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Barretts esophagus, bile salts

Vikas Bhardwaj, Ravindran Caspa Gokulan, Andela Horvat, Liudmila Yermalitskaya, Olga Korolkova, Kay M Washington, Wael El-Rifai, Sergey I Dikalov, Alexander I Zaika
Gastroesophageal reflux disease (GERD) is the strongest known risk factor for esophageal adenocarcinoma. In the center of tumorigenic events caused by GERD is repeated damage of esophageal tissues by the refluxate. In this study, we focused on a genotoxic aspect of exposure of esophageal cells to acidic bile reflux (BA/A). Analyzing cells generated from patients with Barrett's esophagus and human esophageal specimens, we found that BA/A cause significant DNA damage that is mediated by reactive-oxygen species...
August 30, 2017: Scientific Reports
Chunhong Pang, Amy LaLonde, Tony E Godfrey, Jianwen Que, Jun Sun, Tong Tong Wu, Zhongren Zhou
Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett's esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma...
2017: Clinical and Experimental Gastroenterology
Sohaib Abu-Farsakh, Tongtong Wu, Amy Lalonde, Jun Sun, Zhongren Zhou
BACKGROUND: Claudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells. Recently, we found that vitamin D receptor (VDR) enhanced Claudin-2 expression in colon and that bile salt receptors VDR and Takeda G-protein coupled receptor5 (TGR5) were highly expressed in esophageal adenocarcinoma (EAC) and precancerous lesions...
February 17, 2017: BMC Gastroenterology
Romy E Verbeek, Peter D Siersema, Frank P Vleggaar, Fiebo J Ten Kate, George Posthuma, Rhonda F Souza, Judith de Haan, Jantine W P M van Baal
BACKGROUND AND AIMS: Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett's esophagus epithelium cell line...
September 2016: Journal of Gastrointestinal and Liver Diseases: JGLD
Rhonda F Souza
Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface...
2016: Digestive Diseases
Jun Hong, Zheng Chen, Dunfa Peng, Alexander Zaika, Frank Revetta, M Kay Washington, Abbes Belkhiri, Wael El-Rifai
Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0...
March 29, 2016: Oncotarget
Maureen Moore, Cheguevara Afaneh, Daniel Benhuri, Caroline Antonacci, Jonathan Abelson, Rasa Zarnegar
Gastroesophageal reflux disease (GERD) is a very common disorder with increasing prevalence. It is estimated that up to 20%-25% of Americans experience symptoms of GERD weekly. Excessive reflux of acidic often with alkaline bile salt gastric and duodenal contents results in a multitude of symptoms for the patient including heartburn, regurgitation, cough, and dysphagia. There are also associated complications of GERD including erosive esophagitis, Barrett's esophagus, stricture and adenocarcinoma of the esophagus...
January 27, 2016: World Journal of Gastrointestinal Surgery
Dun-Fa Peng, Tian-Ling Hu, Mohammed Soutto, Abbes Belkhiri, Wael El-Rifai
Esophageal adenocarcinoma (EAC) is the most frequent malignancy in the esophagus in the US and its incidence has been rising rapidly in the past few decades. Chronic gastroesophageal reflux disease (GERD), where the esophageal epithelium is abnormally exposed to acid and bile salts, is a pro-inflammatory condition that is the main risk factor for the development of Barrett's esophagus (BE) and its progression to EAC. Glutathione peroxidase 7 (GPX7) is frequently silenced through DNA hypermethylation during Barrett's tumorigenesis...
2014: Journal of Cancer
Nicola H Green, Zoe Nicholls, Paul R Heath, Jonathan Cooper-Knock, Bernard M Corfe, Sheila MacNeil, Jonathan P Bury
Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barrett's metaplasia (BM), with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-κB, driving the aberrant expression of intestine-specific caudal-related homeobox (CDX) genes. However, early events in the pathogenesis of BM from normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression...
June 2014: International Journal of Experimental Pathology
Yu Fang, Xiaoxin Chen, Manisha Bajpai, Amit Verma, Kiron M Das, Rhonda F Souza, Katherine S Garman, Claire L Donohoe, Naoimh J O'Farrell, John V Reynolds, Katerina Dvorak
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...
October 2013: Annals of the New York Academy of Sciences
Shumei Song, James C Byrd, Sushovan Guha, Kai-Feng Liu, Dimpy Koul, Robert S Bresalier
BACKGROUND: Bile reflux contributes to the development of esophageal injury and neoplasia. The mucin 5AC (MUC5AC) is absent in the normal squamous epithelium of the esophagus but is strongly expressed in Barrett esophagus (BE). The objective of this study was to determine whether and how bile acids influence the expression of MUC5AC in the esophagus. METHODS: MUC5AC expression was studied by immunohistochemistry and immunoblotting in human tissues, in tissues from a rat model of BE, and in SKGT-4 cultured esophageal epithelial cells...
June 1, 2011: Cancer
P Bus, P D Siersema, R E Verbeek, J W P M van Baal
Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus that occurs because of chronic gastroesophageal reflux. Previous studies have identified BE-specific microRNAs (miRNAs) in comparison with normal squamous epithelium (SQ). We hypothesized that BE-specific miRNAs could be induced in esophageal SQ cells by exposure to acid and/or bile salts. We aimed to determine whether BE-specific miRNAs are upregulated in an esophageal SQ cell line (Het-1A) in an environment with acid and/or bile salts and whether this is nuclear factor-κB (NF-κB) dependent...
August 2014: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
Juntaro Matsuzaki, Hidekazu Suzuki, Hitoshi Tsugawa, Mitsuhiro Watanabe, Sharif Hossain, Eri Arai, Yoshimasa Saito, Shigeki Sekine, Toshihiro Akaike, Yae Kanai, Ken-ichi Mukaisho, Johan Auwerx, Toshifumi Hibi
BACKGROUND & AIMS: Bile reflux contributes to development of Barrett's esophagus (BE) and could be involved in its progression to esophageal adenocarcinoma (EAC). We investigated whether bile acids affect levels or functions of microRNAs (MIRs) 221 and 222, which bind to the 3'-UTR of p27Kip1 messenger RNA to inhibit its translation. Reduced p27Kip1 increases degradation of the transcription factor CDX2; levels of CDX2 have been reported to decrease during progression of BE to EAC. METHODS: We used quantitative reverse transcriptase polymerase chain reaction to compare levels of MIRs 221 and 222 and immunohistochemistry to compare levels of p27Kip1 and CDX2 proteins in areas of BE and EAC from each of 11 patients...
December 2013: Gastroenterology
Sayak Ghatak, Marie Reveiller, Liana Toia, Andrei Ivanov, Tony E Godfrey, Jeffrey H Peters
BACKGROUND: Barrett's esophagus is a preneoplastic metaplasia in which the normal squamous epithelium of the esophagus changes to an intestinal, columnar phenotype due to long-term gastro-esophageal reflux. The major components of this reflux are bile and stomach acid. Previous in vitro studies on the effect of bile and acid on esophageal cells have predominantly relied on transformed esophageal squamous cells or cancer cells grown in monolayer culture. DISCUSSION: In this study, we expanded our previous work using an immortalized primary esophageal squamous cell line (EPC1)...
October 2013: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
Jingbo Zhao, Hans Gregersen
Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells...
May 14, 2013: World Journal of Gastroenterology: WJG
Katerina Dvorak, Bohuslav Dvorak
Barrett's esophagus (BE) is a metaplastic lesion of the distal esophagus arising as a consequence of chronic gastroesophageal reflux disease. Multiple studies show that BE is associated with increased risk of esophageal adenocarcinoma (EAC). Epidemiological studies and animal models demonstrate that chronic inflammation triggered by repeated exposure to refluxate predisposes to the development of BE and EAC. The chronic inflammation is associated with cytokine alterations. Interleukin 6 (IL-6) is a cytokine that stimulates cell proliferation and apoptosis resistance is frequently increased in different cancers...
April 21, 2013: World Journal of Gastroenterology: WJG
Michael Quante, Julian A Abrams, Yoomi Lee, Timothy C Wang
The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE...
December 1, 2012: Cell Cycle
S Jürgens, F Meyer, S J Spechler, R Souza
Barrett's esophagus (BE) is an intestinal metaplasia of the distal esophagus in which squamous cells are replaced by a columnar epithelium. It is considered as a premalignant lesion, which can lead to esophageal adenocarcinoma, a very aggressive type of cancer, and can often be found in patients with gastro-esophageal reflux disease (GERD). In spite of the widespread use of acid-suppressing therapy with proton pump inhibitors, the incidence of adenocarcinoma has been steadily rising during the last 30 years...
September 2012: Zeitschrift Für Gastroenterologie
P Bus, P D Siersema, J W P M van Baal
BACKGROUND: Barrett's esophagus (BE) is a premalignant condition caused by chronic gastroesophageal reflux. BE patients have an increased risk of developing esophageal adenocarcinoma (EAC). As many aspects of this condition are still unknown, there is a need for in vitro models to study BE development. AIM: To review the literature on cell lines and incubation conditions for studying BE development. METHODS: A literature search was performed using PubMed, EMBASE and the Cochrane library, combining the words esophagus, cell line, culture, Barrett's, bile, acid, exposure, reflux and adenocarcinoma...
June 2012: Cellular Oncology (Dordrecht)
Elke Prade, Moritz Tobiasch, Ivana Hitkova, Isabell Schäffer, Fan Lian, Xiangbin Xing, Marc Tänzer, Sandra Rauser, Axel Walch, Marcus Feith, Stefan Post, Christoph Röcken, Roland M Schmid, Matthias P A Ebert, Elke Burgermeister
Bile acids are synthesized from cholesterol and are major risk factors for Barrett adenocarcinoma (BAC) of the esophagus. Caveolin-1 (Cav1), a scaffold protein of membrane caveolae, is transcriptionally regulated by cholesterol via sterol-responsive element-binding protein-1 (SREBP1). Cav1 protects squamous epithelia by controlling cell growth and stabilizing cell junctions and matrix adhesion. Cav1 is frequently down-regulated in human cancers; however, the molecular mechanisms that lead to this event are unknown...
May 2012: Molecular Endocrinology
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