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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 …


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 …


Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan Mar 2023

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 …


How Some Arboreal Salamanders (Genus Aneides) Jump, Glide, And Generate Lift, Christian E. Brown Mar 2023

How Some Arboreal Salamanders (Genus Aneides) Jump, Glide, And Generate Lift, Christian E. Brown

USF Tampa Graduate Theses and Dissertations

The jumping and subsequent aerial behaviors of arboreal lungless salamanders (genus Aneides) had never been investigated or described. The aims of this research were to (1) compare jumping performance within the family Plethodontidae with a special focus on arboreal species from genus Aneides, (2) describe the biomechanics and kinematics of aerial behaviors after a jump or extended fall, and (3) model airflow over the morphology of the most aerially adept salamanders to investigate if they are capable of generating lift. First, I recorded salamanders jumping, locomoting vertically, dropping, and flying in a vertical wind tunnel. Then, I laser-scanned and reconstructed …


Diet And Salivary Microbiome On Cardiovascular Risk And Glycemic Control In Participants With And Without Type 1 Diabetes: The Cacti Study, Tiantian Pang Mar 2023

Diet And Salivary Microbiome On Cardiovascular Risk And Glycemic Control In Participants With And Without Type 1 Diabetes: The Cacti Study, Tiantian Pang

USF Tampa Graduate Theses and Dissertations

Introduction: The prevalence of type 1 diabetes mellitus (T1DM) has been increasing drastically in the United States. People with T1DM are at a higher risk of developing diabetes-related complications, including cardiovascular disease (CVD). Diet is one of the most modifiable factors and healthy eating could reduce CVD risk among individuals with T1DM. The current 2015-2020 Dietary Guidelines for Americans focus on overall healthy eating patterns rather than individual foods and nutrients. A healthy dietary pattern or high-quality diet can be measured by diet quality indexes, and generally contains minimal ultra-processed foods (UPF). Although substantial evidence has linked poor diet quality …


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 …


Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling, David A. Cline Mar 2023

Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling, David A. Cline

USF Tampa Graduate Theses and Dissertations

Genetic Counseling relies on communication skills to help patients understand and adapt to a genetic disease or risk. However, little is known about which skills are most commonly used or the extent to which genetic counseling sessions vary. A novel process measure titled the "Genetic Counseling Skills Checklist" (GCSC) was developed in a prior pilot study and includes 8 broad categories each consisting of 5-8 skills. This study is the first to apply the final GCSC to characterize 20 mock prenatal sessions conducted by 5 genetic counselors (GCs) for 2 prenatal indications using 3 trained actors as patients. Two experienced …