ArticleGut2007
COX-2 induction by unconjugated bile acids involves reactive oxygen species-mediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma.
Article in Gut, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis.Oncotarget · 2017Pooled it
- Cell culture models for studying the development of Barrett's esophagus: a systematic review.Cellular oncology (Dordrecht, Netherlands) · 2012Pooled it
- A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett's esophagus.Gastroenterology · 2012Trial
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Causal associations between atrial fibrillation and esophageal cancer: a two-sample Mendelian randomization study.Translational cancer research · 2025Article
- Multidimensional mechanisms and therapies underlying gastroesophageal reflux disease: focus on immunity, signaling pathways, and the microbiota-gut-brain axis.Frontiers in immunology · 2025Review
- Altered Microbiome Promotes Pro-Inflammatory Pathways in Oesophago-Gastric Tumourigenesis.Cancers · 2024Review
- A pharmacovigilance study of the association between proton pump inhibitors and tumor adverse events based on the FDA adverse event reporting system database.Frontiers in pharmacology · 2024Article
- Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus.Current gastroenterology reports · 2023Review
- Metabolomic profiling implicates mitochondrial and immune dysfunction in disease syndromes of the critically endangered black rhinoceros (Diceros bicornis).Scientific reports · 2023Article
- Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.Chinese journal of integrative medicine · 2023Article
- Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy.Journal of gastroenterology · 2022Article
- Marked improvement of severe reflux esophagitis following proximal gastrectomy with esophagogastrostomy by the right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Oral Microbiota Variation: A Risk Factor for Development and Poor Prognosis of Esophageal Cancer.Digestive diseases and sciences · 2022Review
- Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis.Cancer metastasis reviews · 2022Review
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Novel Advances in the Evaluation and Treatment of Children With Symptoms of Gastroesophageal Reflux Disease.Frontiers in pediatrics · 2022Review
- The tumour immune microenvironment in oesophageal cancer.British journal of cancer · 2021Review
- Esophageal Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesBile reflux contributes to oesophageal injury and neoplasia. COX-2 is involved in both inflammation and carcinogenesis; however, the precise mechanisms by which bile acids promote COX-2 expression in the oesophagus are largely unknown. We analysed the molecular mechanisms that govern bile acid-mediated expression of COX-2 in Barrett's oesophagus and oesophageal adenocarcinoma (OA).
designThe effects of bile acids on COX-2 expression were analysed in immortalised Barrett's oesophagus and OA cells using immunoblotting and transient transfections. Pharmacological inhibitors, phospho-specific antibodies, dominant-negative mutants and siRNA techniques were used to identify relevant signalling pathways. Flow cytometry and reactive oxygen species (ROS) scavengers were used to examine ROS involvement. Immunohistochemistry was performed on oesophageal mucosa obtained from an established rat model of bile reflux.
resultsUnconjugated bile acids potently stimulated COX-2 expression and induced AKT and ERK1/2 phosphorylation in concert with COX-2 induction. These findings were mimicked in the in vivo rat model. Dominant-negative (DN) AKT and LY294002 (PI3K inhibitor) or U0126 (MEK-1/2 inhibitor) blocked chenodeoxycholic acid (CD) and deoxycholic acid (DC) mediated COX-2 induction. CD and DC also induced CREB phosphorylation and AP-1 activity. CREB-specific siRNA and DN AP-1 blocked CD and DC-induced COX-2 induction. Finally, CD and DC increased intracellular ROS, while ROS scavengers blocked COX-2 induction and the signalling pathways involved.
conclusionsUnconjugated bile acids induce CREB and AP-1-dependent COX-2 expression in Barrett's oesophagus and OA through ROS-mediated activation of PI3K/AKT and ERK1/2. This study enhances our understanding of the molecular mechanisms by which bile acids promote the development of oesophageal adenocarcinoma.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.