Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated.

The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh.

Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer.

Purpose: FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system.

Enhanced recovery pathway after open pancreaticoduodenectomy reduces postoperative length of hospital stay without reducing composite length of stay.

Background/purpose: There is no data regarding the impact of enhanced recovery pathways (ERP) on composite length of stay (CLOS) after procedures with increased risk of morbidity and mortality, such as pancreaticoduodenectomy.

Methods: Patients undergoing open pancreaticoduodenectomy before and after implementation of ERP were prospectively followed for 90 days after surgery and complications were severity graded using the Modified Accordion Grading System. A retrospective analysis of patient outcomes were compared before and after instituting ERP.

Extending Enhanced Recovery after Surgery Protocols to the Post-Discharge Setting: A Phone Call Intervention to Support Patients after Expedited Discharge after Pancreaticoduodenectomy.

The goal of this pilot study was to track patient outcomes after an expedited discharge after enhanced recovery after surgery (ERAS) pathway for pancreaticoduodenectomy (PD). A quantitative content analysis approach was used. All PD patients in a single academic medical center between February 2017 and June 2018 were called twice by specialized physician extenders after discharge.