In Esophageal Squamous Cell Lines Derived From GERD Patients With and Without Barrett's Esophagus, There Are Differences in NF-κB Activation After Acid and Bile Salt Exposure

2011 ◽  
Vol 140 (5) ◽  
pp. S-76 ◽  
Author(s):  
Xiaofang Huo ◽  
Xi Zhang ◽  
Chunhua Yu ◽  
Edaire Cheng ◽  
David H. Wang ◽  
...  
Keyword(s):  
Bile Salt ◽  
Barrett’S Esophagus ◽  
Cell Lines ◽  
Squamous Cell ◽  
Barrett's Esophagus

Mechanisms of oxidant production in esophageal squamous cell and Barrett's cell lines

2008 ◽  
Vol 294 (2) ◽  
pp. G411-G417 ◽  
Author(s):  
Linda A. Feagins ◽  
Hui Ying Zhang ◽  
Xi Zhang ◽  
Kathy Hormi-Carver ◽  
Tojo Thomas ◽  
...  
Keyword(s):  
Bile Acid ◽  
Barrett’S Esophagus ◽  
Acid Medium ◽  
Cell Lines ◽  
Squamous Cell ◽  
Barrett's Esophagus ◽  
Acidic Medium ◽  
Ros Production ◽  
Squamous Cells ◽  
Oxidant Production

We hypothesized that differences among individuals in reflux-induced oxidant production by esophageal squamous epithelial cells might contribute to the development of Barrett's esophagus. We studied the effects of acid and bile acids on the production of reactive oxygen species (ROS) in esophageal squamous cell lines derived from gastroesophageal reflux disease patients with (NES-B3T) and without (NES-G2T) Barrett's esophagus and in a Barrett's epithelial cell line (BAR-T). Cells were incubated with an ROS-sensitive probe and exposed to acidic medium, neutral bile acid medium, or acidic bile acid medium. ROS were quantified in the presence and absence of diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor), NG-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor), and rotenone (a mitochondrial electron transport chain inhibitor). Acidic bile acid medium induced ROS production in both squamous cell lines; however, only DPI blocked ROS production by NES-B3T cells, whereas both DPI and l-NMMA blocked ROS production by NES-G2T cells. In BAR-T cells, acidic medium and acidic bile acid medium induced the production of ROS; l-NMMA prevented ROS production after exposure to acidic medium, whereas ROS production induced by acidic bile acid medium was blocked by DPI. These studies demonstrate that there are differences between esophageal squamous cells and Barrett's epithelial cells and between esophageal squamous cells from gastroesophageal reflux disease patients with and without Barrett's esophagus in the mechanisms of oxidant production induced by exposure to acid and bile acids.

scholarly journals Esophageal Squamous Cell Lines Derived From GERD Patients With and Without Barrett's Esophagus Differ Markedly in Their Expression of SOX9 and Columnar Cytokeratins 8 and 18

2011 ◽  
Vol 140 (5) ◽  
pp. S-75-S-76 ◽  
Author(s):  
David H. Wang ◽  
Anjana Tiwari ◽  
Monica E. Kim ◽  
Qiuyang Zhang ◽  
Stuart J. Spechler ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Cell Lines ◽  
Squamous Cell ◽  
Barrett's Esophagus

248 Differences in CDX-2 Expression After Exposure to Acid and Bile Salts in Esophageal Squamous Cell Lines Derived from GERD Patients with and Without Barrett's Esophagus

2009 ◽  
Vol 136 (5) ◽  
pp. A-48
Author(s):  
Xiaofang Huo ◽  
Hui Ying Zhang ◽  
Xi Zhang ◽  
Kathy Hormi-Carver ◽  
John P. Lynch ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Cell Lines ◽  
Squamous Cell ◽  
Barrett's Esophagus ◽  
Bile Salts

385 MIR-24-3P REGULATES CDX2 DURING THE PROCESS OF INTESTINALIZATION OF THE CARDIAC-TYPE EPITHELIUM IN A HUMAN MODEL OF BARRETT’S ESOPHAGUS

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Manuel Pera ◽  
Marta Garrido ◽  
Gabriel Gil ◽  
Matteo Fassan ◽  
Marta Climent ◽  
...  
Keyword(s):  
Real Time ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Barrett's Esophagus ◽  
Intermediate Stage ◽  
Human Model ◽  
Adenocarcinoma Cell ◽  
Cdx2 Expression

Abstract   Cardiac-type epithelium has been proposed as an intermediate stage between normal squamous epithelium and intestinal metaplasia in the development of Barrett’s esophagus. Deregulation of certain miRNAs and their effects on CDX2 expression might contribute to the intestinalization process of cardiac-type epithelium. The aim of this study was to identify miRNAs differentially expressed between CDX2 positive and negative glands of Barrett’s esophagus and to examine the function of specific miRNAs on the regulation of CDX2. Methods miRNA expression profiling using OpenArrayTM analysis in microdissected cardiac-type glands with and without fully CDX2 expression was performed in biopsies from patients who developed cardiac-type epithelium in the remnant esophagus after esophagectomy. Data were validated using real-time PCR in esophageal adenocarcinoma cell lines and in situ and real-time PCR miRNA/CDX2/MUC2 co-expression analysis in cardiac-type mucosa samples. The effect of miR-24-3p precursor transfection on CDX2 expression was assessed in the esophageal adenocarcinoma cell lines FLO-1 and KYAE-1. Results CDX2 positive glands were characterized by an unique miRNA profile with a significant downregulation of miR-24-3p, miR-520e-3p, miR-548a-1, miR-597-5p, miR-133a-3p, miR-30a-5p, miR-638, miR-625-3p, miR-1255b-1, miR-1260a and upregulation of miR-590 (Figure 1A). miRNA-24-3p was identified as potential regulator of CDX2 gene expression in three bioinformatics algorithms, and this was confirmed in esophageal adenocarcinoma cell lines (Figure 1C). Furthermore, miR-24-3p expression negatively correlates with CDX2 in cardiac-type mucosa samples with different stages of mucosal intestinalization (Figure 1B). Conclusion These results imply that miRNA-24-3p directly targets CDX2, and downregulation of miRNA-24-3p is associated with the acquisition of an intestinal phenotype in cardiac-type epithelium.

Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion

2000 ◽  
Vol 278 (6) ◽  
pp. G1000-G1009 ◽  
Author(s):  
Baljeet S. Kaur ◽  
Rodica Ouatu-Lascar ◽  
M. Bishr Omary ◽  
George Triadafilopoulos
Keyword(s):  
Cell Proliferation ◽  
Bile Salt ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Bile Salts ◽  
Bile Reflux ◽  
Salt Mixture ◽  
Complete Obliteration ◽  
Protein Kinase C Inhibitor ◽  
Incorporation Assay

Barrett's esophagus (BE) results from acid and bile reflux and predisposes to cancer. We investigated the effect of bile salts, with or without acid, on cell proliferation in BE and assessed mechanism(s) involved. To mimic physiological conditions, biopsies of esophagus, BE, and duodenum were exposed to a bile salt mixture, either continuously or as a 1-h pulse, and were compared with control media without bile salts (pH 7.4) for ≤24 h. Similar experiments were also performed with acidified media (pH 3.5) combined with the bile salt mixture as a 1-h pulse. Cell proliferation was assessed by a [3H]thymidine incorporation assay with or without bisindolylmaleimide (BIM), a selective protein kinase C inhibitor. Bile salt pulses enhanced cell proliferation in BE without affecting cell proliferation in esophageal or duodenal epithelia. In the presence of BIM, there was complete obliteration of the bile salt-induced BE hyperproliferation. In contrast, 1-h pulses of bile salts in combination with acid significantly inhibited proliferation in BE but had no effect on esophagus or duodenum. We conclude that in BE explants, brief exposure to bile salts, in the absence of acid, increases proliferation, whereas exposure to a combination of bile salts and acid together inhibits proliferation.

Basaloid Squamous Cell Cancer Arising in Barrett's Esophagus

2003 ◽  
Vol 34 (2-3) ◽  
pp. 095-100 ◽  
Author(s):  
Neeraj Kaushik ◽  
Debra Brody ◽  
Neil Christie ◽  
Kevin McGrath
Keyword(s):  
Barrett’S Esophagus ◽  
Squamous Cell ◽  
Barrett's Esophagus ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Basaloid Squamous

scholarly journals In Barrett’s epithelial cells, weakly acidic bile salt solutions cause oxidative DNA damage with response and repair mediated by p38

2020 ◽  
Vol 318 (3) ◽  
pp. G464-G478
Author(s):  
Xiaofang Huo ◽  
Kerry B. Dunbar ◽  
Xi Zhang ◽  
Qiuyang Zhang ◽  
Stuart Jon Spechler ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bile Salt ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Dna Damage Response ◽  
Barrett's Esophagus ◽  
Oxidative Dna Damage ◽  
Damage Response ◽  
Barrett's Metaplasia ◽  
Barrett’S Metaplasia

The frequency of esophageal adenocarcinoma is rising despite widespread use of proton pump inhibitors (PPIs), which heal reflux esophagitis but do not prevent reflux of weakly acidic gastric juice and bile in Barrett’s esophagus patients. We aimed to determine if weakly acidic (pH 5.5) bile salt medium (WABM) causes DNA damage in Barrett’s cells. Because p53 is inactivated frequently in Barrett’s esophagus and p38 can assume p53 functions, we explored p38’s role in DNA damage response and repair. We exposed Barrett’s cells with or without p53 knockdown to WABM, and evaluated DNA damage, its response and repair, and whether these effects are p38 dependent. We also measured phospho-p38 in biopsies of Barrett’s metaplasia exposed to deoxycholic acid (DCA). WABM caused phospho-H2AX increases that were blocked by a reactive oxygen species (ROS) scavenger. WABM increased phospho-p38 and reduced bromodeoxyuridine incorporation (an index of S phase entry). Repair of WABM-induced DNA damage proceeded through p38-mediated base excision repair (BER) associated with reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease I (Ref-1/APE1). Cells treated with WABM supplemented with ursodeoxycholic acid (UDCA) exhibited enhanced p38-mediated responses to DNA damage. All of these effects were observed in p53-intact and p53-deficient Barrett’s cells. In patients, esophageal DCA perfusion significantly increased phospho-p38 in Barrett’s metaplasia. WABM exposure generates ROS, causing oxidative DNA damage in Barrett’s cells, a mechanism possibly underlying the rising frequency of esophageal adenocarcinoma despite PPI usage. p38 plays a central role in oxidative DNA damage response and Ref-1/APE1-associated BER, suggesting potential chemopreventive roles for agents like UDCA that increase p38 activity in Barrett’s esophagus. NEW & NOTEWORTHY We found that weakly acidic bile salt solutions, with compositions similar to the refluxed gastric juice of gastroesophageal reflux disease patients on proton pump inhibitors, cause oxidative DNA damage in Barrett’s metaplasia that could contribute to the development of esophageal adenocarcinoma. We also have elucidated a critical role for p38 in Barrett’s metaplasia in its response to and repair of oxidative DNA damage, suggesting a potential chemopreventive role for agents like ursodeoxycholic acid that increase p38 activity in Barrett’s esophagus.

PS02.057: INDUCTION OF APOPTOSIS IN ESOPHAGEAL ADENOCARCINOMA CELLS BY CURCUMIN

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 136-137
Author(s):  
René Thieme ◽  
Florian Michiels ◽  
Luisa Maurer ◽  
Albrecht Hoffmeister ◽  
Uwe Eichfeld ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Cell Lines ◽  
Stable Disease ◽  
Barrett's Esophagus ◽  
Conflicts Of Interest ◽  
Curcuma Longa ◽  
Inflammatory Microenvironment ◽  
Induction Of Apoptosis ◽  
Anti Inflammatory ◽  
Proliferation Assays

Abstract Background Curcumin naturally occurring in curry powder from Curcuma longa is an anti-inflammatory and anti-proliferative agent. It represses NFκB activation and induces apoptosis in cancer cells. Because, inflammation favours the onset of an intestinal metaplasia in esophageal squamous epithelial cells and esophageal carcinoma cells, a reduction of such processes may contribute to establish a stable disease and/or sensitization for chemotherapeutic approaches. Methods Curcumin receptivity was investigated in metaplastic (CP-A), dysplastic (CP-B), adenocarcinoma (OE19, OE33), and esophageal fibroblast (FFE3) cell lines, which were treated with 10 or 25 μM Curcumin for 48h or 72h. Response to Curcumin was measured by proliferation assays as well as by induction of apoptosis and Akt activation by western blot analyses. Results The EAC cell lines OE33 and OE19 show a decrease of proliferation with raising curcumin concentration with an IC50 of 9.6 and 14.8 μM, respectively. While the metaplastic and dysplastic cell lines showed a comparable IC50 of 7.7 and 11.6 μM to the EAC cell lines, the FEF3 cell showed a higher IC50 of approx. 20μM. The phosphorylation of Akt was decreased and apoptosis was induced, showing cleaved PARP, when treated with 25μM curcumin after 48h and 72h. Conclusion Metaplastic, dysplastic and EAC cells show a higher receptivity to curcumin than esophageal fibroblasts cells. This constrains the NFκB activation and its contribution in the manifestation of the Barrett's esophagus. The usage of curcumin to generate an anti-inflammatory microenvironment will potentially help to develop a stable disease or to reverse the development of the Barrett's esophagus. Disclosure All authors have declared no conflicts of interest.

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