Bax，Bcl-2在非小细胞肺癌中的表达相关性研究

目的 研究Bax，Bel-2在人类非小细胞肺癌中的表达及其相关性。方法 应用免疫组织化学（S—P法）检测80例非小细胞肺癌组织标本和40例肺良性病变组织中Bax，Bcl-2的表达水平。结果 ①非小细胞肺癌组织中Bax，Bel-2表达水平分别为63．8％，51．2％，二者表达均与组织学类型无关；②Bax，Bel-2在非小细胞肺癌中表达呈负相关。结论 Bax，Bel-2共同参与细胞凋亡，促进非小细胞肺癌的发生发展。     

过敏康Ⅱ号胶囊对AsAb阳性大鼠睾丸Bcl-2、Bax表达影响的实验研究

目的观察过敏康Ⅱ号胶囊对AsAb阳性大鼠睾丸Bcl-2、Bax表达的影响。方法选取健康成年雄性SD大鼠60只，按体重随机分为正常组，模型组，对照组，高、中、低剂量组，每组10只。采用主动免疫法建立血清抗精子抗体（AsAb）阳性动物模型10只，灌胃给药，免疫组化方法观察药物对AsAb阳性大鼠睾丸Bcl-2、Bax表达的影响。结果过敏康Ⅱ号高剂量组睾丸生精细胞和精子Bcl-2表达的平均吸光值显著高于模型组（P〈0．01），而Bax表达的平均吸光值显著低于模型组（P〈0．01）。结论调节睾丸Bcl-2、Bax的表达是过敏康Ⅱ号清除或抑制AsAb起治疗作用的机制之一。     

Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF

Macrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L) because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2 occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent pathway.     

IL-13对小鼠哮喘模型气道黏蛋白基因Muc5ac及Bcl-2、Bax表达的作用

目的研究白细胞介素-13(IL-13)处理小鼠支气管哮喘(哮喘)模型前后肺组织黏蛋白基因Muc5ac、凋亡相关蛋白Bcl-2和Bax表达的作用,探讨气道黏液过度分泌的机制.方法45只雄性BALB/c小鼠随机分为对照组、哮喘组和IL-13组,每组15只.用逆转录-聚合酶链反应(RT-PCR)方法和免疫组化法分别检测Muc5acmRNA、Muc5ac蛋白、Bcl-2蛋白以及Bax蛋白在肺组织的表达.结果哮喘组和对照组肺组织Muc5acmRNA分别为(0.1552±0.0057)和(0.0633±0.0013),Muc5ac蛋白分别为(0.8849±0.0257)和(0.1166±0.0064),两组比较差异均有统计学意义(P<0.01);IL-13组肺组织Muc5acmRNA和蛋白分别为(0.2807±0.0027)和(1.6138±0.0483),与哮喘组、对照组比较差异也均有统计学意义(P均<0.01).与对照组Bcl-2蛋白(0.3279±0.0136)、Bax蛋白(1.7284±0.0263)相比,哮喘组分别增加和降低(分别为0.8383±0.0310和0.8987±0.0106),两组差异均有统计学意义(P均<0.01);IL-13处理后可分别促进Bcl-2和Bax蛋白增加和降低(分别为1.6934±0.0229和0.3522±0.0152),其和哮喘组的差异均有统计学意义(P均<0.01);哮喘组和IL-13组小鼠肺组织Muc5acmRNA、蛋白表达与Bcl-2蛋白表达均呈直线正相关(P均<0.05),而与Bax蛋白表达则均呈直线负相关(P均<0.05).结论IL-13是引起哮喘气道黏液过度分泌的重要细胞因子,它可能通过改变Bcl-2和Bax的表达导致了上述病变.     

Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma

The regulation of apoptosis in atherosclerosis is not completely defined. The aim of this study was to determine the expression of Bcl-2, Bcl-x, Bax, and Bak in relation to apoptosis in advanced atherosclerotic lesions. In atherectomy (15), endarterectomy (10), and control non-atherosclerotic segments of renal (2) and of coronary and carotid (5) arteries, the extent of apoptosis was determined using TdT dUTP nick end labelling (TUNEL) and nuclear morphology (karyorrhexis/pyknosis) and expression of apoptosis regulators by immunohistochemistry and western blot analysis on paraffin-embedded material. In all specimens, the atherosclerotic involvement was advanced: grade V (n=18) and grade VI (n=7). The apoptotic index was high (mean 30%) in advanced lesions compared with controls (<2%) and smooth muscle cells (SMCs) were the predominant cell type undergoing apoptosis. In all TUNEL-positive apoptotic cells, Bax and Bak were present, while Bcl-x was absent. Bcl-2 was absent in a majority of these cells, but occasional TUNEL-positive cells expressed Bcl-2. In non-apoptotic cells, Bcl-x was present and western blot detected only the long isoform, Bcl-xL, from the plaques. In conclusion, increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. Bcl-xL in non-apoptotic cells appears to contribute to prolonged cell survival.     

Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility

Apoptosis has been shown to be an important regulator of endometrial function during the menstrual cycle and implantation. Recently, some possible implantation defects were identified in patients with unexplained infertility. In this study, we investigated the role of spontaneous apoptosis, which is regulated by death regulatory genes, such as Bcl-2, Bax, p53, and isoenzymes of nitric oxide synthases; eNOS and iNOS during the implantation window in women with unexplained infertility. Endometrial samples were evaluated from fertile (n=15) and unexplained-infertile women (n=15) during post-ovulatory 7th or 8th day of their menstrual cycles. Apoptotic cells were detected using the dUTP nick-end labelling assay and Bcl-2, Bax, p53, iNOS and eNOS were assessed immunohistochemically. Reduced apoptotic cells, weak immunoreactivity of p53 and strong immunoreactivity of Bcl-2 were observed in the unexplained-infertile group compared with the fertile group (p<0.001). Bax intensity was similar in both groups. While weak iNOS immunoreactivity was detected in both groups, moderately increased eNOS immunoreactivity was observed in infertile cases. Spontaneous apoptosis is reduced in the endometrium of unexplained-infertile women, and is associated with the changed Bcl-2:Bax ratio. This finding may be a contributing factor to defective implantation causing infertility in this group of patients.     

The role of Bcl-2 family members in the progression of cutaneous melanoma

The overwhelming problem of cutaneous melanoma is chemoresistance. Subversion of the biochemical changes that lead to chemoresistance intersects the apoptosis pathways. The mitochondrion has been a focal point of this intersection for the development of therapeutic strategies aimed at reducing the progression of melanoma. The Bcl-2 family of apoptotic regulators is arguably the most pivotal component to this mitochondrial response. The shear number of studies conducted on the relationship between melanoma and Bcl-2 members prompted us to evaluate the literature available and discern some rational utility of the data. We have found that there are striking inconsistencies for the expression of Bcl-2 family proteins with melanoma progression, particularly for Bcl-2. Roughly one-third of the data suggests an increase in Bcl-2 expression with advancing melanoma, while another third suggests a decrease. Furthermore, the remaining third found on the whole, a detectable level of Bcl-2 in all tissues of melanocytic origin. These discrepancies are difficult to rectify in light of the apparent success of recent clinical trials utilizing Bcl-2 antisense strategies. The general consensus in the literature is that pro-apoptotic Bax is decreased with melanoma progression while anti-apoptotic Bcl-x_L and Mcl-1 appear to increase with progression. We suggest that the biochemical techniques being used for analysis present too great of a heterogeneity, which could be mitigated with more standard procedures and reagents. Finally the utility of ‘multi-specific’ antisense tactics could be a more effective way of targeting advanced melanoma disease. This revised version was published online in July 2006 with corrections to the Cover Date.     

舌癌术前化疗PCNA、bcl-2、Bax基因表达及临床意义

目的 :通过舌癌术前化疗增殖细胞核抗原 (PCNA )和细胞凋亡相关基因 bcl- 2、Bax表达的研究 ,探讨舌癌的化疗作用机制。 方法 :对舌乳头状瘤、舌癌和舌癌术前化疗标本共 34例 ,采用免疫组织化学染色技术——酶标链亲和素生物素法 (L SAB)染色并进行光镜下观察。结果:PCNA在舌癌中的表达最强 ,在舌癌术前化疗中的表达明显减弱 (P <0 .0 5 ) ,其与舌乳头状瘤表达相似 (P >0 .0 5 )。 bcl- 2在舌癌术前化疗及舌乳头状瘤中低表达(P >0 .0 5 ) ,舌癌中表达明显增强 (P <0 .0 5 )。Bax在舌癌组和乳头状瘤组中表达有明显差异 (P <0 .0 5 )。结论 :化疗药物抑制肿瘤生长的机制可能与抑制肿瘤细胞增殖和诱导肿瘤细胞程序性死亡有关 ,提示舌癌术前化疗对肿瘤的预后有重要意义。     

血管紧张素Ⅱ上调BaX表达诱导人内皮细胞凋亡

为了研究血管紧张素Ⅱ(AngⅡ)诱导凋亡的机制,将人脐静脉内皮细胞培养至第3代,用不同浓度Ang Ⅱ培养不同时间,用TUNEL检测细胞凋亡.Bax和Bcl-2蛋白表达用Western Blot和图像分析法测定.结果发现Ang Ⅱ组的凋亡阳性率极显著高于对照组;Bax的表达极显著地升高且具有时间和剂量依赖性,Bcl-2无显著变化,Bax/Bcl-2比值极显著地增加.提示AngⅡ通过诱导Bax的高表达,致Bax/Bcl-2比值极显著地增加而诱发凋亡.     

喉癌组织Bc1-2和Bax基因蛋白表达及其临床相关性研究

目的　探讨喉癌组织Bc1 2和Bax基因蛋白表达与喉癌发生、发展的关系。方法　采用免疫组化SP法测定 5例正常人声带组织和 73例喉癌组织标本中Bc1 2和Bax基因蛋白表达。结果　喉癌组织中Bc1 2基因蛋白表达阳性检出率 45 .2 % ,喉癌组织中Bax基因蛋白达阳性检出率 6 0 .3% ,与正常人相比 ,均无显著性差异 (P >0 .0 5 )。喉癌组织中Bc1 2及Bax基因蛋白的表达呈明显的负相关关系 ,r值 - 0 .71,P <0 .0 5。结论　喉癌组织中Bc1 2和Bax基因蛋白表达的失调可能与喉癌的发生、发展有关。