急性白血病患者肺耐药相关蛋白检测及临床意义

目的：探讨急性白血病（AL）患者肺耐药相关蛋白（LRP）的表达与临床病情和疗效的关系.方法：采用免疫细胞化学方法（SABC）检测57例AL患者及14例对照组骨髓单个核细胞LRP的表达.结果：①AL初治组LRP表达阳性率（30.00%）与完全缓解组阳性率（25.00%）比较差异无统计学意义（P＞0.05），难治复发组LRP表达阳性率（61.90%）较完全缓解组与初治组明显增高（均P＜0.05）.②37例化疗后AL患者LRP阳性表达17例，LRP阴性表达20例，LRP阴性组缓解率显著高于阳性组（P＜0.05）.结论：AL患者LRP高表达与临床耐药有关，有可能成为判断预后的一个重要因素。     

白血病多药耐药基因和多药耐药相关蛋白基因的表达及临床研究

白血病是造血系统常见的恶性肿瘤 ,化疗是白血病治疗的主要手段 ,但白血病细胞产生的多药耐药是导致化疗失败的主要原因。多药耐药基因(ｍｄｒｌ)和多药耐药相关蛋白基因 (ＭＲＰ)的过度表达是引起白血病多药耐药发生的重要机制之一。本文应用半定量ＲＴ ＰＣＲ方法同时检测 40例急性白血病和慢性粒细胞白血病急变患者的ｍｄｒｌ和ＭＲＰ的表达水平 ,并探讨了它们与临床耐药的关系。1　对象与方法1 .1 　 研究对象40例患者均为我院 1 999年 7月～ 2 0 0 0年 5月住院患者 ,男 2 5例 ,女 1 5例 ,中位年龄 37岁 ( 4～ 68岁 )。初治组 2 7例 ,复…     

白血病患者多药耐药基因1和多药耐药相关蛋白检测的临床意义

白血病细胞多药耐药性是影响疗效、导致化疗失败的主要原因。我们检测了３８例急性白血病（ＡＬ）患者多药耐药基因１（ＭＤＲ１）、多药耐药相关蛋白（ＭＲＰ）基因的表达,并探讨其与临床耐药及预后的关系。一、资料和方法１－研究对象：ＡＬ３８例,男１８例,女２０例,年龄１１～６５岁,中位年龄３３岁。其中急性非淋巴细胞白血病（ＡＮＬＬ）２４例（Ｍ１２例,Ｍ２７例,Ｍ３８例,Ｍ４２例,Ｍ５２例,Ｍ６１例;慢性粒细胞白血病急粒变２例）;急性淋巴细胞白血病（ＡＬＬ）１４例（Ｌ１６例,Ｌ２７例,Ｌ３１例）。初治组１３例…     

急性淋巴细胞白血病患儿肺耐药蛋白表达及临床意义

应用免疫组化法 ,对 2 7例初治和 2 1例复发及难治的急性淋巴细胞白血病 (AL L )患儿检测外周血或骨髓中白血病细胞的肺耐药蛋白 (L RP)表达情况 ,同时体外应用 MTT方法观察了所有患儿的白血病细胞对柔红霉素 (DNR)化疗的敏感性。结果 :2 7例初治患儿的 L RP表达率为 18.5 % ,2 1例复发及难治患儿的 L RP表达率为 6 6 .7% ,两者比较 P<0 .0 1。在 2 7例初治患儿组中 ,L RP表达阴性者对 DNR的敏感率为 86 .4 % ,L RP表达阳性者为 2 0 % ,两者比较 P<0 .0 1;在 2 1例复发及难治患儿中 ,L RP表达阴性者对 DNR敏感率为 2 8.6 % ,L RP表达阳性者为 2 1.4 % ,两者比较 P>0 .0 5。在 2 7例初治组患儿中 ,L RP表达阴性者的 CR率为 90 .9% ,L RP表达阳性者为 6 0 % ,两者比较 P<0 .0 1;在 2 1例复发及难治患儿中 ,L RP表达阴性者的 CR率为 4 2 .9% ,L RP表达阳性者为 5 0 % ,两者比较 P>0 .0 5。认为 L RP可能是产生多药耐药 (MDR)的另外一个重要因素     

多药耐药相关蛋白在大肠癌中的表达及其临床意义

多药耐药（ｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ,ＭＤＲ）的产生是大肠癌化疗失败的重要原因．已有研究表明ｍｄｒ１基因编码的Ｐｇｐ表达是大肠癌ＭＤＲ的机制之一［１］．最近发现的另一个ＭＤＲ相关蛋白－多药耐药相关蛋白（ｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅａｓｓｏｃｉａｔｅｄｐｒｏｔｅｉｎ,ＭＲＰ）,成为肿瘤耐药和逆转耐药的热点［２］．我们的初步研究显示,ＭＲＰ在胃肠癌组织中过度表达［３］,但目前国内未见其他有关大肠癌ＭＲＰ表达的报道．我们应用免疫组化方法研究ＭＲＰ在大肠癌中的表达情况,并进一步…     

急性白血病多药耐药基因及多药耐药相关蛋白基因的表达及临床研究

目的探讨急性白血病（ＡＬ）多药耐药基因（ｍｄｒ１）及多药耐药相关蛋白基因（ＭＲＰ）的表达与预后的关系。方法采用逆转录聚合酶链反应（ＲＴＰＣＲ）的方法检测５５例ＡＬ患者的ｍｄｒ１及ＭＲＰ的表达。结果发现复发急变组的ｍｄｒ１及ＭＲＰ基因表达水平（０．７３５±０．２４９,１．１５７±０．４４７）较初治组（０．４０８±０．１８６,０．４６５±０．２５３）明显升高（Ｐ＜０．０１）。而且ｍｄｒ１及ＭＲＰ同时高表达者的完全缓解（ＣＲ）率明显低于ｍｄｒ１及ＭＲＰ同时低表达者（Ｐ＜０．０１）。结论ｍｄｒ１和ＭＲＰ同时高表达是判断ＡＬ患者耐药复发及不良预后的重要因素。     

肠道肿瘤多药耐药相关蛋白和肺耐药蛋白表达的临床意义

ｍｄｒｌ基因编码的Ｐ糖蛋白过度表达是肿瘤产生多药耐药（ｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ,ＭＤＲ）的重要机制之一,最近研究又发现了两个与ＭＤＲ有关的跨膜转运蛋白－多药耐药相关蛋白（ｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅａｓｏｃｉａｔｅｄｐｒｏ...     

急性白血病乳腺癌耐药蛋白基因表达及其与临床的关系

化疗是急性白血病 (AL)的主要治疗手段。耐药是影响化疗疗效的重要因素 ,目前认为AL耐药即多药耐药 (MDR)的发生是多因素、多种机制作用的结果[1,2 ] 。乳腺癌耐药蛋白基因 (BCRP)是 1998年才被发现的又一与耐药有关的糖蛋白 ,它主要参与膜内、外药物转运而改变药物在胞内的分布 ,以药物排出泵的作用参与MDR[3 ] 。有关BCRP与AL临床的关系报道极少 ,为探讨BCRP在成人AL中的表达及其与临床关系 ,本研究应用半定量逆转录 PCR(RT PCR)检测AL患者的BCRP表达 ,并结合mdr 1、耐药相关蛋白基因 1(MRP 1)及肺耐药蛋白基因(LRP)…     

大肠癌中多药耐药相关蛋白表达的研究

目的:研究多药耐药相关蛋白在大肠癌的表达及其意义。方法:应用单克隆抗体 QCR-1行 LSAB免疫组化法研究42例大肠癌组织中多药耐药相关蛋白的表达水平。结果:大肠癌组织中多药耐药相关蛋白表达的总阳性率为69.1%,其中乳头状腺癌66.7%,管状腺癌70.0%,粘液腺癌69.2%,大肠癌不同病理类型与 MRP表达间无显著性差异(p>0.05);癌旁正常肠组织呈阴性表达;在大肠癌不同病理分期中,MRP 表达率癌阳性率分别为 Dukes'A 期87.5%,Dukes'B 期91.7%,Dkes'C 期60.0%,Dukes'D 期28.6%,大肠癌 Dukes'A 期与 Dukes'B 期MRP 表达率和 Dukes'D 期比较有显著性差异(p<0.01);大肠癌不同部位的 MRP 表达阳性率比较中,左半结肠62.5%,右半结肠63.7%,直肠73.9%,两者无显著性差异。结论:表明多药耐药相关蛋白是参与大肠癌多药耐药的重要因素,其表达与大肠癌病理分期相关。     

原位杂交法检测老年急性白血病多药耐药基因表达

目的 将简便可靠的非同位素原位杂交方法应用于老年急性白血病多药耐药基因(mdrl)的临床检测。方法 经光敏生物素标记的RNA探针，直接在细胞甩片上进行原位杂交，检测40例老年急性白血病骨髓细胞mdrlmRNA。结果 杂交信号清晰，重现性好。难治复发病人中mdrl阳性率77．27％，初治病人33．33％，差异有显著性。结论 光敏生物素标记的RNA探针原位杂交方法简便、快速、安全、可靠，可在临床用于老年急性白血病mdrl常规检测，辅助临床治疗方案设计及判断预后。     

急性髓系白血病生存素、多药耐药基因与肺耐药基因的表达及其临床意义

目的：探讨初治急性髓系白血病(AML)细胞生存素(Survivin,S)、多药耐药基因(mdr-1)与肺耐药蛋白(LRP)表达与疗效的关系。方法：应用RT—PCR法检测46例初治AML患者的S、mdr-1和LRP mRNA表达的阳性率。结果：46例AML患者细胞S mRNA阳性率为69．6％，mdr-l mRNA阳性率为52．2％，均分别高于正常对照组(27．8％，11．1％，P＜0．01)，而表达LRP阳性率与正常对照组差异无显著性意义，分别为36．9％和16.7％(P＞0.05)。S阳性者CR(62．5％)明显低于阴性者(92．9％，P＜0.05)。mdr—1阳性者CR(45．8％)明显低于阴性者(100％，P＜0．01)。LRP阳性者CR(41．2％)明显低于阴性者(89．7％，P＜0.01)。S和mdr—1双阳性者CR(45.5％)明显低于双阴性者(100％，P＜0．01)。S和LRP双阳性者CR(35．7％)明显低于双阴性者(100％，P＜0．01)。结论：S、mdr-l和LRP可作为独立预后因素。S和mdr-l或S和LRP双阳性者CR率明显减低。     

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein

Summary The aim of this study was to find out whether only resistant cells of the multidrug-resistant phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210_dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210_dur) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabinoside-resistant (L1210_AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210_ctx) (not multidrug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210_dox and L1210_dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210_AraC or L1210_etx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.Guest Scientist from the National Institute of Oncology, Budapest Hungary     

Itraconazole and multidrug resistance: Possible effects on remission rate and disease-free survival in acute leukemia

Summary Itraconazole, a triazole antifungal agent, has been reported to reverse drug resistance against daunorubicin in acute leukemia. In a subanalysis from a double-blind, placebo-controlled trial examining the effects of itraconazole on the prevention of fungal infections in neutropenic patients, we studied the effects of itraconazole on remission rate and disease-free survival in patients with acute lymphoblastic (ALL) and acute myelogenous leukemia (AML) receiving remission induction treatment schedules containing daunorubicin (DNR). Eleven ALL and 17 AML patients received itraconazole and 12 ALL and 25 AML patients were given placebo. Among AML patients the remission rate was slightly higher in the itraconazole group, whereas the disease-free survival was higher mong ALL patients given itraconazole. In AML patients DFS was comparable in both groups but the number of high-risk patients in the itraconazole group was higher. These preliminary results may suggest a role for itraconazole in reversing multidrug resistance. Larger trials, however, are required to substantiate these findings and to correlate them with its in vitro effects on multidrug resistance.     

食管癌活检标本多药耐药基因表达及意义

目的 研究食管癌活检标本中多药耐药基因（multidrug resistance gene １,ＭＤＲ１基因）和多药耐药相关蛋白（multidrug resistance associatid pritein,ＭＲＰ）表达水平,探讨与食管癌临床特征及化疗的相关性。方法 应用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）技术定量分析标本中ＭＤＲ１基因和ＭＲＰ的表达水平。结果 ５８例标本中,ＭＤＲ１基因阳性表达率为８２．８％（４８/５８）,ＭＲＰ表达率为２９．３％（１７/５８）。     

急性白血病患者白细胞内谷胱甘肽过氧化物酶与化疗耐药关系的研究

检测了35例急性白血病患者白细胞内谷胱甘肽过氧化物酶（GSH－PX）活力，同时用抗多药耐药P一糖蛋白单抗JSll－1检测了其中24例患者白细胞耐卜糖蛋白表达。结果显示：化疗前组白细胞内GSH－PX活力（106．28±15．81U）较正常对照组（8．38±7．42）明显增高（P＜0．05）；化疗后组白细胞内GSH－PX活力（125．21±17．75U）较化疗前组明显增高（P＜0．01）；检测24例化疗后患者P－糖蛋白表达16例表达阳性，其中11例疗效差；8例P－糖蛋白表达阴性，其中6例疗效差。P－糖蛋白表达阳性和阴性疗效差者GSH活力均增高。以上结果表明：急性白血病化疗耐药机制，P－糖蛋白高表达是一个较为重要的因素，但不是唯一的，GSH－PX活力增高可能是MDR形成的另一个重要原因。     

RT-PCR检测白血病患者mdr1表达的临床研究

目的：应用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）方法检测多药耐药基因（ｍｄｒ１）ｍＲＮＡ的表达,以探讨白血病细胞的抗药性及化疗效果的关系。方法：采用ＲＴ－ＰＣＲ法检测３３例不同类型白血病患者ｍｄｒ１、ｍＲＮＡ的表达,同时检测２０例正常骨髓做对照。结论：对照均为阴性表达,而初始组ｍｄｒ１的阳性表达率为３５．００％,复发、难治组ｍｄｒ１阳性表达率为８４．６２％（Ｐ〈０．０１）,ｍｄｒ１阳性与ｍｄｒ１阴性     

Inhibition of protein kinase C in multidrug-resistant cells by modulators of multidrug resistance

We have evaluated the protein kinase C (PKC) activity in two series of cultured cell lines presenting the multidrug-resistance (MDR) phenotype and in the corresponding wild-type cells: the human KB 3.1, KB A1 and KB 8.5 cell lines, and the rat C6, C6 0.5 and C6 1V cell lines. We have observed an increase in PKC activity in the MDR cell lines of the KB cell lineage, proportional to their degree of resistance to doxorubicin. In contrast, the MDR cell lines of the C6 cell lineage presented no change (C6 0.5) or even decrease (C6 1V) in PKC activity; the basal level of PKC activity in C6 cells was, however, 50-fold higher than in KB 3.1 cells. We have tested, in these lines, the effect of four modulators of MDR: verapamil, cyclosporin A, quinine and S-9788, on doxorubicin acytotoxicity and on PKC activity. We observed that cyclosporin A and S-9788, which were the most active on MDR reversal, were able to inhibit PKC activity in the KB resistant lines as well as in all C6 lines, whereas verapamil and quinine had only marginal effects on PKC activity. The distribution of PKC isoenzymes was studied by Western blots. The PKC , and isoforms were increased in the KB resistant lines as compared to wild-type cells, which could account for the increase PKC activity we observed. In contrast, PKC and were decreased in C6 1V cells, as expected from the results obtained for total PKC activity, but we also noticed an important decrease in PKC in the C6 0.5 line. Our results suggest that an increase in PKC activity is not an absolute requirement for expression of MDR, provided that the basal level be high enough; and that some modulators may act on MDR, not only through direct P-glycoprotein interaction, but also through P-glycoprotein phosphorylation or expression. The distribution of PKC isoenzymes revealed that the modifications encountered between sensitive and resistant cells mainly concerned , and isoenzymes of PKC.Abbreviations PKC protein kinase C - MDR multidrug resistance