Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma

Background: The continuous exposure of esophageal epithelium to refluxate may induce ectopic expression of bile-responsive genes and contribute to the development of Barrett's esophagus (BE) and esophageal adenocarcinoma. In normal physiology of the gut and liver, the nuclear receptor Pregnane × Receptor (PXR) is an important factor in the detoxification of xenobiotics and bile acid homeostasis. This study aimed to investigate the expression and genetic variation of PXR in reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma.Methods: PXR mRNA levels and protein expression were determined in biopsies from patients with adenocarcinoma, BE, or RE, and healthy controls. Esophageal cell lines were stimulated with lithocholic acid and rifampicin. PXR polymorphisms 25385C/T, 7635A/G, and 8055C/T were genotyped in 249 BE patients, 233 RE patients, and 201 controls matched for age and gender.Results: PXR mRNA levels were significantly higher in adenocarcinoma tissue and columnar Barrett's epithelium, compared to squamous epithelium of these BE patients (P < 0.001), and RE patients (P = 0.003). Immunohistochemical staining of PXR showed predominantly cytoplasmic expression in BE tissue, whereas nuclear expression was found in adenocarcinoma tissue. In cell lines, stimulation with lithocholic acid did not increase PXR mRNA levels, but did induce nuclear translocation of PXR protein. Genotyping of the PXR 7635A/G polymorphism revealed that the G allele was significantly more prevalent in BE than in RE or controls (P = 0.037).Conclusions: PXR expresses in BE and adenocarcinoma tissue, and showed nuclear localization in adenocarcinoma tissue. Upon stimulation with lithocholic acid, PXR translocates to the nuclei of OE19 adenocarcinoma cells. Together with the observed association of a PXR polymorphism and BE, this data implies that PXR may have a function in prediction and treatment of esophageal disease

QTLs and candidates genes for wood properties in maritime pine (Pinus pinaster Ait.)

A three-generation outbred pedigree of 186 individuals was used to identify the genomic regions involved in the variability of chemical and physical wood properties of Pinus pinaster. A total of 54 quantitative trait loci (QTLs) was detected, with an average of 2.4 QTLs per trait. Clusters of wood properties QTLs were found at several points in the genome, suggesting the existence of pleiotropic effects of a limited number of genes. The colocalizations observed in this study are in accordance with the genetic correlations previously reported in the literature. In addition, in an attempt to identify the genes underlying the QTLs, nine wood quality candidate genes involved in cell wall structure were localized on the genetic map. Only one of them, Korrigan, a gene encoding for a β 1-4 endo-glucanase known in Arabidopis thaliana to be involved in polysaccharide biosynthesis, co-localized with a wood quality QTL cluster involved in hemicellulose content and fibre characteristics. This finding is in accordance with results previously reported for this gene regarding its expression variability (transcriptome and proteome levels) and patterns of molecular evolution. The pertinence of this result will be tested in more rigorous designs in order to identify early selection predictors for wood quality

Functional single-nucleotide polymorphism of epidermal growth factor is associated with the development of Barrett's esophagus and esophageal adenocarcinoma

Reflux esophagitis (RO) and Barrett's esophagus (BO) can cause esophageal adenocarcinoma (OAC). The esophageal mucosa in the RO-BO-OAC cascade is chronically exposed to gastro-esophageal reflux. Epidermal growth factor (EGF) has an important role in the protection and repair of mucosal damage, and non-physiologic levels are associated with gastrointestinal tumors. The aim is to determine the functional effect of EGF gene polymorphisms on RO, BO and OAC development. A cohort of 871 unrelated Dutch Caucasians consisted of 198 healthy controls, 298 RO patients, 246 BO patients and 129 OAC patients. The frequency of the EGF-production-associated 5'UTR A+61G polymorphism was determined in these four groups. EGF immunohistochemistry was performed on BO biopsies. EGF expression was significantly lower in the G/G genotype compared with the A/G (P=0.008) and A/A (P=0.002) group. The G/G genotype was significantly more prevalent in RO (odds ratios (OR)=2.6; 95% confidence intervals (95% Cl): 1.3-5.2), BO (OR=3.0; 95% Cl: 1.5-6.2) and OAC (OR=4.1; 95% Cl: 1.8-9.7) than in controls. The G allele is associated with reduced EGF expression and increased risk for RO, BO and OAC development. This indicates that reduced mucosal protection resulting from genetically decreased EGF expression enhances esophageal tumor development. Journal of Human Genetics (2012) 57, 26-32; doi: 10.1038/jhg.2011.124; published online 1 December 201

The Case On Assessment Of Spilled Oil With Mixed Free Product In Seoul

The purpose of this study is to assess sources of contamination by analyzing the free product and oil compounds in groundwater near the Subway Station, located adjacent to the Yongsan Garrison in Seoul, Republic of Korea. All of the samples collected twice were groundwater and free product in a monitoring well. Analysis items are TPH fingerprinting, pristine/phytane ratio, alkylbenzene pattern, PAH&alkyl PAH, antioxidant, icing inhibitor, PIANO, element(C, N, H), and sulfur. Using ratio of pristine/phytane, we were able to distinguished fuel type between kerosene and JP-8 samples, which was impossible by GC/FID pattern. Alkyl benzene pattern was very effective in distinguishing between JP-8 and kerosene. It is very important that 2,4-dimethyl-6-tert-butyl phenol, an antioxidant used only for JP-8, was detected in free product samples. The concentration of sulfur in kerosene fuel is much lower than that of JP-8, and the total contents of sulfur in environmental samples can be used to differentiate the fuel type of spilled oil between kerosene and JP-8. In conclusion, according to the result of a variety of analytical methods to find the source of spilled fuel, it had been found that the fuel type detected in the tunnel of subway station and monitoring wells outside of Yongsan Garrison and the monitoring wells inside of Yongsan Garrison are the same