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Articles 61 - 66 of 66

Full-Text Articles in Pharmacology

Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell Dec 2017

Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell

Electronic Theses and Dissertations

Cancer is largely a disease of the elderly. In the United States alone, 87% of all cancers in 2017 will be diagnosed in individuals aged 50 years or older. Among them, lung cancer is the deadliest, accounting for 1 in 4 cancer deaths. The 5-year survival rate is below 20%, a number which has not changed substantially over the past several decades. This underscores a desperate need for new strategies in prevention, early detection and treatment of this deadly disease. While tobacco use is unquestionably the number one risk factor for the development of lung cancer, the majority of diagnoses …

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Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre Aug 2017

Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre

Electronic Theses and Dissertations

Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …

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Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole Aug 2017

Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole

Electronic Theses and Dissertations

Background. Individuals who chronically abuse alcohol are almost 4 times more likely to develop Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), but the mechanisms by which alcohol abuse sensitizes the lung to injury are poorly understood. However, the lung appears to share many parallel mechanisms of injury with the liver- a primary target of alcohol abuse. The overarching goal of this dissertation was therefore to expand on established mechanisms of alcohol-induced liver injury to ask innovative questions about mechanisms of alcohol-enhanced acute lung injury, as well as to develop new tools that may …

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Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney Aug 2016

Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various …

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A Plant-Made Cholera Toxin B Subunit Enhances Mucosal Wound Healing And Protects Against Ulcerative Colitis And Colon Cancer., Keegan J Baldauf Dec 2015

A Plant-Made Cholera Toxin B Subunit Enhances Mucosal Wound Healing And Protects Against Ulcerative Colitis And Colon Cancer., Keegan J Baldauf

Electronic Theses and Dissertations

This dissertation describes the previously unidentified effects of a plant-produced recombinant cholera toxin B subunit (CTBp) on the gastrointestinal (GI) tract and its ability to protect against inflammation in a mouse model of colonic injury and ulcerative colitis (UC). To comprehensively analyze CTBp’s impacts on the GI tract, we employed global analysis methodologies based on multi-color flow cytometry to analyze immune cell populations in GI and systemic lymphatic compartments, gene expression microarray to decipher transcript-level changes in the colon and small intestine, and 16S rRNA sequencing to characterize fecal microbiota. Based on a drastic shift observed in the immune cell …

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Mechanisms And Intervention Strategies For Alcohol And Hiv-Antiretroviral Therapy-Induced Liver Injury., Hridgandh Donde Dec 2015

Mechanisms And Intervention Strategies For Alcohol And Hiv-Antiretroviral Therapy-Induced Liver Injury., Hridgandh Donde

Electronic Theses and Dissertations

Chronic alcohol consumption is a leading cause of liver disease and liver-related death worldwide. Alcoholic liver disease includes, hepatic steatosis, steatohepatitis and ultimately fibrosis and cirrhosis. Emerging evidence has established the important role of the “gut-liver” axis in the development of alcoholic liver disease (ALD). Our recent work indicated that chronic alcohol induced perturbations in the gut microbiome and consequent changes in fatty acids have a major impact on the development of intestinal barrier dysfunction and ALD. The aim of this study was to investigate whether treatment with tributyrin - a butyrate prodrug results in protection against ALD in terms …

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