Proteostasis Dysregulation in Pancreatic Cancer

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitinligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.Peer reviewe

Probing the Confining Effect of Clay Particles On an Amorphous Intercalated Dendritic Polyester

The fourth generation of a hydroxylated dendritic hyperbranched polyester (HBP) was combined with sodium montmorillonite clay (Na+MMT) using water to generate a broad range of polymer clay nanocomposites from 0 to 100% wt/wt Na+MMT. Analysis with differential scanning calorimetry (DSC) showed a deviation in heat capacity, ΔCp, with clay content at the Tg from a two-phase trend which was attributed to the formation of an immobilized rigid amorphous fraction (RAF) in the interlayer spacing of the intercalated system. This deviation occurred in a step-like fashion which we attributed to 0.5 nm incremental changes in the interlayer spacing, previously observed through X-ray diffraction analysis. A simple series model was utilized to quantify these interlayer spacings based on the ΔCp values and showed good correspondence with the X-ray results. The RAF was quantified from changes in heat capacity with clay content and was verified by an alternative novel positron annihilation lifetime spectroscopy (PALS) approach. The PALS quantification of the RAF was possible through an analysis of changes in the hole size thermal expansivity of the nanocomposites as a function of clay composition. Results indicated that as much as 32% by weight of the system is made up of the RAF at its maximum