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Randy Jensen M.D. Ph.D. Neurosurgery E-mail: randy.jensen@hsc.utah.edu Research Title:
Inhibition of HIF-1 by siRNA in an intracranial brain tumor |
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Research description: Hypoxia inducible factor-1 is the principle regulator
of vascular endothelial growth factor (VEGF) which is presumed to be the
principal mediator of angiogenesis and peritumoral edema in human
Glioblastoma multiforme. We have used RNA interference (RNAi) to
significantly reduce HIF-1 levels in U251 glioma cells grown in vitro and in
vivo. In vitro, growth was attenuated using small interfering RNAs (siRNA)
and constitutively using short hairpin RNAs (shRNA). Intertumoral injection
of siRNA against HIF-1 effectively curbed tumor growth. As proof of
principle, these studies were conducted in a single glioma cell line and in
a flank brain tumor model. Unfortunately,before these results to be applied
to the clinical situation further studies need to be done in other glioma
cell lines in in an intracranial model. 10/06 |
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