目的:观察人结直肠癌组织磷酸化哺乳动物雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、表皮生长因子受体(EGFR)、生长因子受体结合蛋白2(Grb2)和血管内皮生长因子(VEGF)等的表达,并探讨其可能的临床意义。方...目的:观察人结直肠癌组织磷酸化哺乳动物雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、表皮生长因子受体(EGFR)、生长因子受体结合蛋白2(Grb2)和血管内皮生长因子(VEGF)等的表达,并探讨其可能的临床意义。方法:构建含有185例结直肠癌标本的组织芯片,免疫组化法检测结直肠癌组织及癌旁组织中EGFR、Grb2、p-mTOR和VEGF的表达,并分析不同结直肠癌临床病理学特征下(如年龄、性别、浸润深度、淋巴转移、临床分期和分化程度)各自的表达情况,探讨可能的临床意义。结果:EGFR、Grb2、p-mTOR和VEGF在结直肠癌旁组织中呈少量表达或不表达,在结直肠癌组织中的表达率分别为21.1%、44.9%、42.2%和54.1%,明显高于癌旁组织(P<0.05)。结直肠癌患者不同性别、年龄、肿瘤分化程度下EGFR、Grb2、p-mTOR和VEGF表达率无统计学差异;不同浸润深度和临床分期下EGFR的表达率有统计学差异(P<0.05);不同浸润深度、淋巴转移和临床分期下p-mTOR、VEGF表达率均有统计学差异(P<0.05)。结直肠癌组织EGFR/Grb2/p-mTOR/VEGF蛋白两两间均有一定的相关性(r=0.245～0.567,P<0.05)。结论:EGFR、Grb2、p-mTOR和VEGF表达与结直肠癌的发生、发展相关,值得进一步研究以作为结直肠癌肿瘤靶向治疗新的作用靶点。展开更多
目的:为更深入了解α-硫辛酸如何影响复杂信号通路间的相互作用抑制细胞增殖。方法:我们凭借RNA-Seq与同位素相对标记与绝对定量技术,对α-LA处理24 h HepG2细胞在转录和蛋白表达水平的变化差异进行分析,并借助实时定量PCR免疫印迹技术...目的:为更深入了解α-硫辛酸如何影响复杂信号通路间的相互作用抑制细胞增殖。方法:我们凭借RNA-Seq与同位素相对标记与绝对定量技术,对α-LA处理24 h HepG2细胞在转录和蛋白表达水平的变化差异进行分析,并借助实时定量PCR免疫印迹技术对组学数据进行了鉴定。结果:转录组学提示共有4,446个基因(2,097个基因表达下调,2,349个基因表达上调)的表达在α-LA处理24 h后呈现显著性改变。GO分析提示,编码肿瘤相关细胞膜蛋白的基因是受α-LA影响最为显著的一类mRNA;蛋白质组学进一步提示Grb2可能是受α-LA调控的膜受体信号通路中关键的靶分子。结论:α-LA抑制HCC细胞增殖是通过下调Grb2介导的相关通路而实现。展开更多
Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC ...Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC autophagy remains unclear.In this study,we aimed to explore the role of the GRB2 associated binding protein 1(GAB1)in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression.Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima.Gain-and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor(0.80 vs.0.20,t=6.43,P<0.05).The expression level of GAB1 mRNA(1.00 vs.0.24,t=7.41,P<0.05)and protein(0.72 vs.0.21,t=5.97,P<0.05)was significantly decreased in ASO group as compared with the control group.Loss of GAB1 led to a remarkable decrease in LC3II(1.19 vs.0.68,t=5.99,P<0.05),whereas overexpression of GAB1 significantly led to a decrease in LC3II level(0.41 vs.0.93,t=7.12,P<0.05).Phosphorylation levels of JNK and p38 were significantly associated with gain-and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO.GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.展开更多
文摘目的:观察人结直肠癌组织磷酸化哺乳动物雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、表皮生长因子受体(EGFR)、生长因子受体结合蛋白2(Grb2)和血管内皮生长因子(VEGF)等的表达,并探讨其可能的临床意义。方法:构建含有185例结直肠癌标本的组织芯片,免疫组化法检测结直肠癌组织及癌旁组织中EGFR、Grb2、p-mTOR和VEGF的表达,并分析不同结直肠癌临床病理学特征下(如年龄、性别、浸润深度、淋巴转移、临床分期和分化程度)各自的表达情况,探讨可能的临床意义。结果:EGFR、Grb2、p-mTOR和VEGF在结直肠癌旁组织中呈少量表达或不表达,在结直肠癌组织中的表达率分别为21.1%、44.9%、42.2%和54.1%,明显高于癌旁组织(P<0.05)。结直肠癌患者不同性别、年龄、肿瘤分化程度下EGFR、Grb2、p-mTOR和VEGF表达率无统计学差异;不同浸润深度和临床分期下EGFR的表达率有统计学差异(P<0.05);不同浸润深度、淋巴转移和临床分期下p-mTOR、VEGF表达率均有统计学差异(P<0.05)。结直肠癌组织EGFR/Grb2/p-mTOR/VEGF蛋白两两间均有一定的相关性(r=0.245～0.567,P<0.05)。结论:EGFR、Grb2、p-mTOR和VEGF表达与结直肠癌的发生、发展相关,值得进一步研究以作为结直肠癌肿瘤靶向治疗新的作用靶点。
文摘目的:为更深入了解α-硫辛酸如何影响复杂信号通路间的相互作用抑制细胞增殖。方法:我们凭借RNA-Seq与同位素相对标记与绝对定量技术,对α-LA处理24 h HepG2细胞在转录和蛋白表达水平的变化差异进行分析,并借助实时定量PCR免疫印迹技术对组学数据进行了鉴定。结果:转录组学提示共有4,446个基因(2,097个基因表达下调,2,349个基因表达上调)的表达在α-LA处理24 h后呈现显著性改变。GO分析提示,编码肿瘤相关细胞膜蛋白的基因是受α-LA影响最为显著的一类mRNA;蛋白质组学进一步提示Grb2可能是受α-LA调控的膜受体信号通路中关键的靶分子。结论:α-LA抑制HCC细胞增殖是通过下调Grb2介导的相关通路而实现。
基金supported by the grants from the Shanghai Municipal Science and Technology Commission(No.14430721400)National Natural Science Foundation(Nos.81700421 and 81670442)Clinical innovative research funding of Shanghai Jiaotong University School of Medicine(No.PY2018-IIC-05)。
文摘Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC autophagy remains unclear.In this study,we aimed to explore the role of the GRB2 associated binding protein 1(GAB1)in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression.Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima.Gain-and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor(0.80 vs.0.20,t=6.43,P<0.05).The expression level of GAB1 mRNA(1.00 vs.0.24,t=7.41,P<0.05)and protein(0.72 vs.0.21,t=5.97,P<0.05)was significantly decreased in ASO group as compared with the control group.Loss of GAB1 led to a remarkable decrease in LC3II(1.19 vs.0.68,t=5.99,P<0.05),whereas overexpression of GAB1 significantly led to a decrease in LC3II level(0.41 vs.0.93,t=7.12,P<0.05).Phosphorylation levels of JNK and p38 were significantly associated with gain-and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO.GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
