TGF-β1长期诱导胰腺癌细胞发生上皮间质变而增加其侵袭性

目的：研究TGF-β1对胰腺癌细胞侵袭性的的影响以及上皮间质变（EMT）在其中起的作用。方法：以TGF-β1长期刺激胰腺癌细胞BxPc-3，从形态学动态观察癌细胞变化，同时以RT—PCR动态测定与侵袭性有关的指标E—caderin，N—caderin等的表达，以明确TGF-β1诱导癌细胞上皮间质变的能力及探索引出的条件，同时以Transwell侵袭试验验证上皮间质变对胰腺癌细胞侵袭性的作用。结果：TGF-β1（10ng／m1）长期刺激下（约7天后）胰腺癌细胞发生上皮间质变，细胞形态由上皮形转为单个分散的梭样间质细胞形，同时E—caderin表达逐渐下降，而N—caderin表达未见明显变化；transwell侵袭试验也证实胰腺癌细胞侵袭性和所受TGF—β1刺激时间呈正比，不同刺激时间的癌细胞侵袭率之间有显著差异，证明TGF-β1影响时间越长，胰腺癌细胞侵袭性越强。结论：TGF-β1有增加胰腺癌细胞侵袭性的作用，该作用很有可能是通过上皮间质变而产生，而这一作用需要较长时间的持续刺激。同时钙粘连蛋白的变化是重要的分子学机制之一。     

Expression of TGF-β1, Snail, E-cadherin and N-cadherin in Gastric Cancer and Its Significance

OBJECTIVE To investigate the expression of TGF-β1,Snail,E-cad-herin and N-cadherin in gastric cancer(GC),and to examine its relationship to malignant features of the tumors. METHODS The expression of TGF-β1,Snail,E-cadherin and N-cadherin proteins was detected in GC and adjacent tissues by immunohistochemical staining,and compared with the clinico-pathological data. RESULTS Positive rates of expression for TGF-β1,Snail,E-cadherin and N-cadherin were 63.5%,83.3%,37.5%and 44.8%in GC,and 28.8%, 41.3%,100%,11.3%in adjacent tissues,respectively.The expression of all four proteins showed a significant difference between the GCs and adjacent tissues(P<0.05).The positive rate of TGF-β1,Snail and N-cadherin,or the negative rate of E-cadherin expression was significantly related to the differentiated degree,histological type,invasion and metastasis of GC.In addition,the expression of N-cadherin was positively related to that of TGF-β1, but negatively related to that of E-cadherin.There was negative correlation between expression of E-cadherin and TGF-β1 and Snail in GC(P<0.05). CONCLUSION The over-expression of TGF-β1 and Snail and decreased expression of E-cadherin and the abnormal expression of N-cad-herin were involved in the process of invasion and metastasis of GC.The data showed that E-cadherin might switch to N-cadherin.TGF-β1 and Snail might play a fundamental role in the process.     

International EMS systems: The United States: past, present, and future

Emergency medical services (EMS) is an organised system designed to transport sick or injured patients to the hospital. Though EMS system configurations can be quite varied in design depending on locale, we provide an overview of EMS as it has evolved and is currently modelled in the US. We outline the history of EMS in the US, including the major events and legislation that shaped the current models that are in existence. We provide an overview of provider training, system design, system funding, and dispatch issues. The concepts of medical direction for physician surrogates, as well as EMS as it relates to specialty care are also elucidated.     

Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling

Transforming growth factor (TGFbeta) is a 25-kDa dimeric polypeptide that plays a key role in a variety of physiological processes and disease states. Blocking TGFbeta signaling represents a potentially powerful and conceptually novel approach to the treatment of disorders in which the signaling pathway is constitutively activated, such as cancer, chronic inflammation with fibrosis and select immune disorders. In this paper, we describe the biological properties of a novel series of quinazoline-derived inhibitors of the type I transforming growth factor receptor kinase (TbetaKIs) that bind to the ATP-binding site and keep the kinase in its inactive conformation. These compounds effectively inhibited TGFbeta-induced Smad2 phosphorylation in cultured cells in vitro with an IC(50) between 20 and 300 nM. Moreover, TbetaKIs were able to broadly block TGFbeta-induced reporter gene activation. Finally, TbetaKIs inhibited TGFbeta-mediated growth inhibition of normal murine mammary epithelial cells (NMuMG) and mink lung epithelial cells (Mv1Lu), and TGFbeta-induced epithelial-mesenchymal transdifferentiation (EMT) of NMuMG cells. Thus, these chemical TbetaKIs have the potential to be further developed as anti-cancer and -fibrosis agents. In addition, they represent valuable new tools for dissecting the biochemical mechanisms of TGFbeta signal transduction and understanding the role of TGFbeta signaling pathways in different physiological and disease processes.     

An evaluation of the risk for latex allergy in prehospital EMS providers

Hospital health care providers are increasingly being diagnosed as latex sensitive or allergic. Little is established on incidence or risks to prehospital health care providers. A written survey of EMT-DCs and EMT-Ps was done anonymously using established risk stratification questions to identify factors that indicate higher potential for developing latex allergies. There were 666 surveys distributed with 580 (87%) returned completed. Of the respondents, 533 were male (91%) with 510 (87%) reporting more than 5 years of field experience. Of the survey participants, 435 (75%) were EMT-DC level and 145 (25%) were EMT-P level. We found that latex sensitivities and allergies are present in our population, with an 8% incidence of latex allergies in EMT-DCs and 18% in EMT-Ps. A greater number of respondents report having factors that have been established to be associated with increased risk for latex allergies, indicating the need for more vigilant monitoring for the development of such reactions.     

The role of integrin-linked kinase (ILK) in cancer progression

Integrin-linked kinase (ILK) is an intracellular protein, which interacts with the cytoplasmic domains of integrin beta1 and beta3 subunits. ILK is a 59kDa protein containing a phosphoinositide phospholipid-binding domain flanked by an N-terminal ankyrin repeat domain and a C-terminal serine/threonine protein kinase domain. Genetic and biochemical evidence have established an essential role of ILK in connecting integrins to the actin cytoskeleton. Apart from integrins, ILK interacts with several adaptor and signaling proteins resulting in its activation and localization to focal adhesion plaques. The kinase activity of ILK is stimulated upon integrin engagement, as well as by growth factors and chemokines in a PI-3Kinase-dependent manner. ILK can mediate the phosphorylation of a variety of intracellular substrates, most notable of which are: protein kinase B (PKB/Akt), glycogen synthase kinase-3 (GSK-3) and myosin light chain. Gain and loss of function strategies have shown that overexpression, and/or constitutive activation of ILK results in oncogenic transformation and progression to invasive and metastatic phenotypes. In addition ILK expression and activity are upregulated in several types of cancers. In this review, we summarize the adaptor and signaling properties of ILK, and also progress in the identification of therapeutic strategies for inhibition of ILK activity.     

RNA干扰沉默MIF基因对宫颈癌SiHa细胞上皮细胞间质变的影响

[目的]探讨巨噬细胞移动抑制因子（MIF）对人宫颈癌SiHa细胞上皮间质转化（EMT）的影响。[方法]构建并鉴定重组真核表达质粒Genesil-MIF siRNA,转染人宫颈癌细胞SiHa细胞。RT-PCR检测各组细胞中MIF、E-cadherin、Vimentin mRNA表达水平。免疫细胞化学法组检测E-cadherin、Vimentin蛋白表达水平。[结果]重组质粒Genesil-MIF siRNA成功构建并转染至人宫颈癌SiHa细胞。RT-PCR法证实实验组细胞中E-cadherin mRNA相对高表达（P〈0.05）,而Vimentin、MIF mRNA相对低表达（P〈0.05）。免疫细胞化学法证实实验组细胞中E-cadherin蛋白表达水平升高,Vimentin蛋白表达水平明显降低。[结论]MIF沉默通过促进SiHa细胞中E-cadherin表达,抑制Vimentin表达从而抑制EMT发生。