Document Detail

Establishment and characterization of clinically relevant models of ependymoma: a true challenge for targeted therapy.
MedLine Citation:
PMID:  21653596     Owner:  NLM     Status:  MEDLINE    
The development of new therapies for ependymoma is dramatically limited by the absence of optimal in vivo and in vitro models. Successful ependymoma treatment requires a profound understanding of the disease's biological characteristics. This study focuses on the establishment and characterization of in vivo and in vitro models of ependymoma to study the molecular pathways necessary for growth and progression in ependymoma. In addition, this study also emphasizes the use of these models for therapeutic intervention of ependymomas. We established optimal conditions for the long-term growth of 2 tumor xenografts and cultures of 2 human ependymoma cell lines. This study also describes the establishment of in vivo models. Histopathologic features of tumors from both intracranial and subcutaneous sites in mice revealed perivascular pseudorosettes and ependymal rosettes, which are typical morphologic features of ependymoma similar to those observed in human specimens. The in vitro models revealed glial fibrillary acidic protein and vimentin expression, and ultrastructural studies demonstrated numerous microvilli, caveolae, and microfilaments commonly seen in human ependymoma. To study signaling pathway alterations in ependymoma, we profiled established ependymoma models with Western blot analysis that demonstrated aberrant activation mainly of the phosphoinositide 3-kinase and epidermal growth factor receptor signaling pathways. Targeting phosphoinositide 3-kinase and epidermal growth factor receptor signaling pathways with small molecule inhibitors showed growth inhibitory effects. These models can also be used to study the standard therapies used for ependymomas, as shown by some of the drugs used in this study. Therefore, the models developed will assist in the biological studies and preclinical drug screening for ependymomas.
Su Guan; Ruijun Shen; Tiffany Lafortune; Ningyi Tiao; Peter Houghton; W K Alfred Yung; Dimpy Koul
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-08
Journal Detail:
Title:  Neuro-oncology     Volume:  13     ISSN:  1523-5866     ISO Abbreviation:  Neuro-oncology     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-05     Completed Date:  2011-10-25     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100887420     Medline TA:  Neuro Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  748-58     Citation Subset:  IM    
Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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MeSH Terms
Blotting, Western
Brain Neoplasms / drug therapy*,  metabolism
Cell Line, Tumor
Cell Proliferation
Child, Preschool
Disease Models, Animal*
Ependymoma / drug therapy*,  metabolism
Fluorescent Antibody Technique
Immunoenzyme Techniques
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  metabolism
Signal Transduction*
Grant Support
Reg. No./Substance:
EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC protein, human; EC, Epidermal Growth Factor

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