Oncolytic reovirus has the natural preference to kill transformed cells while sparing normal cells. Its administration has been shown to be safe in clinical trials, but the anti-cancer efficacy... Show moreOncolytic reovirus has the natural preference to kill transformed cells while sparing normal cells. Its administration has been shown to be safe in clinical trials, but the anti-cancer efficacy remains to be improved. In this thesis, we discuss several aspects that are important for the design of a potent anti-cancer therapeutic strategy using reovirus. We explored which cellular factors and pathways are important for efficient reovirus replication. Furthermore, we genetically modified the reovirus genome to encode potentially therapeutic transgenes. We tested the potency of these recombinant reoviruses, and describe what we believe is the most promising strategy to move forward. Moreover, we discuss the stability issues that we encountered during the generation of recombinant reoviruses. Finally, we discuss the various challenges and opportunities in how to proceed. Show less
Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the... Show moreAtherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall. Over time, this accumulation of lipids and immune cells induce morphological abnormalities in the vessel wall which cause the vessel lumen to narrow. This narrowing of the lumen (stenosis) causes ischemia in the downstream tissue. Prolonged ischemia causes myocardial ischemia and/or stroke. The research described in my thesis examines a well-recognized risk factor of atherosclerosis, being dyslipidemia, from an entirely new perspective. More specifically, it describes how dyslipidemia affects intrinsic metabolic processes in T cells, the conductors of the immune response characterizing atherosclerosis, and how this affects their function. My research has contributed to knowledge on the pathophysiology of atherosclerosis and might one day pave the way for the development of novel therapeutic approaches to treat cardiovascular disease. Show less
