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Lung Cancer Cells Survive Egfr Tki Exposure Through Upregulation Of Cholesterol Synthesis, Mark Howell
Lung Cancer Cells Survive Egfr Tki Exposure Through Upregulation Of Cholesterol Synthesis, Mark Howell
USF Tampa Graduate Theses and Dissertations
Lung cancer is the number one cause of cancer related death in both males and females. About 20% of all non-small cell lung cancer (NSCLC) patients are expected to harbor an epidermal growth factor receptor (EGFR) activating mutation. EGFR inhibitors have been shown to provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. However, despite the initial clinical responses to these EGFR targeted therapies, long-term efficacy is not possible because acquired drug resistance hampers the effectiveness of these therapies. We found that a fiber inspired smart scaffold (FiSS) platform established in our laboratory allows growth of …
Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel
Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel
USF Tampa Graduate Theses and Dissertations
Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether …
Efficacy And Resistance Potential Of Jpc-3210 In Plasmodium Falciparum, Siobhan Marie Flaherty
Efficacy And Resistance Potential Of Jpc-3210 In Plasmodium Falciparum, Siobhan Marie Flaherty
USF Tampa Graduate Theses and Dissertations
Combating drug resistant malaria has been historically challenging, and remains so today. Recent reports from Southeast Asia show that Plasmodium falciparum is developing resistance to even our best defenses; artemisinin-based therapies. This development threatens to become a significant challenge in controlling malaria infections worldwide, making research into developing and characterizing new antimalarial drugs increasingly important. The purpose of this study was to characterize the resistance potential of novel antimalarial compound JPC-3210 in vitro using P. falciparum clones. JPC-3210 is a new long acting drug with potential to be used in combination with fast-acting drugs like artemisinins to cure drug resistant …
Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott
USF Tampa Graduate Theses and Dissertations
Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …
Phenotypic And Genotypic Analysis Of In Vitro Selected Miltefosine Resistant Leishmania Donovani, Brian A. Vesely
Phenotypic And Genotypic Analysis Of In Vitro Selected Miltefosine Resistant Leishmania Donovani, Brian A. Vesely
USF Tampa Graduate Theses and Dissertations
Abstract
Visceral leishmaniasis is a devastating neglected parasitic disease caused by infection with Leishmania donovani. It life cycle has two stages with promastigote (insect stage) and amastigote (animal stage) morphologies. Miltefosine is currently the only commercially available oral drug available to treat leishmaniasis and recent evidence suggests clinical resistance has emerged. Due to the importance of this drug and the scarcity of new drugs in the pipeline, work has been done on understanding the mechanism(s) of miltefosine, yet the mechanism of action for resistance is still not known.
In previous studies investigators generated miltefosine resistance on the insect vector stage …