AIM:To provide further insight into the characterization of mucosa-associated Escherichia coli(E.coli)isolated from the colonic mucosa of cancer patients.METHODS:Phylogroups and the presence of cyclomodulin-encoding g...AIM:To provide further insight into the characterization of mucosa-associated Escherichia coli(E.coli)isolated from the colonic mucosa of cancer patients.METHODS:Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E.coli from colon cancer and diverticulosis specimens weredetermined by PCR.Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay.Carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot.Gut colonization,inflammation and procarcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice.Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.RESULTS:Analysis of mucosa-associated E.coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E.coli strains,86%of cyclomodulin-positive E.coli belonged to B2 phylogroup and most harbored polyketide synthase(pks)island,which encodes colibactin,and/or cytotoxic necrotizing factor(cnf)genes.In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E.coli strains were poorly adherent and invasive.However,mucosa-associated B2 E.coli similarly to Crohn’s disease-associated E.coli are able to induce CEACAM6expression in T84 intestinal epithelial cells.In addition,in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E.coli strain11G5 isolated from colon cancer is able to highly persist in the gut,and to induce colon inflammation,epithelial damages and cell proliferation.CONCLUSION:In conclusion,these data bring new insights into the ability of E.coli isolated from patients with colon cancer to establish persistent colonization,exacerbate inflammation and trigger carcinogenesis.展开更多
目的:探讨miR-3163调控癌胚抗原相关黏附分子6(CEACAM6)对顺铂耐药胃癌细胞AGS/DDP增殖和凋亡的影响。方法:RT-qPCR和Western blot检测AGS/DDP细胞及亲本细胞株AGS中miR-3163和CEACAM6表达。将AGS/DDP细胞分为DDP+miR-NC、DDP+miR-3163...目的:探讨miR-3163调控癌胚抗原相关黏附分子6(CEACAM6)对顺铂耐药胃癌细胞AGS/DDP增殖和凋亡的影响。方法:RT-qPCR和Western blot检测AGS/DDP细胞及亲本细胞株AGS中miR-3163和CEACAM6表达。将AGS/DDP细胞分为DDP+miR-NC、DDP+miR-3163、DDP+si-NC、DDP+si-CEACAM6、DDP+miR-3163+pcDNA和DDP+miR-3163+pcDNACEACAM6组。MTT、流式细胞术分别检测细胞增殖和凋亡。双荧光素酶报告实验和Western blot确定miR-3163与CEACAM6的相互作用。结果:与AGS细胞比较,AGS/DDP细胞miR-3163表达显著降低(0.58±0.06 vs 1.00±0.06),CEACAM6表达显著升高(0.61±0.06 vs 0.24±0.03,P<0.05)。与DDP+miR-NC组比较,DDP+miR-3163组AGS/DDP细胞增殖抑制率[(36.32±3.21)%vs(8.41±0.83)%]、凋亡率[(23.14±2.33)%vs(7.55±0.76)%]显著升高(P<0.05)。与DDP+si-NC组比较,DDP+si-CEACAM6组AGS/DDP细胞增殖抑制率[(31.29±3.18)%vs(7.65±0.77)%]、凋亡率[(19.74±1.83)%vs(6.22±0.63)%]显著升高(P<0.05)。与DDP+miR-3163+pcDNA组比较,DDP+miR-3163+pcDNA-CEACAM6组AGS/DDP细胞增殖抑制率[(18.64±1.58)%vs(39.87±3.77)%]、凋亡率[(10.59±1.04)%vs(24.18±2.43)%]显著降低(P<0.05)。miR-3163靶向负调控CEACAM6表达。结论:miR-3163靶向CEACAM6抑制顺铂耐药胃癌细胞增殖,诱导细胞凋亡,提高其对顺铂的敏感性。展开更多
Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the...Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.展开更多
基金Supported by Ministère de l’Enseignement supérieur et de la Recherche,Inserm and Universitéd’Auvergne(UMR1071),INRA(USC-2018)Grants from the Association F.Aupetit(AFA)and Ligue contre le cancer
文摘AIM:To provide further insight into the characterization of mucosa-associated Escherichia coli(E.coli)isolated from the colonic mucosa of cancer patients.METHODS:Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E.coli from colon cancer and diverticulosis specimens weredetermined by PCR.Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay.Carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot.Gut colonization,inflammation and procarcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice.Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.RESULTS:Analysis of mucosa-associated E.coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E.coli strains,86%of cyclomodulin-positive E.coli belonged to B2 phylogroup and most harbored polyketide synthase(pks)island,which encodes colibactin,and/or cytotoxic necrotizing factor(cnf)genes.In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E.coli strains were poorly adherent and invasive.However,mucosa-associated B2 E.coli similarly to Crohn’s disease-associated E.coli are able to induce CEACAM6expression in T84 intestinal epithelial cells.In addition,in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E.coli strain11G5 isolated from colon cancer is able to highly persist in the gut,and to induce colon inflammation,epithelial damages and cell proliferation.CONCLUSION:In conclusion,these data bring new insights into the ability of E.coli isolated from patients with colon cancer to establish persistent colonization,exacerbate inflammation and trigger carcinogenesis.
文摘目的:探讨miR-3163调控癌胚抗原相关黏附分子6(CEACAM6)对顺铂耐药胃癌细胞AGS/DDP增殖和凋亡的影响。方法:RT-qPCR和Western blot检测AGS/DDP细胞及亲本细胞株AGS中miR-3163和CEACAM6表达。将AGS/DDP细胞分为DDP+miR-NC、DDP+miR-3163、DDP+si-NC、DDP+si-CEACAM6、DDP+miR-3163+pcDNA和DDP+miR-3163+pcDNACEACAM6组。MTT、流式细胞术分别检测细胞增殖和凋亡。双荧光素酶报告实验和Western blot确定miR-3163与CEACAM6的相互作用。结果:与AGS细胞比较,AGS/DDP细胞miR-3163表达显著降低(0.58±0.06 vs 1.00±0.06),CEACAM6表达显著升高(0.61±0.06 vs 0.24±0.03,P<0.05)。与DDP+miR-NC组比较,DDP+miR-3163组AGS/DDP细胞增殖抑制率[(36.32±3.21)%vs(8.41±0.83)%]、凋亡率[(23.14±2.33)%vs(7.55±0.76)%]显著升高(P<0.05)。与DDP+si-NC组比较,DDP+si-CEACAM6组AGS/DDP细胞增殖抑制率[(31.29±3.18)%vs(7.65±0.77)%]、凋亡率[(19.74±1.83)%vs(6.22±0.63)%]显著升高(P<0.05)。与DDP+miR-3163+pcDNA组比较,DDP+miR-3163+pcDNA-CEACAM6组AGS/DDP细胞增殖抑制率[(18.64±1.58)%vs(39.87±3.77)%]、凋亡率[(10.59±1.04)%vs(24.18±2.43)%]显著降低(P<0.05)。miR-3163靶向负调控CEACAM6表达。结论:miR-3163靶向CEACAM6抑制顺铂耐药胃癌细胞增殖,诱导细胞凋亡,提高其对顺铂的敏感性。
文摘Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.
