P-选择素与肿瘤转移关系的研究

肿瘤的转移是多因素参与的复杂过程,包括肿瘤细胞侵袭周围组织、从原发灶脱离进入循环系统、逃避免疫监视以及在远隔器官形成与原发瘤同样类型的转移灶。在此过程中细胞粘附分子发挥着重要作用,粘附分子是由细胞产生,存在于细胞表面,介导细胞与细胞间或细胞与基质间相互接触和结合的一类分子。选择素是细胞粘附分子中的一个家族,包括P-选择素、L-选择素和E-选择素,主要参与细胞间选择性识别、粘附,并在肿瘤转移、炎症反应、血栓形成及其他疾病中起重要作用[1]。现就P-选择素的结构、生理功能及其与肿瘤转移关系的相关研究作一综述。1 P-选…     

E-cad与ICAM-1在泌尿生殖系统肿瘤中的研究进展

细胞粘附分子(cellular adhesion molecules,CAMs)是位于细胞表面的糖蛋白.它通过介导细胞与细胞、细胞与外基质间的相互作用,参与多细胞生物的多种生理及病理过程.E-钙粘附素(E-cad)与细胞间粘附分子-1(ICAM-1)是两种重要的细胞粘附分子,与多种肿瘤的发生发展以及浸润转移关系十分密切,近年来正成为研究的重点和热点.现就 E-cad、ICAM-1在泌尿生殖系统肿瘤中的研究现状特别是与肿瘤的侵袭、浸润与转移关系作一综述.     

E-cad与ICAM-1在泌尿生殖系统肿瘤中的研究进展

细胞粘附分子（cellular adhesion molecules，CAMs）是位于细胞表面的糖蛋白。它通过介导细胞与细胞、细胞与外基质间的相互作用，参与多细胞生物的多种生理及病理过程。E-钙粘附素（E-cad）与细胞间粘附分子-1（ICAM-1）是两种重要的细胞粘附分子，与多种肿瘤的发生发展以及浸润转移关系十分密切，近年来正成为研究的重点和热点。现就E-cad、ICAM-1在泌尿生殖系统肿瘤中的研究现状特别是与肿瘤的侵袭、浸润与转移关系作一综述。     

整合素与肿瘤转移

整合素是细胞表面重要的粘附分子,它在机体内具有重要的生物学作用。本文从肿瘤细胞侵袭转移的过程出发,较全面地阐述了整合素与肿瘤转移的密切关系,为深入探讨整合素在肿瘤发生、发展中的作用,开发肿瘤治疗新思路提供了理论依据。     

血管细胞粘附分子1在肿瘤神经侵袭中的作用研究

目的：综述血管细胞粘附分子1在肿瘤神经侵袭中的作用。方法本文就血管细胞粘附分子1在肿瘤神经侵袭中的作用作一综述。结果与结论神经侵袭是多种恶性肿瘤的转移途径之一,常导致局部复发及疼痛,影响疾病预后,但目前神经侵袭的机制尚缺乏定论。血管细胞粘附分子1属免疫球蛋白超家族结构的粘附分子,参入多种恶性肿瘤的发生发展及转移,同时参入神经的发生。     

肿瘤药物治疗的新靶点研究进展

肿瘤是多个病因、多阶段、多基因的长期过程。寻代肿瘤相关基因并以此为靶点已成为肿瘤治疗的新手段。本文综述了两种细胞周期相关激酶,细胞生存有关的Ａｋｔ和ＩＧＦ１Ｒ,细胞凋亡抑制因子及与肿瘤生长浸润转移有关的粘附分子等的作用,并讨论以此为靶点治疗肿瘤的可行性。     

粘附分子与急性肺损伤

1粘附分子概述细胞粘附分子是一类介导细胞与细胞、细胞与细胞外基质间相互结合的重要活性物质,它在维护正常组织的稳定、介导炎症细胞的迁移、血栓的形成以及肿瘤转移等过程中起重要的作用。它主要包括选择素家族、整合素家族、免疫球蛋白超家族。2细胞粘附分子在急性肺损伤中的作用急性肺损伤(AcuteLungInjury,ALI)是一种失控的炎症反应,以肺血管内皮细胞及肺泡上皮细胞广泛损伤为其病理特征。多形核白细胞于肺内大量“扣押”及其释放各种蛋白酶、氧自由基以及促炎症细胞因子引起组织损伤是导致上述损伤的关键,而粘附分子在此过程中发…     

CD44v6在甲状腺肿瘤中的表达

CD44V6是CD44的一种拼接变异体,其表达可改变肿瘤细胞表面粘附分子(CAM)的构成和功能,有助于肿瘤细胞获得转移潜能,与肿瘤的发生、发展、侵袭和转移密切相关.全文就CD44v6在甲状腺肿瘤中的表达简要综述.     

E-cadherin与炎性乳腺癌关系的研究进展

细胞粘附分子是一类介导细胞与细胞、细胞与细胞外基质之间粘附作用的糖蛋白,在肿瘤的发生、发展、侵袭和转移中起着重要作用。存在于成人上皮细胞的上皮细胞钙粘蛋白(E-cadherin/E-cad)是钙粘蛋白家族的主要成员之一,也一种重要的细胞粘附分子,其主要作用是参与形成和维护正常细胞间的连接,与细胞的生长、分化、迁移、信息传递和稳定以及创伤的修复过程有关。E-cadherin也被认为是一种肿瘤抑制基因,与多种上皮恶性肿瘤的分化、侵袭、转移和预后相关,其表达下调在乳腺癌中是一种普遍现象,与乳腺癌的分化程度、淋巴结转移及预后均密切相关。炎性乳腺癌是一种高度恶性的局部晚期特殊类型的乳腺癌,患者大多死于局部组织侵袭和远处转移。研究表明,E-cadherin在炎性乳腺癌组织或细胞系中却呈与功能一致的强阳性表达,与炎性乳腺癌的浸润和转移过程密切相关。本文综述了E-cadherin与炎性乳腺癌关系的最新研究进展。     

抗粘附肽RGD和YIGSR对肿瘤侵袭、转移能力的抑制作用

肿瘤细胞通过膜粘附分子与基底膜和细胞外基质成分层粘连蛋白 (ＬＮ )、纤维粘连蛋白 (ＦＮ )和胶原蛋白 (Ｃｏｌｌａｇｅｎ )等的ＲＧＤ (Ａｒｇ Ｇｌｙ Ａｓｐ)和ＹＩＧＳＲ(Ｔｙｒ Ｉｌｅ Ｇｌｙ Ｓｅｒ Ａｒｇ)序列粘附 ,在肿瘤的转移过程中发挥了重要作用。合成的ＲＧＤ和ＹＩＧＳＲ肽可通过竞争结合肿瘤细胞相应粘附分子 ,干扰肿瘤细胞的侵袭和转移过程[1,2 ] 。本文初步观察了我们采用固相肽合成技术制备的ＲＧＤ和ＹＩＧＳＲ肽的抗肿瘤侵袭、转移作用。方法和结果一、合成肽对高转移肿瘤细胞的粘附抑制作用合成肽ＲＧＤ和ＹＩＧＳＲ…     

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.     

中性粒细胞介导炎症与粘附分子之间的关系

粘附分子与中性粒细胞介导的炎症反应之间有密切关系。炎症过程中,粘附分子介导的中性粒细胞与血管内皮细胞之间的粘附是第1步也是较为关键的步骤。主要有3类粘附分子家族参与中性粒细胞-内皮细胞之间的粘附:选择素家族、整合素家族和免疫球蛋白超家族分子。不同种类的粘附分子依次表达或活化与去活化在这一粘附过程中起着重要作用。首先,中性粒细胞减速,在血管内皮细胞表面滚动,这由选择素介导;接着,活化的整合素分子与内皮细胞表面的免疫球蛋白超家族分子（ICAM_s）结合使中性粒细胞-内皮细胞之间牢固结合;然后,中性粒细胞游出管,这依赖于趋化因子、整合素及PECAM-1。因粘附分子与炎症有密切关系,故可考虑用粘附分子抑制剂来治疗炎症。     

Cell adhesion molecules as pharmaceutical target in atherosclerosis

Cell adhesion molecules (CAMs) are transmembrane proteins that mediate adhesion and interactions between cells or cell and extra-cellular matrix. Increased expression and activation of CAMs in vascular endothelial cells and circulating leukocytes, as occurring in the settings of inflammation, hypercholesterolemia, hypertension and diabetes, stimulates leukocyte recruitment into the vascular endothelium, an important step in the pathogenesis of atherosclerosis. CAMs are a potential therapeutic target in clinical practice and in recent years pharmaceutical agents with specific effects on the production and function of these molecules have been studied and developed. This article reviews recent progress regarding pathophysiology of CAMs in atherogenesis and pharmaceutical products or chemicals that are active against CAMs, and assesses the possibilities for clinical developments in this area that might enhance the prevention, monitoring and treatment of atherosclerotic cardiovascular diseases.     

植物多糖干预细胞黏附研究进展

黏附分子介导的细胞黏附是最基本的生命现象,也是炎症、免疫、感染、血栓形成、肿瘤转移、伤口愈合等生理病理过程的细胞学基础,干预黏附已成为疾病防治的重要策略。植物多糖特别是中草药中的多糖具有抗炎、抗肿瘤、抗感染、调节免疫、保护心血管等多样的药理作用,本文综述了植物多糖对疾病过程中细胞黏附的干预作用。     

细胞黏附分子与药物研制

黏附分子参与多种疾病的过程，目前已经发现许多抗炎药物直接或间接抑制黏附分子表达。近年来以细胞黏附分子为靶点的药物筛选迅速发展起来，诸如小分子抑制剂、黏附分子单抗、非甾体抗炎药、中草药等，本对与细胞黏附分子相关的抗炎药物研究进行综述。     

NADPH oxidase and lipid raft-associated redox signaling are required for PCB153-induced upregulation of cell adhesion molecules in human brain endothelial cells

Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS.     

Barrier protective effects of rutin in LPS-induced inflammation in vitro and in vivo

Rutin, an active flavonoid compound, is well known to possess potent antiplatelet, antiviral and antihypertensive properties. In this study, we first investigated the possible barrier protective effects of rutin against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS) and the associated signaling pathways. The barrier protective activities of rutin were determined by measuring permeability, monocytes adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated HUVECs. We found that rutin inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of monocytes to human endothelial cells. Rutin also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that rutin suppressed the production of tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by LPS. Collectively, these results suggest that rutin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.     

Pharmacology of Cell Adhesion Molecules of the Nervous System

Cell adhesion molecules (CAMs) play a pivotal role in the development and maintenance of the nervous system under normal conditions. They also are involved in numerous pathological processes such as inflammation, degenerative disorders, and cancer, making them attractive targets for drug development. The majority of CAMs are signal transducing receptors. CAM-induced intracellular signalling is triggered via homophilic (CAM-CAM) and heterophilic (CAM - other counter-receptors) interactions, which both can be targeted pharmacologically. We here describe the progress in the CAM pharmacology focusing on cadherins and CAMs of the immunoglobulin (Ig) superfamily, such as NCAM and L1. Structural basis of CAM-mediated cell adhesion and CAM-induced signalling are outlined. Different pharmacological approaches to study functions of CAMs are presented including the use of specific antibodies, recombinant proteins, and synthetic peptides. We also discuss how unravelling of the 3D structure of CAMs provides novel pharmacological tools for dissection of CAM-induced signalling pathways and offers therapeutic opportunities for a range of neurological disorders.     

Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease

In multicellular organisms the development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by molecules which are named adhesion molecules and play a main role both at the early stages of the development of tissue integrity and later. Cell adhesion molecules (CAMs) have a key role in several pathologies such as cancer and inflammatory diseases. Selectins, integrins and immunoglobulin gene superfamily of adhesion receptors mediate different steps of leukocyte migration from the bloodstream towards the inflammatory foci. Leukocyte interactions with the vascular endothelium are highly orchestrated processes that include the capture of free-flowing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion and ensuing diapedesis. These interactions occur under high shear stresses within venules and depend on multiple families of adhesion molecules. As a response to infection mediators, leukocyte gathering is considered to be crucial for the adequate defence of the organism to any kind of injury or infection. Endothelial activation contributes significantly to the systemic inflammatory response to bacteraemia and increased expression. Release of soluble endothelial markers into the circulation has been demonstrated together with elevated plasma levels of CAMs and has been reported in bacteraemic patients. It has been proposed that infection of endothelial cells with Staphylococcus aureus, Streptococcus sanguis, or Staphylococcus epidermidis induces surface expression of ICAM-1 and VCAM-1 and monocyte adhesion. In general, leukocyte/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer be viewed as occurring in discrete steps mediated by individual families of adhesion molecules but rather as a series of overlapping synergistic interactions among adhesion molecules resulting in an adhesion cascade. These cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapid immune responses.     

Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.