目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照...目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照组,检测各组PNPLA3、Sort1基因多态性。结果 PNPLA3基因rs738409位点检测出CC、CG、GG三种基因型,Sort1基因rs646776位点检测出CC、TC、TT三种基因型;病例组PNPLA3基因GG型和等位基因G的比例分布为23.64%和45.45%,明显高于无肝病嗜酒组和对照组(P<0.05);各组Sort1基因多态性分布差异比较无统计学意义(P>0.05);病例组不同PNPLA3基因型患者甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density liptein cholesterol,HDL-C)和低密度脂蛋白胆固醇(Low Density Lipoprotein Chesterol,LDL-C)比较差异无统计学意义(P>0.05);病例组Sort1基因TT型患者TG为1.61±0.30mmol/L,高于CC+CT型患者,而HDL-C为1.80±0.65mmol/L,低于CC+CT型患者(P<0.05)。结论 PNPLA3基因多态性与酒精性肝病易感性有一定关系,Sort1基因多态性与酒精性肝病易感性无明显关系,但与患者的血脂水平具有一定的相关性。展开更多
The drug gefitinib, a specific inhibitor of EGFR tyrosine kinase, has been shown to suppress the activation of EGFR signaling for survival and cell proliferation in non-small cell lung cancer cell lines. For many year...The drug gefitinib, a specific inhibitor of EGFR tyrosine kinase, has been shown to suppress the activation of EGFR signaling for survival and cell proliferation in non-small cell lung cancer cell lines. For many years, EGFR endocytosis has served as a model for investigating ligand-induced, receptor-mediated endocytosis. On EGF stimulation, EGFR is internalized and transported via clathrin-coated vesicles to early endosomes, and EGFR then recruits and phosphorylates signaling molecules, leading to the activation of downstream signaling such as MAPK/PI3K/AKT pathways-an important mechanism for regulating cell growth. Once delivered to the lysosomes, EGFR is degraded to terminate intracellular EGFR signaling via endocytosis;this process is known as receptor downregulation. Therefore, the endocytosis of EGFR is closely related with attenuation of intracellular EGFR signaling. Alternatively, EGFR is returned to cell surface from early endosomes for the continued signaling. Previous reports revealed that a competent EGF-induced endocytosis of EGFR followed by its rapid downregulation efficiently proceeds in the gefitinib-sensitive NSCLC cell lines. In contrast, gefitinib-resistant cell lines showed that EGFR endocytosis is impaired and the internalized EGFR is aggregated in the early endosomes, which is associated with the overexpressed sorting nexin 1 (SNX1), initially identified as a protein that interacts with EGFR. Thus dysregulated EGFR endocytosis is implicated in gefitinib resistance, as it leads to uncontrolled signal transduction. At present, the therapeutic relevance of EGFR endocytosis with regard to drug resistance in lung cancer has not been clarified. This review focused on the mechanism for EGFR endocytosis associated with SNX1 trafficking in gefitinib-resistant lung cancer cells.展开更多
文摘目的探讨PNPLA3、Sort1基因多态性与酒精性肝病易感性的关系。方法选取2017年1月至2018年3月于我院治疗的已确诊酒精性肝病患者110例为病例组,同时选取长期大量饮酒但未被诊断酒精性肝病患者100例为无肝病嗜酒组、健康自愿者200例为对照组,检测各组PNPLA3、Sort1基因多态性。结果 PNPLA3基因rs738409位点检测出CC、CG、GG三种基因型,Sort1基因rs646776位点检测出CC、TC、TT三种基因型;病例组PNPLA3基因GG型和等位基因G的比例分布为23.64%和45.45%,明显高于无肝病嗜酒组和对照组(P<0.05);各组Sort1基因多态性分布差异比较无统计学意义(P>0.05);病例组不同PNPLA3基因型患者甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density liptein cholesterol,HDL-C)和低密度脂蛋白胆固醇(Low Density Lipoprotein Chesterol,LDL-C)比较差异无统计学意义(P>0.05);病例组Sort1基因TT型患者TG为1.61±0.30mmol/L,高于CC+CT型患者,而HDL-C为1.80±0.65mmol/L,低于CC+CT型患者(P<0.05)。结论 PNPLA3基因多态性与酒精性肝病易感性有一定关系,Sort1基因多态性与酒精性肝病易感性无明显关系,但与患者的血脂水平具有一定的相关性。
文摘The drug gefitinib, a specific inhibitor of EGFR tyrosine kinase, has been shown to suppress the activation of EGFR signaling for survival and cell proliferation in non-small cell lung cancer cell lines. For many years, EGFR endocytosis has served as a model for investigating ligand-induced, receptor-mediated endocytosis. On EGF stimulation, EGFR is internalized and transported via clathrin-coated vesicles to early endosomes, and EGFR then recruits and phosphorylates signaling molecules, leading to the activation of downstream signaling such as MAPK/PI3K/AKT pathways-an important mechanism for regulating cell growth. Once delivered to the lysosomes, EGFR is degraded to terminate intracellular EGFR signaling via endocytosis;this process is known as receptor downregulation. Therefore, the endocytosis of EGFR is closely related with attenuation of intracellular EGFR signaling. Alternatively, EGFR is returned to cell surface from early endosomes for the continued signaling. Previous reports revealed that a competent EGF-induced endocytosis of EGFR followed by its rapid downregulation efficiently proceeds in the gefitinib-sensitive NSCLC cell lines. In contrast, gefitinib-resistant cell lines showed that EGFR endocytosis is impaired and the internalized EGFR is aggregated in the early endosomes, which is associated with the overexpressed sorting nexin 1 (SNX1), initially identified as a protein that interacts with EGFR. Thus dysregulated EGFR endocytosis is implicated in gefitinib resistance, as it leads to uncontrolled signal transduction. At present, the therapeutic relevance of EGFR endocytosis with regard to drug resistance in lung cancer has not been clarified. This review focused on the mechanism for EGFR endocytosis associated with SNX1 trafficking in gefitinib-resistant lung cancer cells.
