β-catenin in intranuclear inclusions of hepatocellular carcinoma

来源 :肝癌研究(英文版) | 被引量 : 0次 | 上传用户:oishiocean
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
Aim: β-catenin activation is known to promote liver regeneration and play a role in the pathogenesis of liver cancer. Recently, we detected intranuclear inclusions (NI) in hepatocellular carcinoma (HCC) containing degenerated cell organelles and lysosomal proteins and delimited by a completely closed nuclear membrane. The presence of NI was positively associated with patient survival. The aim of the current study was to investigate a possible association between proteins of the Wnt/β-catenin pathway with NI morphology and survival.Methods: We examined NI in 72 paraffin-embedded specimens of HCC. Immunohistochemistry (IHC) and immunofluorescence (IF) were performed to investigate the content and shape of NI. β-catenin gene (CTNNB1 ) mutations were analyzed by next generation sequencing. Results: We detected the accumulation of β-catenin and glutamine synthetase (a target gene of β-catenin) proteins within NI. Further, we found immunopositivity for the lysine demethylase KDM2A in NI. KDM2A is known to be involved in β-catenin degradation. We detected significant associations between the presence of β-catenin and autophagy-associated proteins in NI. Double-IF revealed co-localization of β-catenin and p62 in the same NI. Kaplan-Meier survival analysis showed that the presence of NI containing KDM2A protein accumulations displayed a significant benefit in overall survival. Conclusion: We detected accumulations of β-catenin and proteins associated with the Wnt/β-catenin pathway partly together with autophagy-associated proteins in the same inclusion. Our finding that KDM2A immunopositivity within NIs was associated with favorable clinical outcomes and suggests a biological significance of NI.
其他文献
牙周炎为牙菌斑导致的牙周组织炎症,可累及牙骨质、牙周膜及牙槽骨,由CD4+T细胞引发的免疫反应是牙周炎加重的关键因素,树突状细胞及核因子⁃κB受体活化因子配体(receptor activatorofNF⁃κB li⁃gand,RANKL)途径的激活是牙槽骨吸收的重要环节,促炎因子IFN⁃γ、TNF⁃α、IL⁃1β在牙周炎的发生发展中亦发挥重要作用。白细胞介素⁃37(interleukin⁃37,IL⁃37)为IL⁃1家族新发现的细胞因子,具有a~e共5个剪切变异体,其中由第4号外显
目前心脏骤停(Cardiac Arrest,CA)已成为全球性的重大公共卫生问题,发病率高,生存率低。体外心肺复苏(Extracorporeal Cardiopulmonary Resuscitation,ECPR)作为一种新的支持治疗手段,可以缩短传统CPR的时间,提高CA患者的生存率。而在ECPR的发展中,动物模型的建立对于ECPR技术的深入探索和推广起着重要的作用。本文对目前ECPR动物模型的研究进行了回顾,主要包括以大鼠和猪为主的ECPR动物模型的动物选取、模型建立方法以及检测指标方面目前主流的研
Aim: To describe the global pattern and trend of liver cancer survival, using data from the population-based studies or cancer registration.Methods: By searchin
The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73, the two other members of the p53 fa
目的探讨颌面颈部巨大神经纤维瘤的多学科诊疗模式,为临床提供参考。方法由口腔颌面外科主诊,麻醉科、ICU、血管外科、胸外科等多学科参与、共同制定治疗方案的2例颌面颈部巨大神经纤维瘤患者实施围术期全程管理的流程进行回顾性分析。结果2例患者的多学科治疗过程(麻醉⁃栓塞⁃协同手术⁃ICU复苏⁃术后管理)均按术前计划顺利实施,术中未出现多学科风险评估未预测到的不良事件或意外,均完成手术治疗,且未发生严重并发症。2例术后病理报告均为神经纤维瘤,患者伤口均I期愈合。结论多学科诊疗模式可在颌面颈部巨大神经纤维瘤的诊治中发
多项研究已经证明了心脏再同步化治疗(CRT)在慢性心力衰竭患者中的有益作用,但仍有20%~40%的患者不能从中获益。CRT无反应或反应不佳有多种潜在原因。左心室电极植入位点的的选择及植入方式是决定CRT疗效的关键性因素。因此,本文就左心室最佳起搏位点的选择机制与植入方案的进展做一综述。
糖尿病相关心力衰竭是临床常见的慢性疾病,其发病涉及多种机制。钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂在多个糖尿病相关临床试验中观察到可以改善心力衰竭患者预后,成为心力衰竭治疗领域的值得关注的药物。本文将介绍糖尿病相关心力衰竭的发病机制、SGLT-2抑制剂治疗心力衰竭的可能机制及糖尿病相关心力衰竭的临床管理,重点介绍SGLT-2抑制剂在心力衰竭中的应用。
Patients with unresectable cholangiocarcinoma (CCA) face a poor prognosis, and there are few effective treatment options for the disease. The standard of care f
目的设计一套核事故医学应急救援模拟训练系统,用于提升受训者在遭遇突发核事故情况下的医学应急救援处置能力。方法分析核事故现场常见伤情,结合医学应急救援流程,利用虚拟现实技术、建模仿真技术、大空间定位技术和动作捕捉技术等进行突发事故模拟、伤员伤情模拟、救援流程模拟等相应功能模块模拟仿真,实现系统功能。结果该系统实现了核事故医学应急救援模拟操作训练,可开展教学和评估。结论该系统实现了核事故现场医学应急救援的训练手段的信息化,缩短了训练周期,降低了训练成本,提升了训练效果。
慢性鼻-鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)是临床常见疾病,复发率较高。对于部分应用传统鼻内镜手术和常规药物疗效并不理想的患者,奥马珠单抗可能成为他们的治疗选择之一。奥马珠单抗是一种重组人源化单克隆抗体,近年来国外应用其治疗CRSwNP的文献多显示出良好的应用前景。本文对目前奥马珠单抗治疗CRSwNP的临床研究进展做一综述