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1.
周期素E(CyclinE)是一种G1期核蛋白 ,它能结合并激活周期素依赖激酶 2 (cyclin dependentkinases,CDK2 )而间接促进细胞从G1向S期过渡。p5 3通过激活 p2 1蛋白而间接抑制细胞从G1向S期过渡。故CyclinE与p5 3的异常将使G1/S期的调控失常 ,有可能引起无限制地细胞增殖 ,进而参与多种肿瘤的发生和发展[1] 。CyclinE在基因和蛋白水平的过度表达[2 ] 及其在癌中的高发生率证实CyclinE也参与和促进了胃癌的发生。本文旨在探讨CyclinE的过度表达在粘膜下胃癌进展中的作用…  相似文献   

2.
原发性肝细胞癌中cyclinD1基因表达的研究   总被引:1,自引:0,他引:1  
目的 研究cyclinD1 基因在原发性肝细胞癌中的表达,并探讨与p16 及CDK4 蛋白表达的关系。方法 用原位杂交检测cyclinD1 基因mRNA 表达,免疫组化检测cyclinD1 蛋白表达。结果 4 例(14-3 % ) HCC 可检测到cyclinD1 基因过表达。均属ⅢⅣ级,4 例HCC 均有CDK4 蛋白表达,其中2 例为p16 蛋白阳性。结论 1)cyclinD1 表达增加只在小部分恶性程度高的HCC 中起作用,可能与肿瘤侵袭有关。2) 在HCC 中,cyclinD1 基因过表达和/ 或p16 蛋白丢失均起重要作用  相似文献   

3.
早期胃癌cyclin E表达的生物学意义   总被引:5,自引:3,他引:2  
目的研究早期胃癌cyclinE表达的生物学意义.方法用免疫组化法检测108例早期胃癌组织中cyclinE和P53的表达.结果正常胃腺体细胞几乎不染色,33%(36/108)的胃癌呈棕黄色.CyclinE的总阳性率,在幽门部为48%(24/50),肉眼观混合型46%(6/13),组织学分化型40%(31/78),P53阳性者54%(19/35),均显著高于对照组.CyclinE的强阳性率,在癌侵入粘膜下者是18%(9/51),侵入静脉者28%(5/18),侵入淋巴管者28%(9/32),侵入淋巴结者30%(4/13),都显著高于对照组.CyclinE强阳性者五年生存率40%(4/10),显著低下.结论CyclinE阳性尤其是强阳性者恶性程度高  相似文献   

4.
p53 C-myc和P-gp蛋白在胃癌细胞中表达   总被引:5,自引:4,他引:5  
目的研究胃癌组织中p53和Cmyc的表达与多药耐药性(MDR)的关系.方法应用LSAB免疫组织化学方法研究67例(男41例,女26例,平均年龄46±158岁)胃癌标本中p53,Cmyc和Pgp的表达.结果本组胃癌中p53阳性32例(478%),Cmyc阳性37例(552%),Pgp阳性39例(582%).淋巴结转移阳性胃癌p53阳性率(569%)和Cmyc阳性率(647%)显著高于淋巴结转移阴性的胃癌(P<005).p53的异常表达与mdr1基因表达呈显著正相关(r=063,P<005),而Cmyc和mdr1的表达无明显相关.结论p53异常表达可增加mdr1基因的表达,从而使胃癌细胞获得MDR表型  相似文献   

5.
C-myc,Bcl-2与胃癌生物学行为和细胞凋亡   总被引:14,自引:5,他引:14  
目的探讨癌基因Bcl2,Cmyc的表达变化与胃癌生物学行为和细胞凋亡的关系.方法采用免疫组化LSAB法,检测60例原发性胃癌组织(男38例,女22例,年龄37岁~75岁)癌基因Bcl2,Cmyc蛋白的表达变化;在普通光学显微镜下对受检组织的HE片进行形态学测量和凋亡细胞计数.结果受检组织60例中,Cmyc阳性表达37例(62%),其表达与分化程度和临床分期呈显著性相关,且Cmyc阳性组织细胞凋亡指数(07±03)明显高于阴性组织(03±02);所检标本中,Bcl2阳性表达率为68%(41/60),其中高分化胃癌的阳性表达率明显高于低分化胃癌(32%vs9%)(P<005),阳性Bcl2组织与阴性Bcl2组织比较,前者凋亡指数明显低于后者(04±03vs09±05)(P<005).结论Cmyc与Bcl2基因的异常表达是胃癌生物学行为的重要影响因素,二者在胃癌形成过程中均起着一定的作用,并对细胞增生与凋亡有重要调节作用.  相似文献   

6.
目的探讨内分泌细胞(EC)在大肠癌及癌旁的表达意义.方法应用LSAB免疫组化法,对117例大肠癌及85例癌旁粘膜中嗜铬蛋白A(CGA)及几种激素进行检测,13例大肠癌行电镜观察.结果EC阳性大肠癌46例(393%),检测到一种以上激素692%(27/39),癌旁粘膜EC数高于正常肠粘膜.电镜观察8例有含内分泌颗粒的癌性EC.在中低分化癌中EC(++)的表达(255%)高于高分化癌(69%)(χ2=754,P<005),含有EC的大肠癌淋巴结转移的发生率(680%)高于不含EC者(437%)(χ2=623,P<005),且预后不良;5HT,βHCG,Glu,Gas阳性癌分化及预后较差(P>005).结论含EC的大肠癌具有更恶性的生物学行为,可能与EC中某些激素,通过旁分泌等途径促进肿瘤的生长转移有关,癌旁EC增生与周围肿瘤生长有关.  相似文献   

7.
采用原位杂交技术检测正常大肠粘膜、息肉及癌组织中P16、细胞周期素D_1、(Cyclin D_1)的表达情况,并结合临床资料进行分析。结果显示,P16在正常大肠粘膜中的阳性表达率最高,息肉组织次之,癌组织最低;癌组织与正常大肠粘膜和息肉组织比较差异显著(P<0.005)。对大肠癌患者术后随访2年发现,其死亡与存活者的P16和Cyclin D_1亦有明显差异(P<0.01)。正常大肠粘膜和炎性息肉组织未发现Cyclin D1过度表达,腺瘤样息肉表达率为7.7%,癌组织表达率大于65%,与正常大肠粘膜和息肉组织比较差异显著(P<0.005)。相关性分析显示,P~(16)、Cyclin D_1在大肠粘膜组织中多数呈反向表达。提示P~(16)、Cyclin D_1在大肠癌发生过程中起重要的作用,其反向表达趋势说明可能存在相互抑制机制。  相似文献   

8.
胃癌及癌前病变组织中c_erbB_2癌基因产物的表达   总被引:4,自引:2,他引:4  
目的探讨cerbB2癌基因产物的表达与胃癌发生及胃癌生物学行为的关系.方法应用抗cerbB2癌基因蛋白(P185)的单克隆抗体,采用免疫组化ABC方法对正常胃粘膜(n=9)、各级胃粘膜异型增生(轻度n=10,中度n=6,重度n=7)、早期胃癌(n=18)及进展期胃癌(n=30)进行研究,并与胃癌类型、大小、有无淋巴结转移等作了比较分析.结果正常胃粘膜为阴性,仅在腺体颈部偶见P185蛋白的弱阳性表达.在异型增生病变中则有较高的表达率,并随异型增生程度的增加,表达率逐渐升高,轻、中、重度异型增生表达率分别为50%,833%,857%.P185蛋白在早期及进展期胃癌中的表达率分别为222%和567%.重度异型增生表达率显著高于早期胃癌(P<005),进展期胃癌表达率显著高于早期胃癌(P<005),淋巴结转移组的表达率高于淋巴结未转移组(593%vs238%,P<005),但P185蛋白的表达与胃癌组织学类型及胃癌肿块大小无相关性(P>005).结论cerbB2癌基因有可能参与正常胃粘膜的增殖、修复及癌变过程,P185蛋白阳性的肿瘤可能具有更强的浸润及转移能力.  相似文献   

9.
应用免疫组织化学技术检测CyclinD1和pRb在胃癌及其癌旁粘膜中的表达,探讨其在胃癌的发生和发展中所起的作用1材料和方法1.1材料共选取胃癌手术切除标本57例,经10%中性福尔马林液固定,常规脱水,石蜡包埋.1.2方法应用免疫组织化学ABC(AvidinBiotinCoplex)法,cyclinD1小鼠单抗DCS-6购自美国Neomarker公司,Rb小鼠单抗购自美国Zymed公司,ABC试剂购自美国Vector公司,微波进行抗原修复2结果2.1CyclinD1和pRb在胃癌、不典型增生和胃…  相似文献   

10.
福建肝癌细胞EBV感染与HBV及P53蛋白表达的关系   总被引:11,自引:2,他引:9  
目的探讨肝细胞癌(HCC)中EBV与HBV感染的相关性及EBV与P53蛋白表达的关系.方法采用原位杂交技术以地高辛标记的单链cDNA探针、生物素标记的双链cDNA探针及免疫组化SP法检测HCC59例(含癌旁肝组织)和9例肝硬变组织中高拷贝数EBER1(EBV编码的小RNA)、HBVDNA和P53蛋白.结果肝癌细胞核内EBER1阳性率为203%,显著高于癌旁肝组织(P<001).肝癌组织内HBVDNA阳性率为593%,EBV存在与HBV感染无明显相关性(P>005).肝癌组织内P53蛋白表达率为339%,P53表达与EBER1无显著关系(P>005).结论肝癌细胞内EBV感染与HBV存在无明显关系,肝癌中P53表达与EBER1无关  相似文献   

11.
目的探讨细胞周期蛋白G1(Cyclin G1)、鼠双微体基因(Mdm2)和P53在胃癌组织中的表达意义及相关性。方法采用免疫组织化学方法(SP法)检测54例胃癌组织中Cyclin G1、Mdm2和P53的表达,以20例正常胃黏膜组织作为对照。结果胃癌组织中Cyclin G1、Mdm2、P53的阳性表达率分别为62.96%、53.70%、44.44%,与正常组织对比,有显著性差异(P<0.05),Cy-clinGl、Mdm2的阳性表达率和表达强度与胃癌的分化程度相关。胃癌组织中Mdm2蛋白的表达与P53的表达呈正相关(r=0.307),而CyclinGl蛋白的表达与P53的表达无明显相关性。结论CyclinGl、Mdm2、P53的过表达在胃癌的发生、发展过程中起着重要的的作用。Mdm2可能是通过调控P53的活性而促进胃癌的发生、发展,Cyclin G1可能以不依赖P53的途径发挥作用。  相似文献   

12.
细胞周期蛋白在胃肠癌中的表达及临床意义   总被引:1,自引:0,他引:1  
目的探讨细胞周期蛋白在胃肠癌中的表达及临床意义.方法用间接免疫荧光双标法在激光扫描共聚焦显微镜下检测33例胃肠癌患者手术标本和内窥镜活检组织标本中cyclin蛋白的表达及其差异.结果在手术切除标本或内镜活检组织标本中,四种cyclin在胃癌和大肠癌中的表达均有一定的阳性表达率,与正常胃肠黏膜相比,具有显著性差异(P<0.05),而四种cy-clin在胃癌和大肠癌中的表达率差异则无显著性意义(P>0.05).cyclin D1、cyclin E、cyclin A和cyclin B1在手术前后肿瘤组织中的表达差异均有显著性意义(P<0.05).结论 cyclin蛋白在胃肠肿瘤的发生、发展中起重要作用.内镜活检组织cyclin的检测对胃肠肿瘤的早期发现有一定意义.  相似文献   

13.
PURPOSE: Cyclin B1 is a key regulator of progression through the G2/M transition during the cell cycle. Although cyclin B1 proteins are overexpressed in various types of human cancers, the relationship between cyclin B1 status in gastric cancer and its clinical significance remains unknown. METHODS: We examined cyclin B1 expression by immunohistological means in 61 patients with gastric cancer in terms of histological type, tumor invasion, and metastatic behavior. Specimens were considered positive when the cytoplasm of over 10% of the cancer cell population was stained. RESULTS: Cyclin B1 was overexpressed in 32 (53%) of 61 patients with gastric cancer. Tumors that expressed cyclin B1 were predominant in older patients, in well- and moderately differentiated adenocarcinomas and in expanding-growth type tumors. Conversely, expression of cyclin B1 was lower in poorly differentiated adenocarcinomas, and in those of the infiltrative growth type. Moreover, the disease was more advanced (stages III and IV) and widespread nodal involvement was more frequent when cyclin B1 expression was low. Logistic regression analyses showed that histological type is a significant factor related to cyclin B1 protein expression. CONCLUSIONS: These findings suggested that cyclin B1 protein overexpression is closely associated with less aggressive tumor behavior. Therefore, G2/M cyclin alternatives and the possible role of cyclins in cancer development warrants further attention.  相似文献   

14.
目的 探讨细胞周期蛋白E、B1在胃肠癌中的表达及意义。方法 用间接免疫荧光双标法在激光扫描共聚焦显微镜下检测49例胃肠癌组织中cyclin E和cylcin Bl的表达。结果 胃肠癌中cyclin E和cylcin Bl的阳性表达率分别为48.9%和40.8%,正常组织未见表达,有显著性差异(P<0.05);cyclin E和cylcin Bl在胃肠癌中的表达与肿瘤的生长方式和分化程度相关,在膨胀性生长和高中分化肿瘤中的表达阳性率显著高于浸润性生长和低分化的肿瘤(P<0.05),cyclin Bl在有远处转移的胃肠癌中的表达阳性率显著高于无远处转移的肿瘤组织(P<0.05)。结论cyclin E和cyclin Bl在胃肠肿瘤的发生、发展中起重要作用。  相似文献   

15.
AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma. METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22 cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma. RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively. The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples. There was no significant correlation between cyclin D1 protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (chi2 = 0.038, 0.059, 0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (chi2 = 3.92, P<0.05). CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.  相似文献   

16.
PURPOSE: Cyclin E is known as a G1-S phase regulatory protein and its abnormal expression has been implicated in cellular proliferation. This study aimed to investigate the correlation of cyclin E expression with tumorigenesis of the endometrium, proliferative activity, and clinicopathological features of endometrial adenocarcinoma. METHODS: Immunohistochemical staining for cyclin E in addition to cyclin-dependent kinase 2 (cdk2), Ki67, p27, and p53 was performed by the labeled streptavidin-biotin method on formalin-fixed, paraffin-embedded tissues of normal endometria (20 cases), endometrial hyperplasias (20 cases), and endometrial adenocarcinomas (endometrioid type) (127 cases). Positive staining was expressed as a labeling index (LI) based on percentages of positive nuclei in tumor cells. RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin E. Both proliferative and secretory endometria, and endometrial hyperplasia regardless of type were negligible for cyclin E expression. The expression in normal endometrium and hyperplasia was significantly less than that in endometrial adenocarcinomas (P<0.0001). LIs of cyclin E in well-differentiated, moderately differentiated, and poorly differentiated endometrial adenocarcinomas were 31.5+/-33.3%, 37.8+/-31.9%, and 51.1+/-30.8%, respectively. Cyclin E expression increased significantly more in histological grades. The LI of cyclin E in carcinoma was positively correlated with that of cdk2, Ki67, and p53 but not with p27. The cyclin E expression was correlated with myometrial invasion and lymph-vascular space involvement, but not with FIGO stage, lymph node metastasis, coexisting endometrial hyperplasia, estrogen receptor, progesterone receptor, and menopause. CONCLUSION: Cyclin E as a complex with cdk2 is associated with carcinogenesis and disease progression in endometrial adenocarcinoma, and might be a prognostic indicator of endometrial adenocarcinoma.  相似文献   

17.
BACKGROUND AND AIMS: A subset of colorectal carcinomas are due to a deficiency in the DNA mismatch repair system. The molecular mechanisms of tumorigenesis in these tumors is not yet well understood. Deregulation of the cell cycle, specifically of the G(1) and S phases, is a hallmark of human cancers. Transition from the G(1) to the S phase is accelerated by increased cyclin E protein expression, and recent studies suggest that overexpression of cyclin E leads to chromosomal instability. The overexpression of cyclin E in a variety of human cancers, for example in colorectal, gastric, lung, breast, and kidney cancer, provides evidence that cyclin E plays a pivotal role in the cell cycle and replication. We examined whether the overexpression of cyclin E is related to the status of the mismatch repair system in colorectal carcinomas. PATIENTS AND METHODS: Frozen tumor samples and adjacent normal colon mucosa obtained from 100 patients were subjected to microsatellite analysis, RT-PCR, western blot analysis and immunohistochemistry. RESULTS: High microsatellite instability was detected in 13 tumors, and in 10 of these (77%) cyclin E protein was overexpressed at least twofold compared to normal mucosa. In contrast, only 28 of the remaining 87 microsatellite stable tumors (32%) overexpressed cyclin E. Lower molecular weight cyclin E proteins were present in 7 of 87 microsatellite stable carcinoma (8%), compared to 7 cases exhibiting lower molecular weight isoforms of 13 MSI carcinoma (54%). CONCLUSION: Increased cyclin E protein expression and the appearance of lower molecular weight cyclin E proteins were significantly associated with MSI in colorectal tumors. The data indicate that increased and/or aberrant expression of cyclin E protein might contribute to the mutator phenotype of colorectal cancer.  相似文献   

18.
目的:探索胃癌中医证型与肿瘤增殖的关系方法:胃癌患者91例,术前按中医辨证分型标准归类成6型,术后标本用免疫组化Envision法检测胃癌组织Ki67与Cyclin E的蛋白表达,观察不同证型肿瘤增殖差异.结果:Ki67,Cyclin E阳性表达率分别为 98.90%(90/91),72.53%(66/91).Cyclin E的表达与胃癌病理分型(P=0.0394)及远处转移(P =0.0096)存在相关性,女性患者有无远处转移与Cyclin E表达有统计学意义(P=0.0193),有远处转移的患者表达较高.Ki67与预后相关因素未见相关性.Ki67的表达与证型存在相关性 (P=0.0377),肝胃不和型与痰湿凝结型、气血双亏型Ki67表达存在差异,肝胃不和型高于痰湿凝结型(P<0.01)、气血双亏型(P<0.05), 胃热伤阴型与痰湿凝结型Ki67存在差异,胃热伤阴型高于痰湿凝结型(P<0.05);Cyclin E的表达各证型未见统计学差异(P<=0.1254).结论:Cyclin E可作为判断胃癌预后的重要指标.胃癌不同证型存在部分增殖差异,Ki67与胃癌证型相关,Cyclin E与证型无关.  相似文献   

19.
Song JH  Kim CJ  Cho YG  Park YK  Nam SW  Yoo NJ  Lee JY  Park WS 《Neoplasma》2007,54(3):235-239
Cyclin D1 is a key cell cycle regulator that is upregulated in gastric cancer. The common G870A polymorphism of cyclin D1 which can influence cancer susceptibility and disease outcome has been the most frequently investigated. The specific aim of this study is to investigate whether the G870A polymorphism of cyclin D1 was associated with individual susceptibility to gastric cancer in Korea. The frequency of the polymorphism was examined in 253 gastric cancer patients and 442 healthy controls. Polymorphism analysis was performed by amplifying exon 4 of cyclin D1 and sequencing the products. The frequencies of genotypes: G/G, G/A and A/A were 28.1% (71/253), 49.4% (125/253) and 22.5% (57/253), respectively, in gastric cancer cases, and 23.1%, 51.1% and 25.8%, respectively, in healthy controls. Statistically, the polymorphism was not associated with increased risk of gastric cancer. When stratified by histological subtype of gastric cancer, the risk was also not statistically significant. However, the male gastric cancer patients showed a significantly higher proportion of the homozygous G/G genotype and the G allele (Chi-Square test, P = 0.0242 & P = 0.0307) compared to males in the control group. Thus, our findings suggested that the G870A polymorphism of cyclin D1 was not associated with an increased risk for gastric cancer in this population, however, it may contribute to susceptibility to gastric cancer in men.  相似文献   

20.
目的:检测胃癌组织中P27的表达及其与cyclin D_1、cyclin E表达的相关性,并探讨其意义.方法:临床病理资料齐全的胃癌蜡块标本54例,正常胃黏膜标本15例,采用SP免疫组化方法检测P27、cyclin D和cyclin E在其中的表达.结果:胃癌组织54例中有20例P27表达阳性(37.0%),正常胃组织中15例有11例P27呈阳性表达(73.3%),胃癌组织与正常胃组织相比,P27的表达有明显差异(P<0.05),胃癌组织中P27的表达与患者的性别、年龄及肿瘤大小,浸润深度,分化程度无相关性(P>0.05),而与TNM分期及有无淋巴结转移明显相关(P<0.05),P27的表达与cyclin D_1的表达呈负相关(r=-0.332),而与cyclin E的表达无明显相关性(p>0.05).结论:胃癌组织中P27表达与正常胃组织有显著差异,胃癌组织中P27蛋白表达与淋巴结转移及临床分期密切相关,与cyclin E的表达呈负相关.  相似文献   

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