Life Sciences Commons^™

Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock

Internal Medicine Faculty Publications

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr^−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …

First-In-Human Clinical Trial Of Oral Onc201 In Patients With Refractory Solid Tumors, Mark N. Stein, Joseph R. Bertino, Howard L. Kaufman, Tina M. Mayer, Rebecca A. Moss, Ann W. Silk, Nancy Chan, Jyoti Malhotra, Loma Rodriguez, Joseph Aisner, Robert Aiken, Bruce G. Haffty, Robert S. Dipaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Sioghan Dickerson, Ling Zheng, Wafik S. El-Deiry, Joshua E. Allen, Martin Stogniew, Wolfgang Oster, Janice M. Mehnert

Internal Medicine Faculty Publications

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D).

Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, …