目的通过检测乳腺黏液癌（以M表述）及浸润性导管癌（符合基底细胞样癌分子分型诊断标准：以D-B表述）标本中乳腺癌阻抑蛋白1关联RING蛋白1（BRCA1-associated RING domain,BARD1）剪切变异体表达水平的差异,结合术后随访结果,探讨BARD...目的通过检测乳腺黏液癌（以M表述）及浸润性导管癌（符合基底细胞样癌分子分型诊断标准：以D-B表述）标本中乳腺癌阻抑蛋白1关联RING蛋白1（BRCA1-associated RING domain,BARD1）剪切变异体表达水平的差异,结合术后随访结果,探讨BARD1基因在乳腺癌中可能的临床意义。方法以本院乳腺中心标本库储存的43例M标本及39例D-B标本提取的目的基因进行RT-PCR,对相应病例石蜡包埋组织切片进行病理免疫组织化学检测;患者术后每半年随访1次,记录无病生存期（disease free survival,DFS）及总生存期（overall survival,OS）;分析BARD1基因的临床意义。结果在所有标本中共发现4种BARD1基因的转录产物：全长BARD1基因（full lenth,Fl）,剪切变异体γ、δ和ε,其中Fl在所有组织中均有表达,剪切变异体δ和ε在M中的阳性表达率低于D-B（P〈0.005）;免疫组织化学检测发现在D-B中BARD1蛋白阳性细胞比率显著高于M（P〈0.005）,两种癌组织中蛋白均异位表达于细胞质中;BARD1剪切变异体的阳性表达与乳腺癌预后差的因素有关（P〈0.05）。研究病例术后随访36~70个月,单因素分析发现,剪切变异体ε阳性表达与乳腺癌术后无病生存期及总生存期缩短均显著相关（P〈0.05）。结论 BARD1剪切变异体在不同类型乳腺癌中的表达存在差异;与正常组织细胞相比,BARD1剪切变异体异位表达在肿瘤细胞质中;剪切变异体δ和ε与乳腺癌预后差的因素相关,并且剪切变异体ε阳性表达的患者无病生存期及总生存期均显著缩短。因此BARD1剪切变异体的异常表达或许影响乳腺癌的生物学行为,进而影响乳腺癌的预后。展开更多
目的探讨乳腺癌基因1相关环指结构域蛋白1（BRCA1 associated RING domain1，BARD1）剪切变异体在乳腺癌组织中的表达及其临床意义。方法对北京医院乳腺中心液氮冷冻储存的39例汉族女性散发性乳腺癌组织、12例癌旁乳腺组织和7例正常汉...目的探讨乳腺癌基因1相关环指结构域蛋白1（BRCA1 associated RING domain1，BARD1）剪切变异体在乳腺癌组织中的表达及其临床意义。方法对北京医院乳腺中心液氮冷冻储存的39例汉族女性散发性乳腺癌组织、12例癌旁乳腺组织和7例正常汉族女性乳腺组织提取目的基因，检测BARD1剪切变异体在不同组织中的表达状况，分析剪切变异体在不同组织中表达的差异及其临床意义。结果在各种组织中共发现4种BARD1基因的转录产物，分别为全长基因、剪切变异体γ、剪切变异体δ、剪切变异体ε。全长BARD1基因在所有组织中均有表达；剪切变异体儿8在乳腺癌组织阳性表达率明显高于其他两组，差异有统计学意义（P〈0．05）。在癌组织中，剪切变异体的表达种类明显增多，与癌旁组织和正常组织相比差异均有统计学意义（P=0．0075）。剪切变异体s在组织分级3级、HER2阳性表达、肿瘤直径大的乳腺癌组织和预后较差的病理类型中表达明显增多，差异有统计学意义（P〈0．05）。结论BARD1剪切变异体在汉族女性散发性乳腺癌组织、癌旁组织及汉族女性正常乳腺组织中的表达存在差异；肿瘤组织中检测到剪切变异体ε的表达的患者预后可能较差。展开更多
This work extends our previous understanding concerning the nonlinear responses of entangled polymer solutions and melts to large external deformation in both simple shear and uniaxial extension. Many similarities hav...This work extends our previous understanding concerning the nonlinear responses of entangled polymer solutions and melts to large external deformation in both simple shear and uniaxial extension. Many similarities have recently been identified for both step strain and startup continuous deformation, including elastic yielding, i.e., chain disentanglement after cessation of shear or extension, and emergence of a yield point during startup deformation that involves a deformation rate in excess of the dominant molecular relaxation rate. At a sufficiently high constant Hencky rate, uniaxial extension of an entangled melt is known to produce window-glass-like rupture. The present study provides evidence against the speculation that chain entanglements tie up into "dead knots" in constant-rate extension because of the exponentially growing chain stretching with time. In particular, it is shown that even Instron-style tensile stretching, i.e., extending a specimen by applying a constant velocity on both ends, results in rupture. Yet, in the same rate range, the same entangled melt only yields in simple shear, and the resulting shear banding is clearly not a characteristic of rupture. Thus, we conclude that chain entanglements respond to simple shear in the manner of yielding whereas uniaxial extension is rather effective in causing some entanglements to lock up, making it impossible for the entanglement network to yield at high rates.展开更多
文摘目的探讨乳腺癌基因1相关环指结构域蛋白1（BRCA1 associated RING domain1，BARD1）剪切变异体在乳腺癌组织中的表达及其临床意义。方法对北京医院乳腺中心液氮冷冻储存的39例汉族女性散发性乳腺癌组织、12例癌旁乳腺组织和7例正常汉族女性乳腺组织提取目的基因，检测BARD1剪切变异体在不同组织中的表达状况，分析剪切变异体在不同组织中表达的差异及其临床意义。结果在各种组织中共发现4种BARD1基因的转录产物，分别为全长基因、剪切变异体γ、剪切变异体δ、剪切变异体ε。全长BARD1基因在所有组织中均有表达；剪切变异体儿8在乳腺癌组织阳性表达率明显高于其他两组，差异有统计学意义（P〈0．05）。在癌组织中，剪切变异体的表达种类明显增多，与癌旁组织和正常组织相比差异均有统计学意义（P=0．0075）。剪切变异体s在组织分级3级、HER2阳性表达、肿瘤直径大的乳腺癌组织和预后较差的病理类型中表达明显增多，差异有统计学意义（P〈0．05）。结论BARD1剪切变异体在汉族女性散发性乳腺癌组织、癌旁组织及汉族女性正常乳腺组织中的表达存在差异；肿瘤组织中检测到剪切变异体ε的表达的患者预后可能较差。
基金supported, in part, by the National Science Foundation of the United States (DMR-0821697, CMMI-0926522, DMR-1105135)
文摘This work extends our previous understanding concerning the nonlinear responses of entangled polymer solutions and melts to large external deformation in both simple shear and uniaxial extension. Many similarities have recently been identified for both step strain and startup continuous deformation, including elastic yielding, i.e., chain disentanglement after cessation of shear or extension, and emergence of a yield point during startup deformation that involves a deformation rate in excess of the dominant molecular relaxation rate. At a sufficiently high constant Hencky rate, uniaxial extension of an entangled melt is known to produce window-glass-like rupture. The present study provides evidence against the speculation that chain entanglements tie up into "dead knots" in constant-rate extension because of the exponentially growing chain stretching with time. In particular, it is shown that even Instron-style tensile stretching, i.e., extending a specimen by applying a constant velocity on both ends, results in rupture. Yet, in the same rate range, the same entangled melt only yields in simple shear, and the resulting shear banding is clearly not a characteristic of rupture. Thus, we conclude that chain entanglements respond to simple shear in the manner of yielding whereas uniaxial extension is rather effective in causing some entanglements to lock up, making it impossible for the entanglement network to yield at high rates.
