Myxoma Virus Treatment for Brain Tumour Initiating Cells: Interrogating and Enhancing Myxoma-Mediated Cell Death

Simple item page
atmire.migration.oldid512
dc.contributor.advisorForsyth, Peter
dc.contributor.advisorKurz, Ebba
dc.contributor.authorMcKenzie, Brienne Alexandra
dc.date.accessioned2012-12-20T17:36:41Z
dc.date.available2013-06-15T07:01:40Z
dc.date.issued2012-12-20
dc.date.submitted2012en
dc.description.abstractBrain tumour initiating cells (BTICs) are stem-like cells hypothesized to mediate recurrence in high-grade gliomas. Preclinical success has been demonstrated in treating patient-derived BTICs with oncolytic virotherapy, using replication-competent viruses to target and kill malignant cells. Myxoma virus (MyxV) is an oncolytic candidate, which is highly effective in conventional glioma models, but only modestly effective in BTICs. The objective of this study was to improve MyxV efficacy in BTICs in vitro, combining chemotherapeutics and virotherapy. Using a pharmacoviral screen, eleven compounds that enhance MyxV-mediated cell death were identified. A lead compound, axitinib, was validated in multiple BTIC models. It was demonstrated that a virally encoded protein, M011L, prevents MyxV-induced apoptosis in BTICs, and M011L disruption was shown to greatly improve MyxV-mediated cell death through apoptosis induction. These studies have elucidated multiple strategies for improving MyxV efficacy in a preclinical glioma model, with implications for the future clinical development of MyxV.en_US
dc.identifier.citationMcKenzie, B. A. (2012). Myxoma Virus Treatment for Brain Tumour Initiating Cells: Interrogating and Enhancing Myxoma-Mediated Cell Death (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27050en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27050
dc.identifier.urihttp://hdl.handle.net/11023/368
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectHealth Sciences
dc.subject.classificationglioblastomaen_US
dc.subject.classificationmyxoma virusen_US
dc.subject.classificationbrain tumour stem cellsen_US
dc.titleMyxoma Virus Treatment for Brain Tumour Initiating Cells: Interrogating and Enhancing Myxoma-Mediated Cell Death
dc.typemaster thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ucalgary_2012_mckenzie_brienne.pdf
Size:
7.49 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.65 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Open Theses and Dissertations