目的观察肿瘤高表达蛋白(high expression in cancer,Hec1)在人膀胱癌组织中的表达及其与临床病理因素和预后的关系。方法运用免疫组织化学和Western印迹法检测手术切除的105例人膀胱癌及20例癌旁正常膀胱组织病理标本中Hec1的表达,其中...目的观察肿瘤高表达蛋白(high expression in cancer,Hec1)在人膀胱癌组织中的表达及其与临床病理因素和预后的关系。方法运用免疫组织化学和Western印迹法检测手术切除的105例人膀胱癌及20例癌旁正常膀胱组织病理标本中Hec1的表达,其中按Elson and Ellis半定量三级分类法:Ⅰ级51例,Ⅱ级39例,Ⅲ级15例;临床TNM分期Ⅰ期31例,Ⅱ期23例,Ⅲ+Ⅳ期51例;伴淋巴结转移者71例,无淋巴结转移34例;肿瘤直径≤2 cm者49例,2~5cm 者35例,>5 cm者21例。采用Prism6.0统计软件分析肿瘤组织Hec1与临床病理因素及5年生存率的关系。采用Cox比例风险模型多因素分析影响膀胱癌预后的独立因子。结果 Hec1在人膀胱癌组织及癌旁正常组织表达率分别为78.2%(82/105)和15.0%(3/20),两者比较差异有统计学意义(P<0.01);Hec1的表达与患者的年龄、组织类型、肿瘤大小均无显著相关性(P分别为0.25, 0.17,0.26)。随临床分期的升级(P=0.042)、淋巴结转移的出现(P=0.033),Hec1表达水平逐渐增高,各组间有显著相关性;Hec1表达阳性的膀胱癌患者,术后5年生存率明显较Hec1表达阴性者低(P=0.025);淋巴结转移、TNM分期及Hec1是影响膀胱癌预后的独立因素。结论 Hec1的表达与膀胱癌的发生、发展和转归有一定相关性,有可能起到肿瘤刺激因子的作用,为临床诊断、治疗及判断预后提供方向。展开更多
癌症高表达蛋白(highly expressed in cancer,Hec1)是一种动粒蛋白,它通过N末端尾巴区与微管间的静电相互作用促进动粒-微管结构的形成。Hec1蛋白与Nuf2p、Spc24p、Spc25p构成Ndc80复合物,Ndc80定位于动粒外板,和其他的动粒蛋白共同作用...癌症高表达蛋白(highly expressed in cancer,Hec1)是一种动粒蛋白,它通过N末端尾巴区与微管间的静电相互作用促进动粒-微管结构的形成。Hec1蛋白与Nuf2p、Spc24p、Spc25p构成Ndc80复合物,Ndc80定位于动粒外板,和其他的动粒蛋白共同作用,参与调节有丝分裂中染色体的正常分离。Hec1蛋白表达量随着细胞周期动态变化,且在分裂旺盛的细胞如肿瘤细胞中高表达。目前Hec1已成为肿瘤基因治疗的靶点,使用不同的病毒载体,如腺病毒载体、腺相关病毒载体、逆转录病毒载体将Hec1的干扰片段导入宫颈瘤或脑胶质瘤细胞后,可引起肿瘤细胞凋亡。展开更多
Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positi...Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positively charged molecules in kinetochores and negative charge on C-termini near the plus ends of microtubules. A clear picture of how kinetochores establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to account for mitotic chromosome motions within a systems approach in terms of experimentally known cellular electric charge distributions interacting over nanometer distances.展开更多
The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the ti...The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the timing of poleward, antipoleward, and oscillatory chromosome movements. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation are necessary for chromosome motions. We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces. We explain this mechanism within the context of Complexity Theory, based on the electrostatic properties of tubulin, known cellular electric charge distributions, and the dynamic instability of microtubules.展开更多
文摘癌症高表达蛋白(highly expressed in cancer,Hec1)是一种动粒蛋白,它通过N末端尾巴区与微管间的静电相互作用促进动粒-微管结构的形成。Hec1蛋白与Nuf2p、Spc24p、Spc25p构成Ndc80复合物,Ndc80定位于动粒外板,和其他的动粒蛋白共同作用,参与调节有丝分裂中染色体的正常分离。Hec1蛋白表达量随着细胞周期动态变化,且在分裂旺盛的细胞如肿瘤细胞中高表达。目前Hec1已成为肿瘤基因治疗的靶点,使用不同的病毒载体,如腺病毒载体、腺相关病毒载体、逆转录病毒载体将Hec1的干扰片段导入宫颈瘤或脑胶质瘤细胞后,可引起肿瘤细胞凋亡。
文摘Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positively charged molecules in kinetochores and negative charge on C-termini near the plus ends of microtubules. A clear picture of how kinetochores establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to account for mitotic chromosome motions within a systems approach in terms of experimentally known cellular electric charge distributions interacting over nanometer distances.
文摘The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the timing of poleward, antipoleward, and oscillatory chromosome movements. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation are necessary for chromosome motions. We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces. We explain this mechanism within the context of Complexity Theory, based on the electrostatic properties of tubulin, known cellular electric charge distributions, and the dynamic instability of microtubules.
