Pancreatic cancer,specifically pancreatic ductal adenocarcinoma(PDAC),ranks among the most prevalent malignancies and is a leading cause of cancer-related mortality worldwide.Therefore,there is an urgent need to ident...Pancreatic cancer,specifically pancreatic ductal adenocarcinoma(PDAC),ranks among the most prevalent malignancies and is a leading cause of cancer-related mortality worldwide.Therefore,there is an urgent need to identify novel anti-pancreatic cancer agents.This study reports a newly identified homogeneous polysaccharide,designated ESPPW,isolated from Arthrospira platensis(A.platensis).The molecular weight of ESPPW is estimated at 356 kDa,and it consists predominantly of glucose and rhamnose,with minor amounts of mannose,glucuronic acid,galacturonic acid,galactose,xylose,arabinose,and fucose.ESPPW inhibits the proliferation and migration of PDAC cells both in vitro and in vivo.Mechanistic investigations reveal that ESPPW induces apoptosis through activation of caspase-3 and is associated with upregulation of the tumor-suppressor protein p53.Notably,treatment with 2.8 nmol·L^(-1) of ESPPW leads to significant time-dependent downregulation of galectin-3(Gal-3)and glypican-6(GPC-6).These findings are corroborated by immunohistochemical analysis of tumor xenograft tissues.Furthermore,overexpression of Gal-3 and GPC-6 reverses the pro-apoptotic effect of ESPPW,as indicated by restored cycle regulatory proteins(CDK2)expression.In conclusion,these data demonstrate that ESPPW suppresses PDAC cell growth by promoting apoptosis and disrupting the functional activity of Gal-3 and GPC-6.展开更多
目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与...目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与鼻咽癌患者免疫密切相关的基因Tim-3及其配体Galectin-9作为研究基因;收集2018年3月~2022年3月广西壮族自治区民族医院收治的65例鼻咽癌患者的肿瘤组织、同期65例鼻咽部炎性标本组织及对应鼻咽癌患者放疗前后应用免疫细胞病理芯片技术检测的外周血T细胞亚群变化的数据,并做随访观察。结果生物信息学分析TCGA数据库中鼻咽癌的测序数据,结果显示,Tim-3在大部分肿瘤组织中呈高表达,在鼻咽癌组织中较癌旁正常组织表达水平显著上调,Tim-3及其配体Galectin-9在癌组织中的表达呈正相关;免疫组化结果显示,鼻咽癌组织中Tim-3和Galectin-9的表达水平均显著高于鼻咽部炎性组织(P<0.05);鼻咽癌组织中Tim-3和Galectin-9高表达与淋巴结受累(P<0.05)以及更晚的TNM分期(P<0.05)紧密相关;Tim-3和Galectin-9的表达水平与患者年龄、性别及EB病毒感染等因素无关(P>0.05);Tim-3和Galectin-9在鼻咽癌中的表达呈正相关(r=0.313,P=0.011);随访发现,Tim-3和Galectin-9的高表达可能与鼻咽癌的不良预后相关;鼻咽癌患者放疗前3天和放疗后7天的T淋巴细胞亚群检测显示,CD4+、CD4+/CD8+较放疗前显著下降(P<0.05),CD3+与CD8+变化差异无统计学意义(P>0.05);Tim-3和Galectin-9蛋白阳性组患者放疗敏感度明显高于于Tim-3和Galectin-9阴性组(P<0.05)。结论Tim-3/Galectin-9信号通路在鼻咽癌发生、发展和转移中起重要作用,T细胞免疫在鼻咽癌治疗中发挥重要作用。联合检测鼻咽癌组织中Tim-3和Galectin-9及T细胞亚群的变化可能为临床评估肿瘤监测病情及肿瘤免疫治疗提供新参数。展开更多
基金supported by Shanghai Municipal Science and Technology Major Projectthe Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA12020373)+2 种基金the New Drug Creation and Manufacturing Program(No.2019ZX09735001)the Ministry of Science and Technology,the People's Republic of China and National Natural Science Foundation of China(No.81903762)the Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University,No.CMEMR2016-B02)。
文摘Pancreatic cancer,specifically pancreatic ductal adenocarcinoma(PDAC),ranks among the most prevalent malignancies and is a leading cause of cancer-related mortality worldwide.Therefore,there is an urgent need to identify novel anti-pancreatic cancer agents.This study reports a newly identified homogeneous polysaccharide,designated ESPPW,isolated from Arthrospira platensis(A.platensis).The molecular weight of ESPPW is estimated at 356 kDa,and it consists predominantly of glucose and rhamnose,with minor amounts of mannose,glucuronic acid,galacturonic acid,galactose,xylose,arabinose,and fucose.ESPPW inhibits the proliferation and migration of PDAC cells both in vitro and in vivo.Mechanistic investigations reveal that ESPPW induces apoptosis through activation of caspase-3 and is associated with upregulation of the tumor-suppressor protein p53.Notably,treatment with 2.8 nmol·L^(-1) of ESPPW leads to significant time-dependent downregulation of galectin-3(Gal-3)and glypican-6(GPC-6).These findings are corroborated by immunohistochemical analysis of tumor xenograft tissues.Furthermore,overexpression of Gal-3 and GPC-6 reverses the pro-apoptotic effect of ESPPW,as indicated by restored cycle regulatory proteins(CDK2)expression.In conclusion,these data demonstrate that ESPPW suppresses PDAC cell growth by promoting apoptosis and disrupting the functional activity of Gal-3 and GPC-6.
文摘目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与鼻咽癌患者免疫密切相关的基因Tim-3及其配体Galectin-9作为研究基因;收集2018年3月~2022年3月广西壮族自治区民族医院收治的65例鼻咽癌患者的肿瘤组织、同期65例鼻咽部炎性标本组织及对应鼻咽癌患者放疗前后应用免疫细胞病理芯片技术检测的外周血T细胞亚群变化的数据,并做随访观察。结果生物信息学分析TCGA数据库中鼻咽癌的测序数据,结果显示,Tim-3在大部分肿瘤组织中呈高表达,在鼻咽癌组织中较癌旁正常组织表达水平显著上调,Tim-3及其配体Galectin-9在癌组织中的表达呈正相关;免疫组化结果显示,鼻咽癌组织中Tim-3和Galectin-9的表达水平均显著高于鼻咽部炎性组织(P<0.05);鼻咽癌组织中Tim-3和Galectin-9高表达与淋巴结受累(P<0.05)以及更晚的TNM分期(P<0.05)紧密相关;Tim-3和Galectin-9的表达水平与患者年龄、性别及EB病毒感染等因素无关(P>0.05);Tim-3和Galectin-9在鼻咽癌中的表达呈正相关(r=0.313,P=0.011);随访发现,Tim-3和Galectin-9的高表达可能与鼻咽癌的不良预后相关;鼻咽癌患者放疗前3天和放疗后7天的T淋巴细胞亚群检测显示,CD4+、CD4+/CD8+较放疗前显著下降(P<0.05),CD3+与CD8+变化差异无统计学意义(P>0.05);Tim-3和Galectin-9蛋白阳性组患者放疗敏感度明显高于于Tim-3和Galectin-9阴性组(P<0.05)。结论Tim-3/Galectin-9信号通路在鼻咽癌发生、发展和转移中起重要作用,T细胞免疫在鼻咽癌治疗中发挥重要作用。联合检测鼻咽癌组织中Tim-3和Galectin-9及T细胞亚群的变化可能为临床评估肿瘤监测病情及肿瘤免疫治疗提供新参数。
