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Characterization Of Epigenetic Plasticity And Chromatin Dynamics In Cancer Cell Models, Diana Lea Gerrard

Graduate College Dissertations and Theses

Cancer progression is driven by cumulative changes that promote and maintain the malignant phenotype. Epigenetic alterations are central to malignant transformation and to the development of therapy resistance. Changes in DNA methylation, histone acetylation and methylation, noncoding RNA expression and higher-order chromatin structures are epigenetic features of cancer, which are independent of changes in the DNA sequence. Despite the knowledge that these epigenetic alterations disrupt essential pathways that protect cells from uncontrolled growth, how these modifications collectively coordinate cancer gene expression programs remains poorly understood. In this dissertation, I utilize molecular and informatic approaches to define and characterize the genome-wide …

Exosomes And Their Role In Asbestos Exposure And Mesothelioma, Phillip Blake Munson

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a locally invasive and highly aggressive cancer arising on the mesothelial surface of organ cavities (mainly pleural) as a direct result of asbestos exposure. The latency period of MM is long (20-50yrs) after initial asbestos exposure, and the prognostic outcomes are dismal with median life expectancy of 6-12 months post-diagnosis. There are no useful biomarkers for early MM diagnosis, no successful therapeutic interventions. These vast voids of knowledge led to our hypotheses that secreted vesicles, termed exosomes, play an important role in MM development and tumorigenic properties. Exosomes are nano-sized particles secreted from all cell types …

Effects Of Tumor-Related Factors And Chemotherapy On Skeletal Muscle And The Protective Effects Of Exercise, Blas Anselmo Guigni

Graduate College Dissertations and Theses

Cancer patients often experience cachexia, a form of weight loss consisting mostly of skeletal muscle wasting. Muscle wasting leads to physical disability, poor quality of life, reduced tolerance to treatments and shorter survival. Although the causes of cancer-related muscle atrophy have been studied for decades, the exact mechanisms through which cancer and its treatments promote muscle wasting have yet to be defined.

The overall aim of this dissertation is to examine the mediators of muscle wasting in cancer patients during their treatment and examine the modulatory role of exercise to maintain muscle size and function. To address these aims, we …

Endotoxin Increases Oxidative Stress And Oxygen Tension While Reducing Milk Protein Gene Expression In The Mammary Gland, Alexander Jonathan Spitzer

Graduate College Dissertations and Theses

Mastitis, the inflammation of the mammary gland by bacterial infection, is one of the costliest diseases to the dairy industry primarily due to a loss in milk production. The aim of this study was to investigate the mechanisms underlying reduced milk production during mastitis. We hypothesized that bacterial endotoxin induces cell apoptosis, oxidative stress and increases hypoxia while inhibiting milk gene expression in the mammary gland. To test this hypothesis, mice were bred to pregnancy, and 3 days post-partum the left and right sides of the 4th pair of mammary glands were alternately injected with either the endotoxin liposaccharide (LPS, …