Yeng S Ang

• The University of Manchester

Introduction PuraStat ® is a novel haemostatic agent without the risk of thermal injury, perforation or loss of mucosal views associated with other treatments such as heat therapy, clips or haemostatic powders. Our aim was to evaluate the efficacy of PuraStat ® in the prevention and treatment of gastro-intestinal bleeding. Methods This is a pros...

Oesophageal adenocarcinoma (OAC) is one of the most frequent causes of cancer deaths and yet compared to other common cancers, we know relatively little about the molecular composition of this tumour type. To further our understanding of this cancer we have used open chromatin profiling to decipher the transcriptional regulatory networks that are o...

Background: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus. Methods: The Aspirin and Esomeprazol...

Background: Oesophageal adenocarcinoma (OA) is the sixth commonest cause of cancer death worldwide and Barrett’s oesophagus (BO) is the most significant risk factor. We evaluated the efficacy of high-dose esomeprazole proton pump inhibitor acid suppression (PPI) and aspirin in improving outcome for BO patients in the largest such randomized control...

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated t...

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of th...

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are freque...

Validation of ETV1 ChIP-seq samples. (PDF)

Transcription factor motifs found at ETV1 binding regions. (PDF)

Functional categories of genes associated with differentially accessible chromatin regions. (PDF)

Expression of PEA3 family and AP1 subunits in patient-derived samples. (PDF)

Patient demographics. Information about samples used in ATAC-seq and for gene expression on the Fluidigm Biomark system are shown on separate tabs. (XLSX)

Chromatin accessibility regions showing differential accessibility in OAC-derived patient samples. Columns H-P show normalised Tn5 cutting frequency within each indicated chromatin regions in each of the indicated tissue samples from normal tissue (N) or OAC tumour samples (T). Regions are included that show significant differential accessibility (...

Validation of ETV1-mediated gene regulation. (PDF)

Transcription factor binding motifs associated with differentially accessible regions in cancer cells. (PDF)

Integrative analysis of motif enrichment and transcription factor expression identifies likely regulatory transcription factors in normal oesophageal cells. (PDF)

Expression of genes associated with differentially accessible chromatin regions in normal and OAC-derived cells. (PDF)

Expression of PEA3 subfamily members and role in OAC cell growth. (PDF)

Reproducibility of ATAC-seq data. (PDF)

Role of AP1 in determining H3K27 acetylation. (PDF)

Expression of putative directly regulated AP1 target genes in OAC tissue samples. (PDF)

Functional categories of genes associated with differentially accessible chromatin regions in OAC tissue samples. (PDF)

Footprinting at ETS and AP-1 motifs located in cancer cell-specific differentially accessible regions. (PDF)

Open chromatin levels in matched normal and tumour samples around ETV1 binding regions. (PDF)

ETV1 binding regions identified from ChIP-seq analysis. Peaks are assigned to the gene with the nearest TSS. (XLSX)

Chromatin accessibility regions showing differential accessibility in OAC-derived cell lines. Columns J-Q show normalized Tn5 cutting frequency within each indicated 500 bp window in each of the indicated cell lines. Peaks are assigned to the gene with the nearest TSS. (XLSX)

RNAseq analysis of gene expression in OE33 cells following DN-FOS expression. Data are shown as averages of three experimental replicates. (XLSX)

Chromatin accessibility at ETV1 binding regions across different OAC-derived cell lines. Columns F-M show normalised Tn5 cutting frequency within each indicated ETV1 binding region in each of the indicated cell lines. The final column shows the clustering from Fig 4C. (XLSX)

RT-qPCR and ChIP-qPCR primer pairs. (XLSX)

Microarray analysis of gene expression in HET1A, HEEPIC and OE33 cells and OE33 cells following ETV1 and ETV4 depletion. Relative expression in each cell line/condition, and fold changes and associated P-values for the indicated comparisons are shown in tab 1. Tab 2 shows the genes that are significantly changed upon siETV1 treatment and the change...

Introduction We prescribe medicines to patients but the key factor determining efficacy is the dose taken. Recent evidence suggests compliance with aspirin therapy is vital to ensuring its chemoprevention efficacy. Therefore we look at the patient’s compliance with aspirin in a large trial. Method In the 2 × 2 factorial AspECT study, Barrett’s pat...

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-ge...

Introduction Provision of single-sex accommodation (SSA) in hospitals is a key National Health Service objective. Department of Health policy to eliminate mixed-sex accommodation (MSA) was implemented in our endoscopy department in 2011. We found no published studies of patients’ views on MSA in endoscopy units. Aim We explored patients’ views on...

New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagu...

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-ampl...

Introduction Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. Me...

Introduction Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is first line treatment for mucosal Barrett’s oesophagus (BE) related neoplasia. The UK Registry collects data from patients at 28 sites undergoing RFA/EMR. We examine differences in outcomes between sites by patient volume. Methods All visible lesions were e...

Introduction From 2005 to 2011 two large UK studies recruited 6,327 evaluable patients with Barrett’s Oesophagus attending hospital clinics. Baseline clinical, patient history and quality of life data was collected prior to randomisation and this rich dataset is the basis for this abstract. Methods Patients were recruited to AspECT and BOSS at loc...

We thank you for your observations and comments about the role of surgical treatment for acid reflux in maintaining long-term disease remission after successful endoscopic therapy. We share your observations that although, in most patents, with combined endoscopic resection and radiofrequency ablation (RFA), we are able to clear the mucosal neoplas...

Background: Gastric cancers present late in life with advanced disease and carry a poor prognosis. Polo-like Kinase 1 (PLK1) is a mitotic kinase with regulatory functions during G2/M and mitosis in the cell cycle. In mammalian cells, there is an intricate co-regulatory relationship between PLK1 and the forkhead transcription factor FOXM1. It has b...

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insi...

Background and study aim: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom R...

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...

Introduction Endoscopic therapy with combined Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is now the recommended first line treatment for patients with Barrett’s (BE) related neoplasia confined to the oesophageal mucosa. Method We examine prospective data from the United Kingdom registry of patients undergoing RFA/E...

Introduction Endoscopic therapy with Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is now recommended as first line treatment for patients with Barrett’s oesophagus (BE) related neoplasia confined to the mucosa. Method We examine prospective data from the United Kingdom registry of patients undergoing RFA/EMR for BE n...

Objectives: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients...

doi: 10.1038/ajg.2015.55 http://www.nature.com/ajg/journal/vaop/ncurrent/abs/ajg201555a.html OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and ev...

Survival rates for oesophageal adenocarcinoma (OAC) remain disappointingly poor and current conventional treatment modalities have minimal impact on long-term survival. This is partly due to a lack of understanding of the molecular changes that occur in this disease. Previous studies have indicated that the transcription factor FOXM1 is commonly up...

Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. We examined prospective data from the UK...

Barrett's esophagus (BE) increases risk for esophageal adenocarcinoma (EAC). Increased risk for BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. The Barrett's and esophageal adenocarcinoma consortium (BEACON) identified risk lo...

Background & Aims: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcino...

Aim: To identify if methylene tetra-hydrofolatereductase (MTHFR) C677T polymorphisms are associated with oesophageal adenocarcinomas in a Caucasian population and to test whether folic acid and homocysteine levels are linked with cancer risk. Methods: A case control study comprising of 58 non cancer and 48 cancer patients, MTHFR C667T genotyping...

To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas. A retrospective search of our tissue archive for esophageal resection specimens containing esophageal adenocarcinoma was performed, for cases which had previously been reported for diagnostic purposes, using the systematised nomenclature of human and veterinary medicine coding...

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature wa...

Introduction The prognosis of oesophageal cancer remains poor with < 10% 5-year survival. Delineating the molecular pathogenesis of oesophageal cancer could inform future research into targeted therapies and may uncover novel biomarkers to aid management decisions. As a transcription factor with important roles in the control of cell cycle transcri...

Introduction Seventeen thousand patients are treated with radical pelvic radiotherapy annually in the UK.50% develop chronic GI symptoms. The structured approach to management used in this service evaluation has been shown to identify treatable diagnoses and improve symptoms in the short term. We report the first 12 month outcome data for the effec...

Introduction The 2007 Chief Nursing Officer’s report on privacy and dignity identified provision of single-sex accommodation (SSA) as a key objective for the NHS. This was formalised in the 2010 Department of Health (DOH) policy to eliminate mixed-sex accommodation and financial sanctions for policy breaches were introduced in 2011. Our endoscopy d...

Introduction BE is the pre-cursor to oesophageal adenocarcinoma (OAC). High grade dysplasia (HGD) & early mucosal neoplasia in BE have a 40–60% risk of progressing to OAC. Endoscopic mucosal resection (EMR) & RFA are alternatives to surgery for curative treatment of these patients. We present prospective data from 19 centres in the UK HALO RFA regi...

Background & aims: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. Methods: We collected data...

Purpose: Fifty percent of patients develop chronic gastrointestinal (GI) symptoms following pelvic radiotherapy that adversely affect quality of life. Fewer than 20 % are referred to a gastroenterologist. We aimed to determine if structured gastroenterological evaluation is of benefit to this patient group. Methods: Sixty patients with GI sympto...

Background: The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been show...

The worldwide pandemic of obesity carries alarming health and socioeconomic implications. Bariatric surgery is currently the only effective treatment for severe obesity. It is safe, with mortality comparable to that of cholecystectomy, and effective in producing substantial and sustainable weight loss, along with high rates of resolution of associa...

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 U...

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 U...

Background: Tissue factor (TF), which has a role in normal tissue haemostasis, was reported to be aberrantly expressed, associated with higher microvascular density and a poor prognosis in intestinal-type gastric adenocarcinoma in the Japanese population. This is the first study to look at the relationship of TF and the metaplasia–adenoma–carcinoma...

Introduction 17 000 patients are treated with radical pelvic radiotherapy per year in the UK. 50% will develop chronic gastrointestinal (GI) symptoms that adversely affect quality-of-life, which have been shown to persist at the same level of severity for at least 3 years following treatment. Despite this, fewer than 20% are referred to a gastroent...

Introduction 17 000 patients are treated with radical pelvic radiotherapy per year in the UK. Although 50% develop significant chronic gastrointestinal (GI) symptoms, <20% are referred for gastroenterological evaluation. We aimed to determine the causes of GI symptoms in this patient group. Methods 60 patients with GI symptoms ≥6 months after radic...

To review the evidence for candidate biomarkers of gastrointestinal toxicity following pelvic radiotherapy to highlight recent findings of potential interest to those involved in the treatment of pelvic malignancies or the management of gastrointestinal consequences of cancer treatments. Multiple serum and faecal biomarkers have been studied for us...

Barrett's esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a "metaplasia-dysplasia-carcinoma" (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers wi...

Cancer treatments are rapidly changing. Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy. Outcomes for both regimes are generally poor as a result of tumor recurrence. We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the...

Transcription factors often play important roles in tumourigenesis. Members of the PEA3 subfamily of ETS-domain transcription factors fulfil such a role and have been associated with tumour metastasis in several different cancers. Moreover, the activity of the PEA3 subfamily transcription factors is potentiated by Ras-ERK pathway signalling, which...

Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world. Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle. A large international effort has led to the development of a large number of inhibitors...

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WT...

Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour met...

Figure S1. mRNA expression levels of PEA3 and ER81 in oesophageal tissue. (A and B) mRNA levels of PEA3 (A) and ER81 (B) relative to 18S RNA in tissue specimens are presented. All samples were standardised to expression in SW480 (for PEA3) and Flo1 (for ER81) cell lines and are presented on a log2 scale. The average relative mRNA levels and standar...

INTRODUCTION/OBJECTIVES: Tissue Factor (TF) was reported to be aberrantly expressed in gastric cancer cells, associated with higher microvascular density (MVD) and poor prognosis in intestinal-type gastric adenocarcinoma in the Japanese population. AIMS & METHODS: TF expression in gastric adenocarcinoma and its relationship to the metaplasiadysplas...

Introduction The PEA3 sub family consists of 3 similar transcription factors, PEA3, ER81 and ERM. In gastric cancer cells PEA3 is activated by H pylori and it has been shown to regulate MMP-7 and invasion. PEA3 mRNA expression correlates with an adverse prognosis in gastric adenocarcinomas. We have previously shown that PEA3 and/or ER81 mRNA correl...

We felt it was important to highlight a problem that we encountered with a bedside glucometer and a patient with end stage renal failure on continuous ambulatory peritoneal dialysis. Vast discrepancies between true venous glucose levels and those estimated by certain glucometers in this situation can be problematic and dangerous. Not all glucometer...

Gastric antral vascular ectasia (GAVE), though a rare disorder, causes up to 4% of non-variceal upper GI bleeding. This paper gives an overview of studies examining clinical presentation and pathophysiology, and reviews the current evidence for invasive and non-invasive treatments. GAVE is often associated with systemic illnesses, such as cirrhosis...

We congratulate Schwartz et al for their first reported Endocinch sham control trial ( Gut 2007; 56 :20–8). The results of this trial confirm those of earlier open-label studies1–3 showing that in the short and intermediate term, endoscopic gastroplication improves gastro-oesophageal reflux disease symptoms and quality of life (QOL), and reduces th...

Gastro-oesophageal reflux disease (GORD) is a common disorder which significantly impairs the quality of life. Recently an EndoCinch system has been described, with an approach to the treatment of GORD that would obviate the need for long-term proton pump inhibitors and the cost and potential risk of laparoscopic Nissen fundoplication. We set outto...

In this study, we identify the nature of the immunological response of human peripheral blood mononuclear cells (PBMC) and lamina propria gastric lymphocytes (LPL) to two Helicobacter pylori antigens, the neutrophil activating protein (NapA) and alkyl hydroperoxide reductase (AphC). These antigens were identified and selected for study based on the...

The early growth response 1 (Egr-1) transcription factor is rapidly induced by various stimuli and is implicated in the regulation of cell growth, differentiation, and gene expression. The aim of this study was to examine the effect of Helicobacter pylori on the expression of Egr-1 and Egr-1-regulated genes in gastric epithelial AGS cells. Egr-1 ex...