Document Detail


An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma.
MedLine Citation:
PMID:  21907928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Using a mouse model of ependymoma-a chemoresistant brain tumor-we combined multicell high-throughput screening (HTS), kinome-wide binding assays, and in vivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both in vitro and in vivo, e.g., 5-fluorouracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation.
Authors:
Jennifer M Atkinson; Anang A Shelat; Angel Montero Carcaboso; Tanya A Kranenburg; Leggy A Arnold; Nidal Boulos; Karen Wright; Robert A Johnson; Helen Poppleton; Kumarasamypet M Mohankumar; Clementine Féau; Timothy Phoenix; Paul Gibson; Liqin Zhu; Yiai Tong; Chris Eden; David W Ellison; Waldemar Priebe; Dimpy Koul; W K Alfred Yung; Amar Gajjar; Clinton F Stewart; R Kiplin Guy; Richard J Gilbertson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer cell     Volume:  20     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2011-11-07     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  384-99     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Boronic Acids / pharmacology
Brain / pathology
Brain Neoplasms / drug therapy*,  metabolism,  pathology
Cell Proliferation
Centrosome / metabolism
Drug Screening Assays, Antitumor*
Ependymoma / drug therapy*,  metabolism,  pathology
Fluorouracil / pharmacology
High-Throughput Screening Assays / methods*
Insulin / metabolism
Mice
Mice, Nude
Neural Stem Cells / drug effects*
Pyrazines / pharmacology
Signal Transduction
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
P01CA96832/CA/NCI NIH HHS; P30CA021765/CA/NCI NIH HHS; R01 CA129541-01/CA/NCI NIH HHS; R01 CA129541-02/CA/NCI NIH HHS; R01 CA129541-03/CA/NCI NIH HHS; R01 CA129541-04/CA/NCI NIH HHS; R01 CA129541-05/CA/NCI NIH HHS; R01CA129541/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Boronic Acids; 0/Insulin; 0/Pyrazines; 0/bortezomib; 51-21-8/Fluorouracil
Comments/Corrections

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