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dc.contributor.authorHum, Maaike
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2014-10-06 08:21:06.586en
dc.date.accessioned2014-10-06T14:14:44Z
dc.date.issued2014-10-06
dc.identifier.urihttp://hdl.handle.net/1974/12565
dc.descriptionThesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2014-10-06 08:21:06.586en
dc.description.abstractHeme oxygenase (HO) is the enzyme that breaks down heme to form carbon monoxide, free iron, and biliverdin. The two major isoforms, HO-1 (inducible) and HO-2 (constitutive), are involved in a number of physiological functions, including apoptosis, inflammation, and angiogenesis. In cancerous cells these effects may promote growth, tumour cell survival, and metastasis. Many tumour types have demonstrated increased levels of HO, and research has shown that HO inhibition results in decreased tumour growth. Previous work using metalloporphyrin-based compounds identified HO inhibition as a potential therapy for some cancers, but these compounds are limited by their lack of selectivity. Novel azole-based HO inhibitors (QC-xx) have demonstrated increased in vitro selectivity for HO and were tested for their effects on AC2M2 mouse breast cancer growth and progression. QC-xx demonstrated a concentration-dependent decrease in AC2M2 cell viability and a decrease in endothelial cell tube-like sprouting in an in vitro model of angiogenesis. While there was some evidence that QC-xx treatment could delay primary AC2M2 tumour growth and the development of lung metastases in vivo, the results were inconclusive. The effects of QC-xx on HO activity were different between rats, from which the initial HO data was obtained, and mice, from which our AC2M2 cells were derived. Further examination indicates that HO activation may help elucidate the role of HO in AC2M2 mouse breast cancer growth and progression. The findings will help determine whether HO is an appropriate target in the treatment of breast cancer.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectazole-based inhibitorsen_US
dc.subjectAC2M2 breast canceren_US
dc.subjectHeme Oxygenaseen_US
dc.titleHeme Oxygenase Modulates AC2M2 Mouse Breast Cancer Growth and Progressionen_US
dc.typethesisen_US
dc.description.restricted-thesisWe would like to restrict the thesis in order to publish some of the data in peer-reviewed journals.en
dc.description.degreePh.Den
dc.contributor.supervisorNakatsu, Kanjien
dc.contributor.departmentPharmacology and Toxicologyen
dc.embargo.terms1825en
dc.embargo.liftdate2019-10-05


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