Life Sciences Commons^™

Network Analyses Of Glomerular Capillaries, Jason Cory Brunson, Justin Sardi, Mark Terasaki

Biology and Medicine Through Mathematics Conference

No abstract provided.

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically achievable enterohepatic …

An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb

Theses and Dissertations

The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the …

Fluvastatin And Microrna-146a Alter Interleukin-33 Mediated Mast Cell Functions., Marcela Taruselli

Theses and Dissertations

Mast cells are tissue-resident immune cells known as effector cells for the innate and adaptive immune systems. Mast cells contribute to host defenses against parasites such as large roundworm parasites, bacterial pathogens, and toxins, and participate in wound healing, but they are mostly known for their role in allergic diseases. It has been well established that during allergic diseases, mast cells are stimulated by IgE cross-linkage to release proinflammatory mediators. However, a newly discovered cytokine, IL-33 has also been implicated in allergic disease. Recently, IL-33 has been implicated as a driver of several Type I sensitivities and previous studies have …

Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

Erbb3 Signaling And Its Effect On Spheroid Formation In Ovarian Cancer, Muskan Bansal, Danielle Burke, Mara P. Steinkamp

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

ErbB3 is a receptor tyrosine kinase in the epidermal growth factor receptor (EGFR) family. Like other family members, it has an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. ErbB3 requires interactions with other receptors and dimerizes with ErbB2 and MET, to activate downstream signaling pathways. Mutations in the ErbB3 gene within the extracellular and kinase domains have been identified in many cancer types. To understand the impact of ErbB3 on cancer growth and metastasis, the human ovarian cancer cell line, OVCAR8, was used as a model. Parental OVCAR8 cells that express ErbB2 and ErbB3 were compared …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle repression by …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …