The human survivin promoter: a novel transcriptional targeting strategy for treatment of glioma

Journal of Neurosurgery
Winan J Van HoudtZeng B Zhu

Abstract

Malignant brain tumors have been proved to be resistant to standard treatments and therefore require new therapeutic strategies. Survivin, a recently described member of the inhibitor of apoptosis protein family, is overexpressed in several human brain tumors, primarily gliomas, but is downregulated in normal tissues. The authors hypothesized that the expression of tumor-specific survivin could be exploited for treatment of gliomas by targeting the tumors with gene therapy vectors. Following confirmation of survivin expression in glioma cell lines, an adenoviral vector containing the survivin promoter and the reporter gene luciferase was tested in established and primary glioma cells, normal astrocytic cells, and normal human brain tissues. High levels of reporter gene expression were observed in established tumor and primary tumor cell lines and low levels of expression in astrocytes and normal human brain tissue. To test oncolytic potency, the authors constructed survivin promoter-based conditionally replicative adenoviruses (CRAds), composed of survivin promoter-regulated E1 gene expression and an RGD-4C capsid modification. These CRAds could efficiently replicate within and kill a variety of established glioma tumor cells, ...Continue Reading

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Citations

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Methods Mentioned

BETA
Assay
PCR
Xenografts
xenograft

Software Mentioned

Statistics Analysis
Primer Express

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