p53、p16、Cyclin D1表达与胃癌增殖细胞核抗原的关系

目的 探讨ｐ５３、ｐ１６、Ｃｙｃｌｉｎ Ｄ１表达与胃癌细胞增生状况的关系。方法 采用免疫组化ＡＢＣ法检测５８例胃癌中ｐ５３、ｐ１６、ＣｙｃｌｉｎＤ１和ＰＣＮＡ的表达状况,并对ＰＣＮＡ免疫阳性细胞作半定量分析。结果 ｐ５３、ｐ１６、Ｃｙｃｌｉｎ Ｄ１阳性表达率分别为５１．７％（３０／５８）、４８．３％（２８／５８）、５３．４％（３１／５８）;ｐ５３、Ｃｙｃｌｉｎ Ｄ１阳性组织中,单位面积ＰＣＮＡ阳性     

单克隆抗体检测膀胱移行细胞癌相关抗原与肿瘤病理分级关系的探讨

为探讨膀胱移行细胞癌相关抗原与肿瘤病理分级及之间的关系，作者应用膀胱移行细胞癌（ＴＣＣ）单克隆抗体（ＭｃＡｂ）１９Ａ２１１和Ｍ３４４，对５１例（１０２个）膀胱ＴＣＣ组织切片进行免疫组化染色。５１例中包括膀胱ＴＣＣ１级１７例、２级１８例、３级１６例。结果１９Ａ２１１抗原表达阳性率在１级是８２．４％（１１／１７），２级是７７．７％（１４／１８），３级是３７．５％（６／１６）。１级阳性表达率与３级相比，Ｐ＜０．０１。２级阳性表达率与３级相比，Ｐ＜０．０５。Ｍ３４４抗原表达阳性率在１级是８８．２％（１５／１７），２级是８３．３％（１５／１８），３级是３７．５％（６／１６）。１级阳性表达率与３级相比，Ｐ＜０．０１。２级阳性表达率与３级相比，Ｐ＜０．０５。１９Ａ２１１和Ｍ３４４联合应用对５１例膀胱ＴＣＣ进行检测，抗原表达阳性率１级是１００％（１７／１７），２级是８８．８％（１６／１８），３级是６８．８％（１１／１６）。结果表明，ＭｃＡｂ１９Ａ２１１、Ｍ３４４适用于膀胱ＴＣＣ的诊断，特别是有利于１、２级表浅性膀胱ＴＣＣ。联合应用２种ＭｃＡｂ可明显提高检测１、２表浅性膀胱ＴＣＣ的阳性率。     

p16和cyclin D1在膀胱癌中的表达及其相关性研究

目的研究ｐ１６和ｃｙｃｌｉｎＤ１在膀胱癌组织中的表达,探讨其与膀胱癌生物学行为的关系。方法应用免疫组化法观察５０例膀胱癌ｐ１６和ｃｙｃｌｉｎＤ１的表达情况。结果（１）膀胱癌组织中ｐ１６阳性率为４４％,明显低于正常膀胱粘膜（Ｐ＜０．０１）;ｃｙｃｌｉｎＤ１阳性率为６２％,明显高于正常膀胱粘膜（Ｐ＜０．０１）。随着肿瘤恶性程度的增高和临床分期的进展,ｐ１６阳性率下降,ｃｙｃｌｉｎＤ１阳性率升高。ｐ１６在未复发组、存活组的表达率显著高于复发组、死亡组（Ｐ＜０．０１）。ｃｙｃｌｉｎＤ１在存活组的表达率显著低于死亡组（Ｐ＜０．０５）。（２）ｐ１６与ｃｙｃｌｉｎＤ１的表达呈负相关。（３）有１５％的病例存在ｐ１６和ｃｙｃｌｉｎＤ１同时表达或失表达。结论ｐ１６与ｃｙｃｌｉｎＤ１异常表达在膀胱癌的发生、发展过程中起重要作用。     

单克隆抗体检测膀胱移行细胞癌相关抗原与肿瘤病理分级关系的 …

为探讨膀胱移行细胞癌相关抗原与肿瘤病理分级及之间的关系，作者应用膀胱移行细胞癌（ＴＣＣ）单克隆抗体（ＭｃＡｂ）１９Ａ２１１和Ｍ３４４，对５１例（１０２个）膀胱ＴＣＣ组织切片进行免疫组化染色。５１例中包括膀胱ＴＣＣ１级１７例、２级１８例、３级１６例。结果１９Ａ２１１抗原表达阳性率在１级是８２．４％（１１／１７），２级是７７．７％（１４／１８），３级是３７．５％（６／１６）。１级阳性表达率与３级相比，     

膀胱癌多向耐药基因P—GP170表达的研究

应用ＭＤＲ（Ａｂ－１）和Ｃ２１９单克隆抗体，免疫组化法对４２例膀胱癌ＭＤＲ１和ＭＤＲ３基因编码的Ｐ－ＧＰ１７０的表达进行了研究，结果发现，３０例膀胱初发瘤Ｐ－ＧＰ１７０的阳性表达率为７０％（２１／３０），其中８例（２７％）为强性染色，１２例（４３％）为阳性或部分阳性染色。１２例化疗后复发的肿瘤切片，Ｐ－ＧＰ１７０的阳性表达率为８３．３％，２４例Ｇ１～２肿瘤Ｐ－ＧＰ１７０阳性表达率为７９％（１９／２     

Rxa对L02细胞增殖的细胞周期分析和对Ki-67、CyclinD1、PCNA蛋白表达的影响

目的　探讨丹参提取物Ｒｘａ 对正常肝细胞（Ｌ０２ 细胞） 增殖速率的影响。方法　应用流式细胞术（ＦＣＭ）分别测定Ｌ０２ 细胞Ｒｘａ 处理组（Ｌａ 组） 和未处理组（Ｌ组）０、２、４、８、１２ 小时Ｇ０Ｇ１ 、Ｓ、Ｇ２Ｍ 期细胞指数,同步进行Ｋｉ６７、Ｃｙｃｌｉｎ Ｄ１ 、ＰＣＮＡ 蛋白表达的免疫组化分析。结果　Ｌａ 组细胞增殖速率较快,Ｋｉ６７ 抗原表达相对较强,ＣｙｃｌｉｎＤ１、ＰＣＮＡ 表达相对提前。结论　Ｒｘａ 可能促进Ｌ０２ 细胞增殖。     

CyclinD1基因扩增及其蛋白表达在乳腺癌中的意义

目的 探讨乳腺癌中ＣｙｃｌｉｎＤ１基因扩增和其蛋白表达的相关性及其临床意义。方法应用半定量ＰＣＲ和免疫组化技术,检测和分析了乳腺癌及其癌旁组织、乳腺良性组织及正常朱标本中ＣｙｃｌｉｎＤ１基因扩增占２２．６％（１４／６２）,蛋白过度表达占４８．４％（３０／６２）,二者有一定相关性,而其它各种乳腺组织的ＣｙｃｌｉｎＤ１基因扩增及蛋白过度表达与之相比差异有显著性意义（Ｐ〈０．０５）。ＣｙｃｌｉｎＤ１基因     

术前,术后放疗的直肠癌治疗中作用的评估和比较

目的：评估和比较辅助性术前、术后放疗在直肠癌治疗中的作用。方法：１９８８年２月～１９９５年２月收治经病理证实的直肠癌１７６例,配合手术分别采用术前单次放疗、术前常规放疗和术后放疗。术前单次放疗组３８例,剂量为５Ｇｙ,并于放疗后４８ｈ内手术;术前４０Ｇｙ常规放疗组４３例,多为临床晚期（Ｔ３～４占６０．５％）,中位剂量４０Ｇｙ,放疗后休４周再行手术;术后放疗组９５例,以病变晚期和淋巴结阳性为主（Ｔ３～４占６２．１％,Ｔ２～４Ｎ＋占８１．１％）,采用中位剂量５４Ｇｙ常规分割,疗程约６周,手术后３～４周开始接受放疗。结果：全部病例平均随访８４个月,Ｋａｐｌａｎ－Ｍｅｉｅｒ法计算生存率。术前单次放疗组３年、５年局部复发率分别为７８．９％和５０．０％,常规术前４０Ｇｙ放疗组为６７．４％和５１．１％;术后放疗组为５８．９％和     

原发性肝细胞癌中细胞周期G1期相关基因Cyclin D1的表达及其临床病理学意义

目的研究原发性肝细胞癌（ＨＣＣ）中ＣｙｃｌｉｎＤ１基因的表达及其与ｐ５３基因、肝癌细胞增殖活性的关系,探讨其在ＨＣＣ的发生、发展中可能的作用。方法应用免疫组织化学及定量ＤＮＡ图像分析的方法,检测ＣｙｃｌｉｎＤ１、Ｐ５３基因在３２例ＨＣＣ和６例正常肝组织中的表达,并分析ｃｙｃｌｉｎＤ１蛋白的表达与肝癌细胞增殖活性的关系。结果肝癌组织中ｃｙｃｌｉｎＤ１蛋白的过表达率明显高于癌旁肝组织（７１．８％,２３／３２对０％,０／３２;Ｐ＜０．０１）。ｃｙｃｌｉｎＤ１蛋白的表达与ＨＣＣ的Ｐ５３基因表型状况及其它临床病理学指标无关。ＨＣＣ中Ｓ期细胞比例在不同ｃｙｃｌｉｎＤ１蛋白水平的ＨＣＣ中未见显著性差异（Ｐ＞０．０５）。结论ＣｙｃｌｉｎＤ１基因的过度表达可能参与ＨＣＣ的发生、发展。ｃｙｃｌｉｎＤ１蛋白的免疫组化染色可作为ＨＣＣ的辅助病理学诊断指标之一。     

Rxa对L02细胞增殖的细胞周期分析和对Ki—67,CyclinD1,PCN …

探讨丹参提取物Ｒｘａ对正常肝细胞增殖速率的影响。方法应用流式细胞术分别测定Ｌ０２细胞Ｒｘａ处理组和未处理组０、２、４、８、１２小时Ｇ０－Ｇ１、Ｓ、Ｇ２－Ｍ期细胞指数，同步进行Ｋｉ－６７、ＣｙｃｌｉｎＤ１、ＰＣＮＡ蛋白表达的免疫组化分析。结果Ｌａ细胞胞增殖速率较快，Ｋｉ－６７抗原表达相对较强，ＣｙｃｌｉｎＤ１、ＰＣＮＡ表砂相提前。结论Ｒｘａ可能促进Ｌ０２细胞增殖。     

Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder

PURPOSE: To determine the association of cyclin D1 and E1 expression with bladder cancer presence, clinical and molecular characteristics, and disease progression in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. METHODS: Immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, pRB, KI-67, and survivin was performed on a tissue microarray containing specimens from 9 normal controls and 74 patients with Ta, Tis, and/or T1 urothelial cell carcinoma of the bladder. Cyclin D1 and E1 immunoreactivity were considered low when samples showed less than 10% and 30% nuclear reactivity, respectively. RESULTS: Normal bladder urothelium from all 9 control patients showed uniformly intense expression of cyclin D1 and cyclin E1. Cyclin D1 and E1 expression were low in 23 of 74 (31.1%) and 27 of 74 (36.5%) specimens. Kaplan-Meier analyses showed that low expression of cyclin E1 was significantly associated with an increased probability of tumor recurrence and progression in univariate, but not multivariate analysis. Cyclin D1 immunoreactivity was not associated with any pathologic characteristics or clinical outcomes. Low cyclin E1 expression was significantly associated with altered expression of p53, pRB, KI-67, and survivin. CONCLUSIONS: Tissue expression of cyclin D1 or E1 seems not to add independent prognostic value to standard features in patients with nonmuscle -invasive urothelial cell carcinoma of the bladder.     

Immunohistochemical demonstration of cyclin D1 in bladder cancers as an inverse indicator of invasiveness but not an independent prognostic factor

BACKGROUND: Cyclin D1 is essential for G1 progression through the cell cycle phase. It is a possible proto-oncogene whose aberrant expression may be responsible for the occurrence of some types of human neoplasms. The objective of the present study was to demonstrate immunohistochemically cyclin D1 expression in bladder cancer tissues and establish any relationship with the histologic findings and the clinical course. METHODS: Tissue from 102 patients with bladder cancers and bladder tissue from five normal subjects were used for an immunohistochemical study of cyclin D1 using the avidin-biotin complex method. RESULTS: Nuclear staining of cyclin D1 was found in 79 (77%) out of the 102 cases of bladder cancer. The five cases of normal epithelium had no immunostaining for cyclin D1. All grade 1 tumors were positive for cyclin D1. With the advance of tumor grade the incidence of cyclin D1 decreased. All pTa tumors stained positively for cyclin D1, whereas the positive staining rates of invasive tumors were 47% in pT1, 73% in pT2, 31% in pT3 and 0% in pT4 tumors. Although a univariate analysis revealed patients with lesions positive to cyclin D1 had more favorable survival rates than those with negative findings, a multivariate analysis showed that positivity for cyclin D1 is not an independent prognostic factor. No relationship was discovered between positivity for cyclin D1 and tumor recurrence in patients with superficial bladder cancers. CONCLUSIONS: These findings suggest that cyclin D1 demonstrated immunohistochemically could be used as an inverse indicator for the level of invasiveness of bladder cancer, but not as an independent prognostic factor.     

Third place--Resident Research Competition, AAO-2000. Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice.

PROBLEM: Cyclin D1 is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin D1 have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin D1 plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin D1 could inhibit tumor growth in vivo. Methods/measures: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly. After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation. RESULTS: Compared with the control tumors, 11 of 19 antisense tumors were smaller, 7 tumors were of equal size, and 1 tumor was larger. Immunohistochemical analysis with an anti-cyclin D1 antibody demonstrated decreased cyclin D1 expression in CCL23 AS and the smaller antisense tumors. Cyclin D1-dependent kinase activity was reduced in CCL23 AS and the smaller antisense tumors, and this was accompanied by a relative decrease in phosphorylated Rb in these samples. CONCLUSION: Antisense cyclin D1 inhibits growth of HNSCC tumors. Cyclin D1 expression, cyclin D1-dependent kinase activity, and Rb phosphorylation are decreased in these tumors. Clinical significance: These findings lend support for the potential use of antisense cyclin D1 as gene therapy for HNSCC.     

Expression of cyclooxygenase-2 in normal urothelium, and superficial and advanced transitional cell carcinoma of bladder

PURPOSE: We compared the differential expression of cyclooxygenase-2 in normal bladder tissue, primary bladder transitional cell carcinoma and transitional cell carcinoma metastases to lymph nodes, and determined whether cyclooxygenase-2 expression is associated with molecular alterations commonly found in bladder transitional cell carcinoma and clinical outcomes after radical cystectomy. MATERIALS AND METHODS: Immunohistochemical staining for cyclooxygenase-2, survivin (Novus Biologicals, Littleton, Colorado), p21, p27, pRB, p53, MIB-1, Bax, Bcl-2, cyclin D(1) (Dakotrade mark), cyclin E (Oncogene, Cambridge, Massachusetts) and caspase-3 (Cell Signaling, Beverley, Massachusetts) was performed on archival bladder specimens from 9 subjects who underwent cystectomy for benign causes, 21 patients who underwent transurethral resection and 157 consecutive patients after radical cystectomy, and on 41 positive lymph nodes. RESULTS: Cyclooxygenase-2 was expressed in none of the 9 normal bladder specimens (0%), 52% of transurethral resection specimens, 62% of cystectomy specimens and 80% of lymph nodes involved with transitional cell carcinoma. Cyclooxygenase-2 expression was associated with higher pathological stage, lymphovascular invasion and metastases to lymph nodes (p=0.001, 0.045 and 0.002, respectively). Cyclooxygenase-2 expression was associated with altered expression of p53 (p=0.039), pRB (p=0.025), cyclin D1 (p=0.034) and caspase-3 (p=0.014). On univariate analysis cyclooxygenase-2 expression was associated with an increased risk of disease recurrence and bladder cancer specific mortality (p=0.0189 and 0.0472, respectively). However, on multivariate analysis only pathological stage and metastases to lymph nodes were associated with disease recurrence (p<0.001 and <0.001) and survival (p<0.001 and 0.015, respectively). CONCLUSIONS: Cyclooxygenase-2 is not expressed in normal bladder urothelium. Cyclooxygenase-2 over expression is associated with pathological and molecular features of biologically aggressive disease, suggesting a role for cyclooxygenase-2 in bladder cancer development and invasion.     

Over expression of metallothionein predicts resistance of transitional cell carcinoma of bladder to intravesical mitomycin therapy

PURPOSE: Metallothionein, a low molecular weight intracellular protein, binds mitomycin with high affinity protecting the tumor DNA. We prospectively studied the relationship of metallothionein expression in bladder transitional cell carcinoma and resistance to intravesical mitomycin. MATERIALS AND METHODS: A series of 45 consecutive patients with superficial transitional cell carcinoma treated with intravesical mitomycin were studied. Resected tumor tissues were stained with metallothionein monoclonal antibody E9. Two pathologists scored staining intensity and distribution. All patients were followed with regular flexible cystoscopy. RESULTS: Median patient age was 73 years (range 44 to 89). Tumor grade was 1 to 3 in 6, 33 and 6 cases, respectively. In 20 patients (44.44%) tumor recurred after mitomycin therapy. Median cytoplasmic staining scores for recurrent and nonrecurrent tumors were 5 (range 0 to 61) and 0 (0 to 14), respectively. Median nuclear staining scores for recurrent and nonrecurrent tumors were 3 (range 0 to 56) and 0 (0 to 11), respectively. Median followup of patients without recurrence was 18 months (range 12 to 36). Nuclear and cytoplasmic staining scores were significantly higher in recurrent than in nonrecurrent tumors. There was no significant relationship of metallothionein expression with tumor grade. CONCLUSIONS: Over expression of metallothionein predicts the resistance of bladder transitional cell carcinoma to intravesical mitomycin therapy.     

Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice

Problem: Cyclin D1 is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin D1 have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin D1 plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin D1 could inhibit tumor growth in vivo. Methods/measures: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly. After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation. Results: Compared with the control tumors, 11 of 19 antisense tumors were smaller, 7 tumors were of equal size, and 1 tumor was larger. Immunohistochemical analysis with an anti-cyclin D1 antibody demonstrated decreased cyclin D1 expression in CCL23 AS and the smaller antisense tumors. Cyclin D1-dependent kinase activity was reduced in CCL23 AS and the smaller antisense tumors, and this was accompanied by a relative decrease in phosphorylated Rb in these samples. Conclusion: Antisense cyclin D1 inhibits growth of HNSCC tumors. Cyclin D1 expression, cyclin D1-dependent kinase activity, and Rb phosphorylation are decreased in these tumors. Clinical significance: These findings lend support for the potential use of antisense cyclin D1 as gene therapy for HNSCC. (Otolaryngol Head Neck Surg 2001;124:656-62.)     

膀胱癌中bcl-2和p16基因的表达与预后的关系

目的 探讨ｂｃｌ－２和Ｐ１６基因蛋白在膀胱癌的表达与预后的关系。方法 采用ＳＡＢＣ法对５１例膀胱癌组织和５例正常膀胱粘膜行ｂｃｌ－２和Ｐ１６基因表达的检测。结果 ｂｃｌ－２在膀胱癌的阳性表达率为８０．２％,生存组和死亡组之间比较差异有显著性意义。Ｐ１６在膀胱癌在阳生表达率为５０．９％。５例正常膀胱粘膜均阳性,两者比较有显著性意义。在病理分级、临床分期和预后的总样本率中比较差异有显著性意义;即随病理     

Inhibition of cell proliferation in head and neck squamous cell carcinoma cell lines with antisense cyclin D1

Cyclin D1 and cyclin G are essential regulatory factors in the progression of the cell cycle from G0 through G1 and S phase. Aberrations in expression of these cyclins may lead to dysregulated cellular proliferation that could result in neoplasia. Amplification and overexpression of cyclin D1 have been observed in many human cancers, whereas cyclin G is a new cyclin recently described in osteosarcoma cells. This study was performed to determine whether these cyclins were amplified in head and neck squamous cell carcinoma (HNSCC) tumors. Polymerase chain reaction of DNA extracted from 22 HNSCC primary tumors and three HNSCC cell lines did not reveal amplification of cyclin D1 in any of the tumor samples. Southern blot analysis identified amplification of cyclin D1 in a single tumor. Amplification of cyclin G was not observed in any of the tumors by Southern blot hybridization with a cyclin G probe. HNSCC cell lines transfected with antisense cyclin D1 were tested for cell proliferation by the incorporation of ³ H-thymidine into cells grown in serum-free media. By 72 hours of incubation, there was a greater than 30% reduction in proliferation of cells transfected with antisense cyclin D1 as compared with nontransfected control cells. The results indicate that cyclin D1 may play an important role in the growth and proliferation of HNSCC cells. (Otolaryngol Head Neck Surg 1998;119:593-9.)     

细胞周期蛋白E和p27kip1在膀胱癌中的表达及意义

目的　探讨细胞周期蛋白E(cyclinE)和p2 7kip1在膀胱移行细胞癌中的表达及临床意义。　方法　采用免疫组化SP法观察 69例膀胱癌石蜡标本中cyclinE和 p2 7kip1的表达情况 ,结合临床资料进行分析。　结果　膀胱癌组织中cyclinE和 p2 7kip1阳性表达率分别为 42 %和 51 %。cy clinE阳性表达率在复发肿瘤中及随病理分级升高而升高 (P <0 .0 5) ,但与临床分期无关 (P >0 .0 5) ;p2 7kip1阳性表达率随病理分级、临床分期升高及在复发肿瘤中下降 (P <0 .0 1 )。cyclinE与 p2 7kip1二者的阳性表达有显著相关性 (P <0 .0 1 )。　结论　cyclinE和p2 7kip1表达可能是判断膀胱癌生物学行为的重要指标