COX-2 mRNA is increased in oesophageal mucosal cells by a proton pump inhibitor

Author version made available in accordance with the publisher's policy.Introduction: Barrett’s oesophagus develops in some individuals with gastro-oesophageal reflux, and is the precursor to oesophageal adenocarcinoma. Proton pump inhibitors (PPIs) suppress gastric acid production and are used to treat reflux. Clinical trials suggest that COX inhibitors might prevent oesophageal cancer, although PPIs could offset this by increasing COX-2 expression in Barrett’s oesophagus. To investigate this, we evaluated the impact of a PPI on COX expression in oesophageal mucosal cells. Methods: The effect of the PPI esomeprazole on COX-1 and COX-2 mRNA levels in oesophageal cells was determined. Oesophageal cell lines OE33 (adenocarcinoma derived) and HET-1A (immortalized squamous cells), and a control intestinal cell line - HT29 (colon carcinoma), were treated for 24 hours with increasing concentrations of the esomeprazole. Results: COX-2, but not COX-1, mRNA levels, dose dependently increased in OE33 and HET-1A cells vs. esomeprazole concentration. COX-2 mRNA levels did not increase in HT29 cells. Conclusions: Exposure to esomeprazole increases COX-2 mRNA in oesophageal cells. This might contribute to the lack of benefit for COX inhibitors for oesophageal cancer prevention in recent clinica

microRNAs and Esophageal Cancer - Implications for Pathogenesis and Therapy

Author version made available in accordance with the publisher's policy.There are several microRNAs that have been consistently reported to be differentially expressed in esophageal squamous cell carcinoma vs. normal squamous tissue, with prognostic associations for miR-21 (invasion, positive nodes, decreased survival), miR-143 (disease recurrence, invasion depth), and miR-375 (inversely correlated with advanced stage, distant metastasis, poor overall survival, and disease-free survival). There is also evidence that miR-375 regulates gene expression associated with resistance to chemotherapy. Hence, microRNA expression assays have the potential to provide clinically relevant information about prognosis and potential response to chemotherapy in patients with esophageal squamous cell carcinoma. Results are inconsistent, however, for microRNAs across different studies for esophageal adenocarcinoma (EAC) vs. its precursor lesion Barrett’s esophagus. These inconsistencies may partly result from pathological and/or molecular heterogeneity in both Barrett’s esophagus and EAC, but may also result from differences in study designs or different choices of comparator tissues. Despite these inconsistencies, however, several mRNA/protein targets have been identified, the cancer related biology of some of these targets is well understood, and there are clinico-pathological associations for some of these mRNA targets. MicroRNAs also have potential for use in therapy for esophageal cancers. The development of new delivery methods, such as minicells and autologous microvesicles, and molecular modifications such as the addition of aromatic benzene pyridine analogs, have facilitated the exploration of the effects of therapeutic microRNAs in vivo. These approaches are producing encouraging results, with one technology in a phase I/IIa clinical trial

Molecular biomarkers and ablative therapies for Barrett’s esophagus

Author version made available in accordance with the publisher's policy.Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma. Endoscopic interventions which ablate Barrett’s esophagus mucosa lead to replacement with a new squamous (neosquamous) mucosa, but it can be difficult to achieve complete ablation. Knowing whether cancer is less likely to develop in neosquamous mucosa or residual Barrett’s esophagus after ablation is critical for determining the efficacy of treatment. This issue can be informed by assessing biomarkers that are associated with an increased risk of progression to adenocarcinoma. Although there are few post-ablation biomarker studies, evidence suggests that that neosquamous mucosa may have a reduced risk of adenocarcinoma in patients who have been treated for dysplasia or cancer, but some patients who do not have complete eradication of non-dysplastic Barrett’s esophagus may still be at risk. Biomarkers could be used to optimize endoscopic surveillance strategies following ablation, but this needs to be assessed by clinical studies and economic modeling

Accurate PCR detection of influenza A/B and respiratory syncytial viruses by use of Cepheid Xpert Flu+RSV Xpress Assay in point-of-care settings: Comparison to Prodesse ProFlu+

ABSTRACT The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting. </jats:p

Accuracy of identification of tissue types in endoscopic esophageal mucosal biopsies used for molecular biology studies

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Vitrified magnesia dissolution and its impact on plutonium residue processing

Aqueous chloride operations at the Los Alamos Plutonium Facility cannot directly dispose of acidic waste solutions because of compatibility problems with existing disposal lines. Consequently, all hydrochloric acid must be neutralized and filtered prior to exiting the facility. From a waste minimization standpoint, the use of spent magnesia pyrochemical crucibles as the acid neutralization agent is attractive since this process would take a stream destined for transuranic waste and use it as a reagent in routine plutonium residue processing. Since Los Alamos National Laboratory has several years of experience using magnesium hydroxide as a neutralizing agent for waste acid from plutonium processing activities, the use of spent magnesia pyrochemical crucibles appeared to be an attractive extension of this activity. In order to be competitive with magnesium hydroxide, however, size reduction of crucible shards had to be performed effectively within the constraints of glovebox operations, and acid neutralization time using crucible shards had to be comparable to neutralization times observed when using reagent-grade magnesium hydroxide. The study utilized non-plutonium-contaminated crucibles for equipment evaluation and selection and used nonradioactive acid solutions for completing the neutralization experiments. This paper discusses experience in defining appropriate size reduction equipment and presents results from using the magnesia crucibles for hydrochloric acid neutralization, a logical precursor to introduction into glovebox enclosures

Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation

BACKGROUND: Metallothionein 3 (MT3) inhibits growth in a variety of cell types. We measured MT3 gene expression by RT-PCR, and DNA methylation in the MT3 promoter by combined bisulphite restriction analysis, in four oesophageal cancer cell lines and the resected oesophagus from 64 patients with oesophageal squamous cell carcinoma (SCC). RESULTS: MT3 expression was not detected in one of the four oesophageal cell lines. The MT3 promoter was methylated in all of the oesophageal cell lines, but the degree of methylation was greater in the non-expressing cell line. After treatment with 5-aza-2'-deoxycytidine there was a reduction in the degree of methylation, and an increase in MT3 expression, in each of the cell lines (p < 0.01). Methylation was detected in 52% (33 of 64) of primary SCC and 3% (2 of 62) of histologically normal resection margins. MT3 expression was measured in 29 tumours, 17 of which had methylation of MT3. The expression of MT3 was significantly less in the methylated tumours compared to either the unmethylated tumours (p = 0.03), or the matched margin (p = 0.0005). There was not a significant difference in MT3 expression between the tumour and the margin from patients with unmethylated tumour. No correlations were observed between methylation of MT3 and survival time, patient age, gender, smoking or drinking history, tumour stage, volume, or lymph node involvement. CONCLUSION: We conclude that MT3 expression is frequently down-regulated in oesophageal SCC, by DNA methylation, but that this is not a prognostic indicator

The role of serological testing in the SARS-CoV-2 outbreak

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies