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- W2313571727 abstract "There has been little improvement in glioblastoma multiforme (GBM) patient prognosis over the past 20 years despite advances in imaging, neurosurgery, post-operative care, radiation delivery and chemotherapy. One reason for treatment failure is the highly invasive nature of glioma cells. Thus, it is essential to understand the mechanisms underlying invasion so that therapeutic targets can be developed and their impact assessed, non-invasively, during treatment.We have identified a trans-membrane protein, Aquaporin 1 (AQP1) whose over-expression correlates inversely with GBM survival (1,2) and drives migration of invading glioma cells (3). Our hypotheses are that the water permeation function of AQP1 drives migration and diffusion-weighted magnetic resonance imaging (DW-MRI) can be used to measure the water permeation and hence, invasion.The goal of our work is to determine the relationship between AQP1 expression and brain tumor invasion as measured in tissue culture by wound assay, in orthotopic murine brain slices by confocal microscopy and in rodent xenografts by DW-MRI. Modulating aquaporin channels alters water diffusion through cells and these changes have been detected with DW-MRI (4,5).We have data on 168 GBM patients that shows AQP1 overexpression correlates inversely with survival. Wound assay data indicates AQP1 overexpression drives migration and we have used an inhibitor of AQP1 water permeation, tetraethylammonium chloride (TEA) (6) to show that inhibiting water permeation also inhibits migration, We have histologic data on rodent xenografts demonstrating the aggressive invasive behavior of AQP1 overexpression compared to empty vector controls. We will present preliminary MRI results using an orthotopic rodent model where we modulate levels of AQP1 expression.References: 1. Verkman AS et al. J Mol Med (Epub), 2008. 2. Nagashima G et al. Brain Tumor Pathol 23(1), 2006. 3. Mirvish et al. Soc Neuro-Onc, 2007. 4. Latour LL. PNAS 91(4), 1994. 5. Thewall PE et al. Magn Reson Med 48(4), 2002. 6. Detmers et al. JBiolChem. 281(20); 14207, 2006.Supported by the Diane and Bruce Halle Fund, and the Barrow Neurological FoundationCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 433." @default.
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- W2313571727 date "2010-04-15" @default.
- W2313571727 modified "2023-10-17" @default.
- W2313571727 title "Abstract 433: Role of AQP1 in invasion of GBM" @default.
- W2313571727 doi "https://doi.org/10.1158/1538-7445.am10-433" @default.
- W2313571727 hasPublicationYear "2010" @default.
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