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dc.contributor.authorWhilding, Lynsey May
dc.date.accessioned2015-09-08T15:24:41Z
dc.date.available2015-09-08T15:24:41Z
dc.date.issued2012-03
dc.identifier.citationWhilding, L.M. 2012. Activity of oncolytic vaccinia virus vectors in ovarian cancer. Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8553
dc.descriptionPhDen_US
dc.description.abstractOncolytic vaccinia virus has great potential in the treatment of cancer and two engineered strains have entered clinical trials. As the advent for oncolytic vaccinia virus as an approved therapy beckons, it is critical to consider some of the barriers that may hinder this progress. These include suboptimal delivery of the virus to tumour sites, incomplete destruction of the tumour mass, and a lack of full understanding of the way in which oncolytic vaccinia kills its target cells. This thesis attempts to address these issues, with a particular focus on ovarian cancer. As ovarian cancer is generally restricted to the peritoneal cavity, intraperitoneal delivery may be preferable over intravenous delivery. Here, it is shown that Lister-dTK, an engineered vaccinia strain, is able to selectively replicate in ovarian tumours, including metastases to the liver following intraperitoneal delivery. To determine whether Lister-dTK could potentially be used in combination with current therapies for ovarian cancer, the effect of cisplatin and Lister-dTK together was assessed in vitro but showed no improvement in overall cell death. In an attempt to further improve the anti-tumour efficacy of Lister-dTK, the extracellular matrix protein (ECM) decorin was expressed from the virus. Decorin interacts with various signalling pathways and is proposed to enhance virus spread. However, abrogation of EGFR and TGFβ signalling could not be demonstrated in vitro, nor could improved virus spread. In an intraperitoneal model of ovarian cancer, Lister-mDCN did not demonstrate enhanced efficacy over a control virus. To determine the mechanisms of ovarian cancer cell death induced by Lister-dTK, the roles of apoptosis, autophagy and necrosis were investigated. Whilst some features of both apoptosis and autophagy were observed, inhibition of these pathways did not attenuate Lister-dTK. It is proposed that necrosis is the primary cause of cell death but that this process may occur in a regulated manner.en_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectMedicineen_US
dc.subjectMolecular Oncologyen_US
dc.subjectOvarian canceren_US
dc.subjectOncolytic vaccinia virusen_US
dc.titleActivity of oncolytic vaccinia virus vectors in ovarian cancer.en_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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    Theses Awarded by Queen Mary University of London

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