Medicine and Health Sciences Commons^™

Aberrantly Low Stat3 And Stat5 Responses Are Associated With Poor Outcome And An Inflammatory Gene Expression Signature In Pediatric Acute Myeloid Leukemia., P Narayanan, T-K Man, R B Gerbing, R Ries, A M Stevens, Y-C Wang, X Long, A S. Gamis, T Cooper, S Meshinchi, T A Alonzo, M S Redell

Manuscripts, Articles, Book Chapters and Other Papers

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low …

Shear Stress Associated With Cardiopulmonary Bypass Induces Expression Of Inflammatory Cytokines And Necroptosis In Monocytes., Lan N. Tu, Lance Hsieh, Masaki Kajimoto, Kevin Charette, Nataliya Kibiryeva, Adriana Forero, Sarah Hampson, Jennifer A. Marshall, James O'Brien, Marta Scatena, Michael A. Portman, Ram Savan, Chris Benner, Alberto Aliseda, Muhammad Nuri, Douglas Bittel, Peter Pastuzsko, Vishal Nigam

Manuscripts, Articles, Book Chapters and Other Papers

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we …

Study Design And Baseline Characteristics Of The Cardinal Trial: A Phase 3 Study Of Bardoxolone Methyl In Patients With Alport Syndrome., Glenn M. Chertow, Gerald B. Appel, Sharon Andreoli, Sripal Bangalore, Geoffrey A. Block, Arlene B. Chapman, Melanie P. Chin, Keisha L. Gibson, Angie Goldsberry, Kazumoto Iijima, Lesley A. Inker, Bertrand Knebelmann, Laura H. Mariani, Colin J. Meyer, Kandai Nozu, Megan O'Grady, Arnold L. Silva, Peter Stenvinkel, Roser Torra, Bradley A. Warady, Pablo E. Pergola

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome.

METHODS: The CARDINAL phase 3 study is an international, …