Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.     

Diffusion MRI changes in the anterior subventricular zone following chemoradiation in glioblastoma with posterior ventricular involvement

Journal of Neuro-Oncology - There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which...     

Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.