EXPRESSION AND CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE AND MULTIDRUG RESISTANCE-ASSOCIATEDPROTEIN GENE IN ACUTE LEUKEMIA

Objective: To evaluate the expression and clinical significance of multidrug resistance gene (mdr1) and multidrug resistance-associated protein (MRP) gene in acute leukemia. Methods: The expression of mdr1 and MRP assay in 55 patients with acute leukemia (AL) by reverse transcription polymerase chain reaction (RT-PCR). Results: The mdr1 and MRP gene expression levels in the relapsed AL and the blastic plastic phases of CML were significantly higher than those in the newly diagnostic AL and controls. The mdr1 and MRP gene expression levels in the clinical drug-resistant group were significantly higher than those in the non-drug-resistant group. The complete remission (CR) rate in patients with high mdr1 expression (14.3%) was significantly lower than that with low mdr1 expression (57.5%); similarly the CR rate in patients with high MRP level was also lower than that with low MRP level. Using both high expression of mdr1 and MRP gene as the indicator for evaluating multidrug resistance (MDR), the positive predictive value and accuracy increased in comparison with single gene high expression. Conclusion: Elevated level of mdr1 or MRP gene expression might be unfavorable prognostic factors for AL patient and may be used as an important index for predicting drug-resistance and relapse in AL patient. Measuring both mdr1 and MRP gene expression would increase accuracy and sensibility of evaluating MDR in acute leukemia.

EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) AND ITS RELATIONSHIP WITH CLINICOPATHOLOGICAL FACTORS IN NON-SMALL CELL LUNG CANCER

Objective: To investigate the relationship between the expression of multidrug resistance-associated protein (MRP) and clinicopathological factors and prognosis. Methods: The expression of MRP in 62 cases with non-small cell lung cancer (NSCLC) was detected using immunohistochemistry method. The expression of MRP in 30 cases of NSCLC and corresponding normal lung tissues were detected using immunohistochemistry and Western Blot. Results: this study of tumor tissues confirmed the plasma membrane and/or cytoplasm locations of MRP. There was apparent difference between normal lung tissues and NSCLC in MRP. The survival analysis of 62 NSCLC showed that the mean survival time of the patients with negative MRP expression was 69.8117.41 months and that of patients with positive MRP expression, 25.384.46 months. Log-rank test suggested that the difference between them was significant (P=0.0156). It was also found that in squamous cell lung cancer the statistically significant difference between the mean survival time of patients with positive MRP expression and those with negative MRP expression (P=0.0153). Multivariate Cox model analysis suggested that the survival time was significantly related to expression of MRP (P=0.035) and lymphatic metastasis (P=0.038). Conclusion: MRP expression in NSCLC is significantly higher compared with normal lung tissues. The mean survival time of patients with negative MRP was relative longer and expression of MRP was an independent factor for prognosis.

Expression and significance of multi-drug resistance-associated protein 3 in different tumor cell lines

Objective To investigate the expression and meaning of MRP3 in different tumor cells. MethodsThe monoclonal antibody against MRP3 was used to identify the expression of MRP3 by flow cytometer in seven tumor cells and human embryo kidney cell lines 293T.And RT-PCR was used to detect the mRNA of MRP3 in eight cell lines. ResultsThe mRNA of MRP3 was expressed in three pancreatic carcinoma cell lines.MRP3 protein was observed in BxPC-3 and AsPC-1 cells. ConclusionMRP3 may express in different tumor in tissue-specific manner.BxPC-3 and AsPC-1 may serve as cellular models for in vitro studies on multidrug resistance of pancreatic carcinoma.

JNK1,JNK2,and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells

BACKGROUND:Multidrug resistance(MDR)is extremely common in hepatocellular carcinoma(HCC)and is a major problem in cancer eradication by limiting the efficacy of chemotherapy.Modulation of c-Jun NH2-terminal kinase(JNK)activation could be a new method to reverse MDR.However,the relationship between JNK activity and MDR in HCC cells is unknown.This study aimed to explore the relationship between MDR and JNK in HCC cell lines with different degrees of MDR.METHODS:A MDR human HCC cell line,SMMC-7721/ ADM,was developed by exposing parental cells to gradually increasing concentrations of adriamycin.The MTT assay was used to determine drug sensitivity.Flow cytometry was used to analyze the cell cycle distribution and to measure the expression levels of P-glycoprotein(P-gp)and MDR-related protein(MRP)-1 in these cells.JNK1,JNK2 and JNK3 mRNA expression levels were quantified by real-time PCR.Expression and phosphorylation of JNK1,JNK2,and JNK3 were analyzed by Western blotting.RESULTS:The MDR of SMMC-7721/ADM cells resistant to 0.05 mg/L adriamycin was mainly attributed to the overexpression of P-gp but not MRP1.In addition,these cells had a significant increase in percentage in the S phase,accompanied by a decrease in percentage in the G0/G1 phase,which is likely associated with a reduced ability for cell proliferation and MDR generation.We found that JNK1,JNK2,and JNK3 activities were negatively correlated with the degree of MDR in HCC cells.CONCLUSION:This study suggests that JNK1,JNK2,and JNK3 activities are negatively correlated with the degree of MDR in HCC cells.

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,

Effects of Hypoxia on Expression of P-gp and Mutltidrug Resistance Protein in Human Lung Adenocarcinoma A549 Cell Line

To study the effects of hypoxia on the expression of P-gp and mutltidrug resistance protein in human lung adenocarcinoma A549 cell line, and to explore the probable mechanism of hypoxia in tumor cell of MDR. The expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein was immunohistochemically detected by culturing human lung adenocarcinoma A549 cell under hypoxia (2 % O_2) for 24 h. After interaction with adriamycin or cisplatin under hypoxia (2 % O_2) for 24 h, the cell survival rate was detected by MTT. Our results showed that the expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein under hypoxia were higher than the expression under normoxia, and correlations between the expression of HIF-1α and P-gp or multidrug resistance-associated protein was observed (P<0.05). The resistance of adriamycin of A549 cell was enhanced under hypoxia. It is concluded that the resistance of tumor chemotherapy is enhanced in hypoxia. The expression of HIF-1α is obviously correlated with the expression of P-gp and mutltidrug resistance protein.

In silico pharmacophore models to predict endogenous substrates for human multidrug resistance-associated proteins

Multidrug resistance-associated proteins （MRPs） can effiux structurally diverse drugs, drug conjugates, drug metabolites, as well as other small molecules out of the cells, and this is the main cause of producing multidrug resistance （MDR） of some anticaneer drugs. Therefore, it is crucial to uncover the molecular features of MRPs substrates in developing anti-MDR cancer therapy. In the present study, common feature pharmacophore models were developed by employing CATALYST Pharmacophore Modeling and Analysis tools using substrates of MRPs, including MRP1, -2, -3, -4, -5, -6, -8 and MRPs family, respectively. The models were validated using independent decoy sets generated in DUD-E, and the ones with best A UC （area under the curve） scores were chosen to predict endogenous substrates by screening the Human Metabolome Database （HMDB）. A number of molecules obtained by pharmacophore screening have been validated in the literatures. By comparing physical properties （ALOGP, Molecular_PolarSurfaceArea, Molecular_Volume, Molecular_Weight, Num H Acceptors, Num H Donors） and scaffold features of the screened candidates with the known substrates, we found that： 1） The two sets have consistent ALOGP, Molecule_Volume and Molecule_Weight distribution trend; 2） Substrates of MRP1 have a better lipophilicity than the other subtypes, which is consistent with the two hydrophobic centers on the MRP1 pharmacophore; 3） In the aspect of the scaffold structures, they have the identical or similar backbone fragments.

Effect of Histone Deacetylase Inhibition on the Expression of Multidrug Resistance-associated Protein 2 in a Human Placental Trophoblast Cell Line

Background： Placental multidrug resistance-associated protein 2 （MRP2）, encoded by ABCC2 gene in human, plays a significant role in regulating drugs＇ transplacental transfer rates. Studies o11 placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases （HDACs） inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC 1/2/3 are preliminarily involved in this process. Methods： The human choriocarcinoma-derived trophoblast cell line （Bewo cells） was treated with the HDAC inhibitors-trichostatin A （TSA） at different concentration gradients of 0.5, 1.0, 3.0, and 5.0 μmol/L. Cells were harvested after 24 and 48 h treatment. Small interfering RNA （siRNA） specific for HDACI/HDAC2/HDAC3 or control siRNA was transfected into cells. Total HDAC activity was detected by colorimetric assay kits. HDAC 1/2/3/ABCC2 messenger RNA （mRNA） and protein expressions were determined by real-time quantitative polymerase chain reaction and Western-blot analysis, respectively. Immunofluorescence for MRP2 protein expression was visualized and assessed using an immunofluorescence microscopy and ImageJ software, respectively. Results： TSA could inhibit total HDAC activity and HDAC 1/2/3 expression in company with increase ofM RP2 expression in Bewo cells. Reduction of HDAC 1 protein level was noted after 24 h of TSA incubation at 1.0, 3.0, and 5.0 μmol/L （vs. vehicle group, all P 〈 0.001 ）, accompanied with dose-dependent induction of MRP2 expression （P = 0.045 for 1.0 μmol/L, P = 0.001 for 3.0 μmol/L, and P 〈 0.001 for 5.0 μmol/L）, whereas no significant diferences in MRP2 expression were noted after HDAC2/3 silencing. Fluorescent micrograph images of MRP2 protein were expressed on the cell membrane. The fluorescent intensities of MRP2 in the control, HDAC2, and HDAC3 siRNA-transfected cells weir week, and no significant differences were noticed among these three groups （all P 〉 0.05）. However, MRP2 expression was remarkably elevated in H DAC1 siRNA-transfected cells, which displayed an almost 3.19-fold changes in comparison with the control siRNA-transfected cells （P 〈 0.001 ）. Conclusions： HDACs inhibition could up-regulate placental MRP2 expression in ritzy, and HDAC 1 was probably to be involved in this process.

靛玉红肠吸收转运机制的研究

目的:探讨靛玉红肠吸收转运机制。方法:采用缚管翻转肠囊模型,以维拉帕米为P-糖蛋白抑制剂,丙磺舒为多药耐药相关蛋白(MRP)抑制剂,2,4-二硝基苯酚(DNP)为能量抑制剂,考察加入抑制剂前后药物在空肠和回肠部位的转运量的变化。结果:靛玉红在空肠和回肠部位的转运量无显著性差异(P>0.05);加入抑制剂前后在空肠和回肠部位的转运量亦无显著性差异(P>0.05);通过吸收动力学的研究,发现靛玉红的吸收符合一级吸收模型,Ka为0.015 min-1,且单位时间吸收药量与浓度成正比,符合Fick′s扩散原理。结论:靛玉红的小肠吸收为典型的被动扩散吸收机制。

在体单向肠灌流模型研究大黄素的大鼠肠吸收特性

目的研究大黄素在大鼠不同肠段的吸收特性,以及P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP2)对大黄素肠吸收的影响。方法采用大鼠在体单向肠灌流模型,HPLC法测定肠灌流液中大黄素的浓度,计算不含抑制剂药物组及含抑制剂药物组大黄素的吸收速率常数(Ka)和表观吸收系数(Papp)。结果十二指肠段吸收能力显著强于其他肠段(P<0.05);大黄素在回肠、结肠、空肠段之间的吸收差异无统计学意义(P>0.05);加入P-gp抑制剂后,大黄素肠吸收的Ka、Papp值与不含抑制剂组比较差异也没有统计学意义(P>0.05);加入高、中浓度MRP2抑制剂后,大黄素肠吸收的Ka、Papp值与不含抑制剂组比较,差异均有统计学意义(P<0.01),且有剂量依赖性。结论大黄素在大鼠体内的主要吸收部位为十二指肠。大黄素的肠吸收过程不受P-gp的外排影响,但受到MRP2的肠道外排转运影响,大黄素可能为MRP2的底物。

温下方逆转A549/DDP细胞的多药耐药及对膜表面蛋白表达的影响

目的运用血清药理学方法,体外研究温下方对A549/DDP细胞多药耐药的逆转作用及机制。方法正常血清及不同浓度的温下方含药血清作用于A549/DDP细胞,四甲基偶氮唑蓝(MTT)法检测温下方含药血清对A549/DDP细胞的逆转作用;运用免疫荧光技术,激光共聚焦显微镜及流式细胞仪检测肺耐药相关蛋白(LRP)、多药耐药相关蛋白(MRP)和P-糖蛋白(P-gp)的表达。结果温下方含药血清能明显逆转A549/DDP细胞的多药耐药,增敏倍数为2～2.5倍。并可明显降低P-gp、LRP、MRP蛋白表达。结论温下方通过降低P-gp、LRP、MRP的表达以增强A549/DDP对化疗药的敏感性,逆转肺腺癌细胞的多药耐药。

人结肠癌羟基喜树碱耐药细胞株SW1116/HCPT的建立与鉴定

背景:肿瘤细胞的多药耐药性是造成化疗失败的主要原因,其机制是多种耐药相关基因表达的改变。目的:探讨消化道肿瘤的多药耐药机制和逆转策略。方法:应用药物浓度递增诱导法建立羟基喜树碱(HCPT)耐药结肠癌细胞株SW1116/HCPT;细胞计数法测定细胞生长曲线;流式细胞仪测定细胞周期分布;细胞染色体染色进行核型分析;四甲基偶氮唑蓝(MTT)比色法进行药物敏感实验;聚合酶链反应(PCR)-酶联免疫吸附测定(ELISA)检测细胞端粒酶活性;肿瘤药物耐受功能分类基因芯片筛选差异表达的耐药相关基因。结果:与亲代细胞相比,SW1116/HCPT细胞生长曲线无明显改变;对HCPT的耐药倍数增加120.0倍,并与阿霉素(48.2倍)、氧化苦参碱(2.1倍)、阿糖胞苷(2.0倍)、5-氟尿嘧啶(1.8倍)、顺铂(1.3倍)存在交叉耐药现象;细胞周期分布明显改变,G1期细胞增加,S期细胞减少;细胞染色体无明显变化,核型为非整倍体54-69;细胞端粒酶活性无明显改变;功能分类基因芯片显示,耐药细胞株表达改变的基因有30个,其中表达下调10个,上调20个。结论:SW1116/HCPT是研究消化道肿瘤多药耐药现象的模型之一。

K562/AS2细胞株对三氧化二砷耐药机制的初步研究

目的:研究K562/AS2细胞株对三氧化二砷(ATO)耐药的机制。方法:采用MTT法检测细胞毒性。细胞表面P-糖蛋白(P-gp)、细胞内柔红霉素(DNR)浓度采用流式细胞术检测。DNA聚合酶、拓扑异构酶Ⅱ(TopoⅡ)、多药耐药基因1(mdr1)、多药耐药相关蛋白1(MRP1)以及肺耐药相关蛋白基因(lrp)表达水平的检测采用RT-PCR法。结果:K562和K562/AS2细胞表面P-gp任意荧光强度、K562/AS2细胞内DNR浓度均无显著差异(P>0.05)。K562/AS2细胞株MRP1和TopoⅡ表达明显高于K562细胞(P<0.05),DNA多聚酶,mdr1和lrp表达与敏感细胞株K562细胞相同(P>0.05)。结论:ATO耐药细胞K562/AS2高表达MRP1,并产生低倍数的多药耐药。K562/AS2细胞TopoⅡ基因表达增高,其意义有待进一步阐明。

结直肠癌组织中PI3KCB蛋白表达及其与多药耐药基因产物的相关性

目的观察PI3KCB蛋白在结直肠癌组织中的表达情况,并探讨其与结直肠癌多药耐药(MDR)基因产物的相关性。方法采用免疫组化SP法检测128例结直肠癌组织、10例正常结肠黏膜组织中的PI3KCB蛋白及MDR基因产物LRP、GST-π、TopoⅡ。结果结直肠癌组织中PI3KCB蛋白呈阳性表达者105例(82.03%),正常结肠黏膜组织呈阳性表达者1例(10.00%),两者相比,P<0.01。结直肠癌组织中PI3KCB蛋白的表达与肿瘤发生部位、分化程度、临床分期及淋巴结转移有关(P均<0.05)。结直肠癌组织中LRP、GST-π、TopoⅡ呈阳性表达者分别为106例(82.81%)、120例(93.75%)、68例(53.13%),PI3KCB蛋白的表达与GST-π的表达呈正相关(rs=0.207,P<0.05)。结论 PI3KCB在结直肠癌组织中表达增加,与结直肠癌的发生发展及MDR密切相关;检测PI3KCB蛋白对于判断结直肠癌的生物学行为以及合理筛选有效的化疗药物具有重要参考价值。

黄芪对肝癌耐药细胞株Bel/Fu化疗敏感性的影响

目的:评估黄芪对肝癌耐药细胞化疗敏感性的影响,探讨黄芪对血红素加氧酶调节作用的可能机制。方法:黄芪注射液作用于Bel/Fu肝癌化疗耐药细胞株,分别应用MTT、免疫细胞化学、流式细胞术、RT-PCR检测细胞株对化疗药物敏感性、P-糖蛋白表达量、P-糖蛋白功能、血红素加氧酶(HO-1)核酸水平表达量。结果:黄芪注射液作用于Bel/Fu细胞诱导24h后,化疗药物半数抑制浓度显著降低;P-糖蛋白阳性表达明显减少,黄芪组罗丹明荧光曲线明显右移,细胞化疗药物外排功能降低;HO-1 mRNA表达显著减少。结论:黄芪注射液可增强肝癌耐药细胞株Bel/Fu的化疗敏感性,下调P-糖蛋白表达,降低P-糖蛋白药物外排功能,实现这种作用的同时伴随有HO-1 mRNA表达的减少。

五味子乙素对MDR1介导的人骨肉瘤细胞U-2 OS/ADR所致多药耐药性的逆转研究

目的研究五味子乙素(schisandrin B,SchB)对人骨肉瘤细胞阿霉素耐药株U-2 OS/ADR多药耐药的逆转效果及逆转机制。方法采用浓度梯度递增法构建U-2 OS阿霉素耐药株U-2 OS/ADR;使用MTT法测定Sch B对于U-2 OS多药耐药逆转的影响,实时荧光定量PCR(Q-PCR)检测SchB对MDR1基因转录的影响,流式细胞术检测细胞膜表面MDR1蛋白的表达,流式细胞术检测五味子乙素对罗丹明123外排和蓄积的影响,Western Blotting检测五味子乙素对PI3K/AKT通路的影响。结果五味子乙素能逆转U-2 OS/ADR细胞的多药耐药,并且能抑制MDR1基因的转录,降低膜表面MDR1蛋白的表达,增加细胞内罗丹明123的蓄积、减少外排,抑制U-2 OS/ADR细胞中PI3K/AKT通路的激活。结论五味子乙素具有强大的逆转人骨肉瘤细胞U-2 OS多药耐药的效果,其机制和下调耐药株的MDR1基因和蛋白水平,抑制PI3K/AKT通路激活有关。

药物转运蛋白对灯盏花素小肠吸收的影响

目的:研究药物转运蛋白P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP2)对灯盏花素小肠吸收的影响。方法:HPLC法测定大鼠肠液中灯盏花素的浓度,以大鼠在体单向灌流实验(SPIP)研究药物的小肠吸收,计算不含抑制剂药物组和含抑制剂药物组的小肠表观渗透系数(Papp)。结果:含P-gp抑制剂药物组与原药组相比,Papp没有显著变化;含MRP2抑制剂药物组与原药组相比,Papp显著增加。结论:P-gp对灯盏花素的小肠吸收基本没有影响,而MRP2可将吸收的灯盏花素从肠上皮细胞内又转运回肠腔,从而降低灯盏花素的吸收。

胆囊和胆管癌组织中多药耐药相关蛋白和GST-π的表达及意义

背景与目的:多药耐药性(MDR)被认为是导致胆囊癌和胆管癌化疗疗效不佳的主要原因,本实验通过免疫组织化学的方法检测胆囊癌、胆管癌组织中MRP1、MRP2和谷胱甘肽S-转移酶-π(GST-π)的表达情况,并探讨其与耐药的关系。方法:采用免疫组化的方法(IHC)检测复旦大学附属中山医院普外科自2000年2月—2006年11月收治的并行手术切除的18例胆囊癌和36例胆管癌中MRP1、MRP2及GST-π的表达情况,并以胆囊炎和胆管炎13例为对照。结果:MRP1、MRP2和GST-π在胆囊癌组织中的表达阳性率分别72.2%、72.2%和61.1%,在胆管癌组织中的表达阳性率为86.1%、80.6%和69.4%,显著高于对照组的23.1%、15.4%和23.1%(P<0.05)。上述指标与性别、年龄、病理分期、病理类型、分化程度淋巴结转移均无关(P>0.05);MRP1和GST-π、MRP2在胆囊癌和胆管癌的表达具有相关性(P<0.05)。结论:MRP1、MRP2、GST-π在未经过化疗的胆囊癌和胆管癌组织中均有不同程度的高表达;胆囊癌和胆管癌的原发性多药耐药可能与MRP、MRP、GST-π有关。

产吲哚金黄杆菌耐药性及其携带MBL-INDuniv研究

目的了解2007-2010年41株产吲哚金黄杆菌(chryseobacterium indologenes)临床分布、耐药特征、产金属酶及其携带MBL-INDuniv的情况。方法 K-B法检测41株产吲哚金黄杆菌对17种抗菌药物的敏感性。三纸片增效法进行金属β-内酰胺酶(metallo-beta-laetamase,MBL)简称金属酶表型检测,通过聚合酶链反应(polymerasechain reaction,PCR)筛查MBL-INDuniv基因的分布情况。结果 41株产吲哚金黄杆菌多来自呼吸科和ICU病房,最常见为呼吸道标本,占53.6%,对头孢他啶、氨曲南耐药率均为100%,亚胺培南、美罗培南的耐药率分别为为90.9%、87.8%,对常用抗阳性球菌药物如万古霉素、克林霉素耐药率在70%以下,米诺环素100%敏感。表型检测MBL菌株32株,MBL产酶率78.0%。PCR IND-univ通用引物扩增出18株阳性占43.9%。结论本地区的产吲哚金黄杆菌具有极强的耐药性和很高的MBL检出率,且MBL以IND基因型为主,应进一步密切关注该菌的传播及流行情况。

Ⅲ期非小细胞肺癌LRP、p53蛋白表达与新辅助化疗疗效及预后的研究

目的了解Ⅲ期非小细胞肺癌患者LRP、p53的表达与含铂新辅助化疗方案的疗效以及预后之间的关系。方法通过免疫组化方法研究43例Ⅲ期非小细胞肺癌患者化疗前后肺癌标本LRP、p53的表达,并分析上述指标的表达与新辅助化疗疗效以及生存期的关系。结果在化疗前后的成对标本中,化疗前肺癌标本LRP、p53的表达明显低于化疗后；化疗前LRP表达与化疗有效率呈负相关(LRP阳性组化疗有效率40％,LRP阴性组73．91％．P=0．033)；化疗前p53表达与化疗有效率正相关(p53阳性组化疗有效率76．19％,p53阴性组40．91％．P=0．031)。中位生存期化疗前LRP阴性组和阳性组分别为17个月和16个月,p53化疗前阴性组和阳性组分别为18个月和15个月。Cox回归分析结果提示化疗前p53表达(P=0．029)以及淋巴结转移(P=0．014)是生存期的预后因素。结论检测Ⅲ期非小细胞肺癌化疗前LRP和p53表达有助预测含铂方案新辅助化疗的疗效。化疗前p53超表达以及淋巴结转移提示Ⅲ期非小细胞肺癌患者预后不良。