Translational Medical Research Commons^™

Drug Response And Metabolism In Crohn's Disease, Aze Wilson

Electronic Thesis and Dissertation Repository

Inflammatory bowel disease (IBD) is an illness of chronic intestinal inflammation comprised of Crohn's disease (CD) and ulcerative colitis (UC). Specialists rely heavily on drugs that target a dysregulated immune system. There is a staggering degree of variation in drug response in CD. Our understanding of drug metabolism and response in IBD is limited. Gaining new insights into IBD-specific modifications of drug metabolism may allow for improved drug efficacy and reduced toxicity. Cytochrome P450 (CYP) 3A4 is the most relevant determinant of drug metabolism and exposure for medications prescribed today. CYP3A4 is highly expressed in the liver, but is also …

Clinical And Pharmacogenetic Determinants Of Plasma Factor Xa Inhibitor Systemic Exposure, Markus Gulilat

Electronic Thesis and Dissertation Repository

Inhibition of blood coagulation via oral anticoagulant therapy is the mainstay for preventing a cardioembolic stroke in patients with atrial fibrillation (AF). Factor Xa inhibitors (FXaIs), rivaroxaban and apixaban, represent a new class of oral anticoagulants that are now widely prescribed in AF patients as an alternative to traditional warfarin therapy. An important advantage of these drugs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, because of their mechanism of action, FXaI antithrombotic effect can be inferred based on the observed drug plasma concentration, with prolonged periods of elevated FXaI systemic exposure associated with increased risk for …

Investigating Ampk Signalling Regulation Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski

Western Research Forum

Investigating AMPK signalling regulation of autophagy in a model of ovarian tumour dormancy

Jeremi Laski and Trevor G. Shepherd

Background:

Ovarian cancer is the most deadly gynecologic malignancy in women. A particular subset of this disease, epithelial ovarian cancer (EOC), is responsible for over 70% of all diagnosed ovarian cancer cases, yet the mechanisms governing disease progression are poorly understood. One of the unique hallmarks of EOC metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into larger 3D structures. These EOC spheroids have been shown to be metabolically dormant, while concurrently up-regulating autophagy (cellular waste …