Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance of Plasmodium falciparum isolates to antimalarial drugs

Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(P.falciparum) isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods:A total of 70 P.falciparum isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year 2008-2009.The in vitro assessment of antimalarial activity of P.falciparum clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified assay.Results:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of P.falciparum isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was found.Based on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST gene.All isolates(70) also carried only one copy number of PfGST gene.There appears to be an association between amplification of PfGR gene and chloroquine resistance.The 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.

Resistance to Anti-Thyroid Drugs in Graves’ Disease: Clinical-Biological Characteristics and Alternative Therapy in Tropical Area

Background: Resistance to anti-thyroid drugs (ATDs) is a rare entity recently described. We report two African observations in the treatment of Graves’ disease. Case 1: A 19-year-old Senegalese woman presented on admission with thyrotoxicosis syndrome associated with diffuse goitre and Grave’s orbitopathy. TSH levels were low (0.005 mIU/ml;N = 0.27 - 4.20) and fT4 elevated (60 pmol/L;N = 12 - 22]. Combination therapy with propranolol (40 mg/day) and carbimazole (starting dose of 45 mg/day and increased to 60 mg/day) was initiated. In view of the persistence of symptoms despite good therapeutic compliance, carbimazole was replaced by methimazole with an initial starting dose of 40 mg/day, followed by 60 mg/day. Despite the change in therapy, clinical symptoms of thyrotoxicosis persisted, and fT4 levels remained elevated. The patient was diagnosed with resistance to ATDs in Graves’ disease. Total thyroidectomy following 10 days of preoperative preparation with 1% Lugol’s solution was performed successfully. Case 2: A 22-year-old woman was referred for continued management of Graves’ disease with elevated thyroid-stimulating hormone receptor antibody (TRAb) levels (34 UI/mL;N < 1.75). Treatment included propranolol (80 mg/day) and carbimazole at an unusual dose of 80 mg/day. Combined therapy was clinically and biologically ineffective, with an fT4 level of 100 pmol/L [N: 12 - 22]. Upon admission, methimazole (40 mg/day) followed by propylthiouracil (800 mg/day) replaced carbimazole. Despite good patient compliance, the patient’s symptoms remained unaltered and fT4 levels elevated. A total robot thyroidectomy using the right axillary approach was performed successfully after 10 days of preoperative preparation, including prednisone (40 mg/day) combined with 1% Lugol’s solution. Conclusion: Resistance to ATDs complicates the management of Graves’ disease. Total thyroidectomy following preoperative preparation with Lugol’s solution and/or corticosteroids was shown to be successful.

Anticancer Drug Resistance of HeLa Cells Transfected With Rat Glutathione S-transferase pi Gene

To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 靏/mL, 10.95 靏/mL and 16.52 靏/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 靏/mL, 7.48 靏/mL and 13.70 靏/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. Conclusions Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.

Tuberculosis of the spine

Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous spread of infection from a central focus,which can be in the lungs or another location.Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply,which can result in severe morbidity even after years of approved therapy.Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body.The clinical,radiographic,microbiological,and histological data are used to make the diagnosis of spinal TB.In Pott’s spine,combination multidrug antitubercular therapy is the basis of treatment.The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection.Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care.Debride-ment,fusion stabilization,and correction of spinal deformity are the cornerstones of surgical treatment.Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.

A Review of <i>Staphylococcus aureus</i>and the Emergence of Drug-Resistant Problem

There are various bacteria living in this world. The most common one is Staphylococcus aureus. Almost everyone has heard of it. It is easy to find their habitats, such as hospitals, homes, parks, schools etc. Some of them are difficult to be eliminated because of drug-resistant mutations. Hence, lots of researchers devoted their efforts to eliminate them. This review illustrates the characteristics of the Staphylococcus aureus and the main threat of their drug-resistant strains, especially methicillin-resistant S. aureus. What’s more, the article also highlights the plight in the drug development.

柔嫩艾美球虫地克珠利和马杜拉霉素抗药株与敏感株孢子化卵囊18 S rDNA基因的差异

为探讨抗球虫药物地克珠利和马杜拉霉素对柔嫩艾美球虫18 S rDNA的影响,分别对人工诱导的柔嫩艾美球虫地克珠利抗药株(ETAD)、马杜拉霉素抗药株(ETAM)和药物敏感株 (ETDS)孢子化卵囊的18 S rDNA基因进行了克隆测序,并通过生物信息软件进行对比差异分析。结果显示,ETAM株有3个碱基发生突变(T170突变为C,T646突变为C,G694突变为C); ETAD株有1个碱基发生突变(T646突变为C)。经进一步分析比较,发现ETAM株18 S rRNA 的二级结构与ETDS株的差异很大,而ETAD株18 S rRNA的二级结构则与ETDS株的完全相同。这些碱基的突变有可能是导致E．tenella产生抗药性的原因之一。

甲基莲心碱抑制K562/A02细胞GST-π的表达

目的探讨甲基莲心碱(Neferine,Nef)对谷胱甘肽S转移酶π(GST-π)的影响。方法应用MTT法测定甲基莲心碱处理的K562/A02细胞对阿霉素(ADM)敏感性的影响。RT-PCR法分析Nef处理后,GST-πmRNA转录的变化。通过Western Blot观察Nef对GST-π蛋白表达的影响。结果甲基莲心碱对K562/A02的耐药性具有明显的逆转作用。用Nef处理后,对阿霉素药物敏感性的相对逆转效率第1天、第3天和第5天分别为9.6%、41.4%和10.7%;GST-πmRNA转录水平在用药后第3天下调最大,为(50.7±2.3)%。GST-π蛋白的表达于用药后第1天、第3天和第5天分别下降25.57%、48.42%和10.68%。结论甲基莲心碱具有较强的逆转K562/A02细胞多药耐药的作用,其逆转机制可能包括下调K562/A02细胞GST-πmRNA的转录和蛋白的表达。

P-gp,LRP和GST-π在非小细胞肺癌组织中的表达及与预后的关系

目的:探讨非小细胞肺癌(NSCLC)患者中耐药基因P-糖蛋白(P-gp),肺耐药相关蛋白(LRP)和谷胱苷肽-S转移酶(GST-π)的表达特点及对预后的影响.方法:用免疫组化方法检测168例非小细胞肺癌组织中的P-gp,LRP及GST-π表达情况并随访部分患者以研究其表达与预后的相关性.结果:在168例非小细胞肺癌患者中,P-gp,LRP和GST-π表达的阳性率分别为60.7%,64.03%和63.1%.P-gp和LRP与肿瘤组织类型有关,腺癌阳性率高于鳞癌(P<0.05);这3种耐药基因与病变大小相关,病变直径≥5 cm患者中,其阳性率高于直径<5 cm患者(P<0.05);有淋巴结转移患者P-gp和LRP的阳性表达率高于无淋巴结转移组(P<0.05);P-gp,LRP和GST-π表达为阴性患者2 a生存率高于阳性患者(P<0.05);三种耐药基因的表达与分化程度和年龄无关.结论:P-gp,LRP和GST-π的表达不仅与非小细胞肺癌的耐药情况有关,同时也可作为判断非小细胞肺癌患者预后的指标之一.耐药基因在非小细胞肺癌中的表达程度及特点不同,因而有必要对其进行联合检测以判断耐药及预后情况.

P-gp,ToPoⅡ和GST-π在胃癌组织中的表达及与预后的关系

目的:探讨胃癌患者中耐药基因P-糖蛋白(P-gp)、DNA拓扑异构酶Ⅱ(TopoⅡ)和谷胱苷肽-S转移酶(GST-π)的表达特点及对预后的影响.方法:用免疫组化方法检测130例胃癌组织中的P-gp,TopoⅡ及GST-π,分析其与临床病理特征的关系,并随访部分患者以研究其表达与预后的相关性.结果:在130例胃癌患者中,P-gp,TopoⅡ和GST-π表达的阳性率分别为24.62%,81.54%和75.38%.这3种耐药基因中,P-gp和GST-π与病变大小相关,病变直径>5cm患者中,其阳性率显著高于直径<5cm患者(χ2=4.56,P=0.033;χ2=5.545,P=0.020),有淋巴结转移患者P-gp的阳性表达率高于无淋巴结转移组(χ2=5.84,P=0.016),有血管侵犯患者P-gp和GST-π阳性表达率高于无血管侵犯患者(χ2=17.69,P<0.001;χ2=5.40,P=0.020),P-gp和GST-π表达为++^+++患者2a生存率明显低于-^+患者(χ2=3.964,P=0.047;χ2=4.2576,P=0.039);TopoⅡ的表达与病理类型及分化程度有关,在印戒细胞癌中表达率低于其他类型(χ2=7.29,P=0.007),且在低分化组中强阳性表达率明显低于中高分化组(χ2=7.79,P=0.005).结论:P-gp和GST-π的表达不仅与胃癌的生物学行为有关,同时也可作为判断胃癌患者预后的指标之一.耐药基因在胃癌中的表达程度及特点不同,因而有必要对其进行联合检测以判断耐药及预后情况.

急性白血病患者谷胱甘肽S-转移酶和肺耐药相关蛋白的检测及临床意义

目的:探讨急性白血病(AL)患者细胞内谷胱甘肽S转移酶活力(GST)及肺耐药相关蛋白(LRP)表达与临床疗效的关系。方法:采用化学比色法检测57例AL患者骨髓单个核细胞内GST活力并同时采用免疫细胞化学(SABC)方法检测LRP表达。结果:AL患者细胞内GST活力明显高于对照组(P<0.01);AL患者细胞内GST活力与骨髓中原始及幼稚细胞百分数有一定相关性(r=0.30,P<0.05)。初治组AL患者细胞内GST活力明显高于化疗后缓解(CR)组(P<0.01),化疗后难治复发组患者细胞内GST活力又明显上升,显著高于缓解组(P<0.01)。化疗后17例AL患者LRP表达阳性,其中13例未缓解(NR),20例LRP表达阴性,其中CR12例,LRP阳性组疗效显著差于阴性组(P<0.05),且LRP阳性组NR患者及LRP阴性组NR患者GST活力均明显增高。结论:AL患者细胞内GST活力增高与临床疗效及骨髓原始及幼稚细胞增殖有关;同时检测AL患者GST活力与LRP表达对提高耐药白血病的疗效和预后有一定价值。

P糖蛋白、谷胱甘肽-S-转移酶和拓扑异构酶Ⅱ在胃癌组织中的表达

背景与目的:P糖蛋白(P-gp)、谷胱甘肽-S-转移酶(GST-π)和拓扑异构酶Ⅱ(Topo-Ⅱ)等多种细胞内物质是恶性肿瘤产生多药耐药的物质基础,胃癌是比较常见的恶性肿瘤,应用免疫组化方法检测化疗前P-gp、GST-π和Topo-Ⅱ三因素在胃癌中表达的报告还比较少,为此,本文检测P-糖蛋白(P-gp)、谷胱甘肽-S-转移酶(GST-π)和拓扑异构酶II(Topo-Ⅱ)在胃癌组织中的表达,探讨其与胃癌分化、转移的关系。方法:应用免疫组化方法,检测75例术前未进行化疗的胃癌患者癌组织中P-gp、GST-π和Topo-Ⅱ的表达。结果:P-gp、GST-π及Topo-Ⅱ在75例胃癌组织中表达率分别为76.0%、85.3%和68.0%,与患者的年龄、性别、肿瘤发生部位及浸润深度无关,其在胃癌组织中的表达管状腺癌分别与粘液腺癌、印戒细胞癌及未分化癌比较差异均有显著性(P<0.05)。P-gp、GST-π高表达及Topo-Ⅱ低表达与其淋巴结转移有显著相关性。结论:P-gp、GST-π及Topo-Ⅱ的表达与胃癌组织类型有关,其表达可能还与胃癌细胞的分化、转移有关。

木犀草素抑制白血病耐药株K562/A02的GST-π表达

目的探讨木犀草素(luteolin)对白血病耐药株K562/A02细胞谷胱甘肽S转移酶π(GST-π)的影响。方法木犀草素30 mmol/L预处理K562/A02细胞第1、35、d后,MTT法测定阿霉素IC50,采用722分光光度计测定细胞内GSH含量及Western Blot法测定木犀草素处理后GST-π蛋白表达。结果木犀草素对K562/A02的耐药性具有明显的逆转作用,用木犀草素处理后,对阿霉素药物敏感性的相对逆转效率第1、3、5 d分别为10.7%4、2.7%和15.8%;木犀草素显著降低K562/A02细胞内GSH含量,GST-π蛋白的表达于用药后第1、35、d分别下降22%5、6%和34%。结论木犀草素具有较强的逆转K562/A02细胞多药耐药的作用,其逆转机制可能与降低细胞内GSH含量,下调K562/A02细胞GST-π蛋白的表达相关。

沉默GST-π基因表达对EC9706/cDDP细胞顺铂耐药性的影响

目的:观察沉默谷胱甘肽S转移酶-π(GST-π)基因的表达对食管鳞状细胞癌顺铂耐药细胞系EC9706/cDDP细胞耐药性的影响。方法:构建靶向GST-π基因的siRNA重组慢病毒GSTsi1、GSTsi2和无义对照GSTsiC,转染EC9706/cDDP细胞。通过RT-PCR及Western blot法检测GSTsi1、GSTsi2和GSTsiC感染前后EC9706/cDDP细胞中GST-πmRNA和蛋白的表达;MTT法检测感染GSTsi2、GSTsiC与未感染的EC9706/cDDP细胞对顺铂敏感性的变化。结果:感染GSTsi1、GSTsi2后EC9706/cDDP细胞GST-πmRNA的表达下调(F=3.490,P<0.001),其蛋白表达也减弱。感染GSTsi2的EC9706/cDDP细胞对顺铂的耐药指数较感染GSTsiC和未感染的EC9706/cDDP细胞降低(F=50.510,P<0.001)。结论:沉默GST-π基因的表达可降低EC9706/cDDP细胞的顺铂耐药性。

耐药相关基因GST-Л、LRP在卵巢上皮性恶性肿瘤组织中的表达及临床意义

目的:观察卵巢上皮性恶性肿瘤组织中GST-Л、LRP的表达与临床和病理因素的关系。方法:采用免疫组化S P法对30例卵巢上皮性恶性肿瘤组织中的GST-Л和LRP的表达进行检测,分析其表达与病理类型、组织学分级、化疗疗效与预后的关系。结果:①30例卵巢上皮性恶性肿瘤组织中GST Л、LRP的阳性表达率分别为6 6 .6 %、73.3%。②LRP、GST Л在临床Ⅲ～Ⅳ期的阳性表达率分别为99.0 %、76 .5 %,均显著高于Ⅰ～Ⅱ的阳性表达率4 6 .2 %,1 6 .7%。③LRP与GST- Л在G3中的表达率均大于G1～G2 ,但相比差异无显著性;④LRP与GST- Л有共表达现象,两者均强阳性者其化疗效果及预后较差。结论:LRP与GST Л在卵巢上皮性恶性肿瘤中有较恒定的表达,且与临床分期有关,检测两者的表达可预测化疗近期疗效,指导临床化疗方案的选择。

GST-π、TopoⅡα在口腔鳞状细胞癌不同区域中的表达差异和临床意义

目的研究口腔鳞状细胞癌的手术切除标本不同区域耐药基因产物GST-π、TopoⅡα的表达差异及其临床意义。方法运用免疫组化方法检测20例未经化疗和19例经诱导化疗的口腔鳞状细胞癌石蜡标本,分表层区和深层浸润区观察GST-π、TopoⅡα的表达。结果GST-π,TopoⅡα阳性表达在20例未经化疗的标本表层区分别为18例(90%),15例(75%),深层浸润区分别为15例(75%),1例(5%);在19例经诱导化疗的标本表层区分别为16例(84.21%),18例(94.74%);深层浸润区分别为12例(63.16%),8例(42.11%)。两组中GST-π、TopoⅡα的阳性表达在表面区和深层区之间均有显著性差异(P<0.05)。而在有否经化疗两组间,GST-π只在深层浸润区的阳性表达有显著性差异(P<0.05),TopoⅡα在表层区及深层区的阳性表达则均有显著性差异(均为P<0.05)。GST-π,TopoⅡα的表达与患者性别、年龄、病理分级、临床分期、肿瘤生长部位、三年无瘤生存期和化疗效果无明显相关。结论口腔鳞状细胞癌在耐药基因和相关蛋白方面存在着异质性;诱导化疗可产生肿瘤的耐药性变化,这对诱导化疗和辅助化疗的选择有一定的指导意义;GST-π,TopoⅡα的表达指标不能预测口腔鳞状细胞癌的化疗效果和预后。

SKP2 siRNA对HL-60/A细胞周期及药物敏感性的影响

【目的】观察S期激酶相关蛋白2(SKP2)siRNA转染后耐阿霉素的HL-60细胞(HL-60/A)P27kip1及多药耐药相关蛋白MRP表达水平的变化,探讨其对细胞周期及药物敏感性的影响。【方法】siRNA转染HL-60/A细胞,荧光显微镜、流式细胞仪检测转染效率,RT-PCR、Western-blot检测转染后细胞SKP2、P27kip1、MRPmRNA及蛋白表达,流式细胞仪检测细胞周期,药物毒性分析CCK-8法检测细胞对化疗药物的敏感性。【结果】SKP2siRNA转染24h后,HL-60/A的SKP2mRNA及蛋白表达分别下调43%(P=0.020)和69.6%(P=0.003);P27kip1蛋白上调78.1%(P=0.049),P27kip1mRNA表达无明显变化;MRPmRNA及蛋白表达分别下调55%(P=0.001)和62.3%(P=0.001);G0/G1期细胞比例升高;细胞对阿霉素、柔红霉素、阿糖胞苷的敏感性分别提高1.15倍、4.79倍和3.76倍。【结论】SKP2siRNA下调HL-60/A细胞的SKP2表达可使P27kip1蛋白表达升高,细胞增殖周期延长;细胞耐药性的改善可能与MRP表达的降低有关。

谷胱甘肽S转移酶与三氧化二砷耐药性的相关研究

目的探讨谷胱甘肽S转移酶π(GSTπ)与三氧化二砷(As2O3)耐药之间的关系。方法选用30例急性早幼粒细胞白血病(APL)患者及10例正常对照组的外周血或骨髓,用RT-PCR方法检测GSTπ的表达。结果APL细胞的GSTπ表达率为36.7%。其中应用As2O3治疗的初治组GSTπ表达率为25%,治疗后复发和耐药的APL的GSTπ表达率为60%,复发或耐药组表达较初治组GSTπ表达明显增高(P<0.05),GSTπ表达较高者临床缓解率低(P<0.05)。结论GSTπ高表达与As2O3耐药密切相关,GSTπ的高表达可作为治疗APL耐药的一个标志。

卵巢恶性肿瘤中GST-π表达与肿瘤内在性耐药及患者预后关系的研究

目的：探讨谷胱甘肽Ｓ－转移酶π型（ＧＳＴ－π）在卵巢恶性肿瘤组织中的表达及其与肿瘤内在性耐药和患者预后的关系。方法：应用免疫组化ＳＰ法检测４５份卵巢恶性肿瘤组织和１０份正常卵巢组织中ＧＳＴ－π的表达，结合肿瘤细胞体外药物敏感试验结果和患者２ａ随访结果。结果：１．４５份卵巢恶性肿瘤组织ＧＳＴ－π阳性表达率为１００％，１０份正常卵巢组织仅２份呈弱阳性。２．１８份卵巢恶性肿瘤组织ＧＳＴ－π染色程度（＋）、（）、（）三组之间阿霉素对肿瘤细胞的抑制率有统计学差异（Ｐ＜０．０５），其中（）组抑制率明显低于（＋）组（Ｐ＜０．０５）。其余５种药物对肿瘤细胞抑制率差异无显著性（均Ｐ＞０．０５）。３．２８例Ⅲ期卵巢上皮性癌患者２ａ存活率为３９．３％，存活时间≥２ａ和＜２ａ两组ＧＳＴ－π表达差异有显著性（Ｐ＜０．０１），前者染色程度明显弱于后者。结论：ＧＳＴ－π表达在卵巢恶性肿瘤对阿霉素内在性耐药中起重要作用，而与顺铂、卡铂、５－ＦＵ、更生霉素、长春新碱内在性耐药无关。ＧＳＴ－π表达高提示卵巢癌患者预后差，可供临床评价患者预后时参考。

GST-π和MDR1在乳腺癌中共表达水平及其临床意义

目的 :研究谷光苷肽S 转移酶 (GST π)和多药耐药基因 (MDR1)mRNA在乳腺癌组织中的表达水平 ,探讨其共表达机制及在临床的应用价值。方法 :复合定量RT PCR技术 ,检测 79例乳腺癌组织中耐药相关基因的表达水平 ,其中MDR179例 ,GST π 6 5例。观察DMR1和GST π的共表达率并与TNM分期、受体表达、是否术前化疗作相关分析。结果 :乳腺癌组织中MDR1和GST π阳性率分别为 96 2 %和 70 7% ,共表达率为78 5 % ,两者的表达水平明显相关。MDR1和肿瘤大小相关 ,而MDR1和GST π均与雌激素、孕激素受体表达及是否术前化疗无关。MDR1、GST π共表达和单独表达率与是否术前化疗无关 ,而MDR1表达水平化疗后增高 ,GST π表达水平无显著差异。结论 :MDR1、GST π共表达是乳腺癌耐药的特征之一 ,而MDR1可能发挥了主导作用。GST π和MDR1表达水平呈明显正相关 ,说明两者可能有互相调节机制。

肺癌中MDR基因产物LRP、P-gp、GST-π、TopoⅡ的表达及临床意义

目的:探讨多药耐药(MDR)基因产物LRP、P-gp、GST-π、TopoⅡ在肺癌中的表达及临床相关性。方法:应用单克隆抗体、免疫组化技术S-P法,对70例肺癌标本进行上述4种MDR指标检测。结果:在肺癌组织中LRP、P-gp、GST-π、TopoⅡ表达的阳性率分别为75.7%、70.0%、82.9%、84.3%,其与性别、年龄、部位、临床分期无关(P>0.05);在未分化、小细胞型肺癌中LRP、P-gp、GST-π表达的阳性率明显降低(P<0.05),而TopoⅡ表达的阳性率则升高(P<0.05,低分化型肺癌除外)。结论:LRP、P-gp、GST-π、TopoⅡ在未化疗过的肺癌组织中均有不同程度的高表达,且与肺癌的某些生物学行为有关,联合检测有助于化疗药物的选择及预后的判断。