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儿童急性白血病初治患者LRP和MRP的表达及其临床意义 总被引:2,自引:0,他引:2
背景与目的:有研究发现肺耐药相关蛋白(lungresistanceprotein,LRP)和多药耐药相关蛋白(multidrugresistance鄄associatedporotein,MRP)的表达与白血病患儿耐药有关,而且患儿耐药不是由于一种耐药机制引起的。本研究旨在观察LRP和MRP在不同类型小儿白血病初治时的表达情况及其与临床疗效的关系。方法:应用逆转录鄄聚合酶链反应法(RT鄄PCR)检测38例不同类型儿童急性白血病[27例急性淋巴细胞白血病(acutelymphoblastic,ALL),11例急性非淋巴细胞白血病(acutenonlymphocyticleukemia,ANLL)]及6名正常儿童LRP、MRP基因的表达,结合患儿化疗后的完全缓解(CR)率分析两种基因表达的意义。结果:38例患儿化疗后CR26例(68.4%)。38例患儿中LRP基因表达阳性11例(28.9%),表达阴性27例(71.1%),6例正常对照儿童LRP基因阴性。LRP基因阳性患儿的CR率低于阴性者(分别为27.3%和85.2%,P<0.05)。MRP阳性者21例,6例正常对照儿童MRP基因阴性。MRP基因阳性者的CR率低于阴性者(分别为47.6%和94.1%,P<0.05)。27例ALL患儿中LRP阳性5例,11例ANLL患儿中LRP阳性6例(分别为18.5%和54.5%,P<0.05)。27例ALL患儿中MRP阳性16例;11例ANLL患儿MRP阳性5例(分别为59.3%和45.5%,P>0.05),ALL和ANLL中MRP的表达无显著性差异。LRP基因阳性患者的MRP阳性率与LRP阴性者MRP阳性率无显著性差异(分别为28.6%和29.4%,P>0.05),说明LRP基因与MRP基因之间无相关性。结论:LRP基因及MRP基因阳性儿童急性白血病者病情重、化疗缓解率低,儿童ANLL相对于ALL化疗缓解率低可能与LRP的表达有关。 相似文献
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目的探讨急性非淋巴细胞性白血病(ANLL)患者乳腺癌耐药蛋白(BCRP)的表达与临床耐药的关系.方法应用半定量反转录-聚合酶链反应(RT-PCR),以MCF7乳腺癌细胞株为参照标准,以β肌动蛋白(β-actin)为内对照,检测了54例患者及9例非恶性血液病BCRP的表达情况,初步探讨了其临床意义.结果BCRP在ANLL中阳性率高,表达水平相差达1000倍以上,由低到高依次为对照组、完全缓解组、初治敏感组和临床耐药组.其中临床耐药组BCRP阳性率显著高于对照组及完全缓解组(P<0.01及P<0.05).结论BCRP在ANLL中表达水平差异较大,30%患者表达水平较高,可能是ANLL患者临床耐药的重要原因,是预后的不利因素. 相似文献
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多药耐药相关蛋白及肺耐药蛋白在人直肠癌组织中的表达及临床意义 总被引:5,自引:0,他引:5
目的 检测多药耐药相关蛋白(MRP) 及肺耐药蛋白(LRP) 在人直肠癌组织中的表达,探讨其与临床分期、分化程度及预后的关系。方法 采用免疫组织化学技术法检测57 例人直肠癌组织中MRP及LRP的表达。结果 57 例人直肠癌组织中可检测到MRP表达者28 例,占49.1 % ;LRP表达者24 例,占42.1 % ;二者同时表达者10 例,占17 .5% ;有MRP或LRP表达者42 例,占73 .7 % ;两蛋白表达阳性率与肿瘤分期、分化程度无显著相关( P> 0 .05) 。MRP表达阳性者术后生存期明显低于该蛋白阴性者( P< 0.05) ,而LRP的表达则与预后无显著相关;两蛋白表达无明显相关性( P> 0.05) 。结论 MRP可能是判断人直肠癌预后的指标之一,对直肠癌患者综合治疗的实施具有指导意义。 相似文献
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目的研究蛋白激酶C(PKC)及多药耐药相关蛋白在膀胱癌多药耐药中的作用。方法 采用Takai法测定膀胱癌及正常膀胱组织中PKC活性, RT-PCR法测定P-gp及MRP mRNA。结果 膀胱癌组织与癌旁组织相比较, 胞浆、胞膜中PKC活性都明显升高, 随分期、分级的增高而增高;P-gp在膀胱癌组织和癌旁组织表达率为88.9%和100%, 膀胱癌组织中的表达低于癌旁组织;MRP在所有膀胱癌组织及癌旁组织都有表达, 膀胱癌组织高于癌旁组织。P-gp在不同临床分期和病理分级之间都无差别, MRP只在不同病理分级之间有显著差异。MRP与PKC活性显著相关, P-gp与PKC无相关性。结论 膀胱癌组织细胞中PKC的过度表达促进了肿瘤多药耐药的发生;PKC在膀胱癌的多药耐药中发挥着重要的作用。 相似文献
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Sorcin基因和mdr1基因的相关性及临床意义 总被引:3,自引:0,他引:3
目的 探讨急性髓细胞系白血病 (AML)患者可溶性耐药相关钙结合蛋白基因 (sorcin)和多药耐药基因 (mdr1)的相关性表达及其与临床耐药和疗效的关系。方法 Northernblot检测K5 6 2 /A0 2细胞株sorcin和mdr1基因的表达 ,用半定量逆转录聚合酶链反应 (RT PCR)检测 6 5例AML患者、2 7例非白血病患者和健康人的sorcin基因和mdr1基因表达 ,并分析sorcin基因和mdr1基因表达的相关性及其临床意义。结果 AML患者中 ,sorcin和mdr1基因表达明显高于正常对照组 ,差异有非常显著性 (P <0 .0 0 1) ;在AML和对照组中 ,sorcin和mdr1基因的表达有较好的相关性 ;sorcin和mdr1基因的共表达与AML患者的临床耐药和预后具有较高的符合率。Sorcin+ 和mdr1+ 组患者临床耐药发生率为 92 .9% ,完全缓解 (CR)率为 7.1% ;sorcin-和mdr1-组患者临床耐药发生率为 8.6 % ,CR率为91.4 %。结论 白血病患者的sorcin和mdr1基因共表达与其临床耐药和预后密切相关 ,可作为检测临床耐药和判断预后的有效手段之一。 相似文献
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多药耐药性相关蛋白在乳腺癌组织中的表达及其与预后关系 总被引:2,自引:0,他引:2
目的:研究多药耐药相关蛋白(Multidrug resistance-associated protein 1,MRP1)在乳腺癌组织中的表达,评估其在乳腺癌预后中的作用。方法:采用免疫组织化学方法(IHC)检测47例手术切除的乳腺癌组织中MRP1的表达,并分析其与临床、病理特征的关系及对预后的影响。结果:(1)MRP1在乳腺癌组织中的阳性表达率为85.1%(40/47例),其中高表达者占53.2%(25/47例);(2)腋淋巴结阳性者MRP1表达水平明显高于腋淋巴结阴性者(P<0.05),MRP1表达与月经状况、肿瘤大小、组织分级和激素受体状况均无关(P>0.05);(3)Kaplan-Meier生存分析结果表明MRP1表达与无病生存期明显相关(P<0.05),但和总生存期无关(P>0.05);(4)Cox单因素分析显示肿瘤大小和MRP1表达与无病生存期明显相关(P<0.05),但仅有肿瘤大小和总生存期明显相关(P<0.05);而多因素分析却显示只有腋淋巴结转移和无病生存期(P<0.01)和总生存期(P<0.05)明显相关。结论:MRP1在乳腺癌组织中具有较高的表达水平,与乳腺癌患者的无病生存期有关,而与总生存期无关。 相似文献
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目的 探讨肝细胞黏附分子(hepaCAM)蛋白与几种多药耐药蛋白在肾癌中的表达及其相互关系.方法 使用免疫组织化学法检测人肾癌组织中不同区域的hepaCAM蛋白、多药耐药相关蛋白(MRP)、P-糖蛋白(P-gp)、肺耐药蛋白(LRP)、拓扑异构酶Ⅱ(TOPOⅡ)的表达并分析其相互关系.结果 在肿瘤的周边区,hepaCAM蛋白与MRP、P-gp、LRP蛋白都呈现阳性表达;而在肿瘤的中心区域,hepaCAM蛋白与P-gp、LRP表达为阴性或弱阳性,而MRP、TOPOⅡ蛋白表达为阳性.与肿瘤周边组比较,MRP、TOPOⅡ在肿瘤中心区表达明显增强(31.23±5.67:23.89±4.56;45.66±2.34:5.23±0.66),差异有统计学意义(t=-6.20,P=0.00;t=-100.16,P=0.00),而hepaCAM、P-gp、LRP表达明显减弱(3.21±1.12:27.25±2.23;2.34±0.33:51.23±3.45;4.22±1.78:44.23±1.45),差异有统计学意义(t=60.87,P=0.00;t=90.35,P=0.00;t =107.18,P=0.00).相关分析结果显示hepaCAM蛋白在肾癌肿瘤中心组织的表达与MRP蛋白表达相关(r=0.94,P=0.01),而与P-gp、LRP、TOPOⅡ蛋白表达无关(r =0.22,P=0.44;r =0.14,P=0.80;r =0.34,P=0.07).结论 hepaCAM蛋白在肾癌中的表达可能与其耐药相关. 相似文献
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目的:研究滑膜肉瘤X断裂点基因2(SSX2)在急性白血病中的表达及临床意义。方法:逆转录聚合酶链反应检测72例急性白血病(AL)中SSX2的表达,包括23例急性淋巴细胞白血病(ALL)及急性髓细胞白血病(AML)。结果:在72例AL患者中有38例SSX2表达阳性(52.78%),在ALL中SSX2表达阳性率为56.52%,而在AML中SSX2表达阳性率为51.02%,两者之间没有显著性差别(P〈0.05)。在非M3型AML患者中SSX2表达阳性的完全缓解率(CR)为60.87%,而在SSX2表达阴性的完全缓解率为89.47%。在随访的16例SSX2表达阳性患者观察治疗后的SSX2表达阳性率,完全缓解后SSX2表达可以转为阴性,SSX2表达持续阳性的患者会较早复发。如果患者没有完全缓解,则SSX2表达不会转为阴性。结论:在AML及ALL患者中SSX2表达没有差别(P〉0.05),SSX2阳性表达非M3型AML患者中CR率较低,SSX2可以作为AML患者较差的预后指标。 相似文献
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Multidrug resistance (MDR) is a main cause of failure in the chemotherapeutic treatment of malignant disorders. One of the well-known genes responsible for drug resistance encodes the multidrug resistance- associated protein (MRP1). The association of MRP1 with clinical drug resistance has not systematically been investigated in Iranian pediatric leukemia patients. We therefore applied real-time RT-PCR technology to study the association between the MRP1 gene and MDR phenotype in Iranian pediatric leukemia patients. We found that overexpression of MRP1 occurred in most Iranian pediatric leukemia patients at relapse. However, no relation between MRP1 mRNA levels and other clinical characteristics, including cytogenetic subgroups and FAB subtypes, was found. 相似文献
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Expression of mdr1, mrp and lrp genes in gastric carcinoma and their clinical significance 总被引:1,自引:0,他引:1
Objective: To explore the expression of mdr1, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP)
genes in human gastric cancer and their clinical significance. Methods: The mdr1 mRNA was assayed by RT-PCR, the MRP and LRP
were detected by flow cytometry. Results: The positive rate of mdr1 mRNA was 44.4% (12/27), and the mean MRP and LRP expression
were independent upon patient histologic type, nodal involvement, and TNM stage. The mdr1 mRNA expression in patients with
serosa invasion was 30.0% (6/20), much lower than that without serosa invasion (85.7%). Conclusion: The multidrug resistance
cells are present in primary gastric carcinomas prior to chemotherapy, and analysis of mdr1 gene, MRP, LRP may have guiding
significance in the treatment of gastric carcinoma. 相似文献
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Atpresentchemotherapyisstilloneofthemainmethodsforcontrollingtherecurrentandmetastasisofmalignanttumors.Butmultidrugresistance(MDR)isamajorobstacleinthesuccessfultreatmentofcancerbychemotherapy.Therelationshipbetweenmultidrugresistance-associatedprotein(MRP)andchemotherapyresistancehasattractedmuchattention[1].ColeseparatedakindofoverexpressingmRNAfromthemultidrugresistancehum ansmallcelllungcancer(SCLC)celllineH69ARwhichhadnooverexpressionofp-gp,andcloneditscDNA.Theproteincodedbelonge… 相似文献
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A. Reichle H. Diddens F. Altmayr J. Rastetter R. Andreesen 《Cancer chemotherapy and pharmacology》1994,34(4):307-316
Reduced drug accumulation may be one reason for intrinsic drug resistance in chronic lymphatic leukemia of the B-cell type (B-CLL). Immunophenotyped leukemic human B-cells from 38 cases of B-CLL were characterized for P-glycoprotein (PGP) content. In all, 30 cases of B-CLL were additionally analyzed for further parameters: accumulation of daunorubicin (DNR,n=20) and rhodamine 123 (Rh123,n=30) in both the presence and the absence of verapamil (VRP). Also, 16 cases of B-CLL were analyzed for vincristine (VCR) accumulation with or without VRP. Concerning the relative expression of PGP, these 16 cases of B-CLL were representative for the whole group of 30 cases. Spontaneous accumulation of Rh123 and VCR varied over a wide range: accumulation of Rh123, by a factor of 11.8; accumulation of VCR, by a factor of 9.7; and accumulation of DNR, by a factor of 3.6. VRP modulated the accumulation of RH123 in 16/30 cases (53%), that of VCR in 69% of cases, and that of DNR in 11% of cases. The maximal VRP-mediated increases in accumulation amounted to factors of 1.3 for DNR, 2.3 for Rh123, and 7.8 for VCR. Spontaneous drug accumulation did not correlate with the extent of chemomodulation. The amount of PGP in B-CLL cells (all cases studied were PGP-positive) did not correlate with drug accumulation or with the extent of VRP-mediated chemomodulation. Thus, high expression of PGP is only partially responsible for defective drug accumulation in B-CLL. Only the degree of chemomodulation by VRP is predictive for the extent of the PGP-related functional drug accumulation defect. Thus, in B-CLL, PGP-independent drug accumulation defects seem to be as important as those mediated by PGP. The extent of this drug accumulation defect varies for the different drugs in the following order VCR>Rh123>DNR. The relevance of PGP-mediated and-independent drug accumulation defects in vivo may depend to a large extent on the drug being used and on the individual cell type. Both types of defect in drug accumulation are of high importance when regimens include VCR a drug commonly used in second-line chemotherapy of B-CLL. Both defects in drug accumulation may be responsible for intrinsic VCR resistance in B-CLL. 相似文献
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目的 探讨细胞表面抗原CD117在各型急性白血病(AL)中的表达规律及其临床意义。方法 采用流式细胞术(FCM)检测139例AL患者骨髓或外周血中CD117的表达情况,并进行分析和比较。结果 急性淋巴细胞白血病(ALL)患者CD117阳性细胞表达水平与正常对照组相比差异无统计学意义(P>0.05);急性髓细胞白血病(AML)患者CD117阳性患者比例及阳性细胞表达水平较正常对照组和ALL组均升高,差异有统计学意义(均P<0.05)。在AML各亚型中,CD117阳性患者比例及阳性细胞表达水平以M0/M1最高,M5b最低;在5种髓系膜抗原标志中,虽然CD117检测AML的灵敏度低于CD13和CD33,但特异性都较高;CD117与CD34及HLA-DR在AML中的表达呈显著正相关,但在M3中,CD117表达明显高于CD34和HLA-DR。结论 CD117可作为AL患者MIC诊断分型的重要髓系免疫表型指征,在AML的诊断分型以及AML和ALL的鉴别诊断中具有重要意义。 相似文献
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小分子干扰RNA对非小细胞肺癌MRP基因和药物敏感性的影响 总被引:1,自引:0,他引:1
目的:观察小分子干扰RNA(siRNA)对非小细胞肺癌(NSCLC)MRP基因、药物敏感性和细胞凋亡的影响,探讨体外肺癌耐药的高效和特异逆转耐药策略。方法:采用MRP siRNA转染,RT-PCR检测多药耐药相关蛋白MRP mRNA表达水平,流式细胞仪检测MRP蛋白表达,MTT法检测MRP siRNA的细胞毒作用,碘化丙啶(PI)染色检测MRP siRNA的细胞凋亡作用。结果:SW1573/2R120细胞转染MRP siRNA后,MRP mRNA表达明显降低,转染24h、48h和72h后MRP siRNA组的MRP蛋白表达阳性率较对照组明显减低,MRP siRNA与对照组相比对细胞生长抑制并无统计学差异,未见明显影响细胞增殖;MRP siRNA明显增加10μM阿霉素对SW1573/2R120细胞生长的抑制,并随作用时间的延长而增强,MRP siRNA+ADM组细胞生长抑制作用与对照组相比有统计学差异,MRP siRNA协同阿霉素增强对化疗耐药肺癌细胞的凋亡作用。结论:MRP siRNA可以明显逆转体外NSCLC MRP基因编码MRP蛋白的多药耐药。 相似文献
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Alessandro Ascione Maurizio Cianfriglia Maria Luisa Dupuis Alessandra Mallano Andrea Sau Francesca Pellizzari Tregno Silvia Pezzola Anna Maria Caccuri 《Cancer chemotherapy and pharmacology》2009,64(2):419-424
Purpose There has been an ever growing interest in the search for new anti-tumor compounds that do not interact with MDR1-Pgp and
MRP1 drug transporters and so circumvent the effect of these proteins conferring multidrug resistance (MDR) and poor prognosis
in AML patients. We have investigated the cytotoxic activity of the strong glutathione S-transferase (GST) inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on AML (HL60) cell lines.
Methods Functional drug efflux studies and cell proliferation assays were performed on both sensitive and MDR AML (HL60) cells after
incubation with NBDHEX. Moreover, the mode of cell death (apoptosis vs. necrosis) as well as the correlation between NBDHEX
susceptibility and GST activity or Bcl-2 expression was investigated.
Results NBDHEX is not a substrate of either MDR1-Pgp or MRP1 efflux pumps; in fact, it is not only cytotoxic toward the parental HL60
cell line, but also overcomes the MDR phenotype of its HL60/DNR and HL60/ADR variants.
Conclusions The data herein reported show that NBDHEX mediates efficient killing of both MDR1-Pgp and MRP1 over-expressing AML cells.
Therefore, this drug can potentially be used as an effective agent for treating MDR in AML patients. 相似文献
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目的 初步分析老年急性髓细胞白血病(AML)患者P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)的表达及其在预后中的意义。方法 流式细胞仪活细胞直接或间接免疫荧光法检测12例初治老年AML(M2a 4例,其中1例由MDS转化而来;M4a 2例;M5a 5例;M6 1例)患者骨髓白血病细胞P-gp、MRP、LRP表达情况。分析这些多药耐药蛋白表达与预后的关系。结果 P-gp、MRP、LRP的表达率分别为58.33 %、8.33 %、50 %;P-gp(+)、MRP(+)0,P-gp(+)、LRP(+)33.33 %,MRP(+)、LRP(+)0,P-gp(+)、MRP(+)、LRP(+)8.33 %,P-gp(-)、MRP(-)、LRP(-)33.33 %,其中P-gp、LRP单独和二者共表达频率较高。P-gp(+)者的完全缓解(CR)率与2年总生存率(OS)均显著低于P-gp(-)者(P=0.01),LRP(+)者的CR率与2年OS亦均低于LRP(-)者。结论 老年AML患者 P-gp、LRP单独及二者共表达频率均较高。P-gp、LRP过度表达是老年AML患者的不良预后因素。 相似文献
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目的:探讨WT1(Wilms tumor gene 1)基因在儿童急性B淋巴细胞白血病(B-ALL)中的表达及临床意义。方法:应用实时荧光定量PCR方法检测77例初诊B-ALL患儿WT1基因的相对表达水平,比较患者年龄、性别、流式亚型、染色体核型、临床危险分级等因素的基因表达差异,并随访分析初诊WT1基因表达水平对患儿预后的影响。结果:77例初诊B-ALL患者中,WT1基因阳性率96.10%(74/77),0~2岁患儿初诊WT1水平高于3~13岁组(P=0.02),WT1基因表达在性别上无统计学差异(P=0.229)。在对B-ALL流式亚型间WT1的分析中显示,Pro-B-ALL患者表达量最高,Pre-B-ALL次之,Com-B-ALL最低(两两比较差异,P值分别为0.002,0.008,0.040)。临床高危(P=0.041)、t(4;11)(P=0.034)、初诊白细胞大于50×109/L(P=0.009)的患者有更高的WT1表达。首次诱导化疗后细胞形态学缓解与否,其初诊时WT1表达无明显差异(P=0.84),但长期随访得到持续缓解的患者初诊WT1表达低于复发或不缓解的患者。结论:WT1基因在儿童B-ALL中表达的高低可能提示患者白血病细胞的分化水平,并与长期预后相关。 相似文献