Toll-like Receptor 4 Mediates Reflux-Induced Inflammation in a Murine Reflux Model

Dysregulation of toll-like receptor (TLR) signaling within the gastrointestinal epithelium has been associated with uncontrolled inflammation and tumorigenesis. We sought to evaluate the role of TLR4 in the development of gastroesophageal reflux-mediated inflammation and mucosal changes of the distal esophagus. Verified human esophageal Barrett's cells with high grade dysplasia (CPB) and esophageal adenocarcinoma cells (OE33) were treated with deoxycholic acid for 24 hours. Cells were pretreated with a TLR4-specific inhibitor peptide 2 hours prior to deoxycholic acid treatment.
Source: Seminars in Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: THORACIC – Original Submission Source Type: research

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ConclusionsOver the study period, there was an increase in the incidence of oesophageal cancer in England. The largest increase was seen in rates of adenocarcinoma. Considering obesity has a strong temporal association with oesophageal adenocarcinoma, further research is needed to understand the biological mechanisms of this association to inform public health efforts to reduce the prevalence of obesity.Key messagesFurther research and analysis of routinely collected data on histological subtypes of oesophageal cancer can provide insight into the increasing trend in incidence.Considering the strong association between obes...
Source: The European Journal of Public Health - Category: General Medicine Source Type: research
Discussion: The transcriptomic gene expression patterns in the BEC model demonstrate evidence of a clear threshold in the progression of BE to malignancy. Catastrophic transcriptomic changes during a window period culminate in the commitment of the BE cells to a “point of no return,” and removal of ABS is not effective in preventing their malignant transformation. Discerning this “point of no return” during BE surveillance by tracking the GEPs has the potential to evaluate risk of BE progression and enable personalized clinical management.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
xel Maximilian Hillmer Esophageal adenocarcinoma (EAC) is a deadly disease with limited options for targeted therapy. With the help of next-generation sequencing studies over the last decade, we gained an understanding of the genomic architecture of EAC. The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes. EAC is characterized by a high burden of point mutations and genomic rearrangements, resulting in amplifications and deletions of genomic regions. The genomic complexity is likely hamper...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionsMost current risk prediction models of esophageal cancer have a high ROB. Prediction models need further improvement in their quality and applicability to benefit esophageal cancer screening.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.PMID:34405732 | DOI:10.1152/ajpgi.00199.2021
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Source Type: research
Biosci Trends. 2021 Aug 10. doi: 10.5582/bst.2021.01288. Online ahead of print.ABSTRACTObesity is a public health concern that is becoming increasingly more serious around the world. Bariatric surgery has become more prevalent due to the obesity epidemic worldwide. Sleeve gastrectomy (SG) is one of the most popular procedures which is safe and efficient. Despite all its favorable features, however, there is an increasing evidence from the literature that the long-term incidence of gastroesophageal reflux disease (GERD) is likely to represent the Achilles' heel of this procedure. Management of severe reflux after SG usually...
Source: BioScience Trends - Category: Biomedical Science Authors: Source Type: research
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