Defense Date

2010

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

William M.D. Ph.D. Broaddus

Second Advisor

Timothy Van Meter PhD

Abstract

Medulloblastoma is the most common brain tumor in children, accounting for 10-20% of primary central nervous system (CNS) neoplasms and approximately 40% of all posterior fossa tumors. It is a highly invasive embryonal neuroepithelial tumor that typically arises in the cerebellar vermis and has a tendency to disseminate throughout the CNS early in its course. The molecular mechanisms of the disease largely remain uncharacterized, as the clinical treatment is still associated with mortality and severe side effects. The development of a clinically relevant in vivo model is important not only to further understand the disease but also to provide a method with which to test novel therapeutics. This study quantified the volumetric growth of a human medulloblastoma (VC312) in the athymic nude mouse cerebellum using Gd- enhanced T1-weighed MRI scans. Additionally, a medulloblastoma flank tumor model was used to explore the in vivo effect of the oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. In the orthotopic intracerebellar tumor model, perifosine significantly increased the survival of treated mice while qualitatively reducing leptomeningeal dissemination. In the flank model, perifosine effectively suppressed the volumetric growth, decreased activation of the AKT pathway and reduced cellular proliferation in treated mice.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2010

Available for download on Thursday, August 13, 2020

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