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Antiangiogenesis
treatment for gliomas: transfer of antisense-vascular endothelial growth factor
inhibits tumor growth in vivo
Im SA, Gomez-Manzano C, Fueyo J, Liu TJ, Ke LD, Kim JS, Lee HY, Steck
PA, Kyritsis AP, Yung WK
Department of Neuro-Oncology, The University of Texas M.D.
Anderson Cancer Center, Houston 77030, USA
Presently, there is no effective treatment for glioblastoma, the most
malignant and common brain tumor.
Angiogenic factors are potentially optimal targets for therapeutic strategies
because they are essential for tumor growth and progression.
In this study, we sought a strategy for efficiently delivering an antisense cDNA
molecule of the vascular endothelial growth factor (VEGF) to glioma cells.
The recombinant adenoviral vector Ad5CMV-alphaVEGF carried the coding sequence
of wild-type VEGF165 cDNA in an antisense orientation.
Infection of U-87 MG malignant glioma cells with the Ad5CMV-alphaVEGF resulted
in reduction of the level of the endogenous VEGF mRNA and drastically decreased
the production of the targeted secretory form of the VEGF protein.
Treatment of
s.c. human glioma tumors established in nude mice with intralesional injection
of Ad5CMV-alphaVEGF inhibited tumor growth.
Taken together, these findings indicate that the efficient down-regulation of
the VEGF produced by tumoral cells using antisense strategies has an antitumor
effect in vivo.
This is the first time that an adenoviral vector is used to transfer antisense
VEGF sequence into glioma cells in an animal model, and our results suggest that
this system may have clinical and therapeutic utility.
PMID: 10029081 [PubMed - indexed for MEDLINE]
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