Brainstem Tumor Model
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Slide 1 :
Efficacy of Local Delivery 3-Bromopyruvate in the Treatment of Brainstem Tumors Cyrus Wong BS, Margaret Penno PhD, Andrey Volkov BA, Young Ko Phd, and George Jallo MD Johns Hopkins University, Baltimore Maryland
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Epidemiology Brainstem location represents 8-15% of all brain tumors in the pediatric population 18-22% of all posterior fossa tumors 80% of all brainstem tumors are located in the pons Midbrain and medulla account for minority
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Classification Systemfor Brainstem Tumors
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Survival for Children with Diffuse Pontine Gliomas (CCG 9941) J Clin Oncol 20:3431-3437, 2002
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Laboratory Methods: Rodent Tumor Model
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Histological Analysis following Brainstem Tumor Cell Implantation
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Kaplan – Meier Survival Curves
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Choice of Chemotherapy Agents 3Br-PA used in hepatocellular tumors Intraarterial Intratumoral Tumor cells exhibit increased glycolysis Upregulate the glycolytic pathway for ATP Hypoxic environment of tumor cells Hexokinase catalyzes: glucose + ATP glucose-6-phosphate + ADP .
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3-Bromopyruvate 3-Bromopyruvate (3-BrPA) Potent inhibitor of hexokinase II Key enzyme if the first step for glycolysis Effective for the treatment of many cancer types Induces cell death by its ability to deplete cellular ATP
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Experimental Design In vitro analysis of 3-bromopyruvate efficacy on F98 cells In vivo studies survival studies in the brainstem tumor model Toxicity study for 3-bromopyruvate
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In vitro Study
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Toxicity of 3-BrPA on Animal Weight
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Animal Weight with Tumor Cells
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Functional Rotorod Times
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Overall Survival Overall survival delayed by several days as compared to controls No “cure” for these tumors
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Conclusions The present study is to our knowledge the first to report on pre-clinical testing of a locally-delivered glycolysis inhibitor to a brainstem tumor. 3-BrPA constitutes a rational agent for brainstem tumor therapy.
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Future Directions Tumor Cell Lines 9L Athymic rats Comparison of systemic versus local delivery Intra-arterial Intravenous Local Delivery Continuous infusion therapy Polymer delivery
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