Medicine and Health Sciences Commons^™

Nanoparticle Toxicity And Molecular Mechanisms In Fish: A Case Study With Silver Nanoparticles, Jiejun Gao

Open Access Dissertations

Nanoparticles (NPs) are widely used in a myriad of commercial and industrial products making their entry to the environment a likely event. NPs have unique physical-chemical properties that result from their small size and high surface area to volume ratio, making them highly reactive and potentially toxic. In Chapter 1, we summarize the effects and mechanisms of metal-based NPs on the vascular system. In vitro studies have shown that NPs are anti-angiogenic because they cause inflammation, oxidative stress, and apoptosis of endothelial cells resulting in increased permeability and decreased proliferation and migration. Whole animal studies examining the effects of NPs …

Ambient Ionization - Mass Spectrometry: Advances Toward Intrasurgical Cancer Detection, Alan Keith Jarmusch

Open Access Dissertations

My dissertation research has focused on the development of ambient ionization – mass spectrometry (MS) for clinical measurements, specifically intrasurgical cancer detection. The molecular differences between normal and cancerous tissue were detected via direct tissue analysis in vitro by touch spray ionization (TS) or by analyzing sectioned or smeared tissue using desorption electrospray ionization (DESI). The physical form of the tissue, e.g. in vitro sampling, sectioned, or smeared, was inconsequential in differentiating normal from cancerous tissue; however, the spectra acquired by TS and DESI differed due to differences in ionization processes. We envision that TS-MS and DESI-MS could impact diagnostic …

Gonadal Intersex In Teleosts: Mechanisms, Molecular Biomarkers And Diagnostic Assays, Ahmed M.E. Abdel-Moneim Mohamed

Open Access Dissertations

Natural and synthetic estrogenic and androgenic compounds are continuously released into aquatic ecosystems. Exposure of teleost fishes to these contaminants can negatively impact sex differentiation and reproductive output. Specifically, development of gonadal intersex in gonochoristic (fixed sex) fish species has been studied extensively in relation to exposure to this class of compounds. The main objectives of this dissertation were to: 1) conduct field and laboratory studies to investigate the molecular signaling pathways behind the development of gonadal intersex; and 2) establish molecular biomarkers and assays for testing the ability of environmental pollutants to develop this condition using a battery of …

Manufacturer Perspectives On Content Transparency And Material Health In The Us Building Products Industry, Alexandra A. Muller

Open Access Theses

Flawed U.S. federal regulation of chemicals has resulted in a materials market that undervalues human and environmental health in favor of the more traditional attributes of price, performance and aesthetics. In the building products industry, global, dynamic supply chains and proprietary information concerns further complicate the task of assessing the material health of products.

Voluntary material health programs in the green building industry are intended to incentivize the manufacture and selection of safer products by getting companies to gather and assess ingredient, hazard and risk information from their supply chain. Building product manufacturers considered early adopters of the main material …

The Interactive Effects Of Pesticide Exposure And Infectious Disease On Amphibian Hosts, Katherine M. Pochini

Open Access Theses

Natural systems are home to a multitude of natural and anthropogenic stressors, which draw an array of effects on ecological communities. While these effects have been investigated individually, it is important, given the routine co-occurrence of these stressors, to understand their interactive effects. Pesticide exposure and infectious disease are two common, co-occurring stressors that each have documented detrimental effects on species and, as evidence suggests, may have interactive effects. Moreover, existing research suggests that these interactive effects are highly context dependent, eliciting different results based on species, disease agent, toxin, and environment. Given the variability with which species may experience …

Ultrasound And Photoacoustic Methods For Anatomic And Functional Imaging In Image Guided Radiation Therapy, Justin T. Sick

Open Access Dissertations

(MATERIAL and METHODS) First, we define the physical principals and optimal protocols that provide contrast when imaging with US and the transducer properties contributing to resolution limits. The US field of view (FOV) was characterized to determine the optimal settings with regard to imaging depth, focal region, with and without harmonic imaging, and artifact identification. This will allow us to determine the minimum errors expected when registering multimodal volumes (CT, US, CBCT).

Next, we designed an in-house integrated US manipulator and platform to relate CT, 3D-US and linear accelerator coordinate systems. To validate our platform, an agar-based phantom with measured …

Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung

Open Access Dissertations

Chemotherapy is currently the mainstay of treatment for most cancer patients. Despite its efficacy in eliminating cancer cells, a high percentage of chemotherapy patients eventually relapse or suffer progression of the disease. Immunosurveillance is capable of recognizing and eliminating continuously arising transformed mutant cells, and thus cancer immunotherapy is one of the emerging therapeutic strategies that harnesses the power of the immune system to eradicate chemotherapy-resistant cancerous cells. However, the adverse side effects of chemotherapy impede the therapeutic effects of immunotherapy. Our previous studies demonstrate that lymphoma patients are refractory to clinical immunotherapy because of chemotherapy-induced immune dysfunction. In addition, …

Investigating The Role Of The Basic Helix-Loop-Helix Transcription Factor Mist1 In Pancreatic Diseases, Anju Karki

Open Access Dissertations

Acinar cells of the exocrine pancreas are dedicated to synthesize, package and secrete immense quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Dysregulation of enzyme secretion in acinar cells can give rise to exocrine diseases including acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis—events that can transition into the earliest stages of pancreatic ductal adenocarcinoma (PDAC). The focus of this thesis is to interrogate transcriptional regulatory networks that are susceptible to AP and the role that these networks play in acinar cell and exocrine pancreas responses. The …

Influence Of The 3d Microenvironment On Glioblastoma Migration And Drug Response, Ruth Marisol Herrera Perez

Open Access Dissertations

Glioblastoma (GBM) is a highly invasive brain cancer characterized by poor prognosis. Despite significant efforts by the basic and clinical research community our understanding of GBM progression and recurrence has been incremental. Improvements in therapeutic response have been dismal, and GBM continues to be the deadliest tumor of the central nervous system, with patient average survival rate of 12 months. Synergistic relationships that the tumor cells establish with the brain microenvironment have been proven fundamental for successful tumor progression and maintenance. Yet, many in vitro GBM studies are performed in formats that fail to recapitulate the most essential component of …

Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman

Open Access Theses

Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …

The Effects Of Acidified Pepsin On Porcine Vocal Fold Tissue: Developing A Porcine Model Of Laryngopharyngeal Reflux Disease, Abigail Cox Durkes

Open Access Dissertations

Approximately 7.5 million Americans are affected by a voice disorder. In the last year, 7.2% of people missed one or more days of work due to a voice problem. For professional voice users, such as teachers, the rate increases to 20% and an annual cost of $2.5 billion. Voice disorders are complex and multi-faceted, as well as difficult to diagnose and treat. Prospective animal studies are necessary to study the pathophysiology of voice disorders, optimize our understanding of laryngeal pathology, and improve treatment outcomes. The pig provides a unique opportunity to test hypotheses relating to laryngeal disease because porcine vocal …

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Pharmacokinetics And Toxicity Of The Novel Oral Demethylating Agent Zebularine In Laboratory And Tumor Bearing Dogs, Christopher Michael Fulkerson

Open Access Theses

The aim of this thesis is to investigate the pharmacokinetics and toxicity of the novel oral demethylating agent zebularine (zeb) in laboratory dogs and tumor bearing dogs. This thesis focuses on the application of this therapeutic strategy in dogs with naturally occurring invasive transitional cell carcinoma (InvTCC), which serve as a relevant model of the human disease.

DNA hypermethylation in the promoter region is a common epigenetic change in cancer that silences tumor suppressor genes. Zeb is an oral cytidine analog that acts as a demethylating agent. Zeb has been investigated extensively in vitro as well as in mice, rodents …

Feasibility Of Pulsed Proton Induced Acoustics For 3d Dosimetry, Fahed M. Alsanea

Open Access Theses

Proton therapy has the potential to deposit its energy in tissue with high conformity to the tumor and significantly reduced integral dose to normal tissue compared to conventional radiation, such as x-rays. As a result, local control can be enhanced while reducing side-effects and secondary cancers. This is due to the way charged Particles deposit their energy or dose, where protons form a Bragg peak and establish a well-defined distal edge as a function of depth (range). To date, the dose delivered to a patient from proton therapy remains uncertain, in particular the positioning of the distal edge of the …

Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio

Open Access Theses

In recent years, the presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has led to research on their fate and effects. PPCPs have been found in mixture in wastewater effluents, surface, ground, and drinking water at low concentrations from areas of intense urbanization. Although adverse effects to human health from the current environmental concentrations are unlikely, the impacts to ecological receptors are not clear. We performed field and laboratory studies to quantify and evaluate effects of PPCPs on fish. First, a field study was conducted at the Baca National Wildlife Refuge, Colorado (2010-2012) because a portion of …

Scheduling In Mohs Micrographic Surgery Clinics, Stephen Vincent Steidle

Open Access Theses

Mohs Micrographic Surgery (MMS) is a surgical method used for the excision of aggressive skin cancers in areas of high cosmetic importance, such as the face and hands. The practice has been gaining popularity worldwide for its low recurrence rates and cosmetic results. Current clinics though are plagued by extreme wait times and an overall poor patient experience. In this paper we look to explore this problem by applying systems engineering principles including optimization and scheduling with the goal of improving the patient experience. Currently, little literature exists exploring the difficulties associated with scheduling for MMS clinic which primarily revolve …