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- Title
- THE ROLE OF ACTIVIN A SIGNALING IN GASTRIC REFLUX-RELATED DISEASES AND THE PROGRESSION TO ESOPHAGEAL ADENOCARCINOMA.
- Creator
-
Roudebush, Cedric J., Andl, Claudia, University of Central Florida
- Abstract / Description
-
Gastroesophageal reflux disease (GERD), or acid reflux, affects 6-9 million people in the United States. It is characterized by a reflux of gastric acid and bile salts from the stomach into the esophagus, causing injuries to the esophagus known as Barrett's esophagus (BE). BE is the main risk factor for the development of esophageal adenocarcinoma (EAC), a devastating cancer in the esophagus whose molecular roots remain poorly understood. In recent years, evidence points to the esophageal...
Show moreGastroesophageal reflux disease (GERD), or acid reflux, affects 6-9 million people in the United States. It is characterized by a reflux of gastric acid and bile salts from the stomach into the esophagus, causing injuries to the esophagus known as Barrett's esophagus (BE). BE is the main risk factor for the development of esophageal adenocarcinoma (EAC), a devastating cancer in the esophagus whose molecular roots remain poorly understood. In recent years, evidence points to the esophageal epithelium itself as responsible for causing and promoting inflammation upon injury by gastric reflux, namely via an increase in inflammatory cytokine secretion. This project was focused on a cytokine of interest, Activin A, which is known for its importance during embryogenesis and stem cell differentiation. It has recently been studied for its role in inflammation and tumor formation, but not in the case of esophageal diseases. Here, we demonstrate that Activin A signaling in esophageal epithelial cells is heavily upregulated shortly after exposure to bile salts and acid. We show evidence that this upregulation causes an increase in cell migration upon a reconstituted extracellular matrix. We also provide further evidence that bile and acid injury causes epithelial cells to secrete cytokines, which drive inflammation. We show that the upregulated Activin A secretion and signaling plays an important role in promoting this inflammatory state. Finally, we provide evidence that bile salts and acid exposure, as well as increased Activin A signaling, causes esophageal epithelial cells to upregulate stem cell and transdifferentiation markers, supporting the latest theories on the origin of Barrett' esophagus stem cells as well as paligenosis.
Show less - Date Issued
- 2019
- Identifier
- CFH2000485, ucf:45887
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000485
- Title
- The Relationship Among Perceptual and Objective Reflux Measures in Singers.
- Creator
-
Lloyd, Adam, Hoffman Ruddy, Bari, Ryalls, John, Ratusnik, David, University of Central Florida
- Abstract / Description
-
Laryngopharyngeal reflux (LPR) is currently one of the most prevalent conditions associated with voice disorders being treated in voice care centers worldwide. Many singers experience voice related disturbances but are unaware that these disturbances may be the result of LPR. The purpose of this study was to quantify the perceptual symptoms and objective measures of LPR in a population of singers in order to understand the relationship between perceived symptoms, laryngeal findings, and...
Show moreLaryngopharyngeal reflux (LPR) is currently one of the most prevalent conditions associated with voice disorders being treated in voice care centers worldwide. Many singers experience voice related disturbances but are unaware that these disturbances may be the result of LPR. The purpose of this study was to quantify the perceptual symptoms and objective measures of LPR in a population of singers in order to understand the relationship between perceived symptoms, laryngeal findings, and evidence of acid exposure to the larynx. The Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and the Dx-pH monitoring system were used to quantify participant symptoms, endoscopic findings, and pH levels in the oropharynx. The population included 12 semi-professional and professional singers. Significant correlations were found between the RFS, RSI and pH mild and moderate pH levels. This indicates that singers are sensitive to even small deviations of pH and this should be taken into consideration when evaluating a singers who have suspected LPR. Due to the variety of etiologies that can produce the symptoms and physical findings mentioned in this study, it is imperative that more objective data be obtained to confirm the presence of reflux in the oropharynx. As such, endoscopic findings and symptoms alone are not a good indication of reflux exposure and more objective data, like an oropharyngeal pH measurement system, should be implemented to quantify reflux in the oropharynx. The RSI and the RFS are valid tools for qualifying perceptions and physical findings however they are not without flaws.
Show less - Date Issued
- 2011
- Identifier
- CFE0004128, ucf:49093
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004128
