摘要
目的探讨实体恶性肿瘤化疗患儿外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)中多药耐药基因(multi-drug resistance1,MDR1)、多药耐药相关蛋白基因(multi-drug resistance-associated protein1,MRP1)、肺耐药蛋白基因(lung resistance protein,LRP)的表达量及其与临床化疗的关系。方法应用实时荧光定量PCR(real-time fluores-cence quantitative PCR,FQ-PCR)技术,检测患儿化疗前后外周血和手术切除新鲜冻存组织,以及对照组外周血中MDR1、MRP1、LRP的mRNA表达量。结果所有化疗患儿外周血MDR1表达量与同期手术切除的肿瘤组织MDR1表达量存在正相关(r=0.894,P=0.000);化疗前后外周血MDR1表达量变化与肿瘤大小变化间存在负相关:神经母细胞瘤(r=-0.733,P=0.000),卵黄囊瘤(r=-0.874,P=0.000),淋巴瘤(r=-0.617,P=0.005);化疗前外周血MDR1表达量与首次化疗后相应肿瘤标志物变化大小呈负相关:神经母细胞瘤尿香草杏仁酸(VMA)(r=-0.440,P=0.046),卵黄囊瘤甲胎蛋白(AFP)(r=-0.831,P=0.000),淋巴瘤乳酸脱氢酶(LDH)(r=-0.495,P=0.031)。随着化疗次数的增加MDR1表达量增加(P<0.05)。结论动态检测患儿化疗前后PBMCs中MDR1mRNA水平对化疗疗效及预后的判定有一定的指导意义,可在一定程度上指导化疗方案的修订。
Objective To investigate the expressions of multi-drug resistance gene (MDR1),multi-drug resistance-associated protein gene (MRP1),and lung resistance protein gene (LRP) in the peripheral blood mononuclear cells in chemotherapy children with malignant solid tumors and its relationship with clinical chemotherapy.Methods A total of 59 children with malignant solid tumors at an age from 9 months to 14 years old who admitted in our hospital from January 2008 to October 2009 were collected in this study.There were 24 cases of neuroblastoma,16 cases of yolk sac tumor,and 19 cases of lymphoma.Another 30 health age-and sex-matched children served as control.The expressions of MDR1,MRP1 and LRP in the peripheral blood mononuclear cells (PBMCs) before and after chemotherapy,in fresh frozen tumor tissue samples and the in the peripheral blood samples of normal control group were detected by real-time fluorescence quantitative PCR (FQ-PCR).Results All MDR1 expression level in the peripheral blood of chemotherapy children was positively correlated with its expression level in the same period tumor tissue samples (r=0.894,P=0.000).There was a negative correlation between the mdr1 mRNA changes and the changes of the tumor size before and after chemotherapy (neuroblastoma:r=-0.733,P=0.000;yolk sac tumor:r=-0.874,P=0.000;lymphoma:r=-0.617,P=0.005).A negative correlation was found between MDR1 mRNA level in peripheral blood before chemotherapy and the changes of corresponding tumor markers after the first time chemotherapy [for neuroblastoma,urine vanillylmandelic acid (VMA):r=-0.440,P=0.046;for yolk sac tumor,alpha-fetoprotein (AFP):r=-0.831,P=0.000;lymphoma:lactate dehydrogenase (LDH):r=-0.495,P=0.031].The increased MDR1 mRNA level in peripheral blood of chemotherapy children was related to the increased times of chemotherapy treatments (P〈0.05).Conclusion Dynamically detection for the mdr1 level in PBMCs before and after chemotherapy is valuable for evaluating the treatment response and prognosis in chemotherapy children with malignant solid tumors,and for revising the chemotherapeutic regimen.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第10期1087-1090,共4页
Journal of Third Military Medical University
基金
重庆医科大学校级重点课题(XBZD200708)~~
关键词
小儿实体恶性肿瘤
多药耐药基因
多药耐药相关蛋白基因
肺耐药蛋白基因
外周血
荧光定量PCR
pediatric malignant solid tumor
multi-drug resistance gene
multi-drug resistance-associated protein gene
lung resistance protein gene
peripheral blood
real-time fluorescence quantitative PCR