BackgroundToll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR-mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis.MethodsWe surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization.ResultsGene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett’s esophagus (60 %) and esophageal adenocarcinoma (100 %), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett’s esophagus (50–70 %) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20–30 %). E. coli was detected in the Barrett’s esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups.ConclusionsWe demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2093-8) contains supplementary material, which is available to authorized users.

'On time' and predictability of 'off time' are highly valued by PwP. Due to substantial diurnal variation of Parkinson's symptoms, standard patient-reported outcome (PRO) assessments may not adequately capture the impact of 'off time' on HRQL and participation in daily activities.

AIMTo efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy.METHODSEnd-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of MUC2, CK19, and CK20, and results were compared to determine significant differences throughout disease progression stages.RESULTSThe overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett’s esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC.CONCLUSIONEsophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics.

Depletion of Sep70 with the presence of pepsin in the hypopharynx may indicate cellular injury in laryngopharynx due to constant proximal reflux. However, the normative data for these markers have to be validated.