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.     

宫内胎肝细胞移植形成血小板GPⅡb Bak a/b嵌合体的研究

目的　探讨宫内胎肝细胞移植是否形成人工血小板杂合子嵌合体 ,评估其在治疗血小板无力症的临床应用前景。方法　选择血小板膜GPⅡbBaka/b(GPⅡb异亮氨酸 84 3丝氨酸多态性 )作为遗传标记 ,采用等位基因特异引物PCR和FOKⅠ限制性内切酶消化技术从 4 2名引产妇筛选一例纯合子GPⅡbBaka/a作为供者 ,一例纯合子GPⅡbBakb/b作为受者 ,制备供者胎肝细胞 ,取 4ml(2 2× 10 5细胞 )在B超引导下通过脐静脉穿刺输给受者。结果　移植后 2 1天 ,用PCR FOKⅠ消化技术检测引产后受者外周血DNA和血小板RNA ,发现已形成Baka/b嵌合体。结论　我们认为宫内胎肝细胞移植可能提供一种治疗血小板无力症和其他遗传性疾病的方法。     

1993～2001年永州市零陵区世界银行贷款结核病控制项目工作效果评价

目的对永州市零陵区世界银行贷款结核病控制项目工作效果进行评价,为制定零陵区结核病控制对策提供依据。方法利用1993～2001年项目工作资料进行总结分析。结果9年间共接诊疑似肺结核症状者9766例,发现活动性结核病人2628例,其中涂阳病人1351例,涂阳病人登记率26.5/10万。初治涂阳病人治愈率为92.06%,复治涂阳病人治愈率为85.00%。结论结控项目的病人发现和治疗效果显著,但如何提高疑似肺结核症状者就诊率是当前急需解决的主要问题。     

Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells

ObjectiveThe mimetic BH3 ABT-737, a potent inhibitor of anti-apoptotic Bcl-2 family proteins, has potential as anti-cancer drug in many cancers. Recently, patients treated with ABT-737 have developed drug tolerance during cancer therapy. Therefore, we examined whether ABT-737 is effective in killing MC-3 and HSC-3 human oral cancer cells either alone or in combination with the oncogenic kinase inhibitor, sorafenib.DesignThe potentiating activities of sorafenib in ABT-737-induced apoptosis were determined using trypan blue exclusion assay, DAPI staining, cell viability assay and Western blot analysis.ResultsCombined use of ABT-737 and sorafenib synergistically suppressed cell viability and induced apoptosis compared with either compound individually. The combination of ABT-737 and sorafenib altered only Bax and Bak proteins and their activations, resulting in mitochondrial translocation of Bax from the cytosol. Additionally, combination treatment-mediated apoptosis may be correlated with ERK and STAT3 pathways.ConclusionsThese results suggest that sorafenib may effectively overcome ABT-737 resistance to apoptotic cell death, which can be a new potential chemotherapeutic strategy against human oral cancer.     

MOMP in the absence of BH3-only proteins

The minimum requirement for mitochondrial apoptosis has been controversial ever since the discovery of BCL-2 as a cell death regulator. In this issue of Genes & Development, O''Neill and colleagues (pp. 973–988) end a long-standing debate by creating a cellular system free of BCL-2 family proteins, thereby identifying the outer mitochondrial membrane rather than BH3-only proteins as the only requirement for BAX/BAK activation and mitochondrial outer membrane permeabilization (MOMP).     

miR-125b�Զ�ͯ���ͼ���������ϸ����Ѫ����Ӱ��

??Abstract??Objective To explore the role of miR-125b in pediatric classical APL?? in order to seek new therapeutic strategies for drug resistant APL. Methods The target genes of miR-125b were predicted online?? validated by Dual-luciferase assay and western blot assay. MiR-125b expression levels were measured in 33 matched-pair APL samples??treated in the First Affiliated Hospital of Sun Yat-sen University and other members of South China Children APL Cooperative Group from March 2007 to September2012??at initial diagnosis and complete remission ??CR?? and in 5 relapsed patients by qRT-PCR. Proliferation and apoptosis were analyzed respectively using the RNA transfection?? MTT assay and flow cytometry. Results The expression of miR-125b was up-regulated in pediatric APL at diagnosis and relapse bone marrow samples?? but returned to normal after complete remission?? miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor Bak1. Remarkably??it was also found to be up-regulated in leukemic drug-resistant cells??NB4-R1??NB4-R2??HL-60/DOX???? and overexpression of exogenous miR-125b could increase their resistance to therapeutic drugs. Conclusion MiR-125b can regulate pediatric classical APL cells proliferation?? apoptosis and drug resistance by repressing BAK1 protein expression.     

Bak和Bcl-xl在豚鼠形觉剥夺性近视眼视网膜的表达及凋亡

目的 观察豚鼠形觉剥夺性近视视网膜变性中细胞凋亡,及Bak和Bcl-xl蛋白在视网膜细胞中的表达.方法 将出生3天的豚鼠40只,单眼半透明眼罩遮盖,对则眼不做任何处理为对照.随机分为A组(遮盖8周)和B组(遮盖12周),分别于实验前及实验后行检影验光、A超测量眼轴,摘出眼球,用TUNEL技术检测视网膜细胞凋亡情况,用免疫组化法分析Bak和Bcl-xl蛋白表达水平.结果 遮盖眼均较对照眼屈光度加深,眼轴延长,且随遮盖时间的延长而增长.TUNEL标记显示A组及B组遮盖眼视网膜内、外核层均发现凋亡细胞,两者凋亡率分别为(0.27±0.14)%和(2.33±0.37)%,差别有统计学意义(P＜0.05).遮盖眼Bak表达均较对照眼增高,且Bak在B组遮盖眼视网膜的表达较A组高,两者差别有统计学意义(P＜0.05);Bcl-xl的表达在遮盖眼及对照眼之间无明显差别(P＞0.05).A组、B组遮盖眼视网膜细胞的Bak表达与视网膜细胞凋亡率的相关系数r值分别为0.79、0.84(P＜0.05),与Bcl-xl的r值分别为-0.37、-0.31(P＞0.05).结论 凋亡是豚鼠形觉剥夺性近视视网膜细胞变性的机制之一,Bak的高表达可能与形觉剥夺性近视视网膜细胞凋亡有关.     

吸烟的慢性阻塞性肺病患者外周血中性粒细胞Bak mRNA的表达

 目的 探讨吸烟的慢性阻塞性肺病（chronic obstructive pulmonary disease,COPD）患者外周血Bak基因表达异常及其与COPD发病的关系。方法 入选者包括健康对照组（不吸烟者10例、吸烟者14例）和轻中度吸烟COPD患者9例。使用Percoll非连续密度梯度沉降法分离人外周血中性粒细胞,使用real-time PCR来检测外周血中性粒细胞中Bak mRNA的表达水平。结果 相对于健康对照组,轻中度COPD患者外周血中性粒细胞中的Bak mRNA水平（0.88±0.38）明显降低,差异有统计学意义（P<0.05）;吸烟健康者外周血中性粒细胞中Bak mRNA水平（1.23±0.29）低于不吸烟健康者（1.33±0.38）,但差异无统计学意义;Bak mRNA水平与FEV1/预计值%、FEV1/FVC%均呈正相关,相关系数r分别为0.438 8（P<0.05）和0.432 1（P<0.05）。结论 Bak基因表达异常可能与COPD发病有一定关系。Bak mRNA水平与临床肺功能之间有明显相关性,推测可能与COPD的严重程度相关。     

肾上腺嗜铬细胞瘤凋亡相关基因bak蛋白表达的意义

目的：探讨凋亡相关基因ｂａｋ在人肾上腺嗜铬细胞瘤中的表达及其对肿瘤发生的意义。方法：应用免疫组织化学的ＳＡＢＣ方法,和兔抗人Ｂａｋ了隆抗体,对２３例肾上腺嗜铬瘤（其中良属于 １８例,恶笥５例）和１０例正常肾上腺组织进行了检测。结果：Ｂａｋ在 腺髓质中不表达,而在良恶笥嗜铬细胞瘤中表达,阳怀率分别为８９％和４０％,在良性肿瘤中Ｂａｋ表达显著强于恶性肿瘤。结论：Ｂａｋ不同程度地参与了良恶性嗜铬细胞中的     

Anti-inflammatory and anti-apoptotic effects of strawberry and mulberry fruit polysaccharides on lipopolysaccharide-stimulated macrophages through modulating pro-/anti-inflammatory cytokines secretion and Bcl-2/Bak protein ratio

This study is the first to isolate strawberry (SP) and mulberry fruit polysaccharides (MP) and assess their anti-inflammatory and anti-apoptotic activities using lipopolysaccharide (LPS)-stimulated mouse primary macrophages. Pro-/anti-inflammatory cytokine levels secreted by LPS-stimulated macrophages cultured with SP and MP for 48 h were determined using ELISA method to evaluate anti-inflammatory effects of SP and MP. The Bcl-2/Bak (anti-/pro-apoptotic) protein levels in the cells were determined using Western blotting method to evaluate anti-apoptotic effects of SP and MP. The results showed that the maximum absorption peak of SP and MP appeared at 240 nm with a small shoulder around 280 ∼ 310 nm, suggesting that SP and MP might be glycoproteins. SP- and MP-treatment significantly (P < 0.05) decreased pro-inflammatory cytokines including interleukin (IL)-1β and IL-6, whereas the anti-inflammatory cytokine IL-10 was markedly increased, suggesting that SP and MP have anti-inflammation potential via modulating pro-/anti-inflammatory cytokine secretion profiles. Both SP and MP modulated Bak and Bcl-2 protein levels in the cells, suggesting that the SP and MP protected LPS-stimulated macrophages from apoptotic cell death. A negative correlation between cytokine secretion levels and Bcl-2 protein levels suggested that pro-inflammatory IL-1β and IL-6 cytokines decreased Bcl-2 levels in the LPS-stimulated macrophages.