Inhibition of glutaminase-1 in DLBCL potentiates venetoclax-induced antitumor activity by promoting oxidative stress.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, but first-line immunochemotherapy fails to produce a durable response in about one-third of the patients. Because tumor cells often reprogram their metabolism, we investigated the importance of glutaminolysis, a pathway converting glutamine to generate energy and various metabolites, for the growth of DLBCL cells. Glutaminase-1 (GLS1) expression was robustly detected in DLBCL biopsy samples and cell lines.

BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis.

Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, is characterized by an aggressive clinical course. In approximately one-third of patients with DLBCL, first-line multiagent immunochemotherapy fails to produce a durable response. Molecular heterogeneity and apoptosis resistance pose major therapeutic challenges in DLBCL treatment.

Load-reducing therapy prevents development of arrhythmogenic right ventricular cardiomyopathy in plakoglobin-deficient mice.

Objectives: We used a murine model of arrhythmogenic right ventricular cardiomyopathy (ARVC) to test whether reducing ventricular load prevents or slows development of this cardiomyopathy.

Background: At present, no therapy exists to slow progression of ARVC. Genetically conferred dysfunction of the mechanical cell-cell connections, often associated with reduced expression of plakoglobin, is thought to cause ARVC.

Regional, age-dependent, and genotype-dependent differences in ventricular action potential duration and activation time in 410 Langendorff-perfused mouse hearts.

Although numerous studies have reported the effects of genetic alterations on murine electrophysiology, the range of normal values for ventricular activation, repolarization, and arrhythmias in mouse hearts is not known. We analyzed right ventricular (RV), left ventricular (LV), and septal activation times, monophasic action potential durations (APD), and right ventricular effective refractory periods during spontaneous rhythm, induced AV nodal block, right ventricular pacing (100-300 ms paced cycle length), and programmed stimulation in 410 beating, Langendorff-perfused, wild-type mouse hearts of CD1, DBAC3H, FVBN, C57/Bl6, and hybrid backgrounds (age 203 +/- 132 days). Action potential duration was longer at longer cycle lengths.