Rabbit Anti-Human beta Catenin (phospho Ser552) monoclonal antibody, clone 2I30M35

Background Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5-2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. Methods Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for thep.A138Vmutant ofTP53. Key polymorphisms atTP53and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. Results Among the total 114 detected somatic mutations,TP53was the most frequently mutated (41%) gene, followed byKRAS,SMAD4,CTNNB1, andERBB3.We identified a novel hotspotTP53mutation (p.A138V, in 17% of all patients). Low frequency ofKRASmutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predictedp.A138Vto have oncogenic characteristics. Patients withp.A138Vmutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138Vsomatic mutation in PDAC and pancreatobiliary PAC patients. Conclusion Detection ofp.A138Vsomatic variant inTP53might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency ofKRAShotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.

Background Atrial fibrillation (AF) is a complex disease and affects millions of people around the world. The biological mechanisms that are involved with AF are complex and still need to be fully elucidated. Therefore, we performed a meta-analysis of transcriptome data related to AF to explore these mechanisms aiming at more sensitive and reliable results. Methods Ten public transcriptomic datasets were downloaded, analyzed for quality control, and individually pre-processed. Differential expression analysis was carried out for each dataset, and the results were meta-analytically aggregated using the rth ordered p value method. We analyzed the final list of differentially expressed genes through network analysis, namely topological and modularity analysis, and functional enrichment analysis. Results The meta-analysis of transcriptomes resulted in 1197 differentially expressed genes, whose protein-protein interaction network presented 39 hubs-bottlenecks and four main identified functional modules. These modules were enriched for 39, 20, 64, and 10 biological pathways involved with the pathophysiology of AF, especially with the disease's structural and electrical remodeling processes. The stress of the endoplasmic reticulum, protein catabolism, oxidative stress, and inflammation are some of the enriched processes. Among hub-bottlenecks genes, which are highly connected and probably have a key role in regulating these processes, HSPA5, ANK2, CTNNB1, and MAPK1 were identified. Conclusion Our approach based on transcriptome meta-analysis revealed a set of key genes that demonstrated consistent overall changes in expression patterns associated with AF despite data heterogeneity related, among others, to type of tissue. Further experimental investigation of our findings may shed light on the pathophysiology of the disease and contribute to the identification of new therapeutic targets.