Gene Expression in Barrett's Esophagus Cell Lines Resemble Esophageal Squamous Cell Carcinoma Instead of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is strongly associated with Barrett's esophagus (BE), a pre-malignant condition resulting from gastric reflux. Esophageal squamous cell carcinoma (ESCC), the other major subtype of esophageal cancer, shows strong association with smoking and alcohol intake and no association with gastric reflux. In this study, we constructed and validated gene expression signatures of EAC vs.

DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment.

Esophageal carcinoma (EC) is one of the most pervasive cancers in the world, with upwards of 500,000 new diagnoses, annually. Despite its prominence, advancements in the detection and treatment of EC have been marginal over the past 30 years and the survival rate continues to stay below 20%. This is due to the uncommonly heterogeneous presentation of EC which presents unprecedented challenges in improving patient survival and quality of care.

Barrett's Epithelium to Esophageal Adenocarcinoma: Is There a "Point of No Return"?

Esophageal adenocarcinoma (EA) arises from Barrett's epithelium (BE), and chronic gastroesophageal reflux disease is considered the strongest risk factor for disease progression. All BE patients undergo acid suppressive therapy, surveillance, and BE removal by surgery or endoscopic ablation, yet the incidence of EAC continues to increase. Despite the known side effects and mortality, the one-size-fits-all approach is the standard clinical management as there are no reliable methods for risk stratification.

Recurring Translocations in Barrett's Esophageal Adenocarcinoma.

Barrett's esophagus (BE) is a premalignant metaplasia in patients with chronic gastroesophageal reflux disease (GERD). BE can progress to esophageal adenocarcinoma (EA) with less than 15% 5-year survival. Chromosomal aneuploidy, deletions, and duplication are early events in BE progression to EA, but reliable diagnostic assays to detect chromosomal markers in premalignant stages of EA arising from BE are lacking.

Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis.

Background: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown.

Aim: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy.

Methods: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years.

Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett's Cells.

Background & Aims: Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett esophagus (BE). This subsquamous intestinal metaplasia might be responsible for cancers that develop despite endoscopic surveillance and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo an epithelial-to-mesenchymal transition (EMT) that produces subsquamous intestinal metaplasia, we assessed EMT in BE cells exposed to acidic bile salts and in rat and human esophageal tissues.

miR-206 as a Biomarker for Response to Mesalamine Treatment in Ulcerative Colitis.

Background: MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown.

Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux.

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk.

Gastrointestinal Dysmotility in the Elderly.

The number of persons 60 years and older has increased 3-fold between 1950 and 2000. Aging alone does not greatly impact the gastrointestinal (GI) tract. Digestive dysfunction, including esophageal reflux, achalasia, dysphagia, dyspepsia, delayed gastric emptying, constipation, fecal incontinence, and fecal impaction, is a result of the highly prevalent comorbid conditions and the medications with which those conditions are treated.

Molecular epidemiology of and genetic susceptibility to esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on clonal evolution in Barrett's carcinogenesis; biomarkers for early detection of esophageal cancer; the role of the methylguanine methyl transferase biomarker in the management of adenocarcinoma; and the discovery of high-risk genes in families.

High resolution integrative analysis reveals widespread genetic and epigenetic changes after chronic in-vitro acid and bile exposure in Barrett's epithelium cells.

Barrett's epithelium (BE) is a premalignant condition resulting from chronic gastroesophageal reflux that may progress to esophageal adenocarcinoma (EAC). Early intervention holds promise in preventing BE progression. However, identification of high-risk BE patients remains challenging due to inadequate biomarkers for early diagnosis.

Barrett's esophagus: cancer and molecular biology.

The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.

Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma.

This paper presents commentaries on animal models used for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) research; acid- and bile-induced chromosomal instability and clonal selection during the progression of BE to EAC; how the components of gastric refluxate, especially acid and bile salts, promote carcinogenesis in metaplastic BE; genome-wide changes in DNA methylation and transcription involved in BE carcinogenesis; the potential role of miRNA in the development of BE and EAC; the effect of inflammatory cytokines linked to obesity on the activation of cell-death pathways and cell survival in BE and esophageal cancer; and the role of autophagy in esophageal cancer development.

Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett's epithelium.

Unlabelled: Barrett's esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence.

Barrett's esophagus: histology and immunohistology.

The following on histology and immunohistology of Barrett's esophagus (BE) includes commentaries on the various difficulties remaining in reaching a consensus on the definition of BE; the difficulties in the characterization of intestinal and cardiac mucosa, and in the role of submucosal glands in the development of BE; the importance of a new monoclonal antibody to recognize esophageal intestinal mucosa; the importance of pseudo goblet cells; the best techniques for the endoscopic detection of Barrett's epithelium; and the biomarkers for identification of patients predisposed to the development of BE.

Barrett's esophagus: genetic and cell changes.

The following includes commentaries on how genetic code of Barrett's esophagus (BE) patients, the mechanisms for GERD-induced esophageal expression of caudal homeobox, and the development of Barrett's metaplasia are increasingly better known, including the role of stromal genes in oncogenesis. Additional lessons have been learned in vitro models in nonneoplastic cell lines, yet there are limitations to what can be expected from BE-derived cell lines. Other topics discussed include clonal diversity in Barrett's esophagus; the application of peptide arrays to clinical samples of metaplastic mucosa; proliferation and apoptosis of Barrett's cell lines; tissue biomarkers for neoplasia; and transcription factors associated with BE.

Transformation of benign Barrett's epithelium by repeated acid and bile exposure over 65 weeks: a novel in vitro model.

The mechanism by which gastroesophageal reflux promotes metaplasia→dysplasia→carcinoma is unknown. The aim of the study is to determine if repeated exposure to acid and bile confers a tumorigenic phenotype in a telomerase (hTERT)-immortalized benign Barrett's cell line (BAR-T). BAR-T cells were exposed to acid (pH 4) (A) and bile salt (200 μM glycochenodeoxycholic acid) (B) daily for 5 min up to 65+ weeks.

Antibody to tropomyosin isoform 5 and complement induce the lysis of colonocytes in ulcerative colitis.

Objectives: Tropomyosins (TMs) are cytoskeletal microfilament proteins present in all eukaryotic cells. Human TM isoform 5 (hTM5) is the predominant isoform in colonic epithelial cells. Antibodies against hTM5 are found both in the sera and in the mucosa of patients with ulcerative colitis (UC) but not Crohn's disease (CD).

Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia.

Although a protective role for mesalamine against colon cancer in ulcerative colitis has been shown epidemiologically, its molecular mechanism is unknown. We cloned and sequenced a novel human tropomyosin (hTM) isoform, TC22, which is an alternatively spliced variant of normal epithelial hTM isoform 5 (hTM5), identical apart from 25 C-terminal amino acids. TC22 is expressed in 100% of colorectal carcinoma but is not expressed in normal colon epithelial cells.

Tropomyosins in human diseases: ulcerative colitis.

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD) that almost always affects the rectal mucosa and variable length of the colon in continuity and at times mucosa of the entire colon. It is not caused by any specific pathogen. Genetics, environmental factors and altered immune responses to dietary macromolecules, colonic bacteria and cellular proteins have been implicated in the pathogenesis of UC.

EPR and optical absorption studies of copper ions in diglycine calcium chloride tetrahydrate.

EPR study of copper ions in diglycine calcium chloride tetrahydrate (DGCCT), [(NH(2)CH(2)COOH)(2).CaCl(2).4H(2)O] single crystals at room temperature is carried out.

EPR and optical study of Mn2+ doped ammonium tartrate single crystals.

EPR study of Mn2+ doped ammonium tartrate single crystals is carried out at room temperature. The spin Hamiltonian parameters are: gx=1.9225+/-0.

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line.

Barrett's epithelium is a precancerous, specialized columnar metaplasia in the distal esophagus. We demonstrate the changes in cellular phenotype in a non-neoplastic Barrett's cell line (BAR-T), following exposure to acid and bile salt, the two important components of gastroesophageal refluxate. Cell phenotypes in BAR-T cell line were quantified by fluorescence-activated cell sorting (FACS) using monoclonal antibodies against markers: cytokeratin 8/18 (CK8/18) for columnar, CK4 for squamous, mAbDas-1 for colonic epithelial cell phenotype and p75NTR for esophageal progenitors.