| Establishment and characterization of clinically relevant models of ependymoma: a true challenge for targeted therapy. | |
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MedLine Citation:
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PMID: 21653596 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Su Guan; Ruijun Shen; Tiffany Lafortune; Ningyi Tiao; Peter Houghton; W K Alfred Yung; Dimpy Koul |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-08 |
Journal Detail:
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Title: Neuro-oncology Volume: 13 ISSN: 1523-5866 ISO Abbreviation: Neuro-oncology Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-05 Completed Date: 2011-10-25 Revised Date: 2012-07-02 |
Medline Journal Info:
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Nlm Unique ID: 100887420 Medline TA: Neuro Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 748-58 Citation Subset: IM |
Affiliation:
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Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Brain Neoplasms / drug therapy*, metabolism Cell Line, Tumor Cell Proliferation Child, Preschool Disease Models, Animal* Ependymoma / drug therapy*, metabolism Female Fluorescent Antibody Technique Humans Immunoenzyme Techniques Infant Male Mice Phosphatidylinositol 3-Kinases / antagonists & inhibitors, metabolism Receptor, Epidermal Growth Factor / antagonists & inhibitors, metabolism Signal Transduction* |
| Grant Support | |
ID/Acronym/Agency:
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CA16672/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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