Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects.

Improved orthostatic dysregulation record after administration of a sustained-release form of urapidil.

The efficacy and safety of urapidil has been demonstrated in a long-term treatment. However, a relatively good record of side effects has been marred by reports of orthostatic dysregulation. This study was designed to examine the blood pressure lowering effect, tolerability and pharmacokinetics of a sustained-release formulation of urapidil.