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Investigating the Therapeutic Effects of Sphingosine-1-Phosphate Aganist Human Breast Cancer in Vitro and in Vivo

dc.contributor.advisorYang, Jianen_US
dc.contributor.committeeMemberAlcorn, Janeen_US
dc.contributor.committeeMemberZhou, Yanen_US
dc.creatorSultan, Ahlamen_US
dc.date.accessioned2014-06-21T12:00:44Z
dc.date.available2014-06-21T12:00:44Z
dc.date.created2012-09en_US
dc.date.issued2014-06-20en_US
dc.date.submittedSeptember 2012en_US
dc.description.abstractBreast cancer is the most common malignancy diagnosed among women and is the first cause of neoplastic death in women globally. In the last decade our understanding of breast cancer biology has increased and led to the development of a number of targeted therapies, one of which is targeting the cell apoptosis pathway. One of the new targeting pathways under investigation, which was found to be involved in both cell apoptosis and cell proliferation processes, is the sphingolipid signalling pathway. The sphingolipid pathway represents a group of intracellular and extracellular bioactive lipid molecules, including ceramide, ceramide- 1-phosphate, sphingosine, and sphingosine-1-phosphate (S1P). In my research, I focused on the role S1P plays in breast cancer and its potential application as a therapeutic agent. I examined the effects of S1P on the apoptosis, proliferation, and cytotoxicity of different types of breast cancer cell lines in vitro. In addition, I evaluated the effect of both low and high doses of S1P when co-administrated with anticancer drugs commonly used in breast cancer treatment in vitro and in vivo. Moreover, I studied the S1P cellular distribution following exogenous administration. My results demonstrate that S1P can selectively induce apoptosis in breast cancer cells without harming normal breast cells and that S1P is more effective against aggressive breast cancer cells. Another major finding of my study is that S1P can increase the efficacy of chemotherapies against human breast cancer cells. Although S1P cannot directly substitute the current chemotherapies, S1P may function as a good candidate for combination therapy. Furthermore, my work showed that the pro-apoptotic and anti-proliferative effect of S1P is correlated with its intracellular action and that chronic exposure of exogenous S1P in vivo is not toxic to the major organs. Certainly, S1P inclusion in breast cancer treatment modalities may decrease the morbidity and mortality of breast cancer patients and improve clinical outcomes. Further investigations are required to understand the mechanism by which S1P induces apoptosis and inhibits cell proliferation.en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2012-09-665en_US
dc.language.isoengen_US
dc.subjectSphingosine-1-phosphateen_US
dc.subjectBreast Canceren_US
dc.subjectApoptosisen_US
dc.subjectCytotoxicityen_US
dc.subjectProliferationen_US
dc.subjectXenograft nude miceen_US
dc.subjectcombination therapyen_US
dc.titleInvestigating the Therapeutic Effects of Sphingosine-1-Phosphate Aganist Human Breast Cancer in Vitro and in Vivoen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentPharmacy and Nutritionen_US
thesis.degree.disciplinePharmacyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US

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