Diseases Commons^™

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Evaluating Kentucky Advanced Practice Registered Nurses’ Confidence, Comfort, And Knowledge Levels Regarding Dermatology Care After A Web-Based Video Training, Victoria Hayden

DNP Projects

Background: It can take an average of 38.9 days to see dermatology from referral to initial appointment. As a result, delays in diagnosis and treatment of life-threatening conditions such as malignant melanoma could occur. Primary care providers frequently refer patients for benign conditions that can be appropriately managed in the primary care setting; often due to lack of knowledge or confidence in their clinical management skills. Educational resources equip providers with the knowledge and tools to feel confident in their management of various skin conditions in a primary care setting. Purpose: The purpose of this project was to …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Keeping Primary Care Providers Informed About Detecting Skin Cancer In Young Adults, Riley J. Spears

Evidence-Based Practice Project Reports

Skin cancer is a common, life-threatening disease that affects anyone, regardless of age or skin color (American Cancer Society [ACS], 2020). The incidence of melanoma is on the rise for young adults, with an estimated 2,400 new cases for individuals aged 15 to 29 (ACS, 2020). Although skin cancer is highly preventable, clinical guidelines are inconsistent regarding skin cancer screening. The purpose of this evidence-based practice (EBP) project was to determine if the implementation of the INternet curriculum FOR Melanoma Early Detection (INFORMED) program would improve primary care providers’ (PCPs’) confidence about skin cancer and the number of completed and …

Unravelling The Potential Applications Of Extracellular Vesicles For The Clinical Management Of Melanoma Patients, Michael Edward Clark

Theses: Doctorates and Masters

Metastatic melanoma is the third most common cancer in Australia with global incidence increasing. After decades without effective systemic treatments for advanced melanoma, the advent of targeted and immune therapies has substantially improved patient survival. While this is encouraging, further research is needed as the majority of patients treated with targeted therapy ultimately develop drug resistance. Immunotherapy can achieve durable responses in many patients however, not all patients respond to current single or a combination of immune checkpoint inhibitors. Considering the cost and potential toxicities to patients being treated with these therapies, there is an urgent need to develop biomarkers …

Assessment Of The Clinical Validity Of Ctdna Analysis For Melanoma Management, Anda-Gabriela Marsavela

Theses: Doctorates and Masters

Metastatic melanoma is responsible for almost 80% of all skin cancer-related deaths and the incidence of people affected continues to rise worldwide. The emergence of targeted therapy and immune-checkpoint inhibitors has improved the clinical management of melanoma, but durable survival benefit is only seen in a minority of patients. The use of these very expensive systemic therapies on all appropriate patients also poses a high economic burden on health systems across numerous countries. Currently, surveillance for treatment failure is not optimal. Thus, reliable and accurate biomarkers of patient disease status are urgently required.

Circulating tumour DNA (ctDNA) analysis has emerged …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations & Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations & Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …