Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer

Background: Breast cancer is the most common malignancy in women. Multidrug resistance (MDR) is still a greatobstacle of breast cancer chemotherapy. We have previously shown that multidrug resistance-associated protein 1 (MRP1)is associated with response to neoadjuvant chemotherapy. The lung resistance-related protein (LRP) is identified asa prognostic marker and response to treatment factor which has been studied mainly in hematological malignancy andleukemia. In this study, we aimed to analyze LRP expression and possible correlation between the expression level ofthis gene with MRP1 as a candidate marker for chemotherapy resistance. Materials and Methods: We collected 54breast tumors and adjacent normal tissues from Iranian breast cancer patients and Real time RT-PCR was employed tomeasure the gene expression level in our samples. Results: MRP1 and LRP expression level were significantly lowerin tumor tissues of the patients responding to chemotherapy compared to non-responding patients. No relation betweenthe expression level of either of these genes and clinicopathology markers was found. Conclusion: Our results suggestthat LRP gene expression is correlated to MRP1 in human breast cancer cells and may affect the clinical response totreatment.     

耐药相关基因表达对Ⅲ期非小细胞肺癌新辅助化疗的临床预测价值探讨

背景与目的P-糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(multidrugresistance-associatedprotein,MRP)、肺耐药蛋白(lungresistanceprotein,LRP)在多药耐药中发挥重要的作用,联合检测它们在评价非小细胞肺癌新辅助化疗中的价值国内外尚未见报道。本研究旨在探讨联合检测P-gp、MRP、LRP对Ⅲ期非小细胞肺癌新辅助化疗敏感性的预测价值。方法应用免疫组化技术检测31例行新辅助化疗的患者化疗前标本及化疗后手术标本。结果化疗前P-gp、MRP、LRP表达的阳性率分别为29.0%(9/31)、45.2%(14/31)及38.7%(12/31),化疗后分别为61.3%(19/31)、51.6%(16/31)及41.9%(13/31)。化疗前MRP和LRP同时阳性者32.3%(10/31),MRP与LRP具相关性(r=0.61,P<0.001)。化疗前P-gp、MRP、LRP表达阳性者化疗有效率分别为44.4%(4/9)、28.6%(4/14)及16.7%(2/12),MRP与LRP同时阳性者有效率为10.0%(1/10)。化疗有效的患者中位生存期为31个月,无效的为15个月,同期直接手术的患者为18个月。结论肿瘤中MRP与LRP共表达者化疗耐药的可能性很大,化疗有效率较低,新辅助化疗意义不大。     

Single static view 99mTc-sestamibi scintimammography predicts response to neoadjuvant chemotherapy and is related to MDR expression

We examined the relevance of a pre-treatment single static view 99mTc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following completion of anthracycline-based chemotherapy, clinical, mammographic, sonographic and pathological responses were determined. 99mTc-sestamibi scintimammography predicted the reduction of tumor size measured by sonography and the pathological response according to Sataloff classification (p<0.05) and tend to predict pathological response according to Chevallier (p<0.1). A negative 99mTc-sestamibi scintimammography predicted chemoresistance with a specificity of 100%. Uptake of 99mTc-sestamibi was inversely correlated to the expression of MDR1 (p<0.05) in invasive ductal carcinoma. A pre-treatment single-view 99mTc-sestamibi scintimammography is an excellent predictor of MDR1 chemoresistance and was highly specific of a lack of pathological response to chemotherapy.     

MRP1蛋白表达情况与乳腺癌新辅助化疗疗效的关系

目的 探讨多药耐药相关蛋白1(MRP1)蛋白表达与乳腺癌患者新辅助化疗临床疗效的关系.方法 选取实施新辅助化疗的150例患者的临床资料进行回顾性分析,根据化疗效果分为有效组105例及无效组45例,对比两组患者化疗前乳腺癌组织中MRP1蛋白的表达水平,并采用多因素分析法探讨MRP1蛋白表达与乳腺癌患者新辅助化疗效果的关系.结果 有效组患者的MRP1蛋白阴性表达率18.10%、弱阳性表达率40.95%、中阳性表达率34.29%、强阳性表达率6.67%,无效组患者的MRP1蛋白阴性表达率6.67%、弱阳性表达率26.67%、中阳性表达率40.00%、强阳性表达率26.67%,两组比较差异有明显统计学意义(P﹤0.01);非条件Logistic回归分析结果显示TNM分期增高、组织学分级低分化、MRP1蛋白阳性表达是乳腺癌患者化疗效果不佳的独立危险因素(P﹤0.05).结论 MRP1蛋白阳性表达是乳腺癌患者新辅助化疗效果不佳的独立危险因素.     

INFLUENCE OF NEOADJUVANT INTRAARTERIAL INFUSION CHEMOTHERAPY ON APOPTOSIS AND MULTIDRUG RESISTANCE ASSOCIATED GENES OF ENDOMETRIAL CANCER

Many researches have proved that neoadjuvantintraarterial infusion chemotherapy (NIAC) is a useful method for the treatment of uterine cervical cancer[1, 2]while there are few reports about endometrial cancer[3Apoptosis has been shown to occur in various tumors in response to chemotherapeutic agents. It is not only related to the tumor response to chemotherapy, but also closely associated with the multidrug resistance[4, 5]. To date, no data have become available that shed light on the timin…     

乳腺癌患者MRP基因表达及临床意义

目的：检测ＭＲＰ基因在人乳腺癌组织中的表达状况，初步分析其临床意义。方法：３７例待手术腺癌患者随机分为直接手术１、术后化疗、术前化疗和三苯氧胺三组。采用ＲＴ－ＰＣＲ法检测癌组织中ＭＲＰ基因表达。结果：本前化疗组ＭＲＰ阳性率２８．６％；直接手术组ＭＲＰ极弱或无表达；加用三苯氧胺ＭＲＰ表达减少为１／８。局部晚期病例ＭＲＰ基因表达多呈阳性。结论：以上结果提示ＭＲＰ是乳腺癌ＭＤＲ产生的机制之一。     

多药耐药相关蛋白在乳腺癌组织中的表达

目的 观察多药耐药相关蛋白(MRP)是否在临床乳腺癌组织中表达,了解MRP在乳腺癌多药耐药现象中的临床相关性.方法 用RT-PCR及免疫组化技术检测乳腺癌、乳腺纤维瘤组织中MRP及MRPmRNA的表达.结果 乳腺癌组织的MRP阳性率为56%,乳腺纤维瘤为20%.阳性染色主要位于癌细胞胞浆,胞膜次之.结论 RT-PCR进一步表明术前化疗的乳腺癌组织MRPmRNA表达明显强于乳腺纤维瘤及术前未受化疗者.MRP是乳腺癌化疗时值得重视的因素.     

LRP,MRP,MDR1基因在非小细胞肺癌中的表达及其临床意义

目的 探讨肺耐药蛋白（ｌｕｎｇ ｒｅｓｉｓｔａｎｃｅ ｐｒｏｔｅｉｎ,ＬＲＰ）,多药耐药蛋白（ｍｕｌｔｉｄｒｕｇ ｒｅｓｉｓｔａｎｃｅａｓｓｏｃｉａｔｅｄ ｐｒｏｔｅｉｎ,ＭＲＰ）,和多药耐药基因（ｍｕｌｔｉｄｒｕｇ ｒｅｓｉｓｔａｎｅ,ＭＤＲ１）ｍＲＮＡ在非小细胞肺癌（ｎｏｎ－ｓｍａｌｌ ｃｅｌｌ ｃａｎｃｅｒ,ＮＳＣＬＣ）中的共表达及临床意义。方法 ＲＴ－ＰＣＲ检测ＮＳＣＬＣ冰冻组织中上述耐药     

非小细胞肺癌中多药耐药基因的表达及意义

探讨多药耐药基因(MDR1)和多药耐药相关蛋白基因(MRP)在非小细胞肺癌(NSCLC)中的表达、意义及相关关系。方法:采用原位分子杂交对113例NSCLC组织中MDR1和MRP基因mRNA的表达进行检测。结果:MDR1和MRP基因mRNA在NSCLC组织中的阳性表达率分别为51.3%(58/113)、80.5%(91/113),二者与NSCLC肿瘤组织类型、分化程度、淋巴结转移、TNM分期等无关(P>0.05)。MDR1和MRP的协同阳性(MDR1⁺/MRP⁺)表达率为48.7%(55/113),二者在NSCLC中的表达之间存在明显相关(P<0.01)。结论:MDR1和MRP是NSCLC原发性多药耐药的重要参与因素,二者联合检测对临床NSCLC的化疗具有指导意义。     

47例原发性乳腺癌多药耐药MDR1基因表达及其临床意义

[目的]探讨原发性乳腺癌多药耐药MDR1基因的表达及其临床意义.[方法]采用荧光定量RT-PCR法检测47例乳腺癌组织及15例正常对照(包括5例乳腺纤维腺瘤、10例癌旁组织)MDR1基因的表达.[结果]乳腺癌MDR1基因表达阳性率为46.8%,与病人年龄、肿瘤大小、淋巴结转移与否、ER、PR状况、绝经与否无关.对照组中无MDR1基因表达.[结论]乳腺癌MDR1基因的表达可作为乳腺癌化疗耐药的评价指标,能否作为判断预后的独立指标尚需进一步研究.     

肺癌组织中多药耐药基因及相关蛋白表达的研究

目的:探讨P-糖蛋白(P-glycopro-tein,P-gp)、肺癌耐药蛋白(lung cancer resis-tence protein,LRP)和多药耐药相关蛋白(multidrug resistence protein,MRP)在肺癌组织中的表达及其临床意义。方法:应用SP法检测116例术前未做化疗的肺癌组织中P-gp、LRP和MRP的表达水平。结果:P-gp在腺癌组织中的阳性表达率为78.26%(36/46),小细胞癌为63.64%(7/11),鳞状细胞癌为47.46%(28/59);三者相比差异有统计学意义,P=0.018。LRP在腺癌组织中的阳性表达率为89.13%(41/46),鳞状细胞癌为44.07%(26/59),小细胞癌为27.27%(3/11);三者相比差异有统计学意义,P=0.0001;MRP在不同癌组织中的表达差异无统计学意义,P=0.4165。在腺癌、鳞状细胞癌和小细胞癌组织中同时有两种或两种以上耐药基因产物表达阳性率分别为89.13%(41/46)、49.15%(29/59)和27.28%(3/11),三种类型间比较差异有统计学意义,P=0.0001。结论:不同组织学类型的肺癌存在不同程度的耐药性,检测P-gp、LRP和MRP的协同表达对于指导临床化疗方案的实施有重要意义。     

Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges

Gastric cancer is the second leading cause of cancer mortality worldwide. The major cause of treatment failure for gastric cancer is the development of multidrug resistance (MDR) to chemotherapy, which is currently one of the primary treatment options. Recently, research into the MDR of gastric cancer has revealed that, in addition to the classical ATP-binding cassette transporters, such as P-glycoprotein (P-gp) and MDR-associated protein (MRP)1, a number of other molecules might mediate the drug resistance of human gastric cancer. The absence of P-gp and MRP1 expression in some gastric cancer cases also indicates that there might be other mechanisms responsible for human gastric cancer MDR. These molecules belong to different functional families and might work together to confer MDR phenotypes. The new findings may provide new clues to the mechanisms of MDR and enable the selection of new candidates for targeting MDR in human gastric cancer.     

Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges

Gastric cancer is the second leading cause of cancer mortality worldwide. The major cause of treatment failure for gastric cancer is the development of multidrug resistance (MDR) to chemotherapy, which is currently one of the primary treatment options. Recently, research into the MDR of gastric cancer has revealed that, in addition to the classical ATP-binding cassette transporters, such as P-glycoprotein (P-gp) and MDR-associated protein (MRP)1, a number of other molecules might mediate the drug resistance of human gastric cancer. The absence of P-gp and MRP1 expression in some gastric cancer cases also indicates that there might be other mechanisms responsible for human gastric cancer MDR. These molecules belong to different functional families and might work together to confer MDR phenotypes. The new findings may provide new clues to the mechanisms of MDR and enable the selection of new candidates for targeting MDR in human gastric cancer.     

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.