Lentiviral-Induced High-Grade Gliomas in Rats: The Effects of PDGFB, HRAS-G12V, AKT, and IDH1-R132H

被引：8

作者：

Lynes, John ^{[1
,2
]}

Wibowo, Mia ^{[1
,2
]}

Koschmann, Carl ^{[1
,2
]}

Baker, Gregory J. ^{[1
,2
]}

Saxena, Vandana ^{[1
,2
]}

Muhammad, A. K. M. G. ^{[1
,2
]}

Bondale, Niyati ^{[1
,2
]}

Klein, Julia ^{[1
,2
]}

Assi, Hikmat ^{[1
,2
]}

Lieberman, Andrew P. ^{[3
]}

Castro, Maria G. ^{[1
,2
]}

Lowenstein, Pedro R. ^{[1
,2
]}

机构：

[1] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

NEUROTHERAPEUTICS | 2014年 / 11卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Gene therapy; HSV1-TK; adenoviral vectors; brain tumors; NEURAL PROGENITORS; VINCRISTINE CHEMOTHERAPY; MOUSE MODELS; BRAIN-TUMORS; GLIOBLASTOMA; MUTATION; THERAPY; OLIGODENDROGLIOMAS; PROCARBAZINE; ASTROCYTES;

D O I：

10.1007/s13311-014-0269-y

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：623 / 635

页数：13

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