转bak基因促膀胱癌多药耐药细胞凋亡的研究(英文)

目的观察转入 bak 基因对膀胱癌多药耐药(MDR)细胞的杀伤效果,探讨其可能的机制。方法用脂质体将 bak 基因导入 MDR 细胞,通过原位杂交法检测 bak mRNA 的表达,同时用 SABC 免疫组化法分析 bak 和 Bcl-2的表达。采用细胞计数法检测细胞生长抑制率,流式细胞仪检测细胞周期的变化。荧光染色观察细胞形态。结果转入 bak 基因后,MDR 细胞的生长明显受抑制(P<0.05)。细胞周期分析可见凋亡峰,凋亡率35%。细胞中可见 bak 阳性表达(P<0.05),Bck-2表达显著减少(P<0.05)。凋亡细胞在荧光显做镜下形成凋亡小体。结论转入 bak 基因可显著促进 MDR 细胞的凋亡,其作用机制与下调 Bcl-2基因的表达有关。     

bak基因过表达对阿霉素杀伤诱导EJ细胞凋亡的增敏作用

目的目的：探讨bak基因过度表达在膀胱癌EJ细胞凋亡途径中的作用以及对阿霉素的可能的增敏作用，并研究其作用机制。方法用脂质体法，膀胱癌细胞中转入bak／pcDNA3的设为实验组，空转pcDNA3的设为对照组，用原位杂交法检测bak在癌细胞中的表达，同时用阿霉素处理后，利用MTT法测出细胞生存率，进而用荧光分光光度计检测细胞内阿霉素的聚集量。比色法检测癌细胞内Caspase-3活性改变。结果脂质体法转基因后，bak的mRNA呈阳性表达，细胞生存率较对照组明显降低（P〈O．05）。癌细胞Caspase-3活性增强（P〈O．05），细胞内阿霉素聚集量元明显增加（P〉O．05）。结论bak基因对阿霉素杀伤膀胱癌细胞具有增敏作用，但并非通过帮助阿霉索进入细胞发挥作用，其作用机制与激活Caspase-3有关。     

开口箭提取物对结肠炎大鼠血小板活性的影响

[目的]研究中药开口箭有效成分对实验性结肠炎大鼠血小板活性的影响.[方法]建立三硝基苯磺酸大鼠结肠炎模型,用开口箭醇提物(主要成分为甾体皂苷)灌肠治疗2周后评价大鼠血小板表面P-选择素以及血小板聚集率改变.[结果]治疗组与模型组比较,血小板聚集率和血小板表面P-选择素下降(P＜0.05).[结论]开口箭醇提物可以抑制血小板的聚集与活化.     

Accelerated apoptosis and low Bcl-2 expression associated with neuroendocrine differentiation predict shortened survival in operated large cell carcinoma of the lung

In order to test the hypothesis that increased apoptotic activity is connected with neuroendocrine differentiation and low differentiation degree in large cell carcinoma (LCLC) and is regulated by bcl-2 family proteins, we analysed the extent of apoptosis and tumor necrosis and their relation to the expression of bcl-2, bax, bak and mcl-1 in 35 LCLCs, of which 20 were classified as large cell neuroendocrine lung carcinomas (LCNEC) and 15 as large cell non-neuroendocrine lung carcinomas (LCNNEC). The extent of apoptosis was determined by detecting and counting the relative and absolute numbers of apoptotic cells and bodies using in situ 3′-end labelling of the apoptotic DNA. The extent and intensity of expression of the bcl-2, bax, bak and mcl-1 proteins were studied by immunohistochemistry. Also the relative volume density of necrosis was evaluated and correlated with the other parameters. Finally, all the parameters were evaluated as prognostic markers and correlated with data on the survival of the patients. Relatively high apoptotic indices were seen in both tumor types (average for both 2.53%, range 0.09–27.01%). Significantly higher bcl-2 and bak indices were detected more often in LCNECs than in LCNNECs. Immunohistochemically detected bax, bcl-2 and bak expression was independent of apoptotic index in both tumor types, while there was a statistically significant positive association between mcl-1 expression and apoptotic index in LCNNEC but not in LCNEC. There was a statistically significant association between high apoptotic index and shortened survival in LCLC. However, no association was found between tumor stage and apoptosis. The patients with LCNEC and low bcl-2 protein expression had a significantly shorter survival time than those with high bcl-2 indices. There was also a clear association between shortened survival and necrotic LCNNEC. LCLCs show relatively high apoptotic activity, which is associated with shortened survival. The expression of bcl-2, bak and mcl-1 is associated with neuroendocrine differentiation in LCLC. Finally, our results support some previous reports suggesting that bcl-2 expression in combination with some other markers involved in apoptosis and/or proliferation may be of prognostic value in cases of lung carcinoma with neuroendocrine differentiation. 179-186, 1999)     

Two relatively distinct patterns of ameloblastoma: an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre)

AIMS: This study was performed to determine the apoptotic behaviour of ameloblastomas by analysing the role of bcl-2 family proteins in ameloblastomas and the location of terminally apoptotic cells in the ameloblastoma epithelial tissues. METHODS AND RESULTS: For immunohistochemistry, tissue sections of 32 patients were treated with an antigen-retrieval METHOD: Primary antibodies against the apoptosis-related proteins, bcl-2, bcl-X, bax, and bak were applied. Besides immunohistochemistry, Western blotting and TUNEL were also performed. Most of the outer layer cells were predominantly stained by the bcl-2 antibody, while most of the inner layer cells were stained by antibodies against the apoptosis-modulating proteins, bax and bak. Among the bcl-2 family, bcl-2 was the most ubiquitously expressed protein in ameloblastomas, while bcl-X was expressed in the greatest concentrations. The major bcl-X protein was bcl-XL. Some of the inner layer cells entered the terminal apoptotic stage, which were revealed by TUNEL. The acanthomatous areas over-expressed the apoptosis-modulating proteins, especially bak. CONCLUSIONS: Ameloblastoma has much more apoptosis-inhibiting protein than the apoptosis-modulating protein. Ameloblastoma has two relatively distinct patterns, an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre). The acanthomatous area, which was stained strongly by bak antibody and contained numerous terminally apoptotic cells, was considered as the differentiated area.     

乳腺浸润性导管癌bak基因的表达及意义

目的 研究细胞凋亡相关基因bak在乳腺浸润性导管癌（invasive ductal carcinoma；IDC）组织中的表达，探讨bak基因在IDC发生演变过程中的意义。方法 采用原位分子杂交技术检测46例IDC组织中bak mRNA的分布及表达。结果bakmRNA的检出率：46例IDC组织为58．7％（27／46），癌旁组织为53．3％（9／16）；在癌组织与癌旁组织中，bak基因表达无显著差异（P〉0．05）；但在IDC中，bak mRNA的表达Ⅱ级组织强于Ⅲ级组织（P〈0．05）。结论 bak mRNA表达可能与IDC的分化程度有关。     

促凋亡基因bak在星形细胞瘤中的表达与意义

目的;研究凋亡基因ｂａｋ在星形细胞瘤（Ａｓｔｒｏｃｙｔｏｍａ）中的表达与意义。方法;采用兔抗人Ｂａｋ多克隆抗体及免疫组织化学ＳＡＢＣ法。结果：在６６例星形细胞瘤中,Ｂａｋ表达３９例（５９．１％）;１０例用于对照的正常脑组织中,Ｂａｋ阳性仅１例（１０）％,ｂａｋ在星形细胞瘤中的表达强于正常对照组,ｂａｋ在Ⅰ,Ⅱ,Ⅲ,Ⅳ级星形细胞瘤相互之间表达无显差异,但在３１例低恶性星形细胞瘤（ＷＨＯⅠ级－Ⅱ级）     

转bak基因促膀胱癌多药耐药细胞凋亡的研究

目的 观察转入bak基因对膀胱癌多药耐药(MDR)细胞的杀伤效果,探讨其可能的机制。方法 用脂质体将bak基因导入MDR细胞,通过原位杂交法检测bak mRNA的表达,同时用SABC免疫组化法分析bak和Bcl-2的表达。采用细胞计数法检测细胞生长抑制率,流式细胞仪检测细胞周期的变化。荧光染色观察细胞形态。结果转入bak基因后,MDR细胞的生长明显受抑制(P<0.05)。细胞周期分析可见凋亡峰,凋亡率35％。细胞中可见bak阳性表达(P<0.05),Bcl-2表达显著减少(P<0.05)。凋亡细胞在荧光显微镜下形成凋亡小体。结论 转入bak基因可显著促进MDR细胞的凋亡,其作用机制与下调Bcl-2基因的表达有关。     

幽门螺杆菌对胃上皮细胞的凋亡作用

目的 研究幽门螺杆菌(Hp)对胃黏膜上皮细胞的凋亡作用。方法 10例Hp阴性的非溃疡性消化不良(NUD)患者,25例Hp相关性胃炎患者,以TUNEL法进行细胞凋亡的检测,免疫组织化学法检测凋亡调控蛋白Bcl-2,Bax,Bak等的表达。结果 与Hp阴性的NUD患者相比,Hp相关性胃炎患者胃黏膜上皮细胞的凋亡指数(AI)明显增加(19.66％vs 3.03％,P＜0.01),其促凋亡蛋白Bak,Bax蛋白的表达明显增加(47.07％ vs 16.63％ ＆ 42.6％ vs 13.8％,P＜0.01)。Bcl-2蛋白表达也与促凋亡蛋白呈现一致的变化(25.1％ vs 8.07％,P＜0.01)。AI与炎症积分无明显相关性(P＞0.05)。AI、Bak、Bax及Bcl-2蛋白之间具有显著相关性(P＜0.01)。结论 Hp诱导胃上皮细胞凋亡伴随着Bak蛋白表达增加,提示Bak蛋白在Hp诱导的胃上皮细胞凋亡中起了作用。     

凋亡相关基因蛋白bcl-xl和bak在肺鳞癌中的表达及意义

目的:探讨肺鳞状细胞癌中凋亡调控因子bcl-xl和bak蛋白的表达及其意义.方法:采用免疫组织化学技术检测50例肺鳞状细胞癌及20例正常肺组织中 bcl-xl和bak蛋白的表达水平.结果:bcl-xl蛋白在肺鳞状细胞癌中表达水平高于正常肺组织(P＜0.05) .bak表达水平低于正常肺组织(P＜0.05). bcl-xl和bak蛋白的表达水平在不同分化程度的肺癌之间差异有显著意义(P＜0.05) .结论:肺鳞状细胞癌的发生、发展与bcl-xl和bak蛋白的异常表达有关,可能是细胞凋亡失衡的结果.