Induction of colonic epithelial cell apoptosis by p47-dependent oxidants11Nucleotide sequence data reported are available in GenBank database under accession # AF540955.

AbstractExogenous oxidants appear capable of initiating both proliferative and death signals, but the role of endogenous oxidants in either tumorigenesis or tumor suppression is unclear. We found that expression of the NAD(P)H oxidase adapter p47phox was suppressed in human colon carcinoma specimens relative to adjacent normal colon. Overexpression of p47phox increased apoptosis in colon cancer cell lines independent of p53 and mismatch-repair competency. p47phox was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47phox coprecipitated with both ABI-1 and c-Abl. Ectopic expression of p47phox in colon cancer cells increased oxidant production with phosphorylation and activation of nuclear c-Abl and consequent apoptosis. Colonic epithelial p47phox may be specifically targeted to a c-Abl-containing complex that serves a physiologic tumor suppressing function

Prohibitin 1 Modulates Mitochondrial Stress-Related Autophagy in Human Colonic Epithelial Cells

Autophagy is an adaptive response to extracellular and intracellular stress by which cytoplasmic components and organelles, including damaged mitochondria, are degraded to promote cell survival and restore cell homeostasis. Certain genes involved in autophagy confer susceptibility to Crohn's disease. Reactive oxygen species and pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), both of which are increased during active inflammatory bowel disease, promote cellular injury and autophagy via mitochondrial damage. Prohibitin (PHB), which plays a role in maintaining normal mitochondrial respiratory function, is decreased during active inflammatory bowel disease. Restoration of colonic epithelial PHB expression protects mice from experimental colitis and combats oxidative stress. In this study, we investigated the potential role of PHB in modulating mitochondrial stress-related autophagy in intestinal epithelial cells.We measured autophagy activation in response to knockdown of PHB expression by RNA interference in Caco2-BBE and HCT116 WT and p53 null cells. The effect of exogenous PHB expression on TNFα- and IFNγ-induced autophagy was assessed. Autophagy was inhibited using Bafilomycin A(1) or siATG16L1 during PHB knockdown and the affect on intracellular oxidative stress, mitochondrial membrane potential, and cell viability were determined. The requirement of intracellular ROS in siPHB-induced autophagy was assessed using the ROS scavenger N-acetyl-L-cysteine.TNFα and IFNγ-induced autophagy inversely correlated with PHB protein expression. Exogenous PHB expression reduced basal autophagy and TNFα-induced autophagy. Gene silencing of PHB in epithelial cells induces mitochondrial autophagy via increased intracellular ROS. Inhibition of autophagy during PHB knockdown exacerbates mitochondrial depolarization and reduces cell viability.Decreased PHB levels coupled with dysfunctional autophagy renders intestinal epithelial cells susceptible to mitochondrial damage and cytotoxicity. Repletion of PHB may represent a therapeutic approach to combat oxidant and cytokine-induced mitochondrial damage in diseases such as inflammatory bowel disease

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed

Quality Indicators for the Management of Barrett’s Esophagus, Dysplasia, and Esophageal Adenocarcinoma: International Consensus Recommendations from the American Gastroenterological Association Symposium

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett’s esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE