C—myc蛋白和增殖细胞核抗原在人膀胱癌组织中表达的意义

应用增殖细胞核抗原（ＰＣＮＡ）和Ｃ－ｍｙｃ单克隆抗体，以免疫组织化学方法检测正常膀胱组织和膀胱组织中Ｃ－ｍｙｃ蛋白和ＰＣＮＡ的表达水平。结果表明：５例正常膀胱中未发现Ｃ－ｍｙｃ和ＰＣＮＡ阳性表达。阳性的Ｃ－ｍｙｃ和ＰＣＡ均定位于肿瘤的细胞核内。５８例膀胱癌中Ｃ－ｍｙｃ和ＰＣＮＡ蛋白阳性表达分别为４３．１％和６２．１％，并且Ｃ－ｍｙｃ和ＰＣＮＡ阳性表达率与膀胱癌的病理分级、临床分期和患者术后生存率相     

c—myc,Fsa蛋白在成骨性肿瘤及瘤样病变中的表达

目的 针对ｃ－ｍｙｃ、Ｆａｓ蛋白在肿瘤细胞中不同表达方式,探索其与成骨性肿瘤细胞分化的相关性。方法 对骨肉瘤３３例,骨化性纤维瘤１３例,骨纤维结构不良２４例,正常骨痂标本５例,进行了ｃ－ｍｙｃ、Ｆａｓ、ｐ５３蛋白免疫组化染色,与肿瘤细胞分化核有丝分裂及组织学分组比较分析。结果 ｐ５３和ｃ－ｍｙｃ蛋白胞核阳性表达主要在低分化骨肉瘤Ｆａｓ和ｃ－ｍｙｃ蛋白胞浆内阳性,在内肉瘤的高分化细胞（骨母细胞型和软     

肾癌组织中增殖细胞核抗原和C－myc蛋白的表达分析

就应用免疫组织化学方法对正常肾组织和肾癌组织中Ｃ－ｍｙｃ蛋白和增殖细胞核抗原（ＰＣＡＮ）表达水平进行检测。结果在５例正常肾组织中未见Ｃ－ｍｙｃ和ＰＣＮＡ的表达。４５例肾癌中Ｃ－ｍｙｃ和ＰＣ－ＮＡ蛋白阳性表达率他别为２６．７％（１２／４５）和４４．％（２０／４５），阳性表的ＰＣＮＡ和Ｃ－ｍｙｃ蛋白均定位于肾癌细胞核上，并且ＰＣＮＡ和Ｃ－ｍｙｃ蛋白阳性表达率与肾癌的病理分级，临床分期及患者术后生存期有关。提示Ｃ－ｍｙｃ和ＰＣＮＡ蛋白阳性表达参入了肾癌发生和发展，并且有可能成为肾癌预后的客观指标之一。     

肾癌组织中增殖细胞核抗原和C—myc蛋白的表达分析

就应用免疫组织化学方法对正常肾组织和肾癌组织中Ｃ－ｍｙｃ蛋白和增殖细胞核抗原（ＰＣＡＮ）表达水平进行检测。结果在５例正常肾组织中未见Ｃ－ｍｙｃ和ＰＣＮＡ的表达。４５例肾癌中Ｃ－ｍｙｃ和ＰＣＮＡ蛋白阳性表达率他别为２６．７％（１２／４５）和４４％（２０／４５），阳性表的ＰＣＮＡ和Ｃ－ｍｙｃ蛋白均定位于肾癌细胞核上，并且ＰＣＮＡ和Ｃ－ｍｙｃ蛋白阳性表达率与肾癌的病理分级，临床分期及患者术后生存期有关。     

喉癌p16,c—myc及PCNA表达的临床病理研究

探讨ｐ１６、ｃ－ｍｙｃ及ＰＣＮＡ在喉癌发病中的作用。方法应用ＳＡＢＣ免疫组化技术，检测４０例喉鳞癌手术标本中Ｐ１６、ｃ－ｍｙｃ及ＰＣＮＡ的表达，对三者表达与喉癌发生部位，临床分期，组织学分级和临床复发之关系进行探讨。     

泰素帝诱导人肺腺癌细胞凋亡的实验研究

目的 探讨泰素帝诱导人肺腺癌细胞凋亡的作用机制。方法 应用形态学方法、流式细胞术（ＦＡＣＳ）、ＤＮＡ凝胶电泳、ＡｎｎｅｘｉｎＶ标记等方法检测细胞凋亡的发生,应用ＲＴ－ＰＣＲ检测凋亡相关基因Ｆａｓ、ｂｃｌ－２、ｃ－ｍｙｃ表达的变化。结果 泰素帝对人肺腺癌细胞系Ａ５４９细胞的生长有明显的抑制作用,使细胞分裂阻滞于Ｇ２Ｍ期,并诱导肿瘤细胞发生凋亡。凋亡细胞表现为细胞固缩,核染色质聚集或断裂,ＤＮＡ凝胶电     

男性乳腺癌癌基因与抗癌基因表达的初步研究

本文观察了１２例男性乳腺癌的癌基因与抗癌基因产物的表达。１２例中ｃ－ｍｙｃ阳性６例，ＥＧＦＲ阳性６例，ｃ－ｅｒｂＢ－２阳性４例，Ｎ－ｒａｓ阳性２例，Ｒｂ阳性５例，ｐ５３阳性３例。上述癌基因与抗癌基因产物中，全部阳性的１例，全部阴性的４例。此外还作了ＣａｔｈｅｐｓｉｎＤ、ＥＲ、ＰＲ、ＡＲ、ＰＣＮＡ与ＡｇＮＯＲ检测，ｃ－ｅｒｂＢ－２或ｐ５３阳性的病例，ＣａｔｈｅｐｓｉｎＤ均阳性。     

人类非小细胞肺癌Fas配体基因转录水平的表达及其临床意义

在肿瘤免疫中人们过去认为ＦａｓＬ Ｆａｓ途径是细胞毒Ｔ淋巴细胞 (ｃｙｔｏｔｏｘｉｃＴｌｙｍｐｈｏｃｙｔｅ,ＣＴＬ)杀伤肿瘤的重要机制之一 ,但最近研究发现人类的某些肿瘤细胞表达Ｆａｓ配体 (ＦａｓＬ)。我们曾报道国人非小细胞肺癌 (ｎｏｎ ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＮＳＣＬＣ)细胞表面ＦａｓＬ蛋白特异性表达[1] ,为进一步研究 ,我们用ＲＴ ＰＣＲ方法检测了 32例手术切除的ＮＳＣＬＣ样本中ＦａｓＬ基因在转录水平的表达情况 ,现报告如下。1　材料与方法1.1　材料　标本取自我科及重庆医科大学第一附属医院胸外科…     

p16、Ki-67和PCNA的表达与胃肠道平滑肌肿瘤性质的关系

探讨Ｐ１６、ｋｉ－６７和ＰＣＮＡ的表达与胃肠道平滑肌肿瘤（ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌ ｓｍｏｏｔｈ ｍｕｓｃｌｅ ｔｕｍｏｒｓ，ＧＬＳＭＴ）性质的关系。方法：采用免疫组织化学Ｓ－Ｐ法检测８６例ＧＩＳＭＴ患者Ｐ１６的表达情况，采用微波修复抗原及免疫组织化学Ｓ－Ｐ法检测人抗增殖细胞核抗原Ｋｉ－６７及增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇ ｃｅｌｌ ｎｕｃｌｅａｒ ａｎｔｉｇｅｎ，ＰＣＮＡ）     

人膀胱移行细胞癌c－myc、Ha－ras mRNA异常表达与临床肿瘤生物学行为的对照研究

目的探讨ｃ－ｍｙｃ、Ｈａ－ｒａｓ癌基因在人膀胱移行细胞癌中的表达及其与肿瘤恶性程度和临床特性的关系。方法应用地高辛（Ｄｉｇ）标记的ｃＤＮＡ探针对５１例膀胱移行细胞癌石蜡切片进行ｃ－ｍｙｃ、Ｈａ－ｒａｓｍＲＮＡ原位杂交检测。结果ｃ－ｍｙｃｍＲＮＡ阳性表达率为６２．７５％（３２／５１），Ｈａ－ｒａｓ为７０．５９％（３６／５１）。两者阳性率或阳性强度随恶性程度升高而增加。在临床分期较高的肿瘤中，两者亦呈高表达。结论ｃ－ｍｙｃ、ｎａ－ｒａｓ癌基因参与人膀胱移行细胞癌恶性转化过程，其异常表达可能与恶性程度及肿瘤浸润程度也有关系。     

细胞凋亡和细胞增殖在胃癌形成中的作用

目的 :探讨细胞凋亡和细胞增殖在胃癌发生发展中的作用。方法 :用原位末端标记法和免疫组织化学染色 ,检测 30例胃癌和 2 0例胃粘膜上皮异型增生中的细胞凋亡和调控基因 (Bcl 2 ,Fas)及增殖细胞核抗原 (PCNA)的表达情况。结果 :随正常胃粘膜胃粘膜异型增生胃癌的梯度 ,细胞凋亡指数(AI)逐渐降低 ,差异有显著性 (P <0 0 5) ;Bcl- 2的阳性表达率逐渐升高 ,Fas的阳性表达率逐渐降低 ,差异均有显著性 (P <0 .0 1) ,且二者有相关性 (P <0 0 5)。PCNA阳性表达率 (即增殖指数 ,PI)逐渐升高 (P <0 .0 1)。结论 :胃粘膜异型增生中已存在细胞凋亡和细胞增殖的异常 ,使增殖 /凋亡比值加大 ,是胃粘膜异型增生向胃癌发展的重要机制之一     

c-myc Fas蛋白在成骨性肿瘤及瘤样病变中的表达

目的　针对 c- myc、Fas蛋白在肿瘤细胞中不同表达方式 ,探索其与成骨性肿瘤细胞分化的相关性。方法　对骨肉瘤 33例 ,骨化性纤维瘤 13例 ,骨纤维结构不良 2 4例 ,正常骨痂标本 5例 ,进行了 c- myc、Fas、p5 3蛋白免疫组化染色 ,与肿瘤细胞分化、核有丝分裂及组织学分级比较分析。结果　 p5 3和 c- m yc蛋白胞核阳性表达主要在低分化骨肉瘤。Fas和 c- m yc蛋白胞浆内阳性 ,在骨肉瘤的高分化细胞 (骨母细胞型和软骨细胞型瘤细胞 )和骨化性纤维瘤、骨纤维结构不良、骨痂组织中骨母细胞呈强表达 ;而在低分化瘤细胞和纤维母细胞则呈弱表达。结论　 Fas蛋白高表达与对抗瘤细胞的增殖有关 ;c- myc蛋白胞浆阳性表达与瘤细胞分化相关。     

大肠癌不同部位增生、凋亡检测及预后分析

目的探讨细胞增生与凋亡在大肠癌组织及不同部位黏膜细胞中的改变以及二者与预后关系。方法76例大肠癌标本分别取癌组织(cancer m ucosa,C M)、癌近旁组织(cancer adjacent m ucosa,C AM)、癌远旁组织(cancer distant m ucosa,C D M),进行PC N A和Fas染色,并进行随访。结果PC N A在C M中表达高于C AM(P<0.05)及C D M(P<0.01)。C AM Fas染色阳性率为67.1%,高于C D M(42.1%)(P<0.05)及C M(32.9%)(P<0.01)。47例完整随访患者中22例死亡。其中,15例癌组织PC N A高表达,与对照组差异无显著性(P>0.05);14例Fas表达阴性者平均生存期同对照组相比差异无统计学意义(P>0.05)。然而,PC N A高表达同时Fas表达阴性的9例患者平均生存期比同组对照缩短(P<0.01)。结论细胞的增生活性是以肿瘤组织为中心逐渐递减,而细胞凋亡在癌近旁组织明显增强。单纯肿瘤增生或凋亡与肿瘤患者生存时间无显著相关,较高的细胞增生同时伴凋亡下降则可能预示患者预后较差。     

大肠癌旁粘膜细胞增殖模式与术后复发机制的探讨

目的：探讨大肠癌旁粘膜细胞增殖模式变化与肿瘤术后复发的关系。方法：用免疫组化染色方法对７８例大肠癌标本的癌组织、癌旁粘膜及１２例正常大肠粘膜进行ｐ５３蛋白、增殖细胞核抗原（ＰＣＮＡ）检测,并进行随访。结果：癌组织ＰＣＮＡ高表达明显高于癌旁（Ｐ＜００１）,癌旁ＰＣＮＡ高表达与隐窝增殖区扩大、上移,明显影响术后第１年局部复发死亡率（Ｐ＜００１）,癌组织ｐ５３蛋白阳性表达率６１５４％,癌旁为２６９２％,癌及癌旁ｐ５３阳性表达不影响细胞增殖活性及术后第一年内的复发死亡率（Ｐ＞００５）。结论：大肠癌的复发可能与大肠癌的发生一样是正常隐窝增殖分化失调的顺序过程。ＰＣＮＡ可直观表现其增殖活性及增殖模式。ｐ５３突变及表达是多中心性的,癌旁ｐ５３突变点的存在是肠癌局部复发的潜在因素。     

Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma.

Tumour growth depends on neovascularisation and tumour cell proliferation. Factor VIII-related antigen (F-VIII RA) localises to vascular endothelium. Expression of proliferating cell nuclear antigen (PCNA) is correlated with cell proliferation. We investigated the correlation between the expression of these antigens and prognosis in gastric carcinoma. A total of 108 specimens resected from patients with gastric carcinoma were investigated by staining with monoclonal antibodies against F-VIII RA and PCNA. Microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200 x magnification) and PCNA labelling index (PCNA LI; percentage of positive cells in more than 500 tumour cells) were determined. The results showed that prognosis was significantly worse in patients who had a tumour with a high MVC (16 or greater) or a high PCNA LI (42% or greater) than in those patients who had a tumour with a low MVC (less than 16) or a low PCNA LI (less than 42%). Furthermore, MVC was significantly associated with the risk of hepatic recurrence. In conclusion, both MVC and PCNA LI may be good prognostic indicators in patients with gastric carcinoma.     

Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma.

Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.     

人肝细胞癌及癌周组织中p53、c-myc基因的表达及临床意义

目的：探讨ｐ５３及ｃｍｙｃ基因表达在原发性肝细胞癌（ＨＣＣ）发生发展过程中的作用。方法：应用免疫组织化学方法分别检测７３例和６０例ＨＣＣ癌及其癌周组织中ｐ５３和ｃｍｙｃ基因的表达状况。结果：ｐ５３基因在ＨＣＣ中阳性表达率显著高于癌周组织（Ｐ＜０．０５,）,癌周组织中ｐ５３基因表达仅见于癌周增生结节,癌周肝硬变及正常肝组织内未见ｐ５３基因阳性表达;ｃｍｙｃ基因的阳性表达率在ＨＣＣ与癌周增生结节中相近（Ｐ＞０．０５）,且两者均显著高于癌周肝硬变和正常肝组织（分别为Ｐ＜０．０５,Ｐ＜０．０１）;ｐ５３及ｃｍｃｙ基因表达均与ＨＣＣ分化程度呈显著正相关,低分化组ｐ５３及ｃｍｙｃ基因的阳性表达率均显著高于高分化组（Ｐ均＜０．０５）。结论：ｐ５３及ｃｍｙｃ基因过度表达均参与了人肝细胞癌的发生发展过程;癌周增生结节属癌前期病变,与肝癌的发生有关。     

Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL).

It has been suggested that the expansion of the leukemic cells in chronic lymphocytic leukemia (CLL) is due to dysregulation of pathways of programmed cell death (apoptosis) rather than cell proliferation, although differences may exist in early vs late and treated vs untreated patients. In the present study, we analyzed the expression of 11 proteins in CLL cells that are implicated in the control of apoptosis, proliferation, and differentiation, and correlated this expression profile with survival. Using a quantitative solid-phase radioimmunoassay (RIA), we measured the cellular protein levels of Bcl-2, cyclin D1, PCNA, ATM, Fas, Bax, retinoic acid receptor alpha (RARalpha), retinoic acid receptor beta (RXRbeta), Flt1, VEGF, and cellular beta2-microglobulin in 230 samples of CLL. Univariate analysis using the Cox proportional hazard model showed a correlation with survival of only the following proteins: Bcl-2 (P < 0.001), cyclin D1 (P = 0.027), Fas (P = 0.055), PCNA (P < 0.001), and ATM (P = 0.028). In a multivariate analysis using classification and regression tree analysis (CART), five groups of patients (nodes) could be generated with significant differences of survival expectation (P < 0.0001) based on levels of expression of the above proteins. Based on CART analysis, Bcl-2 levels emerge as the most important protein in predicting survival between all 11 proteins studied. Patients with marked elevation in Bcl-2 levels had the worst outcome while patients with intermediate levels, but with high levels of PCNA and cyclin D1 or abnormal ATM expression had intermediate survival. These data indicate that intracellular levels of proteins such as Bcl-2, ATM, cyclin D1, and PCNA can be used as markers to predict clinical behavior and survival in patients with CLL. The pathways in which these proteins are involved may also represent possible targets for future therapeutic trials in CLL.     

胃癌组织中Fas、FasL与增殖细胞核抗原表达的临床研究

目的：研究Fas、FasL及PCNA在胃癌组织中的表达，并探讨其临床意义。方法：采用免疫组化S－P法检测50例胃癌组织、癌旁组织、距肿瘤边缘5cm组织及10例正常胃黏膜中Fas、FasL表达，并对正常胃黏膜和肿瘤组织中PCNA表达进行检测。结果：胃癌的TNM分期、分化程度、淋巴结转移与Fas、FasL表达无关（P＞0．05），与PCNA表达有关（P＜0．01）。结论：Fas、FasL表达与胃癌发生有关，与胃癌进展无关；Fas/FasL系统可能在胃癌发生发展中起重要作用；PCNA是反映胃癌细胞增殖活性的重要指标。     

脑星形胶质细胞瘤增殖与分化

 本文应用免疫组化方法在40例呈形胶质细胞瘤中研究PCNA和GFAP两种标记表达，原位观察与比较瘤细胞的增殖与分化。结果表明脑星形胶质细胞瘤中PCNA与GFAP表达率均为100％，PCNA表达强度与肿瘤分级呈正相关（P＜0．05），GFAP表达强度与肿瘤分级呈负相关（P＜0．01）。提示PCNA与GFAP的表达对于判断脑星形胶质细胞瘤的增殖活性，分化程度及判断肿瘤的恶性程度有一定的价值。