Entity

Time filter

Source Type

Memphis, TN, United States

Willis C.M.,Stanley Manne Childrens Research Institute | Willis C.M.,Northwestern University | Willis C.M.,St Judes Childrens Research Hospital | Kluppel M.,Stanley Manne Childrens Research Institute | Kluppel M.,Northwestern University
PLoS ONE | Year: 2014

Expression of the glycosaminoglycan chondroitin sulfate-E (CS-E) is misregulated in many human cancers, including breast cancer. Cell-surface associated CS-E has been shown to have pro-tumorigenic functions, and pharmacological treatment with exogenous CS-E has been proposed to interfere with tumor progression mediated by endogenous CS-E. However, the effects of exogenous CS-E on breast cancer cell behavior, and the molecular mechanisms deployed by CS-E are not well understood. We show here that treatment with CS-E, but not other chondroitin forms, could interfere with the invasive protrusion formation and migration of breast cancer cells in three-dimensional organotypic cultures. Microarray analysis identified transcriptional programs controlled by CS-E in these cells. Importantly, negative regulation of the pro-metastatic extracellular matrix gene Col1a1 was required for the anti-migratory effects of exogenous CS-E. Knock-down of Col1a1 gene expression mimics the effects of CS-E treatment, while exposing cells to a preformed collagen I matrix interfered with the anti-migratory effects of CS-E. In addition, CS-E specifically interfered with Wnt/beta-catenin signaling, a known pro-tumorigenic pathway. Lastly, we demonstrate that Col1a1 is a positively regulated target gene of the Wnt/beta-catenin pathway in breast cancer cells. Together, our data identify treatment with exogenous CS-E as negative regulatory mechanism of breast cancer cell motility through interference with a pro-tumorigenic Wnt/beta-catenin - Collagen I axis. © 2014 Willis Klüppel. Source


Agwu A.L.,00 N Wolfe Street | Korthuis P.T.,Agency for Health Care Research and Quality | Siberry G.K.,Oregon Health And Science University | Ellen J.M.,U.S. National Institutes of Health | And 2 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2011

Objectives: Increasing numbers of youth are becoming HIV-infected and need highly active antiretroviral therapy (HAART). We hypothesized that behaviorally HIV-infected youth (BIY) ages 18 to 24 years are less likely than adults (25 years or older) to receive HAART and, once initiated, more likely to discontinue their first HAART regimen. Methods: Longitudinal analysis of treatment-naïve patients (age 18 years or older) meeting criteria for HAART and followed at HIV Research Network sites (2002-2008). Time from meeting criteria to HAART initiation and duration on first regimen were assessed using Cox proportional hazards regression. Results: A total of 3127 (268 youth, 2859 adult) treatment-naïve, HIV-infected patients met criteria. BIY were more likely to be black (66.8% vs 51.1%; P < 0.01) and less likely to identify injection drug use HIV risk (1.1% vs 8.8%; P < 0.01) than adults 25 years of age or older. Nearly 69% of BIY started HAART versus 79% of adults (P < 0.001). Adults 25 to 29 years of age (adjusted hazards ratio [AHR], 1.39; 95% confidence interval [CI], 1.12-1.73) and 50 years of age or older (AHR, 1.24; 95% CI, 1.00-1.54), but not 30 to 49 years (AHR, 1.19; 95% CI, 0.99-1.44) were more likely to initiate HAART than BIY. Attending four or more HIV provider visits within 1 year of meeting criteria was associated with HAART initiation (AHR, 1.91; 1.70-2.14). CD4 200 to 350 versus less than 200 cells/mm3 (AHR, 0.57; 95% CI, 0.52-0.63), and injection drug use (AHR, 0.80; 95% CI, 0.69-0.92) were associated with a lower likelihood of HAART initiation. There were no age-related differences in duration of the first regimen. Conclusion: BIY are less likely to start HAART when meeting treatment criteria. Addressing factors associated with this disparity is critical to improving care for youth. Copyright © 2011 Lippincott Williams & Wilkins. Source


Poplack D.G.,Texas Childrens Cancer Center | Fordis M.,Center for Collaborative and Interactive Technologies | Landier W.,City of Hope | Bhatia S.,City of Hope | And 2 more authors.
Nature Reviews Clinical Oncology | Year: 2014

Survivors of childhood cancer are at risk of long-term adverse effects and late effects of the disease and/or its treatment. In response to national recommendations to improve evidence-based follow-up care, a web-based support system for clinical decision making, the Passport for Care (PFC), was developed for use at the point of care to produce screening recommendations individualized to the survivor. To date, the PFC has been implemented in over half of the nearly 200 clinics affiliated with the Children's Oncology Group across the USA. Most clinician users report that the PFC has been integrated into clinic workflows, and that it fosters improved conversations with survivors about the potential late effects a survivor might experience and about the screening and/or behavioural interventions recommended to improve health status. Furthermore, clinicians using the PFC have indicated that they adhered more closely to follow-up care guidelines. Perspectives on the challenges encountered and lessons learned during the development and deployment of the PFC are reviewed and contrasted with other nationwide approaches to the provision of guidance on survivor follow-up care; furthermore, the implications for the care of childhood cancer survivors are discussed. © 2014 Macmillan Publishers Limited. All rights reserved. Source


Liu Y.,University of Texas Southwestern Medical Center | Shoji-Kawata S.,University of Texas Southwestern Medical Center | Shoji-Kawata S.,National Center for Global Health and Medicine | Sumpter Jr. R.M.,University of Texas Southwestern Medical Center | And 13 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy- inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxiä Cischemia in vivo. A chemical screen of ~5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na+,K +-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na+,K+-ATPase α1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na+,K+-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented. Source


Dai Q.,University of Alabama at Birmingham | Reddy V.V.B.,University of Alabama at Birmingham | Choi J.K.,St Judes Childrens Research Hospital | Faye-Petersen O.M.,University of Alabama at Birmingham
Pediatric and Developmental Pathology | Year: 2014

We report a case of a male newborn with trisomy 21 and transient abnormal myelopoiesis at birth whose placenta showed extravasated fetal blasts in the perivillous (maternal) space. Concern for possible maternal spread of fetal malignancy prompted a Kleihauer-Betke test and flow cytometric analysis of the maternal peripheral blood on postpartum day 2. Notably, no evidence of the persistence of fetal cells in the maternal blood was identified, a finding that likely reflected successful maternal immunologic clearance of the fetal blasts and erythrocytes, and/or blast cellular fragility and limited viability. Ours is the first report, to our knowledge, documenting maternal peripheral-blood follow-up evaluation of this disorder in the English literature. We discuss our case in the context of a comprehensive review of fetoneonatal solid tumor and leukemic proliferative disorders with placental involvement and evidence of maternal metastasis. © 2014 Society for Pediatric Pathology Source

Discover hidden collaborations