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Project description:The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrett’s oesophagus cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma Background and Aims: The major etiological risk factor for Barrett’s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This study’s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrett’s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrett’s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrett’s esophagus (median gene fold change for Barrett’s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrett’s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Keywords: Acid (pH 4.5) and bile (mixture of primary bile salts or the secondary bile salt deoxycholic acid, both at pH 4.5) challenge to a Barrett's oesophagus cell line. RNA extraction at 2 and 6 hours. Comparison of treatment RNA to control (non-treatment) RNA,
2007-12-05 | GSE9768 | GEO
Project description:The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrettâ??s oesophagus cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma; Background and Aims: The major etiological risk factor for Barrettâ??s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This studyâ??s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrettâ??s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrettâ??s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrettâ??s esophagus (median gene fold change for Barrettâ??s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrettâ??s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Experiment Overall Design: The Barrett's oesophagus cell line CP-A hTERT was treated with a 15 minute exposure of acid (pH 4.5), a mixture of primary bile acids (pH 4.5) or deoxycholic acid (pH 4.5). RNA extraction occurred in treatment and non-treated cells at 2 hours and 6 hours. The treatments were performed in duplicate on 2 different days. RNA was compared in each treatment to each control at the relevant time points, in a 2 x 2 manner by using Affymetrex U133 Plus 2.0 arrays. Results of 12 genes were confirmed by Real Time PCR and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma.
2008-06-16 | E-GEOD-9768 | biostudies-arrayexpress
Project description:To explore the effects of bile reflux on gastric cancer and its precancerous lesions, so as to better prevent the occurrence and development of gastric cancer.
| 2307610 | ecrin-mdr-crc
Project description:The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague Dawley rats, with or without reflux-induction received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis, and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory and immune-implicated proteins and genes including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1β, Lbp, Lcn2, Myd88, Nfkb1, Tlr2 and Tlr4 aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation and cellular damage.
2024-02-08 | GSE254633 | GEO
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrettâ??s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barrettâ??s esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line. HET-1A cells were exposed to 300um DCA over 24 hours in duplicate experiments including matched timepoint controls
2010-02-28 | E-GEOD-13378 | biostudies-arrayexpress
Project description:An essential function of the liver is the formation of bile. This aqueous solution is critical for fat absorption and is transported to the duodenum via the common bile duct. Despite extensive studies of bile salts, other components of bile are less well-charted. Here, we characterized the murine bile metabolome and investigated how the microbiota and enteric infection influence bile composition. We discovered that the bile metabolome is not only substantially more complex than appreciated but is dynamic and responsive to the microbiota and enteric infection. Hepatic transcriptomics identified enteric infection-triggered pathways that likely underlie bile remodeling. Enteric infections stimulated elevation of four dicarboxylates in bile that modulated intestinal gut epithelial and microbiota composition, inflammasome activation, and host defense. Our data suggest that enteric infection-associated signals are relayed between the intestine and liver and induce transcriptional programs that shape the bile metabolome, modifying bile’s immunomodulatory and host defense functions.
2023-05-02 | GSE227180 | GEO
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line.
2010-02-20 | GSE13378 | GEO
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisons with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma.
2010-02-20 | GSE13376 | GEO