Andolina J.R.,University of Rochester |
Morrison C.B.,Memorial Childrens Hospital |
Thompson A.A.,Northwestern University |
Chaudhury S.,Northwestern University |
And 4 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2013
Exocrine pancreatic insufficiency and diarrhea have been hallmarks in the diagnosis of Shwachman-Diamond syndrome (SDS). We report 2 cases of genetically confirmed SDS in patients who presented with an unusual phenotype. Patient #1 presented with pancytopenia without other system involvement, while patient #2 presented with severe neutropenia, anemia, and a bifid thumb. Neither patient had diarrhea or malabsorption. Both patients had the classic heterozygous mutations c183-184 TA>CT and c.258+2 T>C in the Shwachman-Bodian-Diamond syndrome gene. Incomplete phenotypes may be more common than previously recognized in bone marrow failure syndromes; gastrointestinal symptoms should not be considered a prerequisite for SDS. © 2013 Lippincott Williams & Wilkins. Source
Biyashev D.,Lurie Comprehensive Cancer Center |
Veliceasa D.,Lurie Comprehensive Cancer Center |
Kwiatek A.,Northwestern University |
Sutanto M.M.,University of Chicago |
And 2 more authors.
Journal of Biological Chemistry | Year: 2010
Erk-5, a member of the MAPK superfamily, has a catalytic domain similar to Erk1/2 and a unique C-terminal domain enabling binding with transcription factors. Aberrant vascularization in the Erk5-null mice suggested a link to angiogenesis. Ectopic expression of constitutively active Erk5 blocks endothelial cell morphogenesis and causes HIF1-α destabilization/ degradation. However the mechanisms by which endogenous Erk5 regulates angiogenesis remain unknown. We show that Erk5 and its activating kinase MEK5 are the upstream mediators of the anti-angiogenic signal by the natural angiogenesis inhibitor, pigment epithelial-derived factor (PEDF). We demonstrate that Erk5 phosphorylation allows activation of PPARγ transcription factor by displacement of SMRT co-repressor. PPARγ, in turn is critical for NFκB activation, PEDF-dependent apoptosis, and anti-angiogenesis. The dominant negative MEK5 mutant and Erk5 shRNA diminished PEDF-dependent apoptosis, inhibition of the endothelial cell chemotaxis, and angiogenesis. This is the first evidence of Erk5-dependent transduction of signals by endogenous angiogenesis inhibitors. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source
Abel G.A.,Brigham and Womens Hospital |
Abel G.A.,Dana-Farber Cancer Institute |
Vanderplas A.,City of Hope National Medical Center |
Rodriguez M.A.,University of Texas M. D. Anderson Cancer Center |
And 9 more authors.
Leukemia and Lymphoma | Year: 2012
We aimed to characterize surveillance imaging and circumstances of relapse for patients with diffuse large B-cell lymphoma (DLBCL) in the National Comprehensive Cancer Network Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting clinical and outcome data at seven comprehensive cancer centers. Patients presenting with newly diagnosed DLBCL in remission ≥3 months after initial therapy and who had accrued 2 years of follow-up were eligible for analysis (n 625). The median number of imaging studies was 2.5/year (institutional range 0.53.5, p < 0.0001); 48.4% received only dedicated computed tomography (CT) scans, 14.6% received only positron emission tomography (PET)-inclusive modalities, 32.8% received a combination and 4.2% received no imaging. Among all eligible patients, 50 (8.0%) experienced relapse, and approximately one-quarter of subclinical relapses were detected through routine imaging. Our results suggest that despite limited data regarding its effect on outcomes, surveillance imaging is prevalent in DLBCL, and a majority of patients receive PET scans at some point during follow-up. © 2012 Informa UK, Ltd. Source