密集方案新辅助化疗对44例乳腺癌bcl-2 mRNA水平的影响

[目的]探讨密集方案新辅助化疗临床效果及对乳腺癌细胞bcl-2mRNA表达的影响。[方法]44例乳腺癌患者随机分成CEF14组和CEF21组,分别接受CEF14方案和CEF21方案新辅助化疗,观察其临床结果;使用实时定量RT-PCR法测定各组标本化疗前后bcl-2mRNA表达强度。[结果]最终35例患者完成了既定方案化疗,CEF14组临床有效率为50%（9/18）,CEF21组临床有效率为41.18%（7/17）（P〈0.05）。CEF14组、CEF21组化疗前bcl-2mRNA表达强度无差异（P〉0.05）;化疗后CEF14组bcl-2表达强度低于CEF21组bcl-2mRNA表达强度（P〈0.05）。[结论]密集方案新辅助化疗与常规方案新辅助化疗有相似的临床效果,密集方案新辅助化疗较常规方案新辅助化疗更易下调bcl-2mRNA表达。     

bag-1、bcl-2和bax在非小细胞肺癌中的表达和意义及其与化疗多药耐药相关性的研究

背景与目的 bag-1、bcl-2和bax均为凋亡相关蛋白,在肿瘤诊断、病情进展、转移潜能和耐药性以及预后评价等方面具有潜在价值.本研究拟研究bag-1、bcl-2和bax蛋白在非小细胞肺癌中的表达以及与非小细胞肺癌发生发展的关系,并且探讨其与肺癌化疗耐药的相关性.方法 采用免疫组化SP法对140例非小细胞肺癌组织(其中40例为新辅助化疗1个-2个周期后手术的非小细胞肺癌患者组织)与15例支气管扩张组织的石蜡切片标本进行bag-1、bcl-2和bax蛋白表达的检测.结果 非小细胞肺癌组织中bag-1、bcl-2蛋白表达水平高于肺良性病变组织(P<0.05),bax蛋白的表达水平低于肺良性病变组织(P<0.05);bag-1、bcl-2和bax蛋白表达水平与非小细胞肺癌患者的年龄、性别、组织学分类、P-TNM分期及淋巴结转移等均无明显相关性(P>0.05),但是bag-1与肺癌细胞分化程度相关,分化越差,bag-1阳性表达率越高(P<0.05);非小细胞肺癌中bcl-2蛋白表达与bag-1蛋白表达明显止相关(r=0.371)(P<0.01),bcl-2与bax蛋白呈明显负相关(r=-0.225)(P<0.01);新辅助化疗使bag-1和bcl-2蛋白表达水平都有一定水平的增高,但bax蛋白表达水平没有显著变化.结论 非小细胞肺癌组织中存在bag-1、bcl-2蛋白的高表达和bax蛋白的低表达;bag-1蛋白表达水平与非小细胞肺癌的分化程度有密切关系;非小细胞肺癌组织中bag-1表达水平与bcl-2间存在非常显著止相关,bcl-2与bax间存在显著负相关;本研究未观察到bag-1、bcl-2和bax与肺癌多药耐药性间的相关性.     

肝细胞癌细胞凋亡相关蛋白bcl-2和bax的表达及意义

目的:探讨原发性肝细胞癌(简称肝癌)细胞凋亡相关蛋白bcl-2和bax的表达情况及其意义.方法:采用免疫组化ABC法检测bcl-2和bax蛋白在66例人肝癌组织和24例人正常肝组织,以及3种人肝癌细胞系HCC-9204、SMMC-7721、HHCC和1种人正常肝细胞系QZG的表达情况,并分析肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间的关系.结果:bcl-2蛋白在正常肝组织中表达的阳性率只有4.2 %(1/24),在肝癌组织中的阳性率为25.8 %(17/66),二者具有显著性差异(P＜0.05).bax蛋白在正常肝组织中表达的阳性率为70.8 %(17/24),在肝癌组织中的阳性率为43.9 %(29/66),二者也具有显著性差异(P＜0.05).肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间均未见明显的相关性.在正常肝和肝癌组织中,bcl-2蛋白的阳性率均明显低于bax蛋白(P＜0.01,P＜0.05).在正常肝细胞系QZG中未见明显的bcl-2阳性信号,bax蛋白的阳性细胞计数率为61.0%.肝癌细胞系SMMC-7721和HHCC的bcl-2蛋白阳性细胞计数率分别为14.3%和11.8%,bax蛋白阳性细胞计数率分别为58.3%和47.1%.肝癌细胞系HCC-9204中未见明显的bcl-2阳性信号,bax蛋白阳性细胞计数率为43.2%.结论:与正常肝组织相比,肝癌组织可出现bcl-2蛋白表达低度升高,bax蛋白表达下降.正常肝和肝癌组织的bcl-2蛋白表达水平均低于bax蛋白.肝癌和正常肝细胞系的bcl-2蛋白表达水平很低,可见中等程度的bax蛋白表达.     

肝细胞癌细胞凋亡相关蛋白bcl—2和bax的表达及意义

目的探讨原发性肝细胞癌(简称肝癌)细胞凋亡相关蛋白bcl-2和bax的表达情况及其意义.方法采用免疫组化ABC法检测bcl-2和bax蛋白在66例人肝癌组织和24例人正常肝组织,以及3种人肝癌细胞系HCC-9204、SMMC-7721、HHCC和1种人正常肝细胞系QZG的表达情况,并分析肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间的关系.结果bcl-2蛋白在正常肝组织中表达的阳性率只有4.2%(1/24),在肝癌组织中的阳性率为25.8%(17/66),二者具有显著性差异(P＜0.05).bax蛋白在正常肝组织中表达的阳性率为70.8%(17/24),在肝癌组织中的阳性率为43.9%(29/66),二者也具有显著性差异(P＜0.05).肝癌组织的bcl-2和bax蛋白表达阳性率与其病理分级之间均未见明显的相关性.在正常肝和肝癌组织中,bcl-2蛋白的阳性率均明显低于bax蛋白(P＜0.01,P＜0.05).在正常肝细胞系QZG中未见明显的bcl-2阳性信号,bax蛋白的阳性细胞计数率为61.0%.肝癌细胞系SMMC-7721和HHCC的bcl-2蛋白阳性细胞计数率分别为14.3%和11.8%,bax蛋白阳性细胞计数率分别为58.3%和47.1%.肝癌细胞系HCC-9204中未见明显的bcl-2阳性信号,bax蛋白阳性细胞计数率为43.2%.结论与正常肝组织相比,肝癌组织可出现bcl-2蛋白表达低度升高,bax蛋白表达下降.正常肝和肝癌组织的bcl-2蛋白表达水平均低于bax蛋白.肝癌和正常肝细胞系的bcl-2蛋白表达水平很低,可见中等程度的bax蛋白表达.     

bcl-2和bax蛋白表达与鼻咽癌放射敏感性相关关系的探讨

目的:探讨bcl-2和bax蛋白的表达与鼻咽癌放射敏感性的关系.方法:应用免疫组化法检测51例放疗前鼻咽癌活检组织中bcl-2和bax蛋白的表达.结果:51例鼻咽癌组织中bcl-2和bax蛋白表达阳性者均为47例(92.2%);鼻咽癌组织中bcl-2和bax蛋白的表达强度呈显著相关(P＜0.05);bcl-2蛋白的表达与鼻咽癌放射敏感性呈负相关(P＜0.05),而bax蛋白的表达与鼻咽癌放射敏感性无关(P＞0.05);bcl-2/bax的比率与鼻咽癌放射敏感性呈负相关(P＜0.05).结论:bcl-2蛋白和bcl-2/bax的比率是反映鼻咽癌放射敏感性和预测鼻咽癌放疗效果的重要指标,而bax蛋白不能单独作为判断鼻咽癌放射敏感性的指标.     

多基因蛋白表达判断早期非小细胞肺癌术后化疗疗效的价值

目的 探讨多基因蛋白表达联合检查判断早期非小细胞肺癌(NSCLC)术后化疗疗效的价值.方法 采用组织芯片与免疫组织化学技术(二步法)相结合的方法,义寸86例NSCLC组织中caspase-3、Fas、bax、bcl-2,survivin,PCNA,Ki67,MGMT,p53,063,p73,p16、p27,VEGF、nm23、P-gP、MRP、LRP、GST-π、TopoⅡ、c-myc、cyclin D1、Her-2、Cox-2、Ku70、Ku80、DNA-PKcs、ERCCI、MSH2和BCRP等30种化疗相关蛋白进行检测,并分析其表达与早期NSCLC术后化疗疗效的关糸.结果 30种化疗相关蛋白在肺癌组织中的表达阳性率在27 9%～91.9%间.经过单因素分析,与早期NSCLC术后化疗效果密切相关的基因有8个,即survivin、P-gp、LRP、Ki67、p53、ERCC1高表达和bax、VEGF低表达的NSCLC患者术后化疗效果差.通过Logistic回归分析显示,ERCC1、survivin、bax和VEGF等4个基因联合检测对早期NSCLC术后化疗疗效的预测特异度达96.5%.结论 ERCC1、survivin、bax和VEGF是一组判断早期NSCLC术后辅助化疗效果、指导早期NSCLC的术后治疗的分子指标.     

p21、p27、bcl-2和bax在肺癌组织中表达的意义及相关性研究

目的:探讨p21、p27、bcl-2、bax蛋白在肺癌中的表达及其临床意义.方法:采用免疫组化S-P法,检测85例肺癌患者及21例良性肺疾病患者术后组织标本中p21、p27、bcl-2、bax的表达.结果:p21、p27、bcl-2、bax蛋白总阳性表达率分别为72.94%、37.65%、61.18%、41.18%.各种蛋白的阳性表达率在肺癌组织与对照组间均存在差异性(P＜0.05).仅bcl-2蛋白表达与肺癌的不同病理类型有关,其中在小细胞肺癌中表达率最高、鳞癌次之、腺癌最低.p27、bcl-2、bax三者的阳性表达随病理分化程度的降低而降低(P＜0.05).p21与bcl-2蛋白的阳性表达与肺癌临床TNM分期有关(P＜0.05).bax蛋白的表达与有无淋巴结转移有关.p27、bcl-2、bax三者之间存在相关性.结论:p21、p27、bcl-2、bax蛋白与肺癌的发生、发展有密切关系.联合检测p21、p27、bcl-2、bax对于临床诊断肺癌及判断病情、预后有重要意义.     

p53mRNA、bcl-2、bax蛋白在肺癌中的表达

目的 :探讨原发性肺癌中 bcl- 2、bax和 p5 3m RNA表达水平及其与临床病理特征的关系。方法 :用免疫组织化学 Dako Envision TM二步法、反转录聚合酶链反应 (RT- PCR)方法分别检测5 2例肺癌组织中 bcl- 2、bax、p5 3m RNA表达情况。结果 :5 2例肺癌组织中 bcl- 2、bax蛋白表达阳性率分别为 4 2 .3%、5 9.6 1%。肺癌中 bcl- 2蛋白过表达在低分化癌、 期肺癌中高于高分化癌以及 期肺癌差异有显著性意义 (P<0 .0 1)。 p5 3m RNA、bax蛋白的阳性表达与 bcl- 2蛋白呈负相关。结论 :bcl- 2蛋白在晚期肺癌中过表达 ,p5 3m RNA、bax蛋白在早期肺癌中起着重要作用 ,它们共同参与细胞内死亡和存活信息的平衡状态的调节。     

非小细胞肺癌组织中多基因表达的临床意义

目的探讨p27、bcl-2、bax在非小细胞肺癌组织中表达水平及临床意义.方法用免疫组化法检测102例非小细胞肺癌组织和10例正常肺组织中的p27、bcl-2、bax的表达水平.结果 p27、bax蛋白在肺癌组织中呈低表达,bcl-2呈高表达,与正常肺组织比较其表达显著差别(P＜0.05);p27、bcl-2、bax在肺腺癌和鳞癌中表达无差别,与肿块大小,TNM分期无关,bc1-2和bax与组织学分级无关.p27有关,p27表达越低,组织学分级越低;在有淋巴结转移、癌周浸润、复发和转移者p27、bax呈低表达,bcl-2高表达,p27、bax高表达组5年生存率21.6%、22.5%高于低表达组5.9%、4.9%(P＜0.01),bcl-2低表达组5年生存率16.7%高于高表达组10.79%(P＜0.01).p27与bcl-2呈负相关,与bax呈正相关(P＜0.05).结论p27、bcl-2、bax蛋白参与非小细胞肺癌的发生发展过程,其表达水平有助于预后的评估.     

乳腺癌新辅助化疗对凋亡相关基因p53、bc1-2的影响(英文)

目的探讨乳腺癌新辅助化疗对凋亡相关基因p53、bcl-2表达的影响及其意义。方法用免疫组织化学ABC法检测97例新辅助化疗(研究组)和同期76例未行新辅助化疗(对照组)的乳腺癌组织p53、bcl-2蛋白的表达,并结合5年无病生存率(DFS)进行分析。结果研究组p53阳性率为28.9%(28/97),对照组为38.2%(29/76);研究组bcl-2阳性率为40.2%(39/97),对照组为56.7%(43/76);研究组5年DFS为74.2%(72/97),对照组为60.5%(46/76),两者比较均有显著差异。结论新辅助化疗通过凋亡相关基因p53、bcl-2的表达影响预后。     

THE EXPRESSION AND CLINICAL VALUE OF APOPTOSIS CONTROL GENE Bcl-2 AND Bax IN BREAST CANCER

Bcl-2(theB-cellleukemiajlymph0ma2)genefamilyareagr0up0frecentlyfoundtumorgeneswhichcansuppressaPoptosisofcellsandhavesignificantfunctionintUmor'soriginanddevelopment."'However,anothermember0fbcl-2genefaAnlybaxwasfoundwhichcanregulatethefuncti0nofbcl-2andacceleratethedeath0fcells.{2]Joensunl3]f0undthatbcl-2expressi0nwasconnectedwiths0meadvantagedprogn0sisfactorsrelatedtoclinicalpathologicalcharacteristics,butbcl-2wasnotanindependentpr0gn0sisfactorbymultiplefactoranalysis.Sierral']thoughtthatb…     

Prognostic significance of apoptosis related gene family bcl-2 in human breast cancer

Bcl-2 family proteins appear to regulate apoptosis,with hcf-2, hcf-xl function as suppressors of apoptosisand bax, hcf-xs as promoters of cell death.ll] Theprognostic significance of these proteins in breast cancerhas been reported, but a comprehensive study is needed.In the present study, we have investigated the expressionof hcf-2, bax, hcf-xl in this multigene family, as regardsto their prognostic value in breast cancer.MATERIALS AND METHODSPatientsNinety-one breast cancer patients …     

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.     

术前单疗程化疗对非小细胞肺癌细胞凋亡的影响

目的探讨术前单疗程化疗对ⅢA期非小细胞肺癌细胞凋亡率、增殖指数及bcl-2、bax基因表达的影响。方法 2002年1月至2004年1月,对144例ⅢA期非小细胞肺癌进行随机对照试验,术前化疗组（试验组）和单纯手术组（对照组）各72例,前者于术前化疗1个疗程,化疗结束10-14 d后接受手术;对照组直接行手术治疗。手术切除的肺癌组织应用流氏细胞学方法测定细胞凋亡率、增殖指数及bcl-2、bax基因的表达。结果试验组和对照组细胞凋亡率、增殖指数及bcl-2、bax基因表达分别为（7.40±2.39%）、（4.93±2.13）%;（24.99±7.51）%、（31.72±7.43）%;4.70±1.16、6.51±1.09;5.57±0.96、4.65±0.91,两组比较均差异有显著性（P〈0.05）。结论术前单疗程化疗能提高ⅢA期NSCLC的肿瘤细胞凋亡率,降低肿瘤细胞增殖指数,并抑制bcl-2基因（抑制凋亡的基因）的表达,促进bax基因（促进凋亡的基因）的表达,并可能降低细胞生存能力,减少癌转移灶的发生。     

Expression of the bcl-2 gene family in normal and malignant breast tissue: Low bax-α expression in tumor cells correlates with resistance towards apoptosis

We have studied the expression of the apoptosis-regulating genes bcl-2, bcl-x, bax and APO-1/fas (CD95) in human breast cancer. The expression pattern of these genes in human breast-cancer tissues and breast-cancer-derived cell lines was compared to that seen in normal breast epithelium and breast epithelial cell lines. No difference with regard to bcl-2 and bcl-x_L expression was observed between normal breast epithelium and tumor tissue or breast cancer and non-malignant epithelial cell lines. In contrast, bax-α, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal cell lines and breast tissue, whereas only weak or no expression could be detected in cancer-cell lines and malignant tissue. In contrast to malignant cell lines, which express low levels of bax-α, non-malignant epithelial cell lines displaying high amounts of bax-α were highly sensitive to induction of programmed cell death by both serum starvation and APO-1/fas (CD95) triggering. We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti-apoptosis genes (such as bcl-2/bcl-x) and apoptosis-promoting genes (bax).     

The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer.

PURPOSE: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. EXPERIMENTAL DESIGN: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for immunohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. RESULTS: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. CONCLUSIONS: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS.     

Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis

Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21^WAFI about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80–90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells. © 1996 Wiley-Liss, Inc.     

p53及bcl-2蛋白在乳腺癌中的表达及与c-erbB-2表达的相关性

目的探讨p53及bcl-2蛋白在乳腺癌中的表达情况,并分析其与c-erbB-2表达的相关性。方法选取50例乳腺癌患者,搜集其临床资料并进行回顾性分析,所有患者均行手术治疗并采集其乳腺癌组织(观察组,n=50)及癌旁正常乳腺组织(对照组,n=50)。采用免疫组化法检测并比较各组织标本中p53及bcl-2蛋白表达情况,分析其与乳腺癌组织病理分级的关系。另据乳腺癌组织中c-erbB-2蛋白表达情况分为c-erbB-2阳性组(n=37)及c-erbB-2阴性组(n=13),Person相关性分析评估p53、bcl-2蛋白与c-erbB-2蛋白表达的相关性。结果对照组及观察组中p53蛋白阳性表达率分别为0.00%、64.00%;bcl-2蛋白阳性表达率分别为88.00%、64.00%。观察组p53蛋白阳性表达率显著高于对照组,而观察组bcl-2蛋白阳性表达率显著低于对照组(P<0.01);p53蛋白阳性率随乳腺癌组织病理分级升高而逐渐升高,bcl-2蛋白阳性表达率随乳腺癌组织病理分级升高而逐渐降低,各级别间差异显著(P<0.05)。c-erbB-2阳性组中p53蛋白阳性表达率显著高于c-erbB-2阴性组,bcl-2蛋白阳性表达率显著低于c-erbB-2阴性组,且乳腺癌组织中p53蛋白与c-erbB-2蛋白表达显著正相关(γ=0.894,P<0.01),而bcl-2蛋白与c-erbB-2蛋白表达显著负相关(γ=-0.803,P<0.01)。结论乳腺癌组织中p53蛋白高表达,bcl-2蛋白低表达,且乳腺癌组织中p53蛋白与c-erbB-2蛋白表达显著正相关,而bcl-2蛋白与c-erbB-2蛋白表达显著负相关。     

Tamoxifen-induced apoptosis in breast cancer cells relates to down-regulation of bcl-2, but not bax and bcl-X(L), without alteration of p53 protein levels.

Tamoxifen (TAM) has been shown to induce apoptosis in breast cancer cells. bcl-2 family genes, which can interact with each other, have been shown to interfere with apoptosis after various stimuli. In this study, we investigated the effects of TAM on bcl-2 family gene products bcl-2, bax, and bcl-X(L) and on p53 levels in estrogen receptor-positive MCF-7 breast cancer cells. We found that TAM induced time- and concentration-dependent down-regulation of bcl-2 at both the mRNA and protein level. Down-regulation of bcl-2 correlated with TAM-induced apoptosis. In addition, estradiol treatment significantly increased bcl-2 protein expression and blocked the reduction of bcl-2 by TAM. TAM did not, however, affect bax, bcl-X(L), or p53 expression at the mRNA or protein level. Our results demonstrate that TAM can induce apoptosis in a time- and dose-dependent manner by modulating bcl-2 levels in breast cancer cells, and down-regulation of bcl-2 induced by TAM was not accompanied by alterations in p53 levels.