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

Accelerator Engineering and Technology: Accelerator Technology

Magnets are at the core of both circular and linear accelerators. The main function of a magnet is to guide the charged particle beam by virtue of the Lorentz force, given by the following expression:where q is the electrical charge of the particle, v its velocity, and B the magnetic field induction. The trajectory of a particle in the field depends hence on the particle velocity and on the space distribution of the field. The simplest case is that of a uniform magnetic field with a single component and velocity v normal to it, in which case the particle trajectory is a circle. A uniform field has thus a pure bending effect on a charged particle, and the magnet that generates it is generally referred to as a dipole