Hypoxia and the mesenchymal transition in glioma

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Publication Type honors thesis
School or College College of Science
Department Biology
Faculty Mentor Randy Jensen
Creator Weaver, Bradley
Title Hypoxia and the mesenchymal transition in glioma
Year graduated 2014
Date 2014-04
Description Recent advances in targeted therapy for cancer have had little influence on survival for patients diagnosed with Glioblastoma (GBM, WHO Grade IV tumors), and median survival time remains stagnant at 12-15 months post diagnosis. Genomic profiling of GBM indicates clear phenotypic subsets of these tumors, warranting the development of new models and targeted therapies. The mesenchymal phenotype in GBM is associated with poor patient prognosis and most recurrent GBM fall into this phenotype. Additionally, the cancer stem cell model applied to GBM explains the cellular heterogeneity of these tumors and their origin of growth. Glioma stem cells (GSCs) are thought to be responsible for proagation of the bulk tumor mass, resistance to chemotherapy and radiation treatment, and tumor recurrence and progression after surgical resection. Regions of intratumoral hypoxia maintain the stem-like characteristics of GSCs, and hypoxia is associated with worse prognosis and increased aggressiveness in GBM. The transcription factor HIFla is up regulated under hypoxia and its downstream targets include vascular endothelial growth factor (VEGF), which promotes angiogenesis. Research suggests that current anti-VEGF therapy in the form of bevacizumab inhibits angiogenesis, normalizes the tumor vasculature, and has a high response rate. However, many patients treated with bevacizumab experience tumor progression that can be rapid, invasive, and diffuse within the brain, consistent with GBM having mesenchymal phenotypes. This progression may be a direct result of increased intratumoral hypoxia after antiVEGF theraphy.
Type Text
Publisher University of Utah
Subject Glioblastoma multiforme; Gliomas; Hypoxia; Mesenchymal transition
Language eng
Rights Management (c) Bradley Weaver
Format Medium application/pdf
Format Extent 4,603,426 bytes
Permissions Reference URL https://collections.lib.utah.edu/details?id=1314623
ARK ark:/87278/s6bw0rxs
Setname ir_htoa
ID 205917
Reference URL https://collections.lib.utah.edu/ark:/87278/s6bw0rxs
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