Life Sciences Commons^™

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Characterization Of Bacterial Pathogens Involved In Aerobic Vaginitis: Prevalence, Strain Characterization And Sequelae, Leslie A. Lafferty

Graduate School of Biomedical Sciences Theses and Dissertations

Aerobic vaginitis (AV) is a more recently defined infection that involves aerobic pathogenic bacteria that replace the normal flora of the vaginal tract. It is commonly mistaken for other vaginal infections, such as bacterial vaginosis (BV), because they share many common symptoms. AV leads to complications during pregnancy, such as premature delivery and amnion infection, and is diagnosed by indications that range from vaginal discharge to inflammation. Because this infection is difficult to diagnose differentially from other vaginal infections, it is important to determine what pathogens are involved in AV so that we may have the ability to detect them. …

Age-Associated B Cell And T Helper Cell Dysfunction In Rhesus Macaques, Evan Knox Stalvig

Theses and Dissertations

The immune system undergoes drastic changes as we age, known as immunosenescence. An example of this is the dysfunction and subpopulation distribution changes of immune cells. Due to immunosenescence, the elderly have a higher risk of complications and rapid progression of new challenges to the immune system, including human immunodeficiency virus (HIV). In an effort to determine the mechanism of dysfunction of humoral immunity due to age, I compared B cell and T cell responses to non-specific, mitogenic stimuli between aged and young adult rhesus macaque peripheral blood mononuclear cells (PBMCs). Analysis by flow cytometry revealed several differences in B …

Nipt Results Indicative Of Maternal Neoplasms: Genetic Counselors' Preferences And Attitudes, Meagan E. Giles

Dissertations & Theses (Open Access)

Performing non-invasive prenatal testing (NIPT) on a pregnant woman with a chromosomally abnormal neoplasm may incidentally lead to the diagnosis of cancer due to the coexistence of circulating tumor and placental DNA. Published information regarding NIPT’s accuracy for neoplasm screening is limited, and guidance for patient management is currently lacking. This challenges clinicians’ ability to counsel patients regarding the implications of these results, which often is the responsibility of a genetic counselor. Over three hundred board-eligible/certified genetic counselors were surveyed regarding their awareness, preferences, and attitudes towards NIPT’s ability to indicate maternal neoplasms. Despite 95% of this cohort being aware …

A Prediction Model For Acute Core And Lower Extremity Injuries In Division 1 Collegiate Football Players, Alexandra Aline Mcdonald

Graduate Theses and Dissertations

Context: Various intrinsic factors such as high exposure, poor endurance of core muscles, previous injury, strength deficits, suboptimal neurocognitive function, and orthopedic abnormalities have been found as predictors for sprains and strains among collegiate football players. Objective: Assess the applicability of pre-participation assessments as predictors of core or lower extremity injury. Design: Cohort Study. Setting: National Collegiate Athletic Association Division I football program. Patients or Other Participants: Athletes who underwent mandatory pre-participation examinations before preseason football training over two consecutive seasons (n=225). Main Outcome Measure(s): Associations between preseason protocols and injury incidence for core and lower extremity injuries were established …

Improving Access To Care For Arkansas Youth Athletes With Sport-Related Concussion: Establishing “Teleconcussion” In Arkansas, Kristin Maxey

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Proper management of sport-related concussion (SRC) is critical for improved recovery outcomes in youth athletes. Several barriers exist to improving the standard of care for youth athletes with SRC. Many rural areas lack medical professionals with specialized training in SRC. Innovative methods for providing specialized healthcare to youth athletes with SRC are needed. Telehealth may be an effective means of providing specialized care for youth athletes with SRC located in underserved areas that have a shortage of healthcare providers specializing in SRC.

Purpose: The purpose of this study was to compare patient, caregiver, and provider ratings of the therapeutic …

Effects Of Drift, Selection And Gene Flow On Immune Genes In Prairie Grouse, Zachary Bateson

Theses and Dissertations

Fragmentation of natural habitats is related to population decline in many species. The resulting small and isolated populations are expected to lose genetic variation at a rapid rate, which reduces the ability to adapt to environmental change. One concern is that small populations are more susceptible to emerging pathogens due to the loss of variation at immune genes. My dissertation examined the relative effects of gene flow, genetic drift and selection on immune genes in prairie-chickens (Tympanuchus cupido), a species that has undergone drastic population declines across their range. In the first chapter, I examined how artificial gene flow through …

The Effects Of Pulmonary Hypertension In Diabetic Zucker Rats On Pulmonary Vascular Contraction And Right Ventricular Size, Michael Franzetti

Biological Sciences Undergraduate Honors Theses

Pulmonary hypertension is a life-threatening disease that is identified by a resting mean pulmonary arterial pressure over 25 mmHg and established by right heart catheterization (Saglam et al., 2015). The symptoms commonly associated with pulmonary hypertension include fatigue, dyspnea, syncope, and chest pain, which severely limit quality of life in diagnosed patients (Saglam et al., 2015). According to recent studies in patients with pulmonary hypertension, the one, three and five year mortality rates are 8%, 25%, and 34%, respectively (Burudpakdee, Shah, Joish, Divers, & Yaldo, 2014). Although some advances have been made in therapies for pulmonary hypertension, the prognosis is …

Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian

Electronic Theses and Dissertations

SA-4-1BBL is a recombinant costimulatory molecule that is active in its soluble form and has pleiotropic effects on the functions of innate, adaptive, and regulatory immune cells. We have previously shown that SA-4-1BBL makes CD4+ T conventional cells (Tconvs) resistant to suppression by CD4+CD25+Foxp3+ T regulatory cells (Tregs). The mechanistic basis of this observation is the subject of this study. We demonstrate that Tconvs, but not Tregs, are the direct targets of SA-4-1BBL-mediated evasion of Treg suppression without contribution from antigen presenting cells (APCs). SA-4-1BBL engagement with its receptor, 4-1BB, on Tconvs resulted in the production of high levels of …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …

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 …

Reinforcement Learning, Error-Related Negativity, And Genetic Risk For Alzheimer's Disease, Christina Marie Figueroa

Dissertations (1934 -)

Reinforcement learning (RL) has been widely used as a model of animal and human learning and decision-making. The neural networks underlying RL involve many of the same structures primarily affected by Alzheimer’s disease (AD) such as the hippocampus. Yet, RL and non-invasive evaluation of its neural underpinnings have been underutilized as a framework for understanding disease pathology and its pre-clinical states. This study aimed to provide a novel approach for assessing subtle changes in asymptomatic apolipoprotein-E (APOE) carriers and non-carriers. Electroencephalography was collected from forty APOE genotyped older adults (Male n = 11; Mage = 79.30; Meducation = 14.88 years) …

Targeting Histone Deacetylases In Melanoma And T-Cells To Improve Cancer Immunotherapy, Andressa Sodre De Castro Laino

USF Tampa Graduate Theses and Dissertations

Histone deacetylases (HDACs) are key mediators of gene expression and, thus, major regulators of cell function. As such, HDACs play a role in orchestrating tumor biology, and the use of small inhibitors targeting theses proteins is attractive for the field of cancer therapy. Indeed, several HDAC inhibitors have received FDA-approval for the treatment of malignancies, while a myriad of these compounds continue to be evaluated in clinical trials. Besides their direct impact on tumor growth, HDAC inhibitors have been shown to increase immunogenicity of cancer cells, facilitating generation of a productive immune response against tumors. Immunotherapeutic approaches take advantage of …

The Association Between Vitamin A Status Or Supplementation And Hiv/Aids, Mikaela Kathleen Curtis

Food Science and Nutrition

The human immunodeficiency virus (HIV) has infected millions of people since the start of the epidemic in the early 1980s. HIV is the etiologic agent of the acquired immunodeficiency syndrome (AIDS), which has taken millions of lives. It is extremely difficult for particular populations to receive medication to treat HIV infection and prevent the progression of HIV to AIDS. Multiple studies have examined the effect of vitamin A on HIV infection, due to its immune stimulating effects. It is unclear whether an association exists between vitamin A and different aspects of HIV. This review examined the effect of vitamin A …

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 …

Antigen Specific Induced T Regulatory Cellular Therapy For Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation, Jessica Lauren Heinrichs

USF Tampa Graduate Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more …

Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu

Wayne State University Dissertations

The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite T. cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) with sera from patients with chronic ChD, revealing the disaccharide Galα(1,3)Galβ as the immunodominant glycotope (Chapter 2). This disaccharide comprises the two terminal sugars of the known immunodominant glycotope Galα(1,3)Galβ(1,4)GlcNAcα, which is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-α-Gal antibodies (Abs) in infected …

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Determining The Role Of Poly [Adp-Ribose] Polymerase 1 (Parp-1) In Retroviral Infection, Luis Valdes Rodriguez

Open Access Theses & Dissertations

Possible links between PARP-1 and HIV-1 have been previously reported but the role of this protein during viral infection has remained elusive. Based on the high evolutionary conservation of PARP-1, from Drosophila to humans, we have been able to counteract the difficulties related with the functional redundancy manifested in the PARP family by studying the influence of PARP-1 on the expression of an endogenous retrovirus using the chicken B lymphoblastoid cell line DT40, this cell line exhibits low PARP-1 functional redundancy and is viable after PARP-1 knockout. We have determined that the transcription level of the endogenous retrovirus RAV-1 is …

Medical Community Distrust And The Influenza Vaccination Rates Of Black Americans, Kenyatte Irby Winston

Walden Dissertations and Doctoral Studies

Black Americans experience influenza vaccination rates that are lower than the rates of other ethnic groups. Low influenza vaccination rates among the Black community are associated with higher influenza infection rates, influenza-related hospitalizations, and higher influenza mortality rates. There is a belief within the Black American community that the medical establishment does not have the Black American patient in its best interest, leading to feelings of distrust. The purpose of this study was to determine if the distrust of the medical community is a relevant factor in the low influenza vaccination rates of Black Americans aged 18 and older in …

Barriers To Exclusive Breastfeeding Among Mothers During The First Four Weeks Postpartum, Jessy V. Thomas

Walden Dissertations and Doctoral Studies

According to the World Health Organization, breastfeeding is natural and the most effective way of nourishment to feed infants and young children to ensure child health and survival. Currently, the World Health Organization, the American Academy of Pediatrics, and other health organizations recommend exclusive breastfeeding during the first 6 months of life. Although exclusive breastfeeding has been shown to reduce the occurrence of adverse health outcomes to the infant and mother, the duration of exclusive breastfeeding remains relatively low in the United States. The theory of planned behavior was used as a theoretical framework for this study. The purpose of …

The Role Of Src Kinase Activation In Lung Epithelial Alterations In Response To The A,B-Unsaturated Aldehyde Acrolein, Robert Bauer

Graduate College Dissertations and Theses

Cigarette smoke (CS) exposure is the leading cause of preventable death in the United States contributing to over 480,000 deaths a year with over 300 billion dollars in CS related costs spent per year. While the dangers of CS exposure have been studied and characterized for decades being largely attributed to reactive oxygen species and oxidative stress, increasing evidence suggests that reactive aldehydes in CS, specifically the α,β-unsaturated aldehyde acrolein, are responsible for many of the negative pathologies associated CS exposure. Previous work has shown that acrolein can bind directly to a number of cellular proteins containing redox sensitive cysteine …

Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon

PCOM Psychology Dissertations

Background: Psoriasis is a multifactorial disease that effect approximately 7.5 million Americans. There are a variety of traditional treatments for psoriasis (e.g. topical medications, biologics) that for many, are effective in combating the disease. However, traditional treatments often have aversive side effects and may not be appropriate for every patient (e.g. pregnant women). Additionally, the efficacy of these medications are variable leaving some looking for adjunctive treatment options. There is increasing evidence to support the use of adjunctive treatments for psoriatic patients (e.g. psychotherapy, mindfulness). However, research is variable in regards to medical professionals’ attitudes towards integrative medicine (IM) as …

Vitamin D Clinical Relevance In The Recovery From Traumatic Brain Injury Among The Military Population, Yuisa M. Colón

Honors Undergraduate Theses

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI.
Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological …