【摘 要】
：
Background Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis.T
【机 构】
：
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education;Liver Cancer Institute,
论文部分内容阅读
Background Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis.Though it has been suggested HA is involved in progression of HCC, the mechanisms underlying the connection between HA and HCC progression are unclear.Since increased aerobic glycolysis is a metabolic trait of malignant cells and HA-CD44 can modulate glucose metabolism, we aim to investigat the roles of PKM2, a key enzyme in glucose metabolism, in the HA-CD44 axis facilitated the progress of HCC.Methods The effects of HA on HCCs proliferation, metastasis potential and aerobic glycolysis switch were investigated.Lentiviruses transfections were performed to establish PKM2 silenced, over-expressed, or mutated HCC cell lines, which enabled the role of PKM2 in HA-induced HCC progression and its underlying mechanism to be systematically dissected.Furthermore, the expression pattern and the relationship of HA and PKM2 in 105 human HCC liver tissues were examined.Result PKM2 was required for HA-promoted HCC progression, which was not modulated by PKM2 kinase activity but by nuclear translocation of PKM2.PKM2 translocation was Erk (Thr202/Tyr204) phosphorylation dependent, which functioned at the downstream of HA-CD44 binding.Furthermore, elevated HA expression significantly correlated with PKM2 nuclear location and was an independent factors predicting poor HCC prognosis.Conclusion PKM2 nuclear translocation is required for mediating the described HA biological effects on HCC progression and our results imply that inhibition of HA may have therapeutic value in treating HCC.
其他文献
随着肝硬化病程的进展,门脉高压和肝功能减退等症状不断加重,导致病人生活质量明显下降,尤以门脉高压症所致各类并发症使患者预后不良、病死率增加.但当前临床上使用的治疗药物并不能达到十分理想的疗效,尤其对于肝硬化晚期病人药物干预疗效更差.近年随着肝硬化门脉高压治疗研究的增多,对肝硬化门脉高压的干预手段也不断丰富,为门脉高压患者带来了希望.而非手术治疗是临床上应用最多的干预措施,下面本文将从药物治疗、介入
目的:通过肝脏瞬时弹性扫描技术和肝纤维化4项血清学指标,综合分析评价慢性肝病患者肝纤维化程度,为肝纤维化准确诊断及判断肝纤维化的进程提供更加可靠的依据.方法:对同一肝病患者同时做两项检查,一是通过化学发光法对患者血清肝纤维化4项(透明质酸HA,层黏蛋白LN,Ⅲ型前胶原PCⅢ,Ⅳ型胶原CⅣ)进行定量测定;二是通过瞬时弹性成像技术测量肝硬度值(liver stiffness measurement,L
目的:探讨ARID2对人肝癌细胞系凋亡的影响,明确ARID2是否是通过线粒体信号通路诱导肿瘤细胞的发生凋亡.方法:人肝癌细胞系HepG2、SK-Hep1分别被转染ARID2质粒96h后,并给予AnnexinV-FITC/7-AAD,JC-1染料染色30min后.流式细胞术分别被用于检测肝癌细胞的凋亡率以及肝癌细胞的线粒体膜势能的变化.荧光显微镜被用于观察染色后肝癌细胞形态学的变化.采用caspas
乙肝病毒(Hepatitis B Virus,HBV)是一种呈世界性分布、危害严重的传染病,每年导致超过60万人死于原发性肝癌和肝硬化.而肝细胞性肝癌是全世界最常见的恶性肿瘤之一,预后极差,同时肝癌早期诊断率低和影响预后因素广泛而有效干预手段少.MiRNA作为广泛生物学作用的内源性RNA,其在循环血中的稳定存在,已被证实与癌症包括肝癌的发生发展具有密切的生物学相关性,使之具备了成为肝癌诊断和预后生
目的:SALL4作为一种新的肝癌干细胞标志物逐渐被研究,有报道称其表达和预后相关,但其阳性率存在东、西方差异,作为肝癌预后标志物的价值有待被进一步证实,本研究目的是明确SALL4在肝癌中的表达情况及其临床病理特征,确证SALL4表达与肝癌进展及预后的相关性及其作为独立肝癌预后预测因素的可能性.方法:收集本院2015年1月-2015年12月收治的34例肝癌患者的肝切除或肝移植术后标本,选取相关的人口
目的:探讨HBV携带者危害及临床防治的价值.方法:从一个五万人居住区的45人肝硬化、肝癌患者进行回顾性调查,其中慢性乙型肝炎(CHB)12例,占26％,HBV携带者33人,占73％.在这45人中已死亡29人,占64％,死亡人数中CHB7例,占24％,HBV携带者22例,占76％.2008年8月-2015年11月对76例成人HBV携带者用乙肝免疫球蛋白(HB1G)乙肝疫苗(CHO)双嘧达莫联合治疗.
目的:探讨慢性乙型肝炎(CHB)及肝硬化患者血清纤维化指标透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳc)、人Ⅲ型前胶原(PCⅢ)含量及丙氨酸氨基转移酶(ALT)水平与病情严重程度的关系.方法:以30例正常体检人员为对照,检测129例CHB及肝硬化患者血清HA、LN、Ⅳc、PCⅢ的含量及ALT水平,同时结合临床特点,运用统计学方法对上述血清学指标的诊断价值进行分析.结果:CHB患者血清HA、
Objective To evaluate the survival benefit of non-bioartificial liver support system(NBALs) in the treatment of acute or chronic liver failure(ACLF) via a meta-analysis of randomized controlled trials
Background It is well established that some irradiated liver non-parenchymal cells secrete proinflammatory cytokines to facilitate the development of radiation-induced liver disease.However, little is
目的:探讨恩替卡韦联合细胞因子诱导的杀伤细胞(CIK)治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效及安全性.方法:收集50例HBeAg阳性CHB患者,其中治疗组20例,采用恩替卡韦联合CIK治疗,对照组30例,单用恩替卡韦治疗.观察所有患者治疗前及治疗后第12、24、48周肝功能、HBV血清标志物和HBV DNA水平并进行统计学分析,同时对不良反应进行评估.数据处理均用SPSS17.0软件进