Epigenetic Alterations in Pancreatic Cancer Metastasis

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis

A simplified statistic-based procedure for gas dispersion prediction of fixed offshore platform

© 2017 In explosion risk analysis, Frozen Cloud Approach (FCA) and Dimensionless Response Surface Method (DRSM) are both commonly used to achieve a balance between simulation workloads and accurate results. However, the drawbacks of these two approaches are obvious. FCA is not reliable for risk study of fuel-dominated regions. Whereas DRSM usually couples the dimensionless parameters and generates a large numbers of correlations to predict the flammable cloud size, which brings a heavy computation burden for engineers. Therefore, this paper aims to propose a simplified procedure which can quickly and accurately provide a large number of non-simulation data based on limited CFD simulation data. Full Factorial Design of Experiment (FFDOE) based RSM is adopted. Codification is applied to couple all the dimensional parameters into a single correlation. Automatically Selected Model Technology (ASMT) is used to easily determine the suitable structure of correlation. Compared to the conventional procedures, the simplified procedure is proven to be more robust. For subsequent Explosion risk analyses (ERAs) in the fuel-dominated regions, the simplified procedure becomes a superior alternative

Engrailed‐1 Promotes Pancreatic Cancer Metastasis

Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain- and loss-of-function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA