异(Pa>0.05)。3.P-gp在星形细胞瘤和髓母细胞瘤的血管内皮细胞表达较高,而在颅咽管瘤和室管膜瘤组织则不明显。P-gp、GST-π在低恶性组和高恶性组间表达比较均有显著性差异(Pa<0.05)。结论儿童颅内肿瘤化疗失败的主要原因与血脑脊液屏障、血肿瘤屏障对化疗药物阻滞及肿瘤细胞本身的原发耐药密切相关。不同儿童颅内肿瘤的耐药性有各自的特点,有助于临床个体化化疗方案的制订。如果针对性地阻断这些耐药相关因素,能提高儿童颅内肿瘤的化疗效果。
Objective To investigate the expression of P-gp, MRP1, LRP, GST- π) and TopoⅡα expression in children with intracranial tumors, providing an experimental basis for the selection of clinical chemotherapy regimen. Methods The clinical data of 38 patients with intracranial tumors in our hospital from January 2000 to December 2004 were analyzed retrospectively. The clinical data of 38 patients with intracranial tumors confirmed by pathology and complete resection were analyzed by immunohistochemical SP method. The expression of multidrug resistance protein P-gp, MRP1, LRP, GST-π and TopoⅡα in 10 cases of non-tumor children’s brain tissue as a control. The positive expression rates of P-gp, GST-π, TopoⅡα, MRP1 and LRP in brain tissue of children with intracranial tumors were 65.8%, 60.5%, 47.4%, 44.7% and 44.7% -gp positive expression rate of 10%, the other four kinds of multi-drug resistance protein were negative. There was a significant difference between the two groups (P <0.01). There was no significant difference in the expression of five multidrug resistance proteins of the same pathological type and the same multidrug resistance protein in different pathological types (Pa> 0.05). The expression of P-gp was higher in vascular endothelial cells of astrocytoma and medulloblastoma, but not in craniopharyngioma and ependymoma. The expressions of P-gp and GST-π were significantly different between low-grade group and high-grade group (P <0.05). Conclusion The main reasons for the failure of chemotherapy in children with intracranial tumors are closely related to the blood-cerebrospinal fluid barrier and the blood-borne tumor barrier to chemotherapeutic drugs and the primary drug resistance of tumor cells. Different children with intracranial tumors have their own characteristics of drug resistance, contribute to the development of personalized clinical chemotherapy program. If targeted blocking these resistance-related factors, can improve the chemotherapy effect of intracranial tumors in children.