siRNA Library Screening Identifies a Druggable Immune-Signature Driving Esophageal Adenocarcinoma Cell Growth.

Background & Aims: Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barrett's esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation.

Methods: This study used a druggable genome small interfering RNA (siRNA) screening library of 6022 siRNAs in conjunction with bioinformatics platforms, genomic studies of EAC tissues, somatic variation data of EAC from The Cancer Genome Atlas data of EAC, and pathologic and functional studies to define novel EAC-associated, and targetable, immune factors.

The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.

Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear.

Golgi phosphoprotein 2 (GOLPH2) is a novel bile acid-responsive modulator of oesophageal cell migration and invasion.

Background: The aetiology of Barrett's oesophagus (BO) and oesophageal cancer is poorly understood. We previously demonstrated that Golgi structure and function is altered in oesophageal cancer cells. A Golgi-associated protein, GOLPH2, was previously established as a tissue biomarker for BO.

The diagnostic accuracy of endoscopic ultrasound in suspected biliary obstruction and its impact on endoscopic retrograde cholangiopancreatography burden in real clinical practice: a consecutive analysis.

Background And Aims: Performing endoscopic ultrasound (EUS) before endoscopic retrograde cholangiopancreatography (ERCP) has been described to be useful in cases of suspected biliary obstruction where EUS can triage patients for ERCP. We aimed to determine the diagnostic accuracy of EUS and its impact on ERCP burden in real clinical practice. We also evaluated the safety and efficacy of EUS+ERCP in a single endoscopic session.

Inherited Syndromes Predisposing to Inflammation and GI Cancer.

Cancers arising within the gastrointestinal (GI) tract are commonly associated with an immune component at their inception and later in their maintenance. While many of the immune factors and immune cell types surrounding these lesions have been highlighted, the underlying pre-dispositions in immunesupported carcinogenesis are not well characterised. Inherited Mendelian GI disorders such as polyposis syndromes, while classically due to germline mutations in non-immune genes, commonly demonstrate alterations in key immune and inflammatory genes.

An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.

Reflux of gastroduodenal contents and consequent inflammatory responses are associated with the development of Barrett's oesophagus (BO) and the promotion of oesophageal adenocarcinoma (OAC). Deregulation of inflammatory processes is a hallmark of oesophageal cancer. In this study, we aimed to investigate (i) the transcriptional responses to deoxycholic acid (DCA) in cell lines representative of either end of the oesophageal cancer sequence, (ii) the expression of DCA-regulated genes in data charting oesophageal carcinogenesis and (iii) the impact of these genes on oesophageal inflammatory signalling.