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Timothy G. Murray, Christina Decatur, Yolanda Piña, Samuel Houston, Ludimilla Cavalcante, Theodore Lampidis; A Novel, Oral, Non-invasive Method Of Delivery For The Glycolytic Inhibitor 2-deoxy-d-glucose In The Treatment Of Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1592.
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The aim of the current study is to assess the impact of oral delivery of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on tumor burden and hypoxia in the LHBETATAG retinal tumor model.
The study protocol was approved by the University of Miami Institutional Animal Care and Use Review Board Committee and conformed to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. 4-week-old mice received oral delivery of 2-DG in custom made food pellets and were treated for either 8 or 18 weeks. Seventeen week-old mice received oral 2-DG for 8 weeks. At the time of enucleation, all eye samples were snap frozen and analyzed for tumor burden, hypoxia, and angiogenesis using histopathology and immunohistochemistry techniques. Percentages of the different variables were statistically analyzed using ANOVA.
Following oral delivery of 2-DG, there was a difference between the groups treated with 2-DG and the control group (p<0.010). A 20% reduction was found in the 8 weeks early treated, a 50% reduction in the 18 weeks early treated, and a 35% reduction in the 8 weeks late treated group. The percent hypoxia was reduced relative to controls in the 8 weeks and 18 weeks early treated groups (p<0.001) with a 40% and 50% reduction, respectively. New blood vessel density was found to have decreased by 20% in the early treated group that received 2-DG treatment for 18 weeks.
This study documents the efficacy of a novel, oral, non-invasive approach to deliver 2-DG as a potential therapy to decrease intratumoral hypoxia and tumor burden. The use of 2-DG as a therapeutic strategy has the potential to enhance current retinoblastoma treatments.
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