Expression of Coxsackie and Adenovirurus Receptor and its Significance in Human Lung Cancer

OBJECTIVE To study the relationship between the coxsackie and adenovirus receptor (CAR) and the development of human lung cancer. To optimize adenovirus vector-based gene therapy. METHODS The expression of CAR in 112 cases of lung cancer was examined using immunohistochemistry. At the same time, the relationship between CAR expression and clinicopathologic characteristics was analyzed. RESULTS There is a little expression of CAR in normal lung tissue. Compared with paraneoplastic epithelial tissue of the lung, the expression of CAR is generally up-regulated in tumor tissues showing a significant dif- ference (P<0.01). The positive rate of CAR expression in squamous cell carcinoma was 43.1%, and in adenocarcinoma 70.2%, with the difference between the two rates being statistically significant (P<0.01). Compared to the paraneoplastic tissues, the difference in CAR positive expression was 35.4% for squamous cell carcinoma and 38.3% for adenocarcinoma. But the difference in different stages of squamous cell carcinoma had no statistical significance (P>0.05). However, the expression of CAR was at a high level in the bronchioalveolar carcinomas as 80.4% were CAR positive. This research showed that there was a specially high expression of CAR in adenocarcino- mas. CONCLUSION CAR is expressed in human lungs at a low level and up-regulated in the tumor tissues, suggesting that there is a relationship between adenocarcinoma and CAR. This research provides a basis for plan- ning a regimen of gene therapy using an adenovirus vector.     

Expression of Coxsackievirus and Adenovirus Receptor in Human Lung Cancer: Possible Clinical Significance

OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy.METHODS CAR expression was assessed immunohisto-chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed.RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma.Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer, mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results.CONCLUSION CAR is overexpressed in human lung cancer,especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.     

肺癌患者柯萨奇病毒和腺病毒受体的表达及其临床意义

  目的   探索柯萨奇病毒和腺病毒受体（Coxsackie and adenovirus receptor,CAR）与肺癌的关系,为使用基于腺病毒载体的基因治疗方案提供依据。   方法   运用免疫组织化学法检测112例肺癌患者肿瘤组织、癌旁组织以及正常组织中CAR的表达;通过RT-PCR和Western blot法检测32例患者CAR mRNA及CAR蛋白的表达。   结果   在正常肺组织中未见CAR表达,癌旁组织中可见少量的CAR表达。鳞状细胞癌和腺癌中CAR阳性表达比率分别为43%和70%,均较癌旁组织明显升高。同时,腺癌中CAR的表达也显著高于鳞状细胞癌,RT-PCR和Western blot法进一步证实免疫组织化学法检测结果。   结论   肺癌中CAR过表达,在腺癌中尤为明显,提示CAR可能参与了肺癌的发生发展,这可能对基因治疗肺癌的研究提供了较好的理论基础。      

柯萨奇病毒-腺病毒受体在结肠癌组织中的表达及意义

目的：柯萨奇病毒-腺病毒受体（coxsackie and adenovirus receptor，CAR）介导腺病毒与靶细胞之间的粘附，是腺病毒转染靶细胞的限速因子。本文分析CAR在瘤旁上皮组织、结肠肿瘤原发灶和淋巴结转移灶中的表达．为设计腺病毒载体基因治疗方案提供依据。方法：采用免疫组织化学方法检测62例结肠癌组织中CAR的表达．分析CAR表达与临床病理特征的关系。结果：与瘤旁上皮组织相比，肿瘤组织普遍存在CAR表达下调．但CAR在原发灶和淋巴结转移灶的表达水平无明显差异。CAR的表达水平与患者年龄及肿瘤大小相关。结论：结肠癌组织中存在CAR表达下调，提示在设计腺病毒载体基因治疗方案时应充分考虑CAR表达变化对疗效的影响.     

Expression of the coxsackie and adenovirus receptor in human lung cancers

The aim of this study is to elucidate the relation between expression of coxsackie and adenovirus receptor (CAR) and formation of lung cancer. We investigated the expression of CAR by immunohistochemistry, Western blot and real-time RT-PCR in 120 lung cancers. We found that CAR expression in tumor tissues was significantly higher than that in normal lung tissues. CAR expression had a correlation with the histological grade of lung squamous cell carcinoma; however, there was no relationship between the CAR expression and the other clinical pathological features. In vitro, silencing or overexpression of CAR could significantly inhibit or promote colony formation, cell adhesion, and invasion in A549 cells. Our findings demonstrated that CAR may play an essential role in the formation of lung cancer.     

非小细胞肺癌非耐药蛋白基因表达与临床疗效关系的研究

目的探讨肺耐药蛋白（LRP）基因在非小细胞肺癌（NSCLC）气管镜活检组织或淋巴结活检组织中的表达与其临床疗效的关系。方法应用免疫组织化学S-P技术对19例非小细胞肺癌气管镜活检组织和28例肺癌转移的淋巴结活检组织进行LRP表达水平的检测,并观察其经NP方案化疗2个周期后的临床疗效。结果非小细胞肺癌LRP的表达阳性率为61.70%;在肺腺癌和肺鳞癌中的表达阳性率分别为76.92%和42.86%;LRP在两组间的表达有显著性差异（P〈0.05）。LRP表达水平在TNM分期中差异无显著性（P〉0.05）;经2个周期标准NP方案化疗后总有效率为42.55%,其中LRP表达阳性和阴性的临床有效率分别为24.14%和72.22%,两组间存在显著性差异（P〈0.05）。结论LRP在非小细胞肺癌中存在不同程度的表达,阳性者化疗疗效明显高于阴性者。     

非小细胞肺癌P-gp、LRP、MRP和GST-π表达及其临床意义

目的:探讨P-糖蛋白(P-gp)、肺耐药蛋白(LRP)、多药耐药相关蛋白(MRP)和谷光甘肽转移酶(GST-π)在非小细胞肺癌(NSCLC)中的表达及其临床意义.方法:应用免疫组织化学S-P技术对86例治疗前非小细胞肺癌组织标本进行P-gp、LRP、MRP和GST-π表达的检测.结果: LRP和MRP在肺腺癌、鳞癌中的表达阳性率分别为77.78%、51.22%和80.00%、53.66%;LRP和MRP在不同组织类型中的表达有显著性差异(均P<0.05).P-gp和GST-π在肺腺癌和鳞癌中的表达阳性率分别为73.33% 、60.98%和80.00%、70.73%;P-gp和GST-π在不同组织类型中的表达无显著性差异(均P>0.05).所测4种耐药基因除P-gp外其余3种在中高分化和低分化组间表达阳性率有显著性差异(均P<0.01);4种耐药基因在TNM各分期中表达阳性率无显著性差异(均P>0.05).在肺腺癌和肺鳞癌中同时有2种、3种或4种耐药基因协同表达的阳性率分别为46.67%和34.15%、31.11%和24.39%、20.00%和17.07%,在肺腺癌和肺鳞癌中耐药基因共表达在各类型间无显著性差异(均P>0.05).结论:在非小细胞肺癌组织中存在不同程度的耐药,肺腺癌原发耐药高于肺鳞癌,其耐药是多途径多基因参与的过程.联合检测P-gp、LRP、MRP和GST-π耐药相关基因的表达,对化疗药物的选择及预后的评价具有重要的临床意义.     

肺鳞癌和腺癌组织E2F-1和c-myc及p14ARF蛋白表达临床病理学意义的探讨

目的:研究E2F-1、c-myc和p14ARF蛋白在肺鳞癌及腺癌中的表达情况,探讨其在肺癌发生发展中的作用机制及其与临床病理学特征间的关系。方法:应用免疫组化二步法检测71例肺鳞癌、腺癌及相应癌旁组织中E2F-1、c-myc和p14ARF蛋白的表达情况。结果:肺鳞癌及腺癌组织中E2F-1和c-myc蛋白的阳性表达率分别为83.1%(59/71)和81.7%(58/71),高于癌旁组织中的8.5%(6/71),P<0.05。p14ARF蛋白的阳性表达率为52.1%(37/71),低于相应癌旁组织的74.6%(53/71),P<0.05。并与患者年龄、性别、肿瘤大小、组织分化、病理分型、有无淋巴结转移及TNM分期无关,P>0.05。E2F-1、c-myc和p14ARF蛋白表达经相关分析显示两两相关,P<0.05。结论:肺鳞癌及腺癌内可见E2F-1和c-myc蛋白的过表达及p14ARF蛋白的表达缺失,可能与癌的发生发展有关。     

39例肺癌组织雌激素及孕激素受体的研究

本文采用免疫组化法(SP法)对39例肺癌组织及5例正常肺组织进行雌激素受体(ER)及孕激素受体(PR)的测定。结果显示:5例正常肺组织中ER,PR均呈阴性。39例肺癌组织中ER阳性率为28.2％(11/39),PR阳性率为43.6％(1739)。ER、PR的阳性率在性别上无显著差异。11例ER阳性组织中鳞癌7例占鳞癌的46.67％(7/15),腺癌4例占腺癌的26.67％(4/15);17例PR阳性组织中鳞癌10例占鳞癌的66.67％(10/15),腺癌7例占腺癌的46.67％(7/15)。ER PR阳性表达在鳞癌及腺癌之间无显著差异。小细胞癌及肺泡癌未见ER及PR阳性。ER,PR的表达与肿瘤TNM分期、血型、年龄无明显关系。     

肺癌的化疗与多药耐药的研究

目的：检测各种类型肺癌化疗前及化疗后复发病例P－gp蛋白的表达情况,探讨其与肺癌多药耐药及患者预后的关系。方法：采用免疫组化染色方法对66例化疗后复发病例及131例未经化疗的肺癌病例进行耐药基因MDR1表达蛋白P－gp检测,结果：化疗后复发病例P－gp阳性表达率明显高于未经化疗的病例（P＜0．05）,其中,癌,小细胞癌化疗后P－gp阳性表达率均明显高于化疗前（P＜0．05）,而肺腺癌则无明显差异（P＞0．05）,未经化疗组不同病理类型的肺癌P-g[蛋白阳性表达有显著性差异,从高到低依次为腺癌,鳞癌和小细胞癌（P＜0．05）,化疗后复发组各病理类型肺癌中P－gp蛋白阳性表达率无显著性差异（P＞0．1）,P－gp表达阳性的患者3年生存率明显低于阴性者（P＞0．05）。结论;化疗可能诱导各种病理类型肺癌P-gp蛋白表达增加,肺鳞癌和小细胞肺癌可能为获得性MDR1耐药,肺腺癌是原发性MDR1耐药,肺癌患者P－gp表达程度可作为指导化疗用药及预测预后的指标。     

Claudin-7与Slug在肺鳞癌和腺癌中的表达及其临床意义

背景与目的 Claudins是紧密连接的骨架蛋白,Claudin-7是Claudins家族成员之一。本研究旨在观察Claudin-7和Slug在肺鳞癌和腺癌中的表达及其与临床病理因素的关系,并探讨Claudin-7和Slug的相互关系。方法采用免疫组织化学SP法检测101例原发性肺鳞癌、腺癌组织中Claudin-7和Slug的表达,同时应用Westernblot检测30例新鲜肺癌组织及其配对的癌旁组织中Claudin-7和Slug的表达情况。结果 Claudin-7在肺癌中的表达明显低于正常肺组织,并且与分化程度和淋巴结转移有关(P<0.05),Slug在肺癌中的表达明显高于正常肺组织,除与分化程度和淋巴结转移有关外,还与TNM分期有关(P<0.05),肺鳞癌、腺癌中Claudin-7与Slug的表达具有负相关性(r=-0.566,8)。结论肺鳞癌、腺癌中Claudin-7的低表达与Slug的高表达可能是肺组织恶性转变和转移的有关标志物之一。     

非小细胞肺癌P—gP、LRP、MRP和GST-π表达及其临床意义

目的：探讨P-糖蛋白（P—gP）、肺耐药蛋白（LRP）、多药耐药相关蛋白（MRP）和谷光甘肽转移酶（GST-π）在非小细胞肺癌（NSCLC）中的表达及其临床意义。方法：应用免疫组织化学S—P技术对86例治疗前非小细胞肺癌组织标本进行P—gP、LRP、MRP和GST-π表达的检测。结果-LRP和MRP在肺腺癌、鳞癌中的表达阳性率分别为77．78％、51．22％和80．00％、53．66％;LRP和MRP在不同组织类型中的表达有显著性差异（均P〈0．05）。P-gP和GST-π在肺腺癌和鳞癌中的表达阳性率分别为73．33％、60．98％和80．00％、70．73％;P—gp和GST-π在不同组织类型中的表达无显著性差异（均P〉0．05）。所测4种耐药基因除P—gp外其余3种在中高分化和低分化组间表达阳性率有显著性差异（均P〈0．01）;4种耐药基因在TNM各分期中表达阳性率无显著性差异（均P〉0．05）。在肺腺癌和肺鳞癌中同时有2种、3种或4种耐药基因协同表达的阳性率分别为46．67％和34．15％、31,11％和24．39％、20．00％和17．07％,在肺腺癌和肺鳞癌中耐药基因共表达在各类型间无显著性差异（均P〉0．05）。结论：在非小细胞肺癌组织中存在不同程度的耐药,肺腺癌原发耐药高于肺鳞癌,其耐药是多途径多基因参与的过程。联合检测P—gp、LRP、MRP和GST-π耐药相关基因的表达,对化疗药物的选择及预后的评价具有重要的临床意义。     

肺鳞癌及腺癌端粒酶逆转录酶表达的原位定量分析及其病理学意义

目的通过定量检测肺癌组织端粒酶hTERT的表达水平,分析肺癌与hTERT表达的定量关系,为从hTERT的表达方面探讨肺癌的诊断问题提供实验依据。方法采用免疫组化阳性单位定量法检测12例肺癌组织癌细胞和9例非肿瘤性肺组织实质细胞端粒酶hTERT的表达水平。结果端粒酶hTERT在肺癌细胞中的表达水平高于肺非肿瘤性肺组织实质细胞(P=0.0001);肺鳞癌癌细胞端粒酶表达水平高于肺非肿瘤组织实质细胞的表达(P=0.0003);肺腺癌癌细胞端粒酶表达水平高于肺非肿瘤组织实质细胞的表达(P=0.0001);肺鳞癌与肺腺癌癌细胞端粒酶表达的阳性单位差异无显著性(P=0.2282)。结论端粒酶hTERT高表达与肺癌有关。肺组织中端粒酶hTERT表达的阳性单位可作为肺癌诊断的参考指标进行研究。     

p53蛋白、雌激素受体、孕激素受体在非小细胞肺癌中的表达及临床意义

目的 检测非小细胞肺癌（ＮＳＣＬＣ）中ｐ５３蛋白、雌激素受体（ＥＲ）和孕激素受体（ＰＲ）表达与临床病理和预后的相关性。方法 应用免疫组织化学ＳＰ法检测１４７例ＮＳＣＬＣ癌组织标本中ｐ５３、ＥＲ、ＰＲ的表达。结果 ｐ５３蛋白总阳性率为６１．２％（９０／１４７）,鳞癌、腺癌、鳞腺癌、大细胞癌阳性率分别为６３．５％（４０／６３）、５７．６％（３３／６６）、６６．７％（１０／１４）、５０％（２／４）。腺癌     

肺鳞癌组织中磷脂酶A2蛋白表达的相关性及临床病理意义

目的 探讨分泌型磷脂酶A2(sPLA2-Ⅱa)及胞浆型磷脂酶A2(cPLA2)蛋白表达与肺鳞癌发生、发展及浸润、转移的关系.方法 应用免疫组织化学S-P法检测60例肺鳞癌组织及20例正常肺黏膜组织中sPLA2-Ⅱa及cPLA2蛋白表达.结果 肺鳞癌组织中sPLA2-Ⅱa(68.3%)及cPLA2(61.7%)蛋白阳性表...     

肺耐药蛋白基因表达与肺癌临床病理生理特征的关系

目的 探讨肺耐药蛋白（ＬＲＰ）基因表达与肺癌临床病理特征的关系。方法 采用逆转录一多聚酶链反应（ＲＴ－ＰＣＲ）方法,检测４９例肺癌组织和组应的４１例癌旁肺组织中ＬＲＰ基因表达水平,结果 肺癌与癌旁肺组织中均有ＬＲＰ基因表达,两者的阳性率分别为６３．３％（３１／４９）和２１．９％（９／４１）,具有显著性差异（Ｐ〈０．０１）,非小细胞肺癌ＬＲＰ表达阳性率（７０．７％,２９／４１）高于小细胞肺癌（２５％、２／８）（Ｐ〈０．０５）,腺癌（９１．７％,１１／１２）表达阳性率高于鳞癌（５０％,１１／２２）（Ｐ〈０．０５）;吸烟患者的ＬＲＰ基因表达（７４．３％,２６／３５）显著高于非吸烟患者（３５．７％,５／１４）（Ｐ〈０．０５）,结论 ＬＲＰ基因表达与肺癌耐药有关,吸烟可导致ＬＲＰ基因表达增加。     

p53突变蛋白表达与肺鳞癌和腺癌生物学行为的关系

目的探讨ｐ５３基因表达蛋白与肺癌生物学行为的关系。方法应用ｐ５３基因表达蛋白的单克隆抗体，用免疫组织化学的亲和素－生物素－过氧化物酶复合物（ＡＢＣ）法，检测１８例肺鳞癌和２１例肺腺癌石蜡切片中ｐ５３突变蛋白的表达。结果和结论肺鳞癌和腺癌ｐ５３突变蛋白阳性表达率分别为４４．４％和５２．４％，两者无显著差异；ｐ５３突变蛋白阳性表达与肺癌患者的临床病理参数和预后无关。     

Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

肺癌细胞的HLA抗原表达与组织类型及免疫修饰

目的 了解肺癌细胞的ＨＬＡ抗原表达及肺癌的组织类型和免疫饰对其的影响。方法 采用免疫组织化学方法和流式细胞术从体探讨肺癌组织的ＨＬＡ－ＤＲ抗原表达。结果 在５６例病理确诊的肺癌患者癌组织中,腺癌７６％（２３／２９）,鳞癌８％（２／２４）表达为ＨＬＡ－ＤＲ抗原阳性,而３例小细胞癌均为阴性。腺癌的阳必同于鳞癌和小细胞癌（Ｐ〈０．０５）。ＨＡＬ－ＤＲ抗原阳性癌细胞周围可见较多的淋巴细胞浸润,二者呈明显的     

THE STUDY ON RELATIONSHIP BETWEEN CIGARETTE SMOKING AND THE p53 PROTEIN AND P21 PROTEIN EXPRESSION IN NON-SMALL LUNG CANCER

This paper discusses the relationship betweencigarette smoking and the p53 protein and P21 proteinexpression by the immunohistochemical analysis in 93cases with lung cancer in which squamous cell carcinomaaccounted for 45 cases, adenocarcinoma 48 cases. Theresults showed that positive proportion of p53 proteinexpression was 74.20% (28 of 37 squamous cell carcinoma,21 of 30 adenocarcinomas) in cigarette smoking groupwith lung cancers, and 38.46% (3 of 8 squamous cellcarcinoma, 7 of 18 adenocarcinomas) in nonsmokinggroup with lung cancers. The difference was statisticallysignificant. Odds ratio was 4.14 and confidence limitsfor OR was 1.42-12.52. A dose-related presents in thep53 protein expression for the smoking amount andsmoking years. The positive proportion of P21 proteinexpression was 79.31% (21 of 28 squamous cell carcinoma,25 of 30 adenocarcinomas) in cigarette smoking groupwith lung cancers, and 82.75%(10 of 11 squamous,14 of18 adenocarcinomas) in nonsmoking group with lungcancers, the difference