E-cadherin和nm23-H1的表达及其临床意义在胰腺癌

目的探讨上皮细胞钙黏蛋白（E-cadherin）和转移抑制基因（nm23-H1）表达与胰腺癌侵袭转移的关系。方法应用免疫组织化学技术SP法，检测31例癌组织中E-cadherin和nm23-H1的表达水平。结合肿瘤的侵袭转移能力、分化程度和分期等进行分析。结果31例胰腺癌组织中E-cadherin和nm23-H1的表达强度均低于对照的胰腺组织；E-cadherin和nm23-H1的表达强度与胰腺癌的远处转移能力密切相关；胰腺癌中E-cadherin和nm23-H1的表达具有明显正相关。结论E-cadherin和nm23-H1的表达水平能反映胰腺癌的侵袭转移能力。两种蛋白的表达水平之间呈明显正相关。联合检测两种蛋白在胰腺癌组织中的表达，对临床判断胰腺癌的预后可能有一定的意义。     

膀胱癌上皮细胞粘附分子蛋白表达的意义

目的 探讨上皮细胞粘附分子（Ｅ－ＣＤ）表达情况对判断膀胱癌恶性程度、复发及预后的意义。方法 采用免疫组织化学方法对５４例膀胱癌标本中Ｅ－ＣＤ的表达情况进行研究。结果Ｅ－Ｃ原表达情况与膀胱癌的病理分级、分期均有密切关系。（ｘ＾２＝６．６５,Ｐ〈０．０５,Ｘ＾２＝７．１５,Ｐ〈０．０１）。Ｅ－ＣＤ的的民光癌的近期昨发及不良预后有关。（Ｘ＾２＝４．８８,Ｐ〈０．０５;Ｌｏｎｇ－Ｒａｎｋ ｔｅｓｔ;ｘ＾２     

结直肠癌中cyclin D1和CD44V6及E-cadherin蛋白的表达及其意义

目的 :探讨结直肠癌中cyclinD1、CD44V6、E cadherin(E cad)蛋白的表达。方法 :采用免疫组化SP法测定 48例结直肠癌中cyclinD1、CD44V6、E cad蛋白的表达。结果 :48例结直肠癌中cyclinD1、CD44V6、E cad表达的阳性率分别为5 8 3 % ( 2 8/4 8)、75 0 % ( 3 6/4 8)和 45 8%( 2 2 /4 8)。cyclinD1蛋白表达的阳性率 60岁以上年龄组高于 60岁以下年龄组 ,P<0 0 5 ,cyclinD1蛋白的表达与肿瘤组织分化程度呈负相关 ,P <0 0 1。CD44V6高表达及E cad低表达与结直肠癌Duke’s分期、浆膜浸润、淋巴结转移呈正相关 ,P<0 0 5。结论 :cyclinD1蛋白的表达与分化程度相关 ;CD44V6、E Cad蛋白的表达与结直肠癌浸润转移密切相关 ,检测cyclinD1、CD44V6、E cad蛋白是判断结直肠癌预后的客观指标。     

E-钙黏蛋白、β-连接素与不明原因不孕症发病机制的探讨

目的探讨E-钙黏蛋白(E-cadherin)和β-连接素(-βcatenin)在人子宫内膜组织中的表达与不明原因不孕症的关系。方法采用免疫组化S-P法,检测35例正常及41例不明原因不孕症子宫内膜E-cadherin和-βcatenin的表达水平。结果正常组各期子宫内膜腺上皮均见二者的表达,且在分泌中期达到高峰;-βcatenin在间质细胞有同样的变化,而E-cadherin增生期未见表达。不孕组增生期腺上皮二者仅有弱表达,分泌期表达增加(P<0.05),分泌中期与早、晚期比较,差异无显著性(P>0.05);间质细胞E-cadherin的表达无统计学意义。结论E-cadherin和-βcatenin在人子宫内膜腺上皮和间质细胞规律性表达,其表达异常,可能是导致不孕的重要原因。     

E-cadherin和α-catenin及β-catenin在乳腺癌组织中的表达及意义

目的：探讨上皮性钙黏素（E-cd）及α-连接素（cat）、β-cat在浸润性乳腺癌中的表达及意义。方法：免疫组化SP法。结果：60例乳腺癌组织中E-cd、α-cat、β-cat异常表达率分别为51．7％、61．7％和70％，E-cd的表达与乳腺癌分化程度、临床TNM分期、淋巴结转移显著相关，P〈0．005～0．0005，α-cat、β-cat的表达与分化程度、淋巴结转移无关。如果将E-cd、α-cat和β-cat作为一类蛋白分析，这类蛋白分子的异常表达与淋巴结转移显著相关，P〈0．05。结论：E-cd表达下调在乳腺癌浸润、转移中有重要作用，E-cd单独表达下调足以破坏E-cd／cat复合物的功能，导致癌细胞浸润转移。     

Influence of intercellular junctions on endothelin secretion of human umbilical vein endothelial cells in vitro

The endothelium plays a pivotal role in the theological regulation of blood flow by the secretion of vasoactive factors. The interaction between shear forces and the endothelium is determined by the mechanical properties of the endothelial cell layer which are associated with intercellular junctions. Cell-cell contacts could therefore modulate the secretion of vasocative factors in response to theological stimuli. We investigated the relationship between intercellular junctions and the secretion of the vasoconstrictor peptide endothelin and the coagulation co-factor von Willebrand factor (vWF). Human umbilical vein endothelial cells (HUVECs) were used as in vitro endothelial model system. Intercellular junctions were reversibly disrupted by calcium chelation or hypertonic stress; alternatively, the formation of intercellular junctions was inhibited by culturing the cells in suspension or by plating them in the presence of an inhibitory anti-VE-cadherin antibody. The opening of intercellular junctions was verified by assessing transmonolayer electrical resistance (TMR) and immunofluorescence morphology. The concentration of endothelin and vWF was measured in the cell culture supernatants using specific ELISAs. The secretion of endothelin was inhibited by EGTA (5 mM) and stimulated by incubation with tumor necrosis factor α (TNFα, 40 ng/ml). Treatment with hypertonic medium (glycerol, 1200 mosmol/l) for 10 minutes opened intercellular junctions and markedly reduced the secretion of endothelin. HUVECs in suspension culture did not secrete endothelin and failed to respond to TNFα, but readily resumed these functions upon forming a new monolayer on plastic. The reconstitution of intercellular junctions after suspension culture could be inhibited using a specific anti-VE-cadherin antibody. This antibody, but not a non-specific anti-humanIgG antibody reduced endothelin secretion. The secretion of von Willebrand Factor was less dependent on intercellular junctions. The opening of intercellular junctions did not induce cell death, since the cells continued to exclude trypan blue. The results of this study suggest a novel and potentially pathophysiologically/clinically relevant correlation between intercellular junctions and the secretion of endothelin in endothelial cells. Received: 17 December 1999, Returned for revision: 20 January 2000, Revision received: 14 February 2000, Accepted: 2 March 2000     

Mechanisms of tumour invasion and metastasis: emerging targets for therapy

The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.     

nm23H1和E-Cadherin在人非小细胞肺癌中的表达及临床意义

目的研究nm23H1和E-Cadherin蛋白在非小细胞肺癌(NSCLC)的表达及临床意义.方法采用S-P免疫组化法测定NSCLC中nm23H1和E-Cadherin蛋白的表达.结果有淋巴结转移的NSCLC组织中,nm23H1和E-Cadherin蛋白阳性表达率分别为29.4%(5/17)和11.8%(2/17),无淋巴结转移的则分别为82.4%(14/17)和42.9%(9/17),差异有极显著意义,P<0.01或显著意义,P<0.05.nm23H1和E-Cadherin表达与NSCLC的分期及肿瘤分化程度有关,P<0.05;基因蛋白表达在NSCLC组织中呈正相关,P<0.01.结论nm23H1和 E-Cadherin蛋白可作为判断NSCLC转移潜能及预后的重要指标.     

胃癌中α-及β-连接素联合表达

目的 :探讨α 及β 连接素 (catenin)联合表达与胃癌侵袭转移间的关系。方法 :应用ABC染色法在同一胃癌术后标本上进行α 及β catenin抗体染色 ,计数胃癌组织中阳性细胞所占的比例。 结果 :正常胃黏膜上皮细胞全部表达α 及 β catenin。 38例胃癌组织中α 及 β catenin阳性表达率分别为2 8 9% (11/ 38)和 5 0 % (19/ 38)。存在淋巴结转移的胃癌其α 及 β catenin的阳性表达率分别为 8 7%及 2 6 1% ,均远低于无淋巴结转移者 (P <0 0 1)。α 与 β catenin共同阳性表达占 30 % ,共同阴性表达占 36 9%。α catenin(- ) / β catenin(- )表达者最易发生淋巴结转移 ,α catenin( ) / β catenin(- )表达者易发生肝转移。结论 :检测α ,β catenin联合表达可以更为精确灵敏地预测胃癌侵袭转移