黏附分子免疫球蛋白超家族在人脑胶质瘤中的表达及临床意义

目的　通过检测黏附分子免疫球蛋白超家族中的神经细胞黏附分子 (NCAM ,CD5 6 ) ,细胞间黏附分子 1(ICAM 1,CD5 4 ) ,血管细胞黏附分子 (VCAM 1,CD10 6 )在胶质瘤中的表达 ,探讨其与胶质瘤浸润发展的关系 ,从而为临床上治疗胶质瘤提供一定的理论依据。方法　采用免疫组织化学SP法对临床 4 1例人脑胶质瘤标本进行研究。结果　神经细胞黏附分子在胶质瘤Ⅰ～Ⅱ级组与Ⅲ～Ⅳ级组中的表达相比具有统计学意义 (P <0 0 5 ) ;细胞间黏附分子 1、血管细胞黏附分子在胶质瘤中表达较高 ,与对照组相比有统计学意义 (P <0 0 5 ) ,但在胶质瘤Ⅰ～Ⅱ级组与Ⅲ～Ⅳ级组中的表达相比 ,两者无统计学意义 (P >0 0 5 )。结论　CD5 6、CD5 4、CD10 6与胶质瘤的浸润发展相关 ,且CD5 6与胶质瘤的恶性程度相关。     

AZD8055抑制胆管癌细胞HuCCT1的迁移及EMT进程的机制研究

目的探讨哺乳动物雷帕霉素靶蛋白(mTOR)双重抑制剂AZD8055在抑制人胆管癌细胞HuCCT1的迁移及EMT进程中的作用及分子机制。方法 MTT法与平板克隆形成实验检测AZD8055对胆管癌细胞增殖的影响;划痕愈合实验和Transwell小室迁移实验检测AZD8055对HuCCT1细胞迁移能力的影响;Western blot法检测EMT标志相关蛋白、Akt/mTOR信号通路蛋白及DEK蛋白的表达;利用STITCH、GeneMANIA数据库,分析AZD8055、DEK、Akt信号通路相互作用关系;在DEK基因沉默后,检测胆管癌细胞增殖活力、迁移能力及Akt/mTOR信号通路相关蛋白表达水平的变化。结果 AZD8055可抑制胆管癌细胞的增殖及迁移能力,同时抑制Akt/mTOR信号通路相关蛋白、DEK蛋白表达及EMT的进程;沉默DEK基因可明显抑制胆管癌细胞增殖及迁移能力,并降低Akt、S6、4EBP1蛋白的磷酸化水平。结论 AZD8055抑制HuCCT1细胞的迁移及EMT进程,其机制与下调DEK,抑制Akt/mTOR信号通路有关。     

细胞黏附分子与子痫前期发病关系的研究

目的 检测子痫前期患者和正常孕妇胎盘组织中血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)及血小板内皮细胞黏附分子-1(PECAM-1)的表达水平,以探讨细胞黏附分子(CAM)在子痫前期发病机制中的作用.方法 选取2005年5月-2006年5月在郑州大学第三附属医院住院分娩病例80例,分为3组:①轻度子痫前期组20例;②重度子痫前期组30例;③正常晚孕组(NT组)30例;胎盘组织中MCAM-1、ICAM-1及PECAM-1的表达水平采用免疫组化PV-9000法测定.结果 ①重度子痫前期组胎盘组织中VCAM-1和PECAM-1的表达下降(P＜0.05),ICAM-1的表达增强(P＜0.05).②轻度子痫前期组胎盘组织中VCAM-1的表达下降(P＜0.05).ICAM-1和PECAM-1的表达无明显差异(P＜0.05).结论 CAM与子痫前期发病有密切联系,VCAM-1、ICAM-1和PECAM-1参入了子痫前期病理生理过程且与子痫前期的病情程度密切相关.     

Snail介导的EMT在上皮性卵巢癌组织中的作用

目的检测Snail、E-cadherin及Vimentin在上皮性卵巢癌组织中的表达,探讨Snail介导的上皮间质转化(EMT)在卵巢癌发生、发展及转移中的作用。方法采用免疫组化法分别检测Snail、E-cadherin、Vimentin在48例卵巢浆液性腺癌、卵巢交界性浆液性肿瘤及卵巢浆液性腺瘤中的表达,探讨EMT相关因子表达强度的相关性及与临床病理特征之间的关系。结果 (1)Snail、Vimentin在卵巢浆液性腺癌中的表达率为(68.75%/66.67%),高于卵巢交界性浆液性腺瘤的(41.67%/37.50%)及卵巢浆液性腺瘤的(25.00%/18.75%),结果均具有显著的统计学差异(P0.05),E-cadherin在卵巢浆液性腺癌中的表达率为27.08%,低于与卵巢交界性浆液性腺瘤的54.17%及卵巢浆液性腺瘤的75.00%,结果均具有统计学差异(P0.05)。而卵巢交界性浆液性腺瘤组与卵巢浆液性腺瘤组比较,三种蛋白的表达均无统计学差异(P0.05)。(2)Snail、E-cadherin及Vimentin的表达高低与FIGO分期、分化级别、有无淋巴结转移及腹膜种植有关。(3)在卵巢浆液性腺癌中,Snail与Vimentin的表达呈正相关(r=0.477,P0.05),Snail与E-cadherin的表达呈负相关(r=-0.601,P0.05),而E-cadherin与Vimentin表达的相关性不明显(r=-0.206,P0.05)。结论在上皮性卵巢癌组织中,Snail、Vimentin表达上调,E-cadherin表达下调,提示Snail介导的EMT可能与卵巢癌的发生、发展及浸润转移有关。     

米非司酮对早孕绒毛组织中细胞间黏附分子-1和血管细胞黏附分子-1表达的影响

目的 探讨米非司酮对早孕绒毛组织中细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)表达的影响.方法 采用免疫组化染色测定绒毛组织中ICAM-1和VCAM-1的表达,其中正常早孕人工流产组20例,米非司酮药物流产组22例.结果 ICAM-1和VCAM-1在正常早孕绒毛组织中阳性表达率为80%、75%,在米非司酮药物流产组中阳性表达率为45%、41%,两者差异有显著性(P＜0.05).结论 ICAM-1和VCAM-1与胚胎着床及维持正常早孕有关.米非司酮引起ICAM-1和VCAM-1的表达降低可能是抗早孕终止妊娠机制之一.     

支气管哮喘血清可溶性细胞间黏附分子-1和内皮细胞黏附分子-1的表达

目的　探讨可溶性细胞间黏附分子 - 1(s ICAM- 1)和血管内皮细胞黏附分子 - 1(s VCAM- 1)在支气管哮喘发病中的意义。方法　对支气管哮喘患者 2 3例和健康人 2 0名 (年龄均在 15～ 45岁之间 ) ,采用酶联免疫双抗体夹心法 (EL ISA)测定血清中的 s ICAM- 1和 s VCAM- 1;利用荧光酶联免疫法 (Uni- CAP系统 )分析血清中总 Ig E(t Ig E)和特异性 Ig E(s Ig E)。结果　血清 s ICAM- 1、s VCAM- 1、t Ig E水平测定哮喘组均高于对照组 (P<0 .0 1) ;血清中以户尘螨和蒿草花粉的特异性 Ig E含量增高为主 ;经多元逐步回归分析提示血清总 Ig E含量与s ICAM- 1存在线性关系 ,其复相关平方 (R- square)为 0 .5 0 2 ,标准偏回归系数为 0 .0 97,t=2 .841,P=0 .0 2 18。结论　支气管哮喘患者的 s ICAM- 1和 s VCAM- 1含量显著高于正常人 ;血清 s ICAM- 1与血清总 Ig E存在线性依存关系。     

黏附分子CD44与恶性瘤关系的研究进展

在细胞生长和分化过程中,变异性剪接是许多基因表达过程的一部分。CD44作为多功能黏附分子,有10个变异外显子能发生选择性拼接,从而产生CD44s和CD44v,其中CD44v主要表达在转移性肿瘤细胞表面。在许多恶性瘤组织中可见到不同CD44v分子的表达。此文综述了CD44分子与各种肿瘤侵袭转移的相关性。     

黏附分子在糖尿病并发症发病中的作用及药物干预

黏附分子是在细胞表面表达具有介导细胞间或细胞与细胞外基质相互作用的糖蛋白。近年来的研究表明黏附分子在糖尿病并发症的发生发展中起到了重要作用。一些可以降低黏附分子水平的药物 ,有望为预防和治疗糖尿病血管病变提供新的方向。     

α-烯醇化酶在肿瘤发生发展中的作用机制研究进展

肿瘤的发生、发展是一个多基因、多因素、多阶段相互作用的结果 .α-烯醇化酶(ENO1)是一种多功能酶,参与多种生理及病理过程,尤其与肿瘤的发生、发展密切相关.研究已证实,ENO1在多种恶性肿瘤中均有不同程度的表达上调,并阐明了部分可能的分子机制.因此,ENO1有望成为一些肿瘤的早期诊断、判断预后的潜在生物标志物和新的治...     

Alumina nanoparticles induce expression of endothelial cell adhesion molecules

Nanotechnology is a rapidly growing industry that has elicited much concern because of the lack of available toxicity data. Exposure to ultrafine particles may be a risk for the development of vascular diseases due to dysfunction of the vascular endothelium. Increased endothelial adhesiveness is a critical first step in the development of vascular diseases, such as atherosclerosis. The hypothesis that alumina nanoparticles increase inflammatory markers of the endothelium, measured by the induction of adhesion molecules as well as the adhesion of monocytes to the endothelial monolayer, was tested. Following characterization of alumina nanoparticles by transmission electron microscopy (TEM), electron diffraction, and particle size distribution analysis, endothelial cells were exposed to alumina at various concentrations and times. Both porcine pulmonary artery endothelial cells and human umbilical vein endothelial cells showed increased mRNA and protein expression of VCAM-1, ICAM-1, and ELAM-1. Furthermore, human endothelial cells treated with alumina particles showed increased adhesion of activated monocytes. The alumina particles tended to agglomerate at physiological pH in serum-containing media, which led to a range of particle sizes from nano to micron size during treatment conditions. These data show that alumina nanoparticles can elicit a proinflammatory response and thus present a cardiovascular disease risk.     

丹参对实验糖尿病大鼠粘附分子CD54 CD106 CD62p的影响

目的　研究丹参对链脲佐菌素 (STZ)诱导的糖尿病大鼠模型体内三种粘附分子 (CD5 4、CD10 6、CD6 2 p)的变化和对肾脏、主动脉病理变化的影响。方法　随机分正常对照、糖尿病、胰岛素、丹参四组 ,测定各组血糖、糖化血红蛋白、单个核细胞表面CD5 4、血小板表面CD6 2 p表达水平 ,观察肾脏和大血管CD5 4和 /或CD10 6表达强度及病理变化。结果　丹参降低肾脏CD5 4、CD10 6 ,主动脉CD10 6的表达 ,也降低单个核细胞CD5 4的表达(丹参组 30± 2 5vs糖尿病组 6 5± 15 ,P <0 0 5 ) ,但对血小板CD6 2 p的表达无明显影响 ,肾脏及主动脉的病理变化明显减轻。结论　丹参能降低糖尿病大鼠体内CD5 4、CD10 6水平 ,并能改善糖尿病引起的肾脏和主动脉的病理变化     

槲皮素抑制血小板-内皮细胞粘附及粘附分子表达槲皮素抑制血小板-内皮细胞粘附及粘附分子表达

目的研究槲皮素(Que)对人脐静脉内皮细胞(HUVEC)和人血小板的粘附作用,及其粘附分子表达。方法用流式细胞仪测定肿瘤坏死因子(TNF-α)诱导HUVEC表达细胞间粘附分子(ICAM-1)及凝血酶诱导的人血小板P-选择素的表达，用［³H］-Adenine标记人血小板,检测其与HUVEC的粘附反应。结果Que与人血小板作用后，可抑制凝血酶诱导的人血小板表达P-选择素。HUVEC经TNF-α处理后，明显增加细胞表面ICAM-1的表达,加强其与血小板的粘附反应，Que在一定剂量范围内可抑制HUVEC表达ICAM-1,并可抑制其与血小板的粘附作用。结论Que可抑制内皮细胞和血小板粘附及粘附分子表达。     

Inflammation induced by Bothrops asper venom: release of proinflammatory cytokines and eicosanoids, and role of adhesion molecules in leukocyte infiltration.

Bothrops asper venom (BaV) causes systemic and local effects characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. In this study, the effects of BaV on the release of the cytokines IL-1, IL-6 and TNF-alpha and the eicosanoids LTB4 and TXA2 in the peritoneal cavity of mice were analyzed. We also investigated the participation of beta2 integrin chain, l-selectin, LFA-1, ICAM-1 and PECAM-1 adhesion molecules in the BaV-induced leukocyte accumulation. Levels of proinflammatory cytokines IL-6 and TNF-alpha, as well as eicosanoids LTB4 and TXA2 were significantly increased after BaV injection (250 microg/kg), whereas no increment in IL-1 was observed. Anti-mouse l-selectin, LFA-1, ICAM-1, PECAM-1 and beta2 integrin chain monoclonal antibodies resulted in a reduction of neutrophil accumulation induced by BaV injection compared with isotype-matched control injected animals. These data suggest that BaV is able to induce the activation of leukocytes and endothelium to express adhesion molecules involved in the recruitment of neutrophils into the inflammed site. Furthermore, these results showed that BaV induces the release of cytokines and eicosanoids in the local of the venom injection; these inflammatory mediators may be important for the initiation and amplification of the inflammatory reaction characteristic from Bothrops sp envenomation.     

Endothelial cell adhesion molecules and cancer progression

The role of cell adhesion molecules (CAMs), such as intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, has been studied extensively in the process of inflammation. These molecules are responsible for recruiting leukocytes onto the vascular endothelium before extravasation to the injured tissues. Some circulating cancer cells have been shown to extravasate to a secondary site using a process similar to inflammatory cells. The most studied ligands for CAMs expressed on cancer cells, sialyl Lewis (a/x) antigens, are shown to be involved in adhesion to endothelial cells by binding to E-selectin. This process, shared by inflammatory cells and cancer cells, may partially explain the link between inflammation and tumorigenesis. Furthermore, this process may elucidate the therapeutic benefit of anti-inflammatory drugs in cancer treatment. The complexity of the tumor microenvironment has been revealed in the past decade. Currently, intense investigation is aimed at various aspects of the tumor microenvironment in addition to the tumor cells themselves. Here, we review the role of CAMs in extravasation of circulating cancer cells, a key step in metastasis.     

F-box proteins in cancer stemness: An emerging prognostic and therapeutic target

Cancer is a complex heterogenic disease with significant therapeutic challenges. The presence of cancer stem cells (CSCs) in cancer tissue orchestrates tumor growth, progression, and metastasis, the tumor heterogeneity, disease relapse, and therapeutic resistance. Hence, it is imperative to explore how progenitor or cancer-initiating cells acquire stemness features and reprogram different biological mechanisms to maintain their sustained oncogenicity. Interestingly, deregulation of F-box proteins (FBPs) is crucial for cancer stemness features, including drug resistance and disease relapse. In this review, we highlight recent updates on the clinical significance of targeting FBPs in cancer therapy, with emphasis on eliminating CSCs and associated therapeutic challenges. Moreover, we also discuss novel strategies for the selective elimination of CSCs by targeting FBPs.     

肝癌患者血清中可溶性细胞间粘附因子的检测及临床意义

目的 研究肝癌患血清中的可溶性细胞间粘附因子—1(sICAM—1)的临床价值。方法采用ELISA方法分别测定原发性肝癌患和对照组血清中sICAM—l的水平，并同时比较其不同分期的变化。结果 肝癌患sICAM—1含量显高于正常人，且Ⅲ和Ⅳ期肝癌患显高于I期和Ⅱ期患。结论 测定血清中sICAM—1对原发性肝癌的诊断有重要价值，并可预测肝癌的复发和转移。     

Effect of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of adhesion molecules on human neutrophils

The effects of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of CD11b/CD18, CD11c/CD18 integrins and l-selectin on human neutrophils were studied by flow cytometry in a whole blood assay. None of these compounds had any effect on the basal expression of CD11b, CD11c, or l-selectin in the concentration range of 20–100 μM. However, linoleic acid at a concentration of 1000 μM slightly up-regulated CD11b and CD11c by a factor of 2.1 and 1.7, respectively. Linoleic acid, linoleic acid anilide, and arachidonic acid did not affect the formyl-methionyl-leucyl-phenylalanine induced up-regulation of CD11b or CD11c. However, linoleic acid and linoleic acid anilide slightly inhibited the phorbol myristate acetate (PMA)-induced expression of CD11b, which was decreased by 27 and 21% at concentrations of 100 and 1000 μM, respectively. Likewise, arachidonic acid at 40 μM inhibited the PMA-induced expression of CD11b by 19%. Our results suggest that linoleic acid, linoleic acid anilide, and arachidonic acid do not dramatically affect the expression of leukocyte adhesion molecules in a whole blood assay. Received: 17 February 1997  / Accepted: 5 May 1997