β-连环蛋白和细胞周期蛋白D1在宫颈癌组织中的表达及意义

目的：探讨宫颈癌组织中β-连环生白（β-cat）和细胞周期蛋白DI（cyclin D1）的表达及其意义。方法：应用免疫组织化学卵法．检测68例宫颈癌（UCC）、22例宫颈上皮内瘤变（CIN）和10例正常宫颈（NCE）组织中β-cat与cyclin DI的表达,分析两者表达与宫颈癌临床病理特征的关系。结果：正常宫颈组织、宫颈上皮内瘤变组织和宫颈癌（Ⅰ～Ⅱa期）组织中,β-cat异常表达率分别为0％、45．5％、69．1％（P〈0．01）,cyclinD1阳性表达率分别为10．O％、40．9％和60．3％（P〈0．01）;两者异常表达与宫颈癌的临床分期、病理分级和淋巴结转移均有关（P〈0．05）,与患者的年龄、原发灶大小及病理组织类型均无关（P〉0．05）;两者表达有显著的正相关性（P〈0．01）。结论：β-cat异常表达可能通过激活靶基因cyclinD1过度表达,参与了宫颈癌的发生与发展。     

细胞周期蛋白D1、Ki-67和bcl-2的表达与CD117阳性的胃肠道间质瘤生物学行为的关系

目的 检测细胞周期蛋白D1（cyclin D1）、Ki-67和bcl-2在胃肠道间质瘤（GIST）中的表达,探讨它们在GIST发生、发展中的作用及临床病理意义。方法 59例手术切除GIST标本进行CD117、CD34、平滑肌肌动蛋白（SMA）、结蛋白、S-100、cyclin D1、bcl-2和Ki-67免疫组织化学染色,同时进行病理形态学观察包括形态学类型、肿瘤大小、坏死和核分裂象。所有病例随访2～9年。所有数据进行单因素、多因素和相关分析。结果 随访40例患者一直健在,15例患者死于GIST,4例患者死于其他原因。统计学分析显示肿瘤直径〉5cm、有坏死、核分裂象在每50个高倍视野〉5个、Ki-67增殖指数（LI）〉5％、cyclin D1和bcl-2免疫组织化学染色强阳性都可以作GIST患者手术后的预测指标,且具有统计学意义;核分裂象和Ki-67增殖指数是独立的预测指标;Ki-67 LI≥5％和核分裂象≥5／50 HPF呈正相关（r=0．532,P〈0．01）;cyclin D1与bcl-2强阳性表达呈正相关（r=0.273,P〈0．05）。结论 肿瘤大小、坏死、核分裂象、cyclin D1、Ki-67增殖指数和bcl-2可作为GIST患者临床预测指标;核分裂象和Ki-67增殖指数可作为独立的预测指标;cyclinD1与bcl-2呈明显相关性,Ki-67免疫组织化学染色可以代替核分裂象作为一项很有用的预测指标。     

软组织平滑肌肉瘤中细胞周期蛋白D1基因扩增分析及蛋白表达检测

我们采用差异聚合酶链反应 (ｄｉｆｆｅｒｅｎｔｉａｌＰＣＲ ,ＤＰＣＲ)检测软组织平滑肌肉瘤 (ＬＭＳ)中细胞周期蛋白Ｄ1(ｃｙｃｌｉｎＤ1)基因ＣＣＮＤ1的扩增情况 ,并应用免疫组织化学方法检测ｃｙｃｌｉｎＤ1表达 ,以期了解二者的关系。一、材料与方法1.标本 :38例ＬＭＳ、10例平滑肌瘤和 10例正常平滑肌组织取自本院病理科 1989～ 1998年存档蜡块 ,肿瘤发生部位包括躯干、四肢、腹腔和腹膜后 (胃肠道除外 )。2 .ＤＰＣＲ :多巴胺受体基因 (ｄｏｐａｍｉｎｅｒｅｃｅｐｔｏｒＤ2 ,ＤＲＤ2 )与ＣＣＮＤ1基因同位于 11号染色体的长臂上 (…     

p15、细胞周期蛋白D1和转移生长因子β1在非小细胞肺癌中的表达及其意义

一、材料与方法1.材料 :实验材料取自内蒙古医学院病理教研室在1996～ 1998年间的病理组织存档蜡块 ,共 16 5份。按照 1980年ＷＨＯ肺癌分类标准进行组织学分类 ,并均经病理证实。其中鳞癌 80例 ,腺癌 49例 ,不典型增生 19例 ,鳞状上皮化生17例 ;在 12 9例非小细胞肺癌中 ,同一病例手术切取标本存档蜡块不仅有肺癌组织蜡块也有淋巴结组织蜡块 ;其中淋巴结组织经ＨＥ染色证实有淋巴结转移的 35例 ,无淋巴结转移的 2 8例。其余 6 6例中 ,或同一病例手术切取标本存档蜡块仅有肺癌组织而无淋巴结组织 ,或同一病例标本存档蜡块中虽有淋巴结组织 ,…     

细胞周期蛋白D1和bcl-2蛋白在鼻咽区非霍奇金淋巴瘤中的表达及其与细胞增殖和凋亡的关系

我们选择了细胞周期蛋白(cyclin)D1蛋白和bcl-2蛋白及增殖和凋亡指数，分别从淋巴瘤的增殖和凋亡两方面进行观察，以探讨该指标在鼻咽区非霍奇金淋巴瘤中的表达水平及其意义。     

大肠癌组织蛋白酶D表达及其与生物学行为的关系

大肠癌组织蛋白酶Ｄ表达及其与生物学行为的关系王娅兰苗德林周伟目前，国际上对肿瘤细胞分泌的组织蛋白酶Ｄ与肿瘤侵袭力关系意见尚不统一，国内对此报道甚少。我们对不同类型大肠癌及其局部淋巴结转移灶内组织蛋白酶Ｄ表达进行了观察，并对其与大肠癌生物学行为关系进行...     

结直肠癌中β-连环蛋白的表达及意义

近年来的研究表明上皮性肿瘤的侵袭和转移与Ｅ 钙黏附蛋白 (Ｅ ｃａｄｈｅｒｉｎ ,Ｅ ｃａｄ)的功能障碍有关。β 连环蛋白(β ｃａｔｅｎｉｎ ,β ｃａｔ)是直接与Ｅ ｃａｄ连接的连环蛋白 ,并与α ｃａｔ、γ ｃａｔ共同组成Ｅ ｃａｄ/ｃａｔｓ复合体 ,介导同型上皮细胞间的黏附[1] 。我们应用免疫组织化学方法检测 4 6例结直肠癌组织中 β ｃａｔ的表达 ,探讨其与结直肠癌的分化、侵袭和转移的关系。一、材料和方法1.标本来源 :4 6例结直肠癌组织石蜡包埋标本均来自山东省立医院 1996年 6月～ 1997年 9月间普通外科手术标本 ,标本经 4 %…     

细胞周期蛋白D1、p21WAF1蛋白和增殖细胞核抗原在乳腺癌的表达及与淋巴结转移和预后的关系

我们在以往研究的基础上，检测了乳腺癌组织中细胞周期蛋白(cyclin)D1、p21^WAF1蛋白及增殖细胞核抗原(PCNA)的表达以及有cyclin D1过表达乳腺癌淋巴结转移灶中cyclin D1的表达，以探讨其特别是cyclin D1在乳腺癌发生发展中的作用及其与淋巴结转移关系和预后意义。     

双肾上腺皮质激素样激酶-1与细胞周期蛋白D1在结直肠癌组织中的表达及临床意义

目的:探讨双肾上腺皮质激素样激酶-1(DCLK1)与细胞周期蛋白D1(cyclin D1)在结直肠癌组织中的表达及其临床意义。方法:采用免疫组织化学S-ABC法检测59例结直肠癌组织和28例结直肠良性病变组织中DCLK1及cyclin D1的表达及分布。结果:DCLK1及cyclin D1在结直肠癌组织中的表达明显高于结直肠良性病变组织,平均光密度值(AOD)为0.423±0.021及0.386±0.042;而在结直肠良性病变组织中其阳性反应的平均光密度值为0.267±0.053及0.211±0.026,差异具有统计学意义。DCLK1及cyclin D1的阳性表达与患者的年龄、性别、肿瘤分化程度和DUCKs分期无关,而与组织良性或恶性、肿瘤的大小及淋巴结转移相关。结论:结直肠癌组织中DCLK1及cyclin D1的高表达可能与结直肠癌的发生、发展、转移相关,可作为结直肠癌转移及预后监测的一项重要指标。     

17-β-雌二醇对HMGB1过表达THP1细胞的细胞周期进程的影响

目的:研究17-β-雌二醇联合HMGB1的过表达对人单核细胞系THP1细胞细胞周期和NF-κB转录因子的影响。方法:血清饥饿法同步化细胞周期后,利用脂质体法将pFLAG-CMV-HMGB1转染THP1细胞;10-9mol/L17-β-雌二醇刺激同步化THP1细胞16、30小时后,流式细胞术检测细胞周期分布,RT-qPCR检测Cyclin A、Cyclin D1的mRNA表达水平,免疫印迹检测HMGB1蛋白的表达;荧光素酶报告基因检测NF-κB的活性。结果:HMGB1过表达的THP1细胞中HMGB1蛋白的表达水平比正常THP1细胞要高3.7倍,血清饥饿法成功将THP1细胞周期同步化,同步化后G0/G1期细胞百分数由53%上升到78%;17-β-雌二醇刺激HMGB1过表达细胞30小时后出现Cyclin AmRNA表达上升为原来的7.9倍,而Cyclin D1 mRNA表达明显下降,G1期细胞百分比由53.11%下降为33.33%,S期细胞百分比由35.43%上升为53.91%,此改变在刺激后30小时达到最大值;NF-κB活性在17-β-雌二醇刺激HMGB1过表达细胞明显升高,且时间上提前于细胞周期动力学改变。结论:雌激素对THP1细胞周期调节依赖HMGB1,NF-κB可能参与其中。     

The importance of cyclin D1 and Ki67 expression on the biological behavior of pancreatic adenocarcinomas

The aim of this study was to evaluate the role of cyclin D1 and Ki67 proteins involved in cell-cycle control as a prognostic factor in pancreatic carcinomas. We examined formalin-fixed, paraffin-embedded material from 59 pancreatic adenocarcinomas, for which appropriate clinical and prognostic data were available. The standard streptavidin biotin immunoperoxidase method was used for immunostaining with cyclin D1 and Ki67. The extent of positive nuclear and cytoplasmic cyclin D1 staining was graded semiquantitatively. Ki67 reactivity was quantified and expressed as the percentage of stained nuclei. Staining with cyclin D1 and Ki67 was compared with histopathological prognostic features, and their relation with survival was also tested statistically. Patients whose tumors were cyclin D1-positive showed perineural invasion significantly more frequently than did patients with cyclin D1-negative tumors at the immunohistochemical level. In addition, tumors with lymphatic vessel invasion and without showed a significant difference in terms of cytoplasmic cyclin D1 staining. Ki67 indices were statistically different in stage groups. There was a significant and direct correlation between Ki67 index and nuclear cyclin D1 staining scores. No relation with survival was found. Our results suggest that cell-cycle proteins do not directly affect the prognosis of patients with pancreatic adenocarcinoma. Conversely, cyclin D1-positive tumors tend to have perineural invasion more frequently. In addition, lymph vessel invasion is another factor related to cyclin D1 reactivity of the cells. Ki67 indices differ statistically in stage groups.     

Amplification of c-myc and cyclin D1 genes in primary and metastatic carcinomas of the liver

The c-myc and cyclin D1 genes are included among the oncogenes the amplifications of which have been detected in cancers of various organs. However, there have been few reports on the amplification of both these genes in primary and metastatic liver carcinomas. In the present study, c-myc and cyclin D1 gene amplification was examined in 76 primary and metastatic liver carcinomas using formalin-fixed paraffin-embedded tissue sections and a differential polymerase chain reaction procedure. c-myc and cyclin D1 gene amplification was detected in 15 (33%) and two (4%) of 46 hepatocellular carcinomas (HCC), one (10%) and 0 (0%) of 10 intrahepatic cholangiocarcinomas (ICC), one (33%) and 0 (0%) of three combined hepatocellular and cholangiocarcinomas (HCC + ICC), and nine (56%) and three (19%) of 16 metastatic lesions to the liver from colorectal adenocarcinoma (MCA), respectively. The incidence of c-myc amplification was significantly higher in MCA than in ICC (P = 0.023), and it tended to be higher in HCC than in ICC. These results indicate that the amplification of the c-myc proto-oncogene is not unusual in HCC and MCA, and its detection may have a useful diagnostic significance in differentiating ICC from MCA or HCC from ICC.     

Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis

The objective of this study was to determine the correlation of the expression of cyclin D1 and E1 with the expression of commonly altered cell cycle regulators and bladder cancer presence, staging, and clinical outcomes. We performed immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, and retinoblastoma protein (pRB) on serial cuts from normal urothelium from 9 controls, radical cystectomy specimens from 226 consecutive patients with advanced transitional cell carcinoma, and lymph nodes with metastasis from 50 of the 226 cystectomy patients. Cyclin D1 and E1 immunoreactivity were considered low when samples demonstrated less than 10% and 30% nuclear reactivity, respectively. Normal bladder urothelium from all 9 control patients showed uniformly intense expression of cyclin D1 and E1. Cyclin D1 expression was low in 99 (43.8%) of 226 cystectomy specimens and 25 (50.0%) of 50 metastatic lymph node specimens. Cyclin D1 immunoreactivity was not associated with any pathologic characteristics or clinical outcomes. Cyclin E1 expression was low in 125 (55.3%) of 226 cystectomy specimens and 22 (44.0%) of 50 metastatic lymph node specimens. Low cyclin E1 expression was significantly associated with advanced pathologic stage, lymphovascular invasion, and lymph node metastases. In multivariate analyses, low cyclin E1 expression was significantly associated with bladder cancer-specific mortality (P = .048), but not disease recurrence (P = .056). Low cyclin E1 expression was significantly associated with altered expression of pRB, p27, and cyclin D1. Low cyclin D1 expression was significantly associated with altered expression of pRB, p21, and cyclin E1. Cyclin E1 expression stratifies patients with bladder transitional cell carcinoma into those with more "indolent" behavior and those with features of biologically and clinically aggressive disease.     

碱性成纤维细胞生长因子对卵巢癌CAOV3细胞cyclin D1及GADDl53表达的影响

目的:研究碱性成纤维细胞生长因子(bFGF)对人卵巢癌CAOV3细胞细胞周期调节蛋白cyclinD1及GADD153表达的影响,探讨bFGF促进人卵巢癌CAOV3细胞增殖、抑制凋亡的信号机制。方法:利用无血清饥饿诱导卵巢癌CAOV3细胞凋亡。分为对照组、bFGF组。分别应用MTT、流式细胞术、琼脂糖凝胶电泳观察25、50、75μg/L bFGF对CAOV3细胞增殖率、细胞周期及细胞凋亡的影响。利用Western blotting检测bFGF对CA-OV3细胞cyclin D1、GADD153以及转录因子(c-Fos、c-Jun)表达的影响。结果:与对照组相比,bFGF呈剂量依赖性加速CAOV3细胞细胞周期进程,促进细胞增殖,抑制饥饿诱导的凋亡(P<0.01);呈时间依赖性促进cyclinD1、c-Fos、c-Jun,抑制GADD153蛋白表达(P<0.01)。结论:bFGF可能通过上调cyclin D1、c-Fos、c-Jun,下调GADD153表达促进细胞增殖,抑制饥饿诱导的卵巢癌CAOV3细胞凋亡。     

9-顺-维甲酸对肺腺癌细胞cyclin D1、cdk4转录的影响

目的:检测9-顺-维甲酸处理前后人肺腺癌细胞株PG、A_(549)、SPC-A_1的cyclinD1、cdk4转录水平的变化,探讨9-顺-维甲酸抑制肺腺癌细胞生长的分子机制。方法:采用相对定量逆转录PCR方法,分析细胞周期因子cyclinD1、cdk4转录的变化。结果:9-顺-维甲酸既可以降低PG、A_(549)的cyclinD1转录(P<0.01),又可以降低PG、SPC-A_1的cdk4的转录(P<0.01或P<0.05)。结论:9-顺-维甲酸对肺腺癌细胞的生长抑制作用,与其调控细胞周期因子cyclinD1、cdk4的表达密切相关。     

Cyclin D1蛋白表达与卵巢癌转移相关性研究

目的:探讨细胞周期蛋白(CyclinD1)表达与卵巢癌转移的相关性和CyclinD1与P21WAF1、P53蛋白的关系。方法:应用蛋白免疫印迹技术(Westernblot)检测61例人卵巢癌组织及7例卵巢非癌组织中CyclinD1、P53及P21WAF1蛋白的表达。结果:卵巢癌组织中CyclinD1和P53蛋白表达率均明显高于卵巢非癌组织(P<0.05);P21WAF1蛋白表达卵巢癌组织低于卵巢非癌组织(P>0.05)。CyclinD1与P53及P21WAF1蛋白表达与卵巢癌组织类型无关(P>0.05)。P21WAF1蛋白表达与卵巢癌的临床分期相关(P<0.05),CyclinD1、P53蛋白表达与卵巢癌的临床分期无关(P>0.05)。CyclinD1、P53及P21WAF1蛋白表达与卵巢癌转移相关(P<0.05)。结论:CyclinD1蛋白表达与卵巢癌肿瘤转移相关,CyclinD1与P21WAF1、P53蛋白在卵巢癌发生、发展中可能有一定作用,但不起协同作用。     

Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions

Cyclin D1 and E2F-1 proteins are essential for the regulation of the G1/S transition through the cell cycle. Cyclin D1, a product of the bcl-1 gene, phosphorylates the retinoblastoma protein, releasing E2F-1, which in turn activates genes involved in DNA synthesis. Expression patterns of E2F-1 protein in thyroid proliferations have not been reported. This study used monoclonal antibodies for cyclin D1 and E2F-1 proteins to immunostain sections of normal thyroid, hyperplastic (cellular) nodules, follicular adenomas, follicular carcinomas, and papillary carcinomas. The proliferation rate was examined using an antibody specific for the Ki-67 antigen. Fluorescence in situ hybridization (FISH) methods and chromosome 11-specific probes were also employed to determine chromosome copy number and to assess for evidence of amplification at the 11q13 locus in papillary and follicular carcinomas with cyclin D1 overexpression. Concurrent overexpression of Ki-67, cyclin D1, and E2F-1 was found in the majority of benign and malignant thyroid lesions, compared with normal thyroid tissue. Cyclin D1 up-regulation was not due to extra copies of chromosome 11, or bcl-1 gene amplification. Malignant tumours showed the highest expression for all three markers, particularly papillary carcinomas. E2F-1 was detected at the same or slightly lower levels than cyclin D1. It was only found when cyclin D1 was overexpressed. Because cyclin D1 normally activates E2F-1, up-regulation of cyclin D1 may lead to E2F-1 overexpression in benign and malignant thyroid lesions.     

Overexpression of cyclin D1 in nonmelanocytic skin cancer

Although the overexpression of cyclin D1 has been believed to play important roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen’s disease (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell carcinoma (BCC), were investigated immunohistochemically using monoclonal antibody to cyclin D1 by the LSAB method, to assess the expression of cyclin D1 in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respectively. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, only 2 cases, 1 of SCC and 1 of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dysplasia of BCC was correlated with age. Expression of cyclin D1 markedly increased from normal skin through dysplasia to BOD, but was not significantly related to the degree of SCC differentiation. These findings demonstrate that the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is not increased. Comparison with the results for p53 protein expression in these tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 years old. These findings suggested the hypothesis that prior aberrant p53 expression may affect or regulate the overexpression of cyclin D1. Received: 6 September 1999 / Accepted: 10 November 1999     

肝细胞癌细胞周期蛋白D1基因的扩增和表达

目的　探讨细胞周期蛋白 (cyclin)D1基因 (CCND1)扩增和cyclinD1在肝细胞癌 (HCC)中的表达情况及其与HCC发生发展的关系。方法　分别应用差异聚合酶链反应 (DPCR)、逆转录(RT) PCR和免疫组织化学法检测 2 0例HCC中cyclinD1基因扩增率、mRNA和蛋白表达状况 ,并分析其与HCC组织学分级的关系。结果　cyclinD1基因扩增结果为 6/ 2 0 ,其mRNA和蛋白过表达分别为9/ 2 0和 14 / 2 0。cyclinD1mRNA表达与基因扩增相关 (P <0 .0 5) ,也和蛋白表达水平相关 (P <0 .0 5)。cyclinD1蛋白表达与HCC组织学分级具有相关性 (P <0 .0 5)。结论　cyclinD1基因扩增在HCC中较常见 ,是引起cyclinD1mRNA和蛋白过表达的主要原因之一。cyclinD1蛋白过表达与HCC的组织学分级相关。cyclinD1基因扩增及过表达可能在肝癌的演进和分化中起重要作用