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Actinomycin D And Telmisartan Combination Therapy Targets Lung Cancer Stem Cells, Ryan Green
Actinomycin D And Telmisartan Combination Therapy Targets Lung Cancer Stem Cells, Ryan Green
USF Tampa Graduate Theses and Dissertations
The failure of lung cancer treatments has been attributed partly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. It has been suggested that a very small group of specific cells within the heterogeneous tumors, cancer initiating stem cells (CSC), develop resistance to treatment, survive and later initiate the growth of new tumors. Due to their pivotal role in maintenance and relapse of tumors following the acquisition of drug resistance, we reasoned that novel drugs targeting cancer cells and CSC might provide the most effective treatments, if not a cure. To this end, …
Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson
Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson
USF Tampa Graduate Theses and Dissertations
A fatty acid amide is precisely as the name suggests: A fatty acid (CHn-COOH), in which the hydroxyl group of the carboxylic acid is displaced by an amine functional group from a biogenic amine (R-NH2), ultimately forming an amide bond. Furthermore, these fatty acid amides can be composed of a variety of different acyl chain lengths donated by the fatty acid and a myriad of different biogenic amines. Thus, these molecules can be subdivided in a number of different ways including the separation of short chain (acetyl to heptanoyl) and long chain (palmitoyl to arachidonoyl) and also based off the …
Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker
Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker
USF Tampa Graduate Theses and Dissertations
The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …
Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley
Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley
USF Tampa Graduate Theses and Dissertations
Melanoma is the deadliest form of skin cancer. Prognosis for early stage melanoma patients is excellent, and surgery is often curative for these patients. However, once patients have presented with invasive disease, the average 5-year survival rate drops significantly from over 90% to between 10 and 15%. Several therapies have been developed to target a commonly mutated oncogene BRAF, or its downstream effectors. Unfortunately, while these treatments show robust initial response, most patients relapse within a year. Moreover, therapy-resistant tumors are often more invasive and metastatic. Therefore, it is important to investigate the molecular mechanisms underlying melanoma invasion and metastasis, …
Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield
Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield
USF Tampa Graduate Theses and Dissertations
An essential event during early pregnancy is the invasion of trophoblasts into the maternal decidua, which is necessary for proper implantation and establishment of maternal-fetal interface and ultimately allows for proper nutrient exchange and immunological tolerance of the growing fetus. For this invasion to occur, cells originating from the trophectoderm undergo an epithelial to mesenchymal transition to become invasive extravillous trophoblasts and begin invading the uterine decidual tissue. Through the secretion of matrix metalloproteinases and through interactions with many cytokines and cell-adhesion molecules, this well-orchestrated process of trophoblast invasion results in extensive remodeling of the maternal spiral vasculature by the …
Myc Distant Enhancers Underlie Ovarian Cancer Susceptibility At The 8q24.21 Locus, Anxhela Gjyshi Gustafson
Myc Distant Enhancers Underlie Ovarian Cancer Susceptibility At The 8q24.21 Locus, Anxhela Gjyshi Gustafson
USF Tampa Graduate Theses and Dissertations
Ovarian cancer is a leading cause of death among women diagnosed with cancer. Mortality rate is high because an overwhelming majority of new cases are diagnosed with late-stage disease when the survival statistics are very poor with an overall 5-year survival rate of less than 40%. Despite the large burden of disease, the etiology of ovarian cancer is not well understood. In addition to linkage studies that have identified highly penetrant cancer susceptibility genes such as BRCA1 and BRCA2, the emergence of Genome Wide Association Studies (GWAS) in the last decade has facilitated the identification of common genetic variants with …
Interrogation Of Protein Function With Peptidomimetics, Olapeju Bolarinwa
Interrogation Of Protein Function With Peptidomimetics, Olapeju Bolarinwa
USF Tampa Graduate Theses and Dissertations
Proteins can be described as the “machineries” responsible for almost all tasks in the levels of organizational complexity in multi-cellular organisms namely: the cells, tissues, organs and systems. Any disorder in the function of a protein at any of these levels could result in disease, and a study of protein function is critical to understanding the pathological features of the disease at the molecular level. A quick glance at these abundantly present proteins reveals two striking features: large diversity of biological function, and the variations in structural complexity, which varies from simple random coils, to turns and helices, and on …
A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi
A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi
USF Tampa Graduate Theses and Dissertations
Lung cancer is the second most common cancer type and is associated with high mortality rates. The survival rate for lung cancer patients has increased slowly in the last decade mainly as the result of the development of novel targeted and immune therapies. However, non-small cell lung cancer patients lacking known or actionable driver mutations and small cell lung cancer patients with recurrent disease are still in urgent need of new therapies. Drug repurposing is an efficient way to identify new therapies since it uses clinically relevant small molecule drugs. Determination of off-targets of small molecules is a novel approach …
The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin
The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin
USF Tampa Graduate Theses and Dissertations
Chronic liver diseases, which includes alcoholic liver disease (ALD), are consistently among the top 15 leading causes of death in the United States. ALD is characterized by progression from a normal liver to fatty liver disease (hepatic steatosis), which can lead to cirrhosis, alcoholic hepatitis, and liver failure. We have identified a novel role of phosphohistidine signaling, mediated through phosphohistidine phosphatase 1 (PHPT1), in the onset of hepatic steatosis. We have identified PHPT1 as a target of selective oxidation following acute ethanol exposure as well as being downregulated following chronic ethanol exposure. We mapped the oxidative modification site and developed …
Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss
Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss
USF Tampa Graduate Theses and Dissertations
Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction to …
Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson
Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson
USF Tampa Graduate Theses and Dissertations
Elastin-like peptide (ELP) fusions promote therapeutic delivery and efficacy. Recombinant proteins, like neurotrophins, lack bioavailability, have short in vivo half-lives, and require high manufacturing costs. Fusing recombinant proteins with genetically encodable ELPs will increase bioavailability, enhance in vivo solubilization, as well as provide a cost-effective method for purification without the need for chromatography. During expression of neurotrophin-ELP (N-ELP) fusions, dense water-insoluble aggregates known as inclusion bodies (IBs) are formed. Inclusion bodies are partially and misfolded proteins that usually require denaturants like Urea for solubilization. Strong denaturants arrest ELPs stimuli-responsive property and increase unwanted aggregation, making purification difficult, yet possible. The …
Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia
Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia
USF Tampa Graduate Theses and Dissertations
Mitochondria plays a crucial role in cells by maintaining energy metabolism and directing cell death mechanisms by buffering calcium (Ca2+ )from cytosol. Therefore, the Ca2+ overload of mitochondria due to the upregulated cytosolic Ca2+ , observed in many neurological disorders is hypothesized to be a key pathway leading to mitochondrial dysfunction and cell death. In particular, Ca2+ homeostasis disruptions due to Alzheimer’ s disease (AD)-causing presenilins (PS1/PS2) and oligomeric forms of β-amyloid peptides Aβ commonly found in AD patients are presumed to cause detrimental effects on the mitochondria and its ability to function properly. We begin …
Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide
Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide
USF Tampa Graduate Theses and Dissertations
Bacterial infections have posed a serious threat to the public health due to the significant rise of the infections caused by antibiotic-resistant bacteria. There has been considerable interest in the development of antimicrobial agents which mimic the natural HDPs, and among them biodegradable polymers are newly discovered drug candidates with ease of synthesis and low manufacture cost compared to synthetic host defense peptides. Herein, we present the synthesis of biocompatible and biodegradable polymers including polycarbonate polymers, unimolecular micelle hyperbranched polymers and dendrimers that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. The developed amphiphilic polycarbonates are highly …