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
Slide 2 : 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
Slide 3 : Classification Systemfor Brainstem Tumors
Slide 4 : Survival for Children with Diffuse Pontine Gliomas (CCG 9941) J Clin Oncol 20:3431-3437, 2002
Slide 5 : Laboratory Methods: Rodent Tumor Model
Slide 6 : Histological Analysis following Brainstem Tumor Cell Implantation
Slide 7 : Radiographic Images
Slide 8 : Kaplan – Meier Survival Curves
Slide 9 : 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 .
Slide 10 : Results
Slide 11 : 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
Slide 12 : 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
Slide 13 : In vitro Study
Slide 14 : Toxicity of 3-BrPA on Animal Weight
Slide 15 : Animal Weight with Tumor Cells
Slide 16 : Functional Rotorod Times
Slide 17 : Overall Survival Overall survival delayed by several days as compared to controls No “cure” for these tumors
Slide 18 : 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.
Slide 19 : Future Directions Tumor Cell Lines 9L Athymic rats Comparison of systemic versus local delivery Intra-arterial Intravenous Local Delivery Continuous infusion therapy Polymer delivery
Slide 20 :

 


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