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Full-Text Articles in Medicine and Health Sciences

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

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 …


Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

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 Jun 2023

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 Jun 2023

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 …


Role Of Hla-Drb1 Fucosylation In Anti-Melanoma Immunity, Daniel K. Lester Mar 2023

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 Mar 2023

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, …


Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy Mar 2023

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 Mar 2023

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 …