人胰腺癌中bcl-2基因和蛋白的过度表达

目的分析胰腺癌中bcl-2基因的mRNA转录和蛋白翻译,探讨其在胰腺癌发生、发展中的作用.方法以50例胰腺癌组织、15例胰腺癌转移灶组织和10例慢性胰腺炎为研究对象,采用免疫组织化学(SP法)和原位分子杂交法检测bcl-2的表达.结果 Bcl-2蛋白表达与患者年龄、性别、TNM分期无关,与肿瘤分化程度、有无转移病灶有关.在胰腺癌组织中的表达低于胰腺炎组织,但明显高于转移灶.免疫组织化学与原位杂交技术检测胰腺癌组织中的bcl-2基因表达结果一致.结论 Bcl-2蛋白可能作用于胰腺细胞的癌变阶段,并与胰腺导管上皮癌变有关;bcl-2基因在mRNA和蛋白水平表达是相对稳定的.     

胆管癌中抗凋亡基因bcl—2的表达及意义

采用免疫组织化学ＳＡＢＣ法检测抗凋亡基因ｂｃｌ－２在７２例胆管癌中的表达，２５例肝细胞肝癌的癌旁肝组织汇管区胆管上皮作为对照。结果ｂｃｌ－２在５３例高，中分化胆管癌中的表达强于在１９例分化胆管癌的表达，在３７例肝内胆管癌的表达强于在３５例肝外胆管癌的表达，在全部胆管癌中的写     

凋亡相关性基因bcl—2和bax在肺癌中的表达及意义

为探讨B细胞淋巴瘤／白血病-2（bcl-2）基因及其同源类似物bax基因的表达与肺癌发生的关系,应用免疫组化SP法检测了51例肺癌患者的肺癌标本及其癌旁组织中bcl-2、bax的表达。结果显示,bcl-2在肺癌中染色比在癌旁组织中深,bax在肺癌中染色比在癌旁组织中浅,两者之间均有极显著差异（P＜0.01）;bcl-2、bax表达与肺癌的组织分型、患者的性别、吸烟史、临床分型、分期及淋巴结转移无关（P＞0.05）。提示①bcl-2、bax在肺癌发生中具有重要作用。②在癌前病变组织中检测并比较bcl-2和bax的表达,有利于肺癌的早期诊断。③可通过药物使bcl-2表达降低,促进凋亡,提高患者对放、化疗的敏感性。     

bcl—2蛋白在肝肿瘤组织的表达及意义

目的 探讨抗凋亡基因ｂｃｌ－２蛋白在常见肝肿瘤发生中的作用。方法 应用ｂｃｌ－２癌蛋白单克隆抗体对６４例四种类型的肝恶性肿瘤进行ＬＳＡＢ免疫组织化学标记。结果 １６．２％（６／３７）的肝细胞癌，６９．２％（９／１３）的胆管细胞癌，２０．０％（１／５）的肝母细胞瘤和２２．２％（２／９）肝转移癌呈ｂｃｌ－２癌蛋白阳性表达，其中胆管细胞癌的阳性率显著高于其癌旁组织（Ｐ值〈０．０５）和肝细胞癌（Ｐ值〈０．     

胃粘膜中增殖细胞核抗原及p53,K—ras,bcl—2基因蛋白的表达

为了解胃粘膜癌变过程中多基因蛋白的表达及意义，应用免疫组化技术检测１０７例内镜活检胃粘膜组织中增殖细胞核抗原（ＰＣＮＡ）及ｐ５３、Ｋ－ｒａｓ，ｂｃｌ－２基因蛋白。结果各基因蛋白阳性率随病变程度加重而增加。Ⅲ型肠化生者增殖细胞核抗原标记指数（ＰＣＮＡ ＬＩ）及Ｋ－ｒａｓ、ｂｃｌ－２基因蛋白阳性率较之Ⅰ、Ⅱ型肠化亦有增高趋势但未见统计学差异（Ｐ≥０．０５）。１２例Ⅲ型肠化中有９例出现Ｋ－ｒａｓ和ｂｃｌ     

bcl—2蛋白在原发性肝癌中的表达研究

bcl-2蛋白具有抑制细胞调亡作用，bcl-2蛋白过度表达与肿瘤的发生密切相关．为探讨bcl-2蛋白与原发性肝细胞癌（HCC）发生的关系，我们用免疫组织化学方法观察了不同肝脏疾病组织中bcl-2蛋白的表达情况．材料和方法一、标本收集我院1995年～1997年手术切除存档石蜡包埋标本67例     

病毒性肝炎患者肝组织中bcl-2蛋白的表达

目的探讨抗凋亡基因ｂｃｌ－２蛋白与Ｆａｓ抗原在病毒性肝炎肝组织中表达和分布的关系。方法采用免疫组织化学双标记技术，以ｂｃｌ－２癌蛋白单克隆抗体、抗－ＨＢｓ单克隆抗体及抗－Ｆａｓ多克隆抗体，检测８７例急、慢性肝炎患者肝组织中ｂｃｌ－２、Ｆａｓ及ＨＢｓＡｇ的表达和分布。结果６２例（７１．３％）肝细胞中检出ｂｃｌ－２癌蛋白，阳性物质主要表达于肝细胞胞浆内，少数位于核膜。在急性轻型肝炎，阳性细胞于小叶内弥散分布；在慢性肝炎则多聚集在碎屑样坏死周围。Ｆａｓ抗原的检出率为７５．９％（６６／８７），其阳性细胞的分布类同ｂｃｌ－２阳性肝细胞，但不如后者广泛。ｂｃｌ－２／Ｆａｓ双标记染色显示较多的肝细胞有两种抗原的双表达。结论乙型病毒性肝炎肝组织中ｂｃｌ－２的表达和分布与Ｆａｓ抗原密切相关，ｂｃｌ－２原癌基因可能具有抑制Ｆａｓ介导肝细胞凋亡的作用。     

胃癌前病变不同转归中p53,bcl—2基因的表达以及细胞增？…

目的 探讨ｐ５３、ｂｃｌ－２基因和增殖细胞核抗原（ＰＣＮＡ）等生物学指标在胃癌前病变不同转归中的作用。方法 采用免疫组化（ＬＳＡＢ）法检测５２例胃癌患者胃癌及癌的病变组织标本及５６例非胃癌患者有病变「胃黏膜中度以上肠上皮化生和（或）异型增生」组织标本的ｐ５３、ｂｃｌ－２和ＰＣＮＡ的表达。结果 ⑴在癌前病变中,ｐ５３、ｂｃｌ－２在癌组与非癌组之间的表达差异无显著性（ｐ〉０．０５）,ＰＣＮＡ标记指数（     

白血病细胞p53和bcl—2表达与化疗药诱导凋亡的关系

目的 探索ｐ５３和ｂｃｌ－２表达及化疗药物体外诱导白血病细胞凋亡与患者化疗疗效的关系。方法 用免疫组化法测定４２例急性白血病患者骨髓细胞ｐ５３和ｂｃｌ－２表达水平;用Ｔｃｌ－２表达水平;用ＴｄＴ介导的脱氧核苷酸切口和末端标记法（Ｔｕｎｅｌ法）、Ｗｒｉｇｈｔ－Ｇｉｅｍｓａ梁色及超微结构观察等方法检测化疗药物诱导的白血病细胞凋亡。结果 ４２例急性白血病患者ｐ５３和ｂｃｌ－２总体表达水平显著高于对照组。     

hClock基因mRNA及其蛋白在结直肠肿瘤中表达的研究

目的探讨人类生物钟基因hClockmRNA及其蛋白在不同Dukes分期结直肠肿瘤中的表达,研究它们的表达与结直肠肿瘤的侵袭及转移的关系。方法采用原位杂交检测结直肠癌与相应癌旁组织中hClock基因mRNA的表达,并采用免疫组织化学检测相应标本中hCloek基因蛋白产物（CLOCK蛋白）的表达。结果21例结直肠肿瘤中hCloekmRNA弱阳性表达率47．62％,中或强阳性表达率52．38％,且与Dukes分期相关（P〈0．05）;CLOCK蛋白均呈中或强阳性表达。相应癌旁组织中hClockmRNA及蛋白呈弱阳性表达（P〈0．01）。结论hCloek基因可能与结直肠肿瘤的发生、发展及侵袭、转移有相关性。     

FasL基因的克隆化及其mRNA在肺癌组织中的表达

用植物凝集素激活正常人单核细胞，诱导FasL mRNA表达，提取总RNA，经逆转录多聚酶链反应(RT—PCR)筛选FasL基因片段。定向克隆入质粒pSPTl9，多克隆位点获取重组质粒，经DNA测序后体外转录制备Dig—FasL cRNA探针。收集经病理证实的肺癌及癌周正常肺组织新鲜标本，用液氮速冻，4％多聚甲醛固定。在冰冻切片上以cRNA探针原位杂交进行FasL mRNA表达分布的观察。结果：在鳞癌、腺癌和小细胞肺癌的癌组织及癌旁肺组织中均可检出FasL的杂交信号。镜下见鳞癌组织中FasL的表达水平高于腺癌和小细胞肺癌。     

Clinicopathological significance of Bcl-2 and Bax protein expression in human pancreatic cancer

AIM: To assess the clinicopathological significance of the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. METHODS: Fifty-nine surgical specimens of IDCs of the pancreas were stained immunohistochemically to detect pBcl-2 and pBax expressions whose correlation to tumor classification, staging, and prognosis was analyzed by univariate and multivariate analyses. RESULTS: The expression of pBcl-2 and pBax was detected in 21 of 59 (35.6%) and in 29 of 59 (49.2%) patients with IDCs of the pancreas, respectively. Neither pBcl-2 nor pBax alone was correlated to TIMM staging and differentiation degree of IDCs of the pancreas according to univariate analysis. By Mantel-Cox test, the median survival time after surgery for pBcl-2(+) and pBcl-2(-) groups were 14.3 and 7.3 mo, respectively (x~2=9.357, P=0.002) and that for pBax(+) and pBax(-) groups were 12.9 and 10.2 mo, respectively (x~2=0.285, P＞0.05). Contingency coefficient between pBcl-2 and pBax expression was 0.298, indicating that there was correlation between them (x~2=5.74, P＜0.05). The median survival time after surgery for pBcl-2(+)pBax(+) and pBcl-2(+)pBax(-) groups were 14.3 and 14.1 mo, respectively, and that for pBcl-2 (-)pBax(+) and pBcl-2(-)pBax(-) groups were 5.9 and 9.9 mo, respectively. There was a significant difference between pBd-2(+)pBax(+) and pBd-2(-)pBax(+) (x~2=5.06, P＜0.05), such was the case for pBcl-2(+)pBax(+) and pBd-2(-)pBax(-) (x~ 2=7.18, P＜0.01). Cox proportional hazards model for multivariate analysis was applied, indicating that pBcl-2, TNM staging, age and pBax were high risk factors of post-surgical survival time. CONCLUSION: Both pBcl-2 and pBax have high expression in IDCs of the pancreas, indicating that co-expression of pBcl-2 and pBax is a good indicator of favorable prognosis in IDCs of the pancreas.     

Clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer

AIM: To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. METHODS: To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, and the relationships between the p53 and mdm2 protein expression and clinicopathological parameters in pancreatic cancer. RESULTS: The positive expression of p53 protein was found in 40 of 59 patients (67.8%) and that of mdm2 protein in 17 of 59 patients (28.8%). No obvious relationships were found between p53 as well as mdm2 expression and sex, tumor site,TNM staging and histological differentiation. p53 expression was increased in patients younger than 65 years old, while mdm2 had no relationship with age. The survival time of the patients with the positive expression of p53 and mdm2 proteins was obviously shorter than the other groups. CONCLUSION: Both p53 and mdm2 presented relatively high expression in human pancreatic cancer.The overexpression of p53 and mdm2 might reflect the malignant proliferation of pancreatic cancer and their co-expression might be helpful to evaluate the prognosis of the patients with pancreatic cancer.     

Significance of MUC2 gene methylation detection in pancreatic cancer diagnosis

PurposeThis study was conducted to explore the diagnostic value of MUC2 gene methylation in pancreatic cancer.MethodsMethylation restriction enzyme digestion (Msp I/Hap II) and polymerase chain reaction (PCR) were performed to detect methylation of the MUC2 gene in fecal and blood specimens from seven study subjects with pancreatic cancer (PC), chronic pancreatitis (CP), or normal controls (CON). Simultaneously, blood CA 19-9 levels were detected as a positive indicator of PC.ResultsMUC2 methylation was detected in 50% of PC cell lines. In fecal samples, the MUC2 methylation rate in PC (n = 30) was 43.3%, which was significantly higher than those in CP (n = 8, 0%, P < 0.05) and CON (n = 20, 5.0%, P < 0.05). In blood samples, the MUC2 methylation rate in PC (n = 40) was 52.5%, which was significantly higher than those in CP (n = 15, 0%, P < 0.01) and CON (n = 25, 4.0%, P < 0.01). For PC diagnosis, MUC2 gene methylation in blood samples showed higher specificity and positive predictive value than CA 19-9. The combined detection in the feces and blood showed a 60% MUC2 methylation rate in PC (n = 10), which was higher than those in the CP (n = 5, 0%, P < 0.01) and CON (n = 12, 0%, P < 0.01).ConclusionsThe study can clearly indicate that combined detection of MUC2 gene methylation in the peripheral blood and feces could be used as a new screening and early diagnosis method for pancreatic cancer.     

p57kip2蛋白和增殖细胞核抗原在胰腺癌组织中的表达及其临床意义探讨

目的　探讨细胞周期调控抑制因子 p5 7kip2 蛋白和增殖细胞核抗原 (PCNA)表达在胰腺癌发生发展中的作用及其临床意义。方法　采用免疫组织化学技术SP法 ,检测p5 7kip2 和PC NA在 32例胰腺癌组织和癌旁胰腺组织中的表达情况。结果　p5 7kip2 蛋白阳性表达率在胰腺癌组织中为 46 9% ,显著低于癌旁胰腺组织 (P <0 0 5 ) ,并与胰腺癌组织分化程度有关 (P <0 0 5 )而与淋巴结转移无关 ( χ2 =3 698,P >0 0 5 ) ;PCNA蛋白阳性表达率在胰腺癌组织中为71 9% ,显著高于癌旁胰腺组织 (P <0 0 5 ) ,并与胰腺癌组织分化程度和淋巴结转移均有关 (P<0 0 5 )。结论　p5 7kip2 、PCNA可能与胰腺癌发生、发展密切相关 ;p5 7kip2 蛋白表达降低、PCNA蛋白过度表达有助于胰腺癌的发生及细胞分化程度及预后的判定 ,但 p5 7kip2 蛋白低表达与胰腺癌淋巴结转移无关     

重症肺炎时心肌bcl-2、bax基因表达及相关因素的实验研究

目的 研究重症肺炎的bcl-2基因和bax基因表达及其相关因素。方法 30只大鼠建立金葡菌肺炎模型、20只大鼠作对照,检测大鼠心肌细胞凋亡率、心肌病理积分、心肌细胞bcl-2、bax基因表达、心功能及血清脑钠肽,并分析其相互关系。结果 重症肺炎时心肌心功能降低者bcl-2基因及bax基因表达增加,bcl-2基因及bax基因表达与心肌病理积分、心肌细胞凋亡、脑钠肽呈正相关;bax基因表达与心功能呈负相关;bax基因与上述指标之间的相关性高于bcl-2基因。结论 重症肺炎可并发心衰,其发生机制与bcl-2基因及bax基因过度表达有关。     

IHC和FISH检测胃癌Her-2蛋白表达及基因扩增的比较

目的:对比研究胃癌组织中免疫组织化学法(IHC)检测Her-2蛋白表达和荧光原位杂交法(FISH)检测Her-2基因扩增结果的差异性和相关性,并评估其临床应用价值.方法:采用EliVisionTMplus免疫组织化学染色方法和荧光原位杂交法检测118例胃癌组织中Her-2蛋白表达及Her-2基因扩增状况,并进行对比分析.结果:118例胃癌组织中,IHC检测Her-2蛋白表达(0)40例,(+)33例,(++)16例,(+++)29例,Her-2蛋白过表达率24.6%;FISH检测Her-2基因扩增38例,无扩增80例,Her-2基因扩增率32.2%.40例Her-2蛋白表达为(0)的标本中38例经FISH检测Her-2基因无扩增(95.0%);33例表达为(+)的标本中30例无扩增(90.9%);16例表达为(++)的标本中9例无扩增,7例扩增;29例表达为(+++)的标本中26例扩增(89.7%).结论:Her-2蛋白表达为(0-+)或(+++)时,IHC和FISH检测结果较一致,两种方法总符合率为85.6%,两者呈显著相关(P<0.01),IHC可作为初步筛查胃癌Her-2的首选方法.当Her-2表达为(...