摘要
目的 本实验旨在通过不同类型的小儿颅内肿瘤中多药耐药相关因素的表达情况分析 ,探讨小儿颅内肿瘤化疗疗效较差的原因以及血脑、血肿瘤屏障与颅内肿瘤耐药性的关系 ,以寻求克服这些耐药因素的策略 ,提高颅内肿瘤化疗疗效。方法 标本选自重庆医科大学附属儿童医院及附属第一医院近 3年存档的小儿颅内肿瘤标本共 5 2例 ,星形细胞瘤 8例 ,分化不良的星形细胞瘤 8例 ,多形性胶质母细胞瘤 8例、脑膜瘤 8例、髓母细胞瘤 10例和颅咽管瘤 10例 ,此外还作了 5例正常脑组织作对照。所有患儿均为初诊 ,年龄 1～ 18岁 ,中位年龄 5岁 ,男∶女 =2∶1。 2 9例获随访资料 ,随访时间 2个月～ 3年 ,术后生存期自手术日至失访或死亡日止。应用SP免疫组化方法检测小儿颅内肿瘤中P gp、MRP、LRP、TopoIIα的表达。 结果 在所有检测的颅内肿瘤中P gp、MRP、LRP、TopoIIα的表达阳性率分别是 6 1.5 %、36 .5 %、2 6 .9%、36 .5 %。P gp、MRP、LRP在星形细胞瘤和髓母细胞瘤中主要表达于血管内皮细胞 ,而肿瘤细胞几乎不表达。但在脑膜瘤、颅咽管瘤中却没有这种差异。TopoIIα主要表达于肿瘤细胞核内 ,偶见其他细胞的散在弱阳性表达。 结论 小儿颅内肿瘤化疗失败的原因主要与血脑、血肿瘤屏障对化疗药物的阻滞以及肿瘤细胞本?
Objective To determine if drug resistance is a possible cause of the low efficacy of chemotherapy in intracranial tumors of children.Methods Immunoreactivity of monoclonal antibodies to P-gp, MRP, LRP, Topo IIα were examined in intracranial tumors in 52 children by SP immunohistochemistry.Results The intracranial tumors expressed P-gp, MRP, LRP, Topo II, with positive rates being 62.5%, 36.5%, 26.9% and 36.5%, respectively, irrespective of the tumor type. P-gp, MRP, LRP demonstrated strong cytoplasmic expression in endothelial cells of the small blood capillaries in the astrocytoma and medulloblastoma. In contrast, they were almost absent in tumor cells. However, significant difference in meningioma and craniopharyngioma was not found. The expression of topoisomerase IIα, predominantly was associated with the nucleus in tumor cells. Besides, there was occasionally weak immunostaining in the others. Conclusions Several reasons have been proposed as an explanation for the low efficacy of chemotherapy in intracranial tumors of children. The entry of drugs into the brain has been strictly regulated by blood-brain barrier or blood-tumor barrier and intrinsic drug resistance at the tumor cell level. Different intracranial tumors of children have different characteristics of drug resistance. If the resistance mechanisms could be manipulated, the efficacy of chemotherapy will be highly improved.
出处
《中华小儿外科杂志》
CSCD
北大核心
2004年第1期13-17,共5页
Chinese Journal of Pediatric Surgery
基金
国家自然科学基金资助项目 (项目编号 :3 0 0 70 781)
