Medicine and Health Sciences Commons^™

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

Understanding How Cancer Adapts To Stress And Therapy Using Evolutionary Game Theory, Mariyah Pressley

USF Tampa Graduate Theses and Dissertations

Adaptive responses in cancer promote disease initiation, progression, and resistance to treatment. Understanding the underlying evolutionary dynamics behind these adaptive responses is crucial for developing effective therapeutic strategies. Evolutionary game theory (EGT) has proven a useful tool in analyzing how different cellular behaviors and evolutionary forces shape the dynamics of tumor growth, response to therapy, and the emergence of resistance. In this dissertation, we utilize EGT to understand the adaptive responses of cancer through the lens of ecology and evolution. By employing fitness-generating models and exploring various ecological contexts, we aimed to unveil critical factors influencing aggressive cell phenotypes, treatment …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Contribution Of Contextual Factors And Neuropathology To Dementia, Monica E. Nelson

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has extensive biological heterogeneity. It is not clear the extent to which this heterogeneity may be detected in participants without dementia, how it relates to incident AD dementia, and whether contextual factors may change how neuropathology relates to incident AD dementia. Therefore, this dissertation was completed using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 1,703) and the Czech Brain Aging Study (CBAS; n = 385) to address the following aims: to assess biological heterogeneity in participants without dementia, to relate this heterogeneity to incident AD dementia, and to …

Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan

USF Tampa Graduate Theses and Dissertations

Background: Traumatic Brain Injury (TBI) is a major contributor to death and disability due to motorvehicle accidents, sports, physical abuse, and battlefield injuries. The primary insult to the brain leads to inflammation, vascular dysfunction, and oxidative stress in the brain as well as in the eye. This leads to loss of Retinal Ganglion Cells (RGCs) and downregulation of Brain derived Neurotopic Factor (BDNF). BDNF is a neurotrophic factor that binds to Tropomyosin Receptor Kinase B (TrkB) receptor to promote cell growth, survival, and differentiation. Current treatment strategies do not promote neuronal regeneration. Therefore, novel treatments are needed to restore vision …

Role Of Hla-Drb1 Fucosylation In Anti-Melanoma Immunity, Daniel K. Lester

USF Tampa Graduate Theses and Dissertations

Melanoma is the one of the most lethal skin malignancies due to its ability to rapidly metastasize and evade the immune system. One factor that influences melanoma’s ability to metastasize and evade the immune system is the tumor microenvironment. The tumor microenvironment is a complex ecosystem that consists of melanoma cells interacting with different proteins and cell types such as cytokines, extra cellular matrix proteins, and various immune cells. While different immune cells can have various implications in the tumor microenvironment, some tumor infiltrating lymphocytes (TIL) have the potential to suppress these tumors. Recent therapeutic strategies aim to enhance TILs …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Development And Implementation Of Telemetry Devices To Identify And Characterize Sources Of Intraocular Pressure Variability In Rats, Christina M. Nicou

USF Tampa Graduate Theses and Dissertations

Eye health depends partially on intraocular pressure (IOP) as abnormal levels can lead to ocular tissue damage. Glaucoma is a neurodegenerative disease that affects nearly 80 million people worldwide [1]. It is associated with elevated IOP, which can lead to irreversible blindness. Relatively little is known about IOP dynamics and the physiological factors that affect it as IOP is typically monitored using tonometry. Tonometry is a common tool used by clinicians and researchers to measure IOP noninvasively. It provides a good estimate of IOP mean but not variance because data collection takes time. Readings can also be influenced by subject …

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

Young Adult Cancer Patients And Survivors’ Adherence To Healthy Eating And Physical Activity Guidelines, Sandra Soca Lozano

USF Tampa Graduate Theses and Dissertations

Many Adolescents and Young Adult (AYA) cancer patients/survivors do not engage in healthy eating and physical activity recommendations. The present study assessed the role of race/ethnicity, health literacy, and home environmental influences and its association with adherence to healthy eating and physical activity. AYA patients/survivors from Moffitt Cancer Center (n = 273) completed an anonymous online survey. Self-reported measures about eating habits, physical activity, health literacy, and social support were used. Black/African Americans reported worse eating habits than White and Hispanic participants. Obese participants showed a similar trend compared to all other Body Mass Index groups. Adherence to physical activity …

Accelerating Multiparametric Mri For Adaptive Radiotherapy, Shraddha Pandey

USF Tampa Graduate Theses and Dissertations

MR guided Radiotherapy (MRgRT) marks an important paradigm shift in the field of radiotherapy. Superior tissue contrast of MRI offers better visualization of the abnormal lesions, as a result precise radiation dose delivery is possible. In case of online treatment planning, MRgRT offers better control of intratumoral motion and quick adaptation to changes in the gross tumor volume. Nonetheless, the MRgRT process flow does suffer from some challenges that limit its clinical usability. The primary aspects of MRgRT workflow are MRI acquisition, tumor delineation, dose map prediction and administering treatment. It is estimated that the acquisition of MRI takes around …

Going Flat: Challenging Gender, Stigma, And Cure Through Lesbian Breast Cancer Experience, Beth Gaines

USF Tampa Graduate Theses and Dissertations

This paper explores the decision-making process of reconstruction surgery among lesbian breast cancer patients to better understand how identity impacts healthcare decisions. Breast cancer patients experience the disease in unique ways due to gender, sexuality, race, and class, impacting their individual decisions regarding treatment plans. Many breast cancer patients face mastectomy surgery as the first plan of treatment after diagnosis. By exploring the impact of gender, sexuality, stigma, and ideas of cure, this research aims to advance research about breast cancer by recognizing why some lesbian breast cancer patients forego reconstruction surgery and instead choose to “go flat.

Determining The Role Of Dendritic Cells During Response To Treatment With Paclitaxel/Anti-Tim-3, Alycia Gardner

USF Tampa Graduate Theses and Dissertations

Intratumoral CD103+ dendritic cells (cDC1) are required for anti-tumor immune responses. In tumors that are poorly responsive to immunotherapeutic approaches targeting T cells, targeting cDC1 represents an alternative approach that may be useful in improving patient response rates. As such, it is critical to understand cDC1 function within tumors, and what may be preventing optimal function of cDC1. TIM-3 is a receptor that is highly expressed by cDC1 in murine and human mammary tumors, and TIM-3 blocking antibodies are currently being evaluated in clinical trials for a number of solid and hematological malignancies. In order to best design combinatorial therapeutic …

A Biocultural Analysis Of The Impacts Of Interactions Between West Africans And Europeans During The Trans-Atlantic Trade At Elmina, Ghana, Heidi Ellen Miller

USF Tampa Graduate Theses and Dissertations

This project utilizes a biocultural approach to assess the demographics and health of the West African population from Elmina, Ghana. Elmina, selected by the Portuguese in 1482 as the site of the first European trade fort in sub-Saharan Africa, grew from a small coastal fishing village to a large settlement over the course of more than 400 years of trade and cultural entanglement. Taken over by the Dutch and then ceded to the British, the people of Elmina navigated significant cultural changes, changes and experiences that can be detected in their skeletal remains. Bioarchaeological research concerned with the effects of …

Stressors, Resources, And Psychological Well-Being Among Working Black And White Caregivers In The United States, Maureen E. Templeman

USF Tampa Graduate Theses and Dissertations

By the year 2060 in the United States (U.S.), not only will the number of adults aged 65 and older double, non-Hispanic Whites (Whites), who currently constitute 77% of the older adult population, will constitute just slightly more than half of older adults. As the older adult population diversifies, so will their caregivers. Over 60% of informal caregivers of older adults (caregivers) are employed, and the majority of these are employed full time. Little is known about the unique experiences of working Black or African American (Black/AA) and White caregivers and non-caregivers in the U.S. This dissertation consists of three …

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …

The Relationship Of Hope To Goals And Psychological Outcomes In Patients With Advanced Lung Cancer: A Test Of Hope Theory, Kelly A. Hyland

USF Tampa Graduate Theses and Dissertations

Background. Hope is an important positive psychological construct that may help to explain how individuals cope in the context of life-threatening illness. Snyder’s hope theory states that humans are goal-oriented, and that goals link hope to psychological outcomes. The purpose of the current study was to investigate the relationship of hope to emotional well-being, meaning and purpose in life, and positive and negative affect in a sample of patients with advanced stage lung cancer. The study also sought to identify how hope relates to patients’ goals and to explore whether goal characteristics and progress in achieving goals mediated the relationship …

Serious Mental Illness In Nursing Homes: Quality Concerns, Dylan J. Jester

USF Tampa Graduate Theses and Dissertations

Objective: This dissertation is made of two academic papers followed by a chapter discussing policy implications of the findings. The objective of this dissertation is to better understand if high-serious mental illness (SMI) nursing homes (NHs) provide poorer quality of care (e.g., operationalized as staffing levels, NH Compare quality star ratings, and health deficiencies) and whether quality in high-SMI NHs is confounded by payer mix (e.g., the proportion of residents who are Medicaid-reimbursed). A modified Donabedian Structure, Process, Outcome (SPO) Model was used as the main theoretical framework.

Methods: Data came from the Certification and Survey Provider Enhanced Reports (CASPER) …

Bone Microenvironmental Control Of Skeletal Malignancy, Chen Hao Lo

USF Tampa Graduate Theses and Dissertations

Bone is a common site of metastasis for many solid malignancies. Bone-metastatic cancers pose a significant clinical problem worldwide and is among the main causes for cancer patient morbidity and mortality. Patients with advanced bone-metastatic diseases often present with either osteolytic or osteogenic bone diseases as their cancers progress. These bone pathologies are products of the cancer co-opting the local bone remodeling stroma to yield important growth nutrients and factors. Unfortunately, skeletal metastases remain incurable and are fatal. Identifying and understanding the causal multicellular and molecular interactions underlying skeletal malignancies can yield crucial ideas for targeting and inhibiting disease progression. …

Evaluation Of Aging And Genetic Mutation Variants On Tauopathy, Amber M. Tetlow

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is characterized by amyloid β plaques and neurofibrillary tau tangles (NFTs). While research has demonstrated amyloid pathology occurs prior to tau pathology, or tauopathy, tau has proven to be more toxic. Tauopathy is associated with cognitive declines and neurodegeneration. These findings have highlighted the importance of further understanding tauopathy. In the progression of tauopathy, there is an observable immune response that can be measured by glial cells such as microglia. Activated microglia are known to exacerbate tauopathy rather than reducing the pathology. Research has indicated that with increased age there is an increased risk for AD-related tauopathy …

The Impact Of Myeloid-Mediated Co-Stimulation And Immunosuppression On The Anti-Tumor Efficacy Of Adoptive T Cell Therapy, Pasquale Patrick Innamarato

USF Tampa Graduate Theses and Dissertations

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. However, only a minority of patients that receive ACT with tumor infiltrating lymphocytes (TILs) exhibit durable benefit. Thus, there is an urgent need to define strategies that potentiate anti-tumor activity conducted by adoptively transferred T cells. In these studies, we aimed to identify novel strategies to enhance the therapeutic efficacy of ACT. Accordingly, we describe the disparate roles of myeloid cells in the context of ACT characterized by the augmentation of TIL proliferation in …

Active Deep Learning Method To Automate Unbiased Stereology Cell Counting, Saeed Alahmari

USF Tampa Graduate Theses and Dissertations

Cell quantification in histopathology images plays a significant role in understanding and diagnosing diseases such as cancer and Alzheimers. The gold-standard for quantifying cells in tissue sections is the unbiased stereology approach. Unfortunately, in unbiased stereology current practices rely on a well-trained human to manually count hundreds of cells in microscopy images. However, this human-based manual approach is time-consuming, labor-intensive, subject to human errors, recognition bias, fatigue, variable training, poor reproducibility, and inter-observer error. Thus, the lack of high-throughput technology for automating unbiased stereology analyses remains a major obstacle to further progress in a wide range of neuroscience and cancer …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …

Multimodal Treatment And Neoadjuvant Chemotherapy Trends, Utilization And Survival Effects In Intrahepatic Cholangiocarcinoma – A Propensity Score Analysis, Ovie Utuama

USF Tampa Graduate Theses and Dissertations

Intrahepatic Cholangiocarcinomas (ICC) are fatal malignancies common among the elderly. Patients are diagnosed late and often relapse, even after curative-intent surgery (CIS). In this context, additional systemic chemotherapy (multimodal treatment) is recommended for most patients but reported survival benefits are minimal and are limited to small single institutional studies. For this reason, using a national cancer registry, we sought to characterize multimodal treatment trends and utilization in general and neoadjuvant chemotherapy, specifically, as well as evaluate their survival effects among the larger population. We hypothesized that, 1). Elderly ICC patients would have survival benefits equivalent to younger patients, 2). Neoadjuvant …

Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell

USF Tampa Graduate Theses and Dissertations

Cancer is a complex and heterogeneous disease. Not only is there considerable variability between different cancer types, but there is enormous variability between and within patients who have the same type of cancer. Within tumors, there are multiple cell types, including cancer cells, stromal cells, and immune cells. The tumor microenvironment often induces the healthy cells to become pro-tumorigenic. Cell metabolism is exquisitely sensitive to changes in the tumor microenvironment and can be measured to infer the aggressiveness of cancer and predict response to therapy. In this dissertation, we aim to understand how the microenvironment, specifically low pH, affects the …

Widow Narratives On Film And In Memoirs: Exploring Formula Stories Of Grief And Loss Of Older Women After The Death Of A Spouse, Jennifer R. Bender

USF Tampa Graduate Theses and Dissertations

This dissertation analyzes narratives (written and mediated) about widows’ post-loss experiences—specifically the ways in which these women embody and adjust/adhere to their post-loss widow identities—and whether or not the canonical/formula stories about widows reflect current experiences of widowhood. I look at older widowed women—both those in well-read widow memoirs and also in media portrayals of widows on film. The canonical view of widows as not attractive, not useful, and not interesting needs to be reexamined in light of changing ideas about gender roles and increased longevity. Surely older women have experiences, desires, and goals that encompass more than being socially …

The Left Behind Generation: Instructional Practices To Increase The Technological Literacy Of Older Adults, Daphne Pace Phillips

USF Tampa Graduate Theses and Dissertations

This study sought to explore the utilization and perception of best practices by community-based technology training programs when instructing older adults to become technologically literate. The target population included adults age 55 years and older of the Baby Boomer generational cohort who ranged academically from possessing a high school diploma or General Education Diploma (GED) through a college degree and had enrolled in a local technology training program to improve their technological skill level with the goal of obtaining employment and/or to remain functionally independent. This study was conducted at three community technology training centers located in the southeast that …

Supporting Persons With Dementia In Communicating Their Care Preferences, Vanessa L. Burshnic

USF Tampa Graduate Theses and Dissertations

Person-centered care is important to the quality of life of nursing home residents with dementia. Preference assessments enable person-centered care by documenting residents’ preferred activities. Residents with severe dementia are less likely to have a role in preference assessment due to communication challenges associated with the disease. External supports (visual and text cues) are effective in improving the communication of residents with dementia, but these cues are often not used in practice. Standard assessment (verbal questioning) places greater demands on short-term memory and attention, which are known deficits in dementia.

Applying a within-subjects design, this study evaluated two conditions (standard …

Using A Stress Process Model To Examine Longitudinal Racial Differences In Well-Being And Health: Results From A Population-Based Study Of Caregiving, Adrian N. S. Badana

USF Tampa Graduate Theses and Dissertations

As the older adult population of the United States increases over the next decade, many family caregivers will be needed to provide care for aging loved ones. The growing diversity of the population may also mean that more racial/ethnic minority caregivers will be providing care to older family members. Most of the studies examining race and caregiving have focused on racial differences in stress, coping, well-being and health among White and Black family caregivers. However, previous research examining racial differences in caregiving has often been limited to smaller convenience samples of caregivers, which limit generalizability of study findings. In this …