p53, mgmt, and temozolomide sensitivity in high grade astrocytic gliomas
Date
2012
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Glioblastoma multiforme (GBM) is a uniformly fatal type of brain cancer. Despite intensive research, only minor progress has been made in improving prognosis. Current treatment modalities for GBM involve surgical resection, followed by chemoradiotherapy, with the same treatment generally administered to all patients. Intriguingly, differential patient outcomes are not uncommon: some patients respond favourably, some do not, suggesting that tumour subsets with unique molecular alterations that determine the effectiveness of treatment must exist. If the nature and consequence of these alterations can be clarified, it may be possible to individualize patient treatments. Indeed, ensuring effective treatments for treatment-responsive cases, while eliminating unnecessary treatments and side effects from administering ineffective therapeutics is envisioned. The work presented in this dissertation focuses on the tumour suppressor p53 and the DNA repair protein 06-methylguanine DNA methyl transferase (MGMT). Specifically, we investigate the roles these proteins play in response of GBM to the chemotherapeutic Temozolomide (TMZ). The following three objectives are presented, aimed at improving our understanding of how these two molecules are related and the role they play in treatment response: i) examine the relationship between p53 and MGMT expression, two genes commonly altered in GBM; ii) define the relationship between p53 and response to TMZ; and iii) determine the link between MGMT and TMZ sensitivity in brain tumour initiating cells (BTICs), a potential 'disease reservoir' for GBM. Successful completion of these objectives provides an improved understanding of how p53 relates to MGMT expression and TMZ response, and whether MGMT determines TMZ sensitivity in BTICs.
Description
Bibliography: p. 51-69, 96-100, 134-137, 155-158, 175-180
Some pages are in colour.
Includes copy of animal protocol approval. Original copy with original Partial Copyright Licence.
Some pages are in colour.
Includes copy of animal protocol approval. Original copy with original Partial Copyright Licence.
Keywords
Citation
Blough, M. D. (2012). p53, mgmt, and temozolomide sensitivity in high grade astrocytic gliomas (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/5020