Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial.

Background: The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose-response relationship of everolimus.

A phase II, double-blind, placebo-controlled, ascending-dose study of Eritoran (E5564), a lipid A antagonist, in patients undergoing cardiac surgery with cardiopulmonary bypass.

Background: Lipid A, the toxic moiety of endotoxin, is linked to multiple complications after cardiac surgery, including fever, vasodilation, and pulmonary and renal dysfunction. The lipid A antagonist eritoran (or E5564) prevents endotoxin-induced systemic inflammation in animals and humans. In this study we assessed the safety of eritoran administration in patients undergoing cardiac surgery and obtained preliminary efficacy data for the prophylaxis of endotoxin-mediated surgical complications.

Characterization of isoprenaline- and salmeterol-stimulated interactions between beta2-adrenoceptors and beta-arrestin 2 using beta-galactosidase complementation in C2C12 cells.

beta-Arrestin is an adaptor protein that has been shown to couple G protein-coupled receptors (GPCRs) to clathrin-coated pits and target them for subsequent internalization. More recently, beta-arrestin 2 has also been shown to be involved in the activation of mitogen-activated protein kinase cascades by G protein-coupled receptors independently of G protein activation. Direct interactions between proteins can be monitored using enzyme complementation between two inactive deletion mutants of beta-galactosidase (beta-gal; Deltaalpha and Deltaomega).