肿瘤多药耐药机制及其逆转

肿瘤多药耐药(multidrug resistence,MDR)是制约肿瘤成功化疗的重要因素之一.人恶性肿瘤对化疗的耐药性可分为先天性耐药和获得性耐药;根据耐药谱又分原药耐药(primary drug resisance,PDR)和多药耐药(multidrug resis-tence,MDR).PDR只对诱导的原药产生耐药,而对其它药不产生产交叉耐药;MDR是指肿瘤细胞对一种抗肿瘤药物产生耐药性的同时,对结构和作用机制完全不同的其他抗肿瘤药物产生交叉耐药性的现象[1].本文主要向大家简单介绍MDR的机制及其逆转的部分研究进展,以供大家参考.     

白血病多药耐药逆转研究进展

多药耐药(multidrugresistance, MDR)是肿瘤细胞接触一种抗肿瘤药物后, 不仅对该药可产生耐药性, 对其他结构和作用机制不同的多种抗肿瘤药物也可产生交叉抗药性。白血病细胞的MDR是化疗失败和疾病复发的主要原因之一。目前认为MDR产生的机制有: .药物外排介导的耐药, 主要有P 糖蛋白 (permeability glycoprotein, P gp, P 170 )、多药耐药相关蛋白 (multidrugresistance associatedprotein, MRP)、乳腺癌耐药蛋白(breastcancerresistanceprotein, BCRP)和肺耐药相关蛋白(lungresistance relatedprotein, LRP)介导的耐药; 谷胱…     

乳腺癌多药耐药性机制及逆转方法研究近况

乳腺癌严重威胁着女性健康,化学药物治疗在乳腺癌的治疗中起着举足轻重的作用,但临床治疗中常因乳腺癌细胞产生多药耐药性而导致化学药物治疗的失败。笔者就乳腺癌细胞多药耐药性的相关蛋白及基因、酶类等多药耐药性相关机制进行了详细论述．并介绍了化学药物、基因技术、中药、药物载体在逆转乳腺癌多药耐药性中的应用及目前研究进展。     

环孢菌素类药物逆转急性白血病多药耐药的研究进展

化学治疗是急性白血病治疗的基本手段，应用现代化疗手段已使急性白血病的疗效取得了长足进步，不少患者得以治愈．但是，白血病细胞对化疗药物产生耐药性已成为白血病化疗失败的主要原因之一，因此，化疗耐药性也成为白血病研究的热门课题．l急性白血病耐药的机理急性白血病耐药的机理一般分为3类：①P一糖蛋白介导的MDR（也称经典MDR）泪拓朴异构酶11介导的MDR又称不典型MDR）；③谷跳甘肽S转移酶（GST）和金属硫基系统介导的MDR（又称非P一糖蛋白一MDR）．其中，P一糖蛋白一MDR的研究较多．P一精蛋白是细胞膜上的一种能量依…     

乳腺癌多药耐药机制研究进展

乳腺癌癌细胞表现多药耐药性 (ｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ ,ＭＤＲ)往往是导致临床化疗失败的主要原因之一。ＭＤＲ有两种不同的表型 ,一种是对第一次化疗就产生耐药 ,称天然性耐药 (ｎａｔｕｒａｌｒｅｓｉｓｔａｎｃｅ)或称内源性耐药 (ｉｎｔｒｉｎｓｉｃｒｅｓｉｓ ｔａｎｃｅ) ;另一种是在化疗过程中产生耐药 ,故称获得性耐药(ａｑｕｉｒｅｄｒｅｓｉｓｔａｎｃｅ)。ＭＤＲ的特点是一旦对某种化疗药物产生耐药 ,对其他结构上无关、作用靶点和机制不同的抗癌药物产生交叉耐药。目前研究认为 ,肿瘤产生ＭＤＲ的分子机制主要…     

白藜芦醇逆转肿瘤耐药的分子机制研究进展

白藜芦醇(Res)作为一种天然植物的提取物,毒性极低。近年研究表明Res可通过ATP结合盒(ABC)跨膜转运蛋白家族、信号传导通路、SIRT1、诱导凋亡等机制增强耐药细胞对化疗药物的敏感性,具有显著的逆转肿瘤多药耐药(MDR)的作用,为有效解决肿瘤MDR的问题提供新的思路。Res有望成为一种新型耐药逆转剂。     

单克隆抗体逆转肿瘤耐药的研究进展

肿瘤耐药是化疗失败的重要原因，逆转肿瘤对药物的耐受性是肿瘤治疗工作者关心的热点之一。本文对引起肿瘤耐药的Ｐ－糖蛋白抗体逆转研究作一回顾。具有逆转作用的单抗均识别Ｐ－糖蛋白膜外表位，且不同抗体能够逆转的耐受药物不同；同时抗体介导的免疫反应也参与了逆转；单抗的逆转作用取决于肿瘤是否有Ｐ－糖蛋白的表达。单克隆体逆转作用特异性好，但也存在许多问题。     

肺耐药相关蛋白及其介导的多药耐药研究进展

肺耐药相关蛋白 (lungresistance─relatedprotein ,LRP)是一人类主要穹窿蛋白 ,分子量为12 0KD ,它定位于核孔复合物上 ,作为该复合物的转运单位LRP基因控制着多种底物的双向转运。本文对肺耐药相关蛋白的分子生物学特征和生理功能及其在肿瘤细胞中的过度表达所产生的临床意义作一综述     

单克隆抗体逆转肿瘤耐药的研究进展

肿瘤耐药是化疗失败的重要原因，逆转肿瘤对药物的耐受性是肿瘤治疗工作者关心的热点之一．本文对引起肿瘤耐药的Ｐ－糖蛋白抗体逆转研究作一回顾．具有逆转作用的单抗均识别Ｐ－糖蛋白膜外表位，且不同抗体能够逆转的耐受药物不同；同时抗体介导的免疫反应也参与了逆转；单抗的逆转作用取决于肿瘤是否有Ｐ－糖蛋白的表达。单克隆抗体逆转作用特异性好，但也存在许多问题。     

肿瘤多药耐药机制研究进展

肿瘤多药耐药(MDR)是目前临床肿瘤化疗失败的主要原因之一.关于肿瘤多药耐药产生的机制有多种,针对这些不同的机制来研发相应的逆转药物则是目前解决临床耐药现象的主要途径.就目前国内外肿瘤多药耐药机制的研究进展作一综述.     

非小细胞肺癌多耐药基因产物(P-gp)表达与多种预后因素的关系

探讨非小细胞肺癌（NSCLC）多药耐药基因-1（MDR-1）产物P-糖蛋白（P-gp）在术前未经治疗的非小细胞肺癌组织中的表达及与多种预后因素间的关系。采用免疫组化法检测P-gp在56例NSCLC组织中的表达及其与性别、病理类型、病理分级、淋巴结状况、细胞增殖指数（Ki67）、肿瘤细胞修复能力（TOPOⅡ、MGMT）、表皮生长因子受体（EGFR）、肿瘤的免疫状态（HSP70）以及参与肿瘤恶变、凋亡及转移的癌基因和抑癌基因（P53、Bcl-2、C-erb-2、MDM2）的相关性。结果显示,P-gp在非小细胞肺癌组织中的阳性表达率是53.6%（30/56）,P-gp与TOPOⅡ之间（r=0.279,P=0.037）、P-gp与EG-FR之间（r=0.320,P=0.016）、P-gp与HSP70之间（r=0.279,P=0.037）以及P-gp与C-erb2之间（r=0.249,P=0.043）有相关性。结论：非小细胞肺癌组织中P-gp的表达与多种基因的表达密切相关。采用MDR-1逆转剂可增加非小细胞肺癌的化疗敏感性,行多基因联合检查可为预测非小细胞肺癌预后及指导化疗提供实验依据。     

The Role of Phenethyl Isothiocyanate on Bladder Cancer ADM Resistance Reversal and Its Molecular Mechanism

Adramycin (ADM) resistance is an essential aspect of bladder cancer treatment failure and phenethyl isothiocyanate (PEITC) has been found to exhibit antitumor properties; however, the effect and potential mechanism of PEITC on bladder cancer ADM resistance reversal is not fully clear. The aim of this study was to explore the role of PEITC in bladder cancer cells ADM resistance reversal and the underlying molecular mechanisms. In this report, we identified the role of PEITC on ADM resistance reversal of human bladder carcinoma T24/ADM cells, including an increased drug sensitivity to ADM, cell apoptosis rates, intracellular accumulation of Rhodamine‐123 (Rh‐123), an increased expression of DNA topoisomerase II (Topo‐II), and a decreased expression of multidrug resistance gene (MDR1), multidrug resistance‐associated protein (MRP1), bcl‐2 and glutathione s transferase π (GST‐π).We also found that there was a decreased expression of NF‐κB, Survivin, Twist, and p‐Akt, and an increased expression of PTEN and p‐JNK after PEITC treatment for T24/ ADM cells. The results indicated that PEITC might be used as a potential therapeutic strategy to ADM resistance through blocking Akt and activating MAPK pathway in human bladder carcinoma. Anat Rec, 296:899–906, 2013. © 2013 Wiley Periodicals, Inc.     

RKIP在不同类型肺癌中表达的变化及临床意义

目的 观察Raf激酶抑制蛋白（RKIP）在不同类型肺癌中表达的变化及探讨其临床价值。方法 选取鳞癌21例、腺癌23例及小细胞肺癌10例设为实验组,肺良性病变10例设为对照组,采用免疫组化的方法检测RKIP的表达,观察在不同类型肺癌中表达的差异及与临床分期的关系。结果 与对照组比较,实验组中RKIP的表达水平均降低,差异有统计学意义（P＜0.05）。实验组中RKIP的表达最低的是小细胞癌,其次为鳞癌,再次腺癌。对腺癌进一步研究发现,与Ⅰ及Ⅱ期比较,RKIP在Ⅲ及Ⅳ期的表达更低;与Ⅰ期比较,RKIP在Ⅱ期中表达稍有减低,但差异无统计学意义（P＞0.05）;与Ⅲ期比较,RKIP在Ⅳ期中表达稍有减低,但差异无统计学意义（P＞0.05）。磷酸化ERK1/2（p-ERK1/2）的表达趋势与RKIP相反,与Ⅰ和Ⅱ期比较,在Ⅲ和Ⅳ期中表达明显升高。相关性分析显示,RKIP与p-ERK1/2的表达呈负相关（r=-0.893,P＜0.05）。结论 RKIP表达水平的缺失可能促进了ERK1/2的磷酸化,从而促进了肺癌的发生及发展,因此检测RKIP的表达水平可能对诊断肺癌及分期预后有重要的临床价值。     

细胞色素P45A1基因变异与肺癌易患性

Individual susceptibility to cancer induced by environmental agents may be influenced by polymorphic metabolic genes responsible for the activation or detoxification of carcinogens．The association between genetic polymorphisms in cytochrome P4501A1 (CYP1A1) and lung cancer susceptibility has been extensively studied．The various CYP1A1 alleles exhibit population frequencies that depend on race and ethnicity．An increased risk of lung cancer in Asians was found to be associated with genetic polymorphisms in CYP1A1．However,reports from Caucasians are not consistant,probably suggesting the ethnic-sepecific effect of the polymorphisms in the locus on the cancer．Evidence also exists for the association between levels of carcinogen-DNA adducts or frequency of oncogene and tumor suppressor gene mutations and CYP1A1 polymorphisms．These findings provide a better understanding of the relationship between CYP1A1 and lung cancer susceptibility．     

肺癌患者的血液流变性变化及其与预后的关系

对８５例肺癌患者进行了血细胞压积等５项指标的测定，发现其血细胞压积较健康人为低，而血沉、全血比粘度、血浆比粘度、纤维蛋白原均高于健康人。治疗后好转的患者其血浆比粘度、全血比粘度、纤维蛋白原均明显低于治疗后恶化者，有远处转移者的血沉、全血比粘度、血浆比粘度与纤维蛋白原较无转移者的要高。     

原发性肺癌外科手术临床路径应用研究

目的：评价原发性肺癌外科手术临床路径实施效果。方法：回顾性统计2011年9月至2012年8月在首都医科大学宣武医院胸外科因原发性肺癌接受外科手术实施临床路径管理的98例患者（实验组）资料,包括平均住院日、次均费用、抗菌药物应用、患者满意度等,并与112例未实施临床路径管理患者（对照组）进行比较。结果：实验组患者平均住院日、术前住院日、住院费用、药品费用、抗菌药物使用时间均较对照组显著降低（P〈0．05）;术后住院时间和药费比例有下降的趋势,患者满意度有所上升,但组间比较差异无统计学意义（P〉0．05）。结论：实施临床路径管理可以缩短肺癌外科治疗住院时间,降低医疗费用,提高医疗质量和患者满意度,使医患双方受益。     

Natural Progression of Ground-glass Nodules after Curative Resection for Non-small Cell Lung Cancer

BackgroundThis retrospective study investigated the natural course of synchronous ground-glass nodules (GGNs) that remained after curative resection for non-small-cell lung cancer (NSCLC).MethodsProspectively collected retrospective data were reviewed concerning 2,276 patients who underwent curative resection for NSCLC between 2008 and 2017. High-resolution computed tomography or thin-section computed tomography data of 82 patients were included in the study. Growth in size was considered the most valuable outcome, and patients were grouped according to GGN size change. Patient demographic data (e.g., age, sex, and smoking history), perioperative data (e.g., GGN characteristics, histopathology and pathological stage of the resected tumours), and other medical history were evaluated in a risk factor analysis concerning GGN size change.ResultsThe median duration of follow-up was 36.0 months (interquartile range, 23.0–59.3 months). GGN size decreased in 6 patients (7.3%), was stationary in 43 patients (52.4%), and increased in 33 patients (40.2%). In univariate analysis, male sex, the GGN size on initial CT, part-solid GGN and smoking history (≥ 10 pack-years) were significant risk factors. Among them, multivariate analysis revealed that lager GGN size, part-solid GGN and smoking history were independent risk factors.ConclusionDuring follow-up, 40.2% of GGNs increased in size, emphasising that patients with larger GGNs, part-solid GGN or with a smoking history should be observed.     

肺癌手术病人的血液流变学变化及临床意义

目的了解肺癌病人的血液流变学变化及手术对血粘度的影响。方法对４７例肺癌病人及４２例健康者血液流变学相关指标进行比较并对肺癌病人手术前后血液流变学指标比较。结果肺癌病人全血低切粘度、血浆粘度及血沉差异均有极显著性（Ｐ＜０． ０１）,高切粘度及红细胞压积差异无显著性（Ｐ＞０．０５）。肺癌病人术前后全血低切粘度、高切粘度、血浆粘度及血流差异均有极显著性（Ｐ＜０．０１）。结论肺癌病人有明显血液流变学改变。手术对血液流变学有较大影响。如能对血粘度异常进行适当治疗,可望减少和预防肺癌的血运转移和复发。     

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score

BackgroundThis study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer.MethodsThis retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes.ResultsOf the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001).ConclusionStratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.     

TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean Population

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.

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