非小细胞肺癌中细胞周期蛋白D1与E的作用及相互关系

目的 :研究细胞周期蛋白D1与E在非小细胞肺癌 (NSCLC)发生、发展中的作用及相互关系。方法 :免疫组化方法检测 87例NSCLC肿瘤组织中细胞周期蛋白D1、E的表达及PCNA估计增殖指数 (PI) ,并将上述结果与临床病理及预后资料进行对比分析。结果 :87例NSCLC中细胞周期蛋白D1、E阳性率分别为 4 4 .8% (39/87)、4 8.3% (42 /87) ,细胞周期蛋白D1阳性组的PI值显著高于阴性组 (P〈0 .0 5 ) ,细胞周期蛋白E阳性组PI值与阴性组无显著差异 (P〉0 .0 5 ) ;细胞周期蛋白D1阳性组肿瘤直径、淋巴结转移率和生存率均与阴性组有显著差异(P〈0 .0 1、〈0 .0 5、〈0 .0 1) ,细胞周期蛋白E阳性组淋巴结转移率、临床分期和生存率均与阴性组有显著差异 (P〈0 .0 5、〈0 .0 5、〈0 .0 1) ;细胞周期蛋白D1阳性组中细胞周期蛋白E的阳性率显著高于其阴性组 (P〈0 .0 5 ) ;细胞周期蛋白D1与细胞周期蛋白E双阳性组的PI值、肿瘤直径、淋巴结转移率显著高于非双阳性组 (P值均〈0 .0 5 ) ,生存率显著低于非双阳性组 (P〈0 .0 1)。结论 :细胞周期蛋白D1、细胞周期蛋白E均参与NSCLC的发生、发展 ,并影响其预后 ,但两者在其中所起作用不同 :细胞周期蛋白D1是调节NSCLC增殖的主要因素 ,细胞周期蛋白E主要与NSCLC进展有关 ;细胞周期蛋白D1可促     

Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer.

Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 +/- 3.9 months vs 50.1 +/- 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 +/- 6.1 months vs 74.6 +/- 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor.     

非小细胞肺癌中DEC1与cyclin D1的表达及其临床意义

目的:分析differentiated embryonic chondrocyte expressed gene 1（DEC1）和cyclin D1在非小细胞肺癌组织中的表达和相关性及其与临床病理因素间的关系。方法:采用免疫组化方法检测DEC1和cyclin D1在134例非小细胞肺癌中的表达情况。结果:在134例非小细胞肺癌中,DEC1细胞核的平均阳性表达率为（27.6±9.26）%,明显低于DEC1癌旁正常组织中细胞核的平均阳性表达率（84.3±19.70）%。DEC1表达下调或缺失与肺癌的低分化（P=0.008）以及高p-TNM分期(P=0.001)相关。而cyclin D1表达与肺癌低分化（P=0.003）,肿瘤大小（P=0.038）,高p-TNM分期（P=0.017）及淋巴结转移（P=0.037）正相关。并且DEC1在肺癌中的细胞质表达与cyclin D1的表达显著负相关（P=0.003）。结论:DEC1表达与cyclin D1表达负相关,并与肿瘤分化,肺癌患者高p-TNM分期负相关。     

cyclin D1和kip1在肾细胞癌组织中的表达

目的：采用免疫组化方法检测cyclin D1和kip1在肾细胞癌中的表达,以期获得评估肾细胞癌恶性程度及预后评价的指标.方法：将肾细胞癌肿瘤组织及正常组织用免疫组化方法进行染色,按半定量方法进行结果判定,结合临床资料进行分析.结果：cyclin D1和kip1在肿瘤组织与正常组织中的表达具有显著性差异（P＜0.01）.cyclin D1和kip1在不同性别组、年龄组和直径组肿瘤患者组织中的表达对比不具有显著性差异（P＞0.05）.cyclin D1和kip1在不同病理分级组肿瘤患者组织中的表达具有显著性差异（P＜0.01）.kip1表达与肿瘤分化程度呈正相关（r=0.40）.cyclin D1表达与肿瘤分化程度呈负相关（r=0.45）.结论：cyclin D1和kip1在肿瘤细胞的表达呈现一定规律,可以作为判断肾细胞癌肿瘤细胞分化程度及预后的重要指标,同时也为靶向治疗提供了更多的靶点选择.     

细胞周期蛋白cyclin D1、CDK4在食管癌中的表达及其意义

目的：获得食管癌发生过程中调节Ｇ１细胞周期各种因子的作用。方法：采用抗ｃｙｃｌｉｎＤ１和ＣＤＫ４的单克隆抗体对１０例下沉食管和５０例食管鳞状上皮癌标本进行免疫组织化学染色。结果：ｃｙｃｌｉｎＤ１和ＣＤＫ４在正常食管上皮呈现较低水平的表达,在食管鳞状上皮癌中则过表达。２７／５０食管鳞状上皮癌ｙｃｙｃｌｉｎＤ１染色阳性,其中８例强阳性,１２例只表达ＣＤＫ４,１１例只表达ｃｙｃｌｉｎＤ１,１４例既表达ｃ     

非小细胞肺癌中DEC1与cyclinD1的表达及其临床意义

目的：分析differentiated embryonic chondrocyte expressed gene 1（DEC1）和cyclin D1在非小细胞肺癌组织中的表达和相关性及其与临床病理因素间的关系。方法：采用免疫组化方法检测DEC1和cyclin D1在134例非小细胞肺癌中的表达情况。结果：在134例非小细胞肺癌中,DEC1细胞核的平均阳性表达率为（27.6±9.26）%,明显低于DEC1癌旁正常组织中细胞核的平均阳性表达率（84.3±19.70）%。DEC1表达下调或缺失与肺癌的低分化（P=0.008）以及高p-TNM分期（P=0.001）相关。而cyclin D1表达与肺癌低分化（P=0.003）,肿瘤大小（P=0.038）,高p-TNM分期（P=0.017）及淋巴结转移（P=0.037）正相关。并且DEC1在肺癌中的细胞质表达与cyclin D1的表达显著负相关（P=0.003）。结论：DEC1表达与cyclin D1表达负相关,并与肿瘤分化,肺癌患者高p-TNM分期负相关。     

Pin1、β-连接素和细胞周期素D1在老年肺癌组织中的表达及临床意义

Objective:To investigate the expressions and correlations of Pin1,β-catenin and cyclin D1 in elderly lung carcinomas.Methods:The expressions of Pin1,β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors.Results:(1) The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 (50%)cases and 60 (65.22%) cases respectively and 56 (60.82%) cases showed positive immunoreactivity for β-catenin in the nuclear and (or) cytoplasmic fraction in tumor tissues,In normal tissue,the expressions of Pin1 and cyclin D1 were negative,the expression of β-catenin was lied in cell membrane.(2) In lung carcinomas the expressions of Pin1,β-catenin and cyclin D1 correlated with tumor differentiation (P＜0.05).The pesitive expression rate and intensity of Pin1 correlated with tumor stage (P=0.032) and lymph node positive disease (P=0.041).The expression of β-catenin correlated with lymph node positive disease (P=0.012).(3) High expression levels of Pin1 correlated with aberrant β-catenin expression (P=0.000) but did not show a correlation with cyclin D1 (P=0.157).Conclusion:In elderly lung carcinomas,the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene,however,this target gene was not cyclin DI.The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.     

Cyclin B1和survivin在非小细胞肺癌中的表达和意义

Objective  

We studied the expression of cyclin B1 and survivin in human non-small cell lung cancer (NSCLC), and the relationship between such expression and clinicopathological features of NSCLC.     

三氧化二砷抑制人胆囊癌细胞生长及对细胞周期蛋白D1表达的影响

背景与目的:三氧化二砷(As2O3)在治疗急性早幼粒细胞白血病中取得了突破性成果,近年来它在实体瘤的研究中颇受关注。胆囊癌由于缺乏特异性的临床表现,确诊时多属晚期,手术切除率较低,且常规化疗药物对胆囊癌的疗效较差,因此需寻找治疗胆囊癌新的有效药物。本研究旨在探讨As2O3对人胆囊癌GBC细胞系生长的生物学效应及作用机制。方法:不同浓度As2O3作用于胆囊癌GBC细胞,MTT法检测细胞生长情况,流式细胞仪检测细胞周期分布。Western blot及RT-PCR检测细胞周期蛋白(cyclin)D1、D2、D3、CDK4和CDK6的表达。构建cyclinD1启动子pGL3重组质粒,并转染GBC细胞,测定不同浓度As2O3作用下pGL3相关的荧光素酶活性。结果:As2O3能抑制体外GBC细胞生长,作用呈时间、剂量-效应关系;流式细胞仪检测发现As2O3可将增殖过程中的GBC细胞阻滞于G1期;Western blot及RT-PCR检测显示cyclin D1表达下降;As2O3能降低cyclin D1启动子的表达,作用呈剂量-效应关系,4μmol/L的As2O3处理后cyclin D1的启动子活性下调近70%。结论:As2O3能明显抑制体外人胆囊癌GBC细胞的生长并引起G1期阻滞,主要通过下调cyclin D1的表达来实现。     

p27~(Kip1)和细胞周期蛋白D1在胃癌中的表达及其预后意义

目的 :研究p2 7Kip1、细胞周期蛋白D1(cyclinD1)在胃癌组织中的表达水平以及与生物学行为的关系和对预后评价的意义。方法 :以免疫组化方法检测 92例胃癌组织中p2 7Kip1、cyclinD1蛋白的表达水平。结果 :本组 92例胃癌中 ,p2 7Kip1蛋白阳性 39例 ,占 42 .4% ;cyclinD1蛋白表达阳性 44例 ,占 47.8% ;胃癌组织中 ,p2 7Kip1蛋白水平与胃壁浸润深度、TNM分期、病理组织学分级、区域淋巴结转移均相关 (P <0 .0 5 ) ;cyclinD1蛋白表达与病理组织学分级负相关 (P <0 .0 5 ) ;p2 7Kip1与cyclinD1蛋白阳性表达显著相关 (P <0 .0 5 ) ;单变量生存分析结果 ,p2 7Kip1高表达组三年、五年生存率分别为 77.1%、5 7.8% ,明显高于低表达组的 33.7%、2 6 .3 % (P =0 .0 0 7) ,多变量分析显示p2 7Kip1是一个独立的预后指标 (P =0 .0 0 0 3)。结论 :p2 7Kip1可作为反映肿瘤恶性表型的指标 ,对胃癌预后具有一定的价值 ;cyclinD1是胃癌发生、发展过程中早期的分子事件 ;p2 7Kip1在胃癌进展中起着比cyclinD1更重要的作用。     

口腔鳞癌中活化细胞外信号调节激酶1/2和cyclin D1的表达

ras／raf/丝裂原活化蛋白激酶（mitogen-activated protein kinase,MAPK）级联是细胞增殖信号的关键。MAPK信号通路位于ras基因下游,通过激活cyclin D1基因刺激细胞增殖,从而引起恶性肿瘤发生。细胞外信号调节激酶（extracellular signal-regulated kinase,ERK）是MAPK家族的成员之一,包括ERK1和ERK2。ERK1／2被活化及cyclin D1过度表达与肿瘤的发生有关。我们应用免疫组化方法,检测了活化ERK1／2和cyclin D1蛋白在口腔鳞癌及相应癌旁正常组织中的表达,以探讨其与口腔鳞癌临床生物学特性和细胞增殖的关系,并同时检测了作为细胞增殖因子的Ki-67。     

人脑胶质瘤组织中cyclin D1和cyclin E表达的研究

目的 :研究人脑胶质瘤中细胞周期素 (cyclin)D1和cyclinE的表达与肿瘤病理等级的关系。方法 :采用免疫组织化学法检测 5 2例人脑胶质瘤和 8例正常脑组织标本中cyclinD1和cyclinE的表达。结果 :人脑胶质瘤组中有 2 9例cyclinD1的表达。随着胶质瘤病理分级增高 ,高、低恶性度胶质瘤的阳性率和平均标记指数均显著升高 ,两者差异有统计学意义 ,P <0 0 5。cyclinD1与cyclinE的平均标记指数之间呈明显正相关 ,Pearson相关系数r =0 64 4,P <0 0 1。结论 :cyclinD1与cyclinE在胶质瘤中被异常表达 ,是肿瘤发生和恶性转化的重要促进因子。     

MiR-210 regulates cell cycle in nasopharyngeal carcinoma cell line （CNE-1） under hypoxic condition by reducing the expression of cyclin DI

Objective： The aim of our study was to determine the underlying mechanism of miR-210 on regulation of the cell cycle in nasopharyngeal carcinoma cell line CNE-1, particularly through regulation of cyclin D1, under hypoxic conditions. Methods： The CNE-1 cell line was induced with hypoxia, and the expression levels of endogenic miR-210 and cyclin D1 were detected by real-time PCR and Western blotting. Next, the luciferase assay was used to confirm that cyclin D1 is a target gene for miR-210. Cell cycle and cell proliferation were detected in CNE-1 cells that were cultured under hypoxic conditions with either overexpression or knockout of miR-210 using flow cytometry and MTT assay, respectively. Results： Hypoxia induced the expression of miR-210, resulting in reduced mRNA and protein levels of cyclin D1 and repression of cyclin D1 in CNE-1 cells. Further analysis indicated that miR-210 directly binded to the 3＇UTR of the cyclin D1 gene, thus regulated the expression of cyclin DI. The flow cytometry assay showed that, under hypoxic conditions, miR-210 blocked CNE-1 cells in the G1 phase, and miR-210 also inhibited the proliferation of CNE-1 cells. Conclusion： Under hypoxic conditions, miR-210 directly reduced the expression of cyclin D1, leading to CNE-1 cells blocked in G1 phase.     

Galectin-3 and cyclin D1 expression in non-small cell lung cancer

Introduction

Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC). We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue.

Materials and methods

We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90). years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA) and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA).

Results

Galectin-3 expression was positive in 18 cases (38.29%) and cyclin D1 in 39 (82.97%). We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07) and cyclin D1 expression was higher in this group (p = 0.080). We didn''t reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn''t demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn''t find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi² Yatesa 7.53, p = 0.0061) and we revealed negative correlation between cyclin D1 and galectin-3 expression (R Spearman -0.458, p = 0.0011). In squamous cell lung cancer we didn''t observed correlations between these both examinated markers (R = -0.158, p = 0.460), and in adenocarcinoma the negative correlation was very strong (R = -0.829 p = 0.000132).

Conclusions

We didn''t reveal any important correlations between clinicopathological findings and galectin-3 and cyclin D1 expression and in non small cell lung cancer. We didn''t observed also prognostic value of cyclin D1 or galectin-3 expression. But we showed higher cyclin D1 expression in galectin-3 negative tumor tissues. We revealed also differences in correlations between galectin-3 and cyclin D1 expression in two main histopathological types of NSCLC.     

Cell proliferation,apoptosis, and expression of cyclin D1 and cyclin E as potential biomarkers in tamoxifen-treated mammary tumors

Tamoxifen has been widely used for treatment, and more recently, for the prevention of breast cancer. Since breast carcinomas are composed of heterogeneous populations of estrogen receptor-positive (ER+) cells, we hypothesized that tamoxifen may suppress tumor growth by differentially affecting cell proliferation and apoptosis. ER+ mammary tumors were induced in Sprague–Dawley rats by N-methyl-N-nitrosourea (MNU) and when they became palpable, the animals were treated for 5, 10, or 20 days with tamoxifen, 1.0 mg/kg body weight. Tamoxifen induced a time-dependent decrease in proliferating (BrdU-labeled) cells, arrested the cells in G1/0 phase, and differentially decreased the cyclin E and cyclin D1 expression at mRNA and protein levels. In the same tumors, apoptotic cells increased during the first 10 days of treatment, but their number remained unchanged with extension of the treatment to 20 days. Thus, we provide data that tamoxifen may differentially affect cell proliferation and apoptosis in mammary tumors and that the expression levels of cyclin D1 and cyclin E might also be considered potential intermediate biomarkers of response of mammary tumors to tamoxifen and possibly to other selective estrogen receptor modulators (SERMs).     

肺癌组织中细胞周期素D1的扩增与表达

目的 :研究肺癌组织中细胞周期素 (cyclin)D1的扩增和表达及其与肺癌临床病理特征的关系。方法 :采用免疫斑点法和差异PCR方法 ,对 4 0例肺癌组织及 4 0例正常肺组织进行cyclinD1蛋白表达与基因扩增研究。结果 :肺癌组织cyclinD1蛋白表达的阳性率为 6 5.0 % ,高于正常肺组织的 2 2 .5% ;肺癌cyclinD1基因扩增的阳性率达 55.0 % ,也显著高于正常肺组织的 17.5% ;肺癌cyclinD1的高度扩增和过度表达与肺癌的转移及分期密切相关。结论 :cyclinD1基因的高度扩增和过度表达状态在肺癌的恶性进展中起重要作用 ,可作为判定肺癌恶性度的重要参数之一。     

Cyclin B1在结直肠癌中的表达及意义

Objective： To study the relationship between the expression of human cyclin B1 in colorectal carcinomas and the pathological characters. Methods： The Expression of cyclin B1 in 66 cases of colorectal carcinomas were detected by flow cytometry and immunohistochemistry. Then the relationship between the expression of cyclin B1 in colorectal carcinomas and pathological characters was analyzed with statistics. Results： The expression of cyclin B1 in colorectal carcinomas had associativity with the cancer cell differentiation （P〈0.05）; However, the expression of cyclin B1 in colorectal carcinomas had no obvious associativity with cancer cell infiltrate depth and lymph nodes metastasis （P〉0.05）. Conclusion： In the colorectal cancers with high expression of cyclin B1, the cancer cells would present high differentiation; with low expression of cyclin B1 the cancer cells would present low differentiation. Along with the expression of cyclin B1 from high to low, the cancer cells differentiation has the tendency from high to low too.     

颌骨软骨肉瘤cyclin D1和cdk4的表达及意义

 目的　分析细胞周期素D1(cyclinD1)和细胞周期素依赖激酶 (cdk4 )在颌骨软骨肉瘤的表达及意义。方法　免疫组化ABC法检测cyclinD1和cdk4在 2 0例颌骨软骨肉瘤、8例骨软骨瘤和 4例软骨瘤的表达。结果　软骨肉瘤cyclinD1和cdk4阳性表达率分别为 70 % (14 /2 0 )和 6 5 % (13/2 0 ) ,二者的阳性表达存在正相关 (rs=0 .5 2 6 ,P <0 .0 5 ) ;而它们在骨软骨瘤的阳性表达率均为 12 .5 % (1/8) ,在软骨瘤无表达 ,与软骨肉瘤相比有显著性差异 (P <0 .0 5 )。结论　CyclinD1和cdk4在颌骨软骨肉瘤过表达且与其发生和发展有关。     

TAM诱导MA782细胞凋亡与Cyclin D1、CDK4、TGF-β1的关系

目的 :探讨Tamoxifen(TAM )诱导ER(- )小鼠乳腺癌细胞MA782细胞凋亡及其分子作用机制。方法 :TAM体外作用于MA782细胞 ,用MTT法检测细胞增殖活性、流式细胞仪检测细胞凋亡和细胞周期分布 ,免疫组化检测cyclinD1、CDK4、TGF β1蛋白表达 ,并用病理图像分析软件进行半定量分析。 结果 :TAM在体外能明显抑制MA782细胞生长 ,诱导细胞凋亡 ,下调cyclinD1、CDK4表达 ,上调TGF β1表达。免疫组化半定量分析显示 6μmol/L作用 72小时后 ,cyclinD1、CDK4蛋白平均灰度值分别从 132 .5± 0 .0 2、10 7.2± 0 .0 1下降至 12 6 .18± 0 .0 3、76 .2 1± 0 .0 3,10 μmol/L作用 72小时后分别为 73.5 6± 0 .0 2、72 .0 3± 0 .0 1,与对照组相比差异极其显著性 (P <0 0 1)。MA782细胞TGF β1平均灰度值为 5 9.72± 0 .0 2 ,2 μmol/L作用 4 8小时后无明显变化 ,72小时后上升到97 1± 0 .0 3,6、10 μmol/L作用 4 8小时后平均灰度值分别为 83.2± 0 .0 4、96 .83± 0 .0 2 ,72小时后分别上升到12 1 75± 0 .0 3、139.0 1± 0 .0 5 ,与对照组相比差异极其显著 (P <0 .0 1)。结论 :TAM诱导MA782细胞凋亡其分子作用机制可能与下调cyclinD1、CDK4蛋白表达 ,上调TGF β1蛋白表达有关。