基于在位和异位内膜Bcl-w蛋白表达的子宫内膜异位症机制探讨

目的 探讨凋亡抑制基因Bcl-w在子宫内膜异位症的发生发展中的作用.方法 采用免疫组织化学染色法(SP法)检测凋亡抑制基因Bcl-w分别在正常子宫内膜组织、子宫内膜异位症患者的异位内膜组织和在位内膜组织中的表达水平.结果 Bcl-w在子宫内膜的腺上皮细胞和间质细胞中均有表达,以腺上皮细胞浆中表达明显,偶有细胞膜和细胞核表达.异位子宫内膜组和在位子宫内膜组Bcl-w的表达高于正常子宫内膜组,差异有统计学意义(均P＜ 0.01);Bcl-w在异位子宫内膜组的表达高于在位子宫内膜组,差异有统计学意义(P＜0.05).结论 凋亡抑制基因Bcl-w在子宫内膜异位症的发生发展中起着很重要的作用.     

Bcl-w在大肠癌中的表达及临床意义

目的 检测 Bcl- w 在大肠癌中的表达, 了解 Bcl- w 与临床重要病理因子的关系; 研究 Bcl- w 与Bcl- 2 基因及其 P53 基因的关系; 探讨 Bcl- w 表达对肿瘤细胞凋亡的影响。方法 免疫组化法检测 Bcl- w,Bcl- 2 及其 P53 在大肠癌中的表达; Western blot 进一步定量检测 Bcl- w 在大肠癌中的表达; TUNEL 检测大肠癌中的细胞凋亡情况。结果 全组 52 例病人中, 39 例 Bcl- w 表达阳性, 占 75%。随肿瘤浸润深度增加, 淋巴转移, 肝转移, Bcl- w 表达亦增加。3 年随访中, Bcl- w 表达阳性大肠癌患者均死亡。与 Bcl- 2 相反, Bcl- w 在大肠腺瘤中并不表达。Bcl- w 与 P53 成显著正相关, Bcl- w 与肿瘤细胞凋亡呈显著负相关。结论 Bcl- w 与大肠癌的浸润与转移密切相关。它可能是大肠癌预后相关因素之一。与 Bcl- 2 不同, Bcl- w 在肿瘤进展阶段起重要作用。此外, Bcl-w 在大肠癌细胞中起到抗凋亡作用, P53 基因下调 Bcl- w 的表达。     

中药活性成分雷公藤红素通过抑制Bcl-w的表达逆转宫颈癌细胞的顺铂耐药

目的：研究中药活性成分雷公藤红素是否能逆转耐药宫颈癌细胞株Hela/R对顺铂的耐药性并探讨其机制。方法：采用顺铂梯度暴露法构建顺铂耐药宫颈癌细胞株Hela/R;采用MTT法检测雷公藤红素是否能增强顺铂对Hela/R的杀伤活性;Western blot试验检测常规Hela细胞及Hela/R细胞Bcl-2, Bcl-w及Bcl-xl的表达水平;采用流式细胞术检测雷公藤红素联合顺铂对Hela/R细胞的凋亡诱导效应及对线粒体膜电位的影响。结果：不同浓度顺铂对Hela及Hela/R细胞的细胞活力抑制率如下：1μmol/L顺铂组: 18.6±1.5 (Hela), 1.9±1.0 (Hela/R); 2μmol/L顺铂组: 23.9±2.4 (Hela), 3.1±1.2 (Hela/R); 4μmol/L顺铂组: 47.8±3.9 (Hela), 6.8±1.5 (Hela/R); 8μmol/L顺铂组: 63.4±5.4 (Hela), 11.6±1.8 (Hela/R); 16μmol/L顺铂组: 72.7±5.9 (Hela), 20.4±2.0 (Hela/R); 32μmol/L顺铂组: 85.7±6.7 (Hela), 41.2±3.3 (Hela/R); 64μmol/L顺铂组: 91.8±7.9 (Hela), 55.8±4.3 (Hela/R)。雷公藤红素联合顺铂对Hela/R细胞的细胞活力抑制率如下: 雷公藤红素组: 6.6±1.1; 10μmol/L顺铂组: 12.4±1.2; 20μmol/L顺铂组: 27.8±1.9; 40μmol/L顺铂组: 45.2±3.1; 10μmol/L顺铂+雷公藤红素组: 57.2±3.9; 20μmol/L顺铂+雷公藤红素组: 71.4±5.1; 40μmol/L顺铂+雷公藤红素组: 84.8±6.8。Hela及Hela/R细胞Bcl-2抗凋亡蛋白家族成员的相对表达水平如下: Bcl-2/β-actin: 37.9±1.8 (Hela), 41.4±2.1 (Hela/R); Bcl-xl/β-actin: 32.1±1.9 (Hela), 30.2±1.7 (Hela/R); Bcl-w/β-actin: 22.1±1.3 (Hela), 70.9±4.9 (Hela/R)。雷公藤红素显著增强顺铂对Hela/R细胞线粒体膜电位的损伤,促进细胞色素C的释放,进而诱导Hela/R细胞发生凋亡。结论：雷公藤红素通过抑制Bcl-w的功能促进顺铂对耐药宫颈癌细胞的凋亡诱导效应。     

Bcl-w在肿瘤发生发展中的作用

Bcl-2家族在肿瘤的发生发展中具有重要作用并在很大程度上决定了肿瘤对放化疗的敏感性。研究表明Bcl-w在膀胱癌的发生发展过程中起到重要作用。文章从下游效应和上游调控两个方面对Bcl-w在肿瘤中的研究进展作一综述。     

Effect of massive small bowel resection on the bax/bcl- w ratio and enterocyte apoptosis

Following small bowel resection (SBR), the remnant intestine undergoes adaptation. Enterocyte proliferation is increased and counterbalanced by increased rates of apoptosis. To elucidate a mechanism for increased enterocyte apoptosis, this study tested the hypothesis that the ratio between pro-apoptotic Bax and pro-survival Bcl- w correlates with the apoptosis that occurs following SBR. Mice (C57B1/6; n = 76) underwent a 50% proximal SBR or sham operation. After 12 hours and 1,2,3, and 7 days, the ileum was removed, the apoptotic index (apoptotic bodies/crypt) was recorded, and the messenger RNA and protein for Bax and Bcl-w were quantified. The apoptotic index was equivalent in the sham and SBR mice at 12 hours; however, it was significantly elevated following SBR at every other day measured. The ratio of Bax to Bcl-w messenger RNA relative to sham operation increased after SBR at 24 hours, decreased by day 3, and returned to baseline levels by 1 week. The protein ratio showed an increase by day 1, which remained elevated through day 7. An augmented ratio of Bax to Bcl-w messenger RNA and protein corresponded with the increase in enterocyte apoptosis. Alterations in the expression ratio of these genes may play a role in establishing a new homeostatic set point between proliferation and apoptosis during adaptation. Supported by grants F32 DK09882 (Dr. Stern) and RO-1 DK53234 (Dr. Warner) from the National Institutes of Health and by a grant from the Children’s Hospital Campaign for Children Fund, Children’s Hospital Medical Center, Cincinnati, Ohio. Presented at the Fortieth Annual Meeting of The Society for Surgery of die Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

Bcl-w基因在胃癌中的表达对化疗预后的影响分析

目的探讨Bcl-w（B细胞淋巴因子-w）在胃癌中的表达对化疗和预后的影响。方法通过免疫组化SP法,检测100例人胃癌组织中Bcl-w的表达。结果①100例胃癌中Bcl-w表达的阳性率为69.0%。②胃癌组织中Bcl-w的表达与肿瘤的大小、浸润深度、组织分化程度和淋巴结转移正相关（P〈0.01）。③Bcl-w表达与胃癌的整体生存时间及5年生存率有统计学意义阴性预后好（P〈0.01）;Bcl-w阳性患者中化疗患者与非化疗患者预后无显著差异;Bcl-w阴性者化疗患者预后优于非化疗患者。结论①Bcl-w在抑制胃癌细胞凋亡,促进胃癌侵袭转移中发挥了重要的作用,②Bcl-w在胃癌中的表达与预后负相关,Bcl-w在胃癌中的表达干扰了化疗效果,可作为胃癌预后以及化疗敏感性的评价指标。     

Bcl-w expression in colorectal adenocarcinoma

We have found that the anti-apoptotic Bcl-2 family protein, Bcl-w, was frequently expressed in colorectal adenocarcinomas, with 69/75 showing positive staining with anti-Bcl-w IgG. Adenomas demonstrated a much lower frequency of Bcl-w expression (only 1 of 17), as did adenocarcinomas from other epithelial tissues such as breast (0/8), stomach (1112) and cervix (0/12). Bcl-w status could be related to the histopathological classification of the tumours, with TNM stage III tumours showing significantly higher levels of expression than tumours of better prognostic grade (at P = 0.009). Those patients with node involvement also had tumours with significantly elevated levels of Bcl-w (at P = 0.02), compared to those which were node-negative. The results suggest that Bcl-w could play a general role in the progression from adenoma to adenocarcinoma in the colorectal epithelium. Currently, more data are being collected to allow us to assess the importance of Bcl-w for disease progression and patient survival.     

细胞凋亡在结肠腺癌组织中的变化及其相关蛋白的表达

目的:观察结肠腺癌组织细胞凋亡的变化,探讨抑制凋亡蛋白Bcl-2、Bcl-xL及Bcl-w在结肠腺癌中的作用.方法:收集14例我院手术切除结肠腺癌标本,肠镜取正常结肠黏膜组织27例,所有标本均经病理明确诊断.用TUNEL法检测其组织细胞凋亡水平,并用免疫组织化学PV法检测蛋白Bcl-2、Bcl-xL及Bcl-w的表达水平.结果:正常结肠黏膜组织的细胞凋亡指数明显高于结肠腺癌,有统计学显著性差异(t=3.35,P=0.002);结肠腺癌中Bcl-xL与Bcl-w的表达均高于正常结肠黏膜组织,有统计学差异(92.86% vs 11.11%;85.71% vs 0%,P<0.01或P<0.05);Bcl-2的表达与正常结肠黏膜组织没有统计学差异(P>0.05).结论:结肠腺癌的组织细胞凋亡明显低于正常结肠组织:结肠腺癌中抑制凋亡蛋白Bcl-xL与Bcl-w的高表达可能发挥了重要的作用.     

miR-20 b对大肠癌细胞增殖和凋亡的影响及其机制的研究

目的：探讨miR-20b对大肠癌（ CRC）细胞增殖凋亡的影响及机制。方法将miR-20b模拟物转染CRC细胞株HCT-116,qRT-PCR检测转染后miR-20b的表达,分别应用CCK-8实验及流式细胞仪检测转染后细胞增殖和凋亡情况。 qRT-PCR和western blot检测转染后Bcl-w mRNA和蛋白的表达情况。结果转染miR-20b模拟物后,HCT-116细胞中miR-20b表达水平明显上调,HCT-116细胞增殖减弱（P＜0．05）,凋亡增强（P＜0．05）。 miR-20b可作用于Bcl-w mRNA的3′-UTR,使海肾荧光素酶活性显著降低。转染后Bcl-w mRNA及蛋白表达水平明显下调,差异均有统计学意义（P＜0．05）。结论上调HCT-116细胞中miR-20b表达水平,可抑制其靶基因Bcl-w的表达,发挥抑制细胞增殖、增加凋亡的作用。     

Bcl-w基因在胃癌中的表达和临床病理因素的关系

目的 探讨B细胞淋巴因子-w(Bcl-w)在胃癌中的表达与预后的关系.方法 通过免疫组化SP法,检测100例胃癌组织中Bcl-w和MMP-2(基质金属蛋白-2)的表达.结果 (1)100例胃癌中Bcl-w和MMP-2表达的阳性率分别为69.0%、77.0%;(2)胃癌组织中Bcl-w和MMP-2的表达与肿瘤的大小、浸润...