| Literature DB >> 24752661 |
John Lynes1, Mia Wibowo, Carl Koschmann, Gregory J Baker, Vandana Saxena, A K M G Muhammad, Niyati Bondale, Julia Klein, Hikmat Assi, Andrew P Lieberman, Maria G Castro, Pedro R Lowenstein.
Abstract
In human gliomas, the RTK/RAS/PI(3)K signaling pathway is nearly always altered. We present a model of experimental gliomagenesis that elucidates the contributions of genes involved in this pathway (PDGF-B ligand, HRAS-G12V, and AKT). We also examine the effect on gliomagenesis by the potential modifier gene, IDH1-R132H. Injections of lentiviral-encoded oncogenes induce de novo gliomas of varying penetrance, tumor progression, and histological grade depending on the specific oncogenes used. Our model mimics hallmark histological structures of high-grade glioma, such as pseudopalisades, glomeruloid microvascular proliferation, and diffuse tumor invasion. We use our model of gliomagenesis to test the efficacy of an experimental brain tumor gene therapy. Our model allowed us to test the contributions of oncogenes in the RTK/RAS/PI(3)K pathway, and their potential modification by over-expression of mutated IDH1, in glioma development and progression in rats. Our model constitutes a clinically relevant system to study gliomagenesis, the effects of modifier genes, and the efficacy of experimental therapeutics.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24752661 PMCID： PMC4121445 DOI： 10.1007/s13311-014-0269-y
Source DB: PubMed Journal: Neurotherapeutics ISSN： 1878-7479 Impact factor: 7.620