Smac/DIABLO过表达对人结肠癌细胞凋亡的影响

Smac／DIABLO是一种线粒体促凋亡蛋白，研究表明其在结肠癌细胞中表达降低。目的：研究Smac／DIABLO对人结肠癌细胞生长的影响及其可能的促凋亡机制。方法：将pcDNA3.1-Smac质粒或pcDNA3.1空质粒以脂质体转染人人结肠癌细胞株LoVo,以未转染细胞作为空白对照。以逆转录聚合酶链反应（RT-PCR）检测Smac mRNA表达，蛋白质印迹法检测Smac蛋白表达，Hoechst33258染色观察凋亡细胞核形态学变化，Annexin V-FITC／PI双染流式细胞仪分析检测细胞凋亡率,PI染色流式细胞仪分析检测细胞周期。Caspase-3分光光度法检测试剂盒检测Caspase-3活性。结果：pcDNA3.1-Smac质粒转染12h后，kVo细胞Smac mRNA表达增加；转染48h后，Smac蛋白表达增加。转染48h后,Smac组LoVo细胞呈现明显凋亡细胞核形态学特征。凋亡率显著高于hVo细胞组和空质粒组，GO／G1期细胞增多,Caspase-3活性亦显著高于空质粒组（P〈0．05）。结论：Smac／DIABLO可激活caspase-3途径，抑制人结肠癌细胞生长,促进细胞凋亡。使细胞周期阻滞于G0／G1期。     

替罗非班对发病6～12h急性ST段抬高型心肌梗死患者急诊PCI中无再流的作用

目的:探讨血小板Ⅱb/Ⅲa受体拮抗剂替罗非班对发病6～12 h的急性ST段抬高型心肌梗死(STEMI)患者急诊经皮冠状动脉介入治疗(PCI)后无再流的影响. 方法:将症状发生至急诊PCI 6～12 h的STEMI患者随机分为替罗非班组(50例)和对照组(50例).记录两组基础临床情况、PCI后无再流、心力衰竭、住院期间及术后180d主要心脏不良事件(MACE),包括死亡再梗死再次靶血管重建的发生率.结果:两组梗死相关动脉(IRA)PCI后TIMI 3级血流发生无显著差异.与对照组相比,替罗非班组PCI前IRA TIMI 3级血流、术后梗死区心肌灌注分级(TMP)3级明显增加,无再流发生率降低(P<0.05).心力衰竭减少27.4%,住院期间MACE发生率相似,但于术后180 d降低10.85%(P<0.05). 结论:急诊PCI联合替罗非班治疗发病6～12 h的STEMI患者,可进一步减少无再流发生,提高心肌灌注,并改善临床预后.     

CagA与幽门螺杆菌致病的相关性研究

本文调查了114例胃镜受检者的 Hp 感染率,应用血清 ELISA 技术检测了 Hp 菌株中 CagA 阳性数,并对该蛋白与慢性胃病的关系进行了初步分析。结果发现54例中 Hp 阳性者,CagA 阳性25例;阳性率46.3%;胃炎、十二指肠溃疡和胃癌组织 CagA 阳性率分别为27.3%,71.4%和85.7%(P<0.01)。CagA 阳性菌株感染者胃粘膜的炎症程度、活动度及萎缩、肠化与淋巴滤泡形成数均高于阴性者。证实了 CagA 在 Hp 致病中的重要作用。     

凝血酶活化的富血小板血浆促进人骨髓间充质干细胞增殖

目的探索凝血酶活化的富血小板血浆(Thrombin-activated platelet-rich plasma,tPRP)替代牛血清,进行人骨髓间充质干细胞(Mesenchymal stme cells,MSC)分离及培养扩增的可行性。方法分别用MTT法和羧基荧光素二醋酸盐琥珀酰亚胺酯标记细胞技术,观察人骨髓MSC在含有tPRP和胎牛血清培养体系中的增殖状态:利用流式细胞学技术检测细胞表面表型;细胞化学染色法分析不同培养体系所获细胞的成骨及成脂细胞分化能力。结果tPRP培养的人骨髓MSC呈典型的成纤维细胞样形态,且tPRP促MSC增殖能力优于筛选后的胎牛血清。tPRP培养的MSC均表达CD29、CD73、CD166和HLA-ABC,而不表达CD31、CD34、CD45和HLA-DR。体外分化实验显示,利用tPRP培养的MSC具有体外成骨和成脂能力。结论tPRP可以替代胎牛血清,用于人骨髓MSC的培养。     

EFA6A enhances glioma cell invasion through ADP ribosylation factor 6/extracellular signal-regulated kinase signaling

EFA6A, or Pleckstrin and Sec7 domain protein, is a member of guanine nucleotide exchange factors for ADP ribosylation factor 6 (ARF6). Whereas EFA6A is specifically expressed in the brain, little is known about its function in glial cells or glioma. Here we show that elevated EFA6A expression is detectable in both low-grade and high-grade human glioma tissues samples. To investigate the role of EFA6A in glioma carcinogenesis, we generated a human glioblastoma cell line which conditionally overexpresses EFA6A (U373-EFA6A). We showed that overexpression of EFA6A had no effect on cell proliferation, apoptosis, or cell cycle control. However, as shown by wound healing and in vitro cell invasion assays, it significantly enhanced the cell motility and invasiveness whereas silencing EFA6A by its dominant negative mutant EFA6A(E242K) produced opposite effects. We further showed that ARF6/extracellular signal-regulated kinase (ERK) signaling is required for the EFA6A-mediated cell invasion because both EFA6A(E242K) and ARF6 dominant negative mutant ARF6(T27N) markedly reduced the phosphorylated ERK level and EFA6A-mediated invasive capacity. Consistently, mitogen-activated protein kinase/ERK kinase inhibitor U0126 could abolish the EFA6A-induced cell invasion. These results suggest for the first time a potential role of EFA6A/ARF6/ERK signal cascade in glioma cell migration and invasion.     

A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and islet allograft rejection

Reactive oxygen species, such as superoxide, and nitrogen oxides, such as peroxynitrite, are thought to contribute to beta-cell destruction during the disease process that leads to type 1 diabetes. EUK-8 is a member of a new class of synthetic salen-manganese compounds with low toxicity that possess catalytic superoxide dismutase, peroxidase, and catalase activity that can inactivate superoxide and nitrogen oxides (e.g., peroxynitrite and nitrogen dioxide). We observed that EUK-8 administration inhibited the adoptive transfer of type 1 diabetes to NOD mice. In addition, administration of EUK-8 to NOD mice with established autoimmunity completely prevented the development of type 1 diabetes for up to 1 year in age, even though the treatment was discontinued after 35 weeks of age. EUK-8 treatment also prolonged the survival of islet allografts in newly diabetic NOD mice. Thus, reactive oxygen and nitrogen species contribute to the pathoetiology of both spontaneous type 1 diabetes and allograft rejection. In cultures of NIT-1 cells, EUK-8 inhibited cytotoxicity caused by superoxide as well as nitric oxide. Collectively, our findings implicate a greater role for nitrogen oxides (other than peroxynitrite) in beta-cell damage. Antioxidants designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen species may effectively protect beta-cells from spontaneous autoimmunity and alloresponses.     

长春瑞滨为主的联合方案治疗晚期非小细胞肺癌45例疗效观察

目的 观察长春瑞滨(navelbine，NVB)加顺铂(cisplatin，DDP)联合化疗治疗晚期非小细胞肺癌的疗效和不良反应。方法 45例晚期非小细胞沸癌病人接受NP(NVB DDP)方案治疗，21d为1个周期。结果 45例病人中无完全缓解者，21例部分缓解，16例稳定，8例进展，总有效率46．7％。中位生存时间9个月。主要不良反应为恶心、呕吐和骨髓抑制。结论 NVB DDP可作为治疗晚期非小细胞肺癌的一个有效安全的方案。     

吉西他滨联合顺铂治疗62例晚期非小细胞肺癌的临床观察

目的观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应.方法62例晚期非小细胞肺癌患者给予吉西他滨与顺铂联合治疗,吉西他滨1250 mg/m^2,静脉滴注第1、8天,顺铂80 mg/m^2,分两天静点,21天为一周期,每例患者治疗2周期以上.结果全组完全缓解1例,部分缓解24例,稳定20例,进展17例,总有效率为40.3%.初治组有效率为42.6%,复治组为25%.全组中位生存期10月,1年生存率为36.1%.ECOG评分增加者占67.7%（42/62）.最常见的毒副反应为骨髓抑制,Ⅲ～Ⅳ度白细胞和血小板下降发生率分别为29.1%和25.8%,其余毒副反应均轻微,可耐受.结论吉西他滨联合顺铂治疗晚期非小细胞肺癌均有较好的疗效,毒性可以耐受并可以改善生活质量.