Medicine and Health Sciences Commons^™

The Role Of Niacinamide In Skin Cancer Risk Reduction, Britny Ruilova Tellez

Doctor of Medical Science (DMSc)

The contents of this article are the author’s original unpublished findings.

Background: Each year, approximately 6 million Americans are treated for skin cancer, resulting in a total annual medical expense of $8.9 billion 1. The two most common types of skin cancer are basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC)2. The metastatic potential of these cancers is minimal; however, their treatment may involve severe scarring and disfigurement2. In contrast, melanoma is an aggressive skin malignancy that grows rapidly and can metastasize in a quick manner2. Risk factors of these skin cancers include UV exposure, fair skin complexions, …

Symptom Experience Of Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy, Natalie Jackson-Carroll

Dissertations & Theses (Open Access)

Background: Immune checkpoint inhibitors (ICIs) are novel therapeutic agents utilized in the management of advanced melanoma. Though generally well-tolerated, patients receiving ICIs experience treatment-related toxicities at varying onset and intensity. Assessment and evaluation of these toxicities and their impact on a quality of life is essential to comprehensive cancer care. Patient-reported outcomes (PRO) contribute vital data to a clinical assessment, supporting clinicians in their ability to improve outcomes. To date, there is no melanoma-specific or ICI-specific PRO measure of symptom burden available.

Purpose: The purpose of this study was to describe the symptom experience from the patient's perspective and how …

Educating And Improving Collegiate Athlete Sunscreen Use, Julia Pederson

Doctor of Nursing Practice Final Manuscripts

Introduction: The purpose of this evidence-based practice Doctor of Nursing Practice (DNP) project was to prospectively evaluate the ability to alter the behavior of young adults by providing sunscreen education and thereby reduce their risk of skin cancer from sun exposure. Twenty-three collegiate athletes ages 18 to 21 years old who were on the university softball team were enrolled. These student athletes were then educated about the impact of daily sun protection and risk factors. The goal was to observe an increase in sunscreen use and increase sun exposure awareness.

Background: Skin cancer is the most frequently diagnosed cancer in …

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 …

Labeling Melanoma Cells With Black Microspheres For Improved Sensitivity In Detection Via Photoacoustic Flow Cytometry, Tori Kocsis

Electronic Theses and Dissertations

Melanoma is an aggressive form of skin cancer known for developing into metastatic disease. Current clinical diagnostics, including medical imaging and tissue biopsy, provide a poor prognosis since the cancer is in the late stages of disease progression. In recent years, photoacoustic flow cytometry has allowed for the detection of circulating melanoma cells within patient blood samples in vitro. Although this method exploits the naturally-produced melanin within the cells, it has only successfully detected highly-pigmented melanoma cell lines. Since various forms of melanoma exist, each with varying melanin concentrations, this research aims to provide a novel method for detecting lightly-pigmented …

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

Dissertations & Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Braf^v600e Pten^-/- Cdkn2a^-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …

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 …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

Computer-Aided Diagnosis For Melanoma Using Ontology And Deep Learning Approaches, Xinyuan Zhang

Dissertations & Theses (Open Access)

The emergence of deep-learning algorithms provides great potential to enhance the prediction performance of computer-aided supporting diagnosis systems. Recent research efforts indicated that well-trained algorithms could achieve the accuracy level of experienced senior clinicians in the Dermatology field. However, the lack of interpretability and transparency hinders the algorithms’ utility in real-life. Physicians and patients require a certain level of interpretability for them to accept and trust the results. Another limitation of AI algorithms is the lack of consideration of other information related to the disease diagnosis, for example some typical dermoscopic features and diagnostic guidelines. Clinical guidelines for skin disease …

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 …

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …

Characterizing The Role Of Uchl5 In Metastatic Melanoma, Seenya Vincent

Dissertations & Theses (Open Access)

Metastatic melanoma is one of the most aggressive cancers. In recent years, the survival rate has improved with the introduction of immunotherapy. Our lab conducted an in vivo ORF screen to identify potential drivers of metastasis. UCHL5/UCH37 was identified as one of the top candidates. UCHL5 is a deubiquitinating enzyme and interacts with the 26S proteasome complex and the INO80 chromatin remodeling complex. While UCHL5 has been shown to be overexpressed in many cancers, it has not been well characterized in melanoma. We investigated the role of UCHL5 in metastatic melanoma in vitro through overexpressing and knocking down UCHL5 in …

A Comparative Study On Cannabidiol In Melanoma Migration And Invasion: Charlotte's Web Vs. Purified Cbd, 2020–2021, Ruby Thamert

Theses

Over the last decade, much attention has been focused on compounds from Cannabis sativa in treating a variety of diseases including cancer. This study examines the abilities of two different cannabidiol oils to decrease the migration and invasion of melanoma cells in vitro. Skin cancers are the most common cancers in the world. While malignant melanoma is the least common type of skin cancer, it is the deadliest. Patients diagnosed with stage IV disease have only a 15-20% five-year survival rate even with aggressive multimodal treatment, demonstrating the need for additional therapeutic options. Because melanoma is often fatal when …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations & Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Improving Skin Cancer Screening In Primary Care, Jaclyn Barnhouse, Rebecca Baietto

Doctor of Nursing Practice Projects

Skin cancer is one of the most common forms of cancer in the United States, with melanoma having the highest rate of mortality of all forms of skin cancer (CDC, 2019). However, there is hesitancy among primary care providers to perform skin cancer screenings (Oliveria et al., 2011). Prevention and early detection of melanoma is key. Melanoma has been known to be highly curable when found early. This makes early detection even more important in order to prevent metastasis and potential mortality (Bruce et al, 2017). The use of targeted screening tools can potentially save lives when utilized in primary …

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 …

Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker

Theses and Dissertations

In cases of metastatic melanoma, BRAF is frequently mutated to the V600E oncoprotein causing uncontrolled cell proliferation driven by the MAPK-ERK pathway. There are several BRAF inhibitors, such as vemurafenib, which are FDA approved, but patients treated with these Type-I kinase inhibitors frequently observe relapse under mutant RAS and BRAF-wt conditions due to paradoxical activation. The mechanism of this resistance occurs through binding of the inhibitor to BRAF-wt initiating conformational changes which leads to BRAF dimerization. Once in the dimerized state, the inhibited monomer induces allosteric transactivation of the second monomer. This drug-induced activation of BRAF in cells with mutant …

Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic

Theses and Dissertations--Epidemiology and Biostatistics

The incidence of melanoma and lung cancer has been gradually increasing in the United States over the past three decades with the reputed causes due to etiological and environmental exposures, and tobacco usage. There has been concern that melanoma and lung cancer incidence among military personnel may be associated with deployment to environments with intense sun exposure and increased smoking rates due to post-traumatic stress disorder. The aim of this study was to examine associations between deployment in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), from 2001 through 2015, with subsequent melanoma and lung cancer incidence. …

The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill

Pharmaceutical Sciences (MS) Theses

Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …

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 …

Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations & Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai

Graduate Theses, Dissertations, and Problem Reports

With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …

The Association Between Melanoma And Exposure To Arsenic Among U.S. Adults Using The National Health And Nutrition Examination Survey (Nhanes) From 2003 To 2016, Ahmed Bedaiwi

Capstone Experience

Background: Melanoma is a deadly skin cancer at late stages, and its incidence has been increasing significantly over the last ten years in the United States. Chronic exposure to arsenic has been associated in many studies as a risk factor for non-melanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited regarding melanoma and long-term arsenic exposure.

Methods: We conducted a cross-sectional study using the 2003-2016 cycles of the National Health and Nutrition Examination Survey (NHANES), to investigate the association between arsenic exposure and self-reported melanoma and non-melanoma skin cancer diagnoses. Univariate and multivariate logistic regressions were conducted. …

Access To Care And Melanoma Incidence And Mortality In Nebraska, Natalia Trinidad

Capstone Experience

The purpose of this study is to determine incidence and mortality of melanoma across all counties in Nebraska in the context of access to primary care providers and dermatologists. Crude and age-adjusted incidence rates of melanoma from 2001-2016 by county were calculated for the following year intervals: 2001-2005, 2006-2010, 2011-2016. Variables for melanoma cases were obtained from the Nebraska Cancer Registry and included the case’s zip code at diagnosis, race, ethnicity, sex, age at diagnosis, year, cancer site, vital status, stage of disease, and the ICD-O code for the cancer type. Crude and age-adjusted mortality rates were calculated for the …

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 …

Melanoma, Dianna Lauer

Nursing Student Class Projects (Formerly MSN)

There are many types of skin cancer prevalent in the world today. The three most common types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and melanoma (Watson et al, 2015). In the words of Hawryluk & Tsao (2014), “Melanoma is an aggressive malignancy borne of melanocytes, the pigment-generating cells of the skin”. Melanoma is known to cause the most deaths of the three main skin cancers and has many risk factors. The personal risk factors include, “family history, multiple moles, fair skin, blue eyes, red hair, and freckles” (Watson et al, p.e92, 2015). There are risk factors …

Bill To Restrict Indoor Tanning For Minors In The State Of Maine, Jamie M. Lowery

DNP Scholarly Projects

Background: Melanoma is the deadliest and the most common type of cancer in individuals age 15 to 29. Evidence has shown that ultraviolet radiation overexposure at younger ages significantly increases the risk of developing non-melanoma and melanoma skin cancer in later years. Despite these concerns, approximately 1.6 million minors under the age of 18 participate in the use of indoor tanning devices annually. The high prevalence of skin cancer in the United States continues to be a public health issue that warrants continued preventative and regulatory action. In spite of the health risks associated with indoor tanning, the state of …

Evaluation Of The Mechanisms Of Anti-Cancer Immune Responses, Noel Turner

Yale Medicine Thesis Digital Library

Metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Melanoma is highly immunogenic, and the development of immunotherapies has dramatically changed the landscape of metastatic melanoma treatment. To study the immune mechanisms engaged by these therapies, the Bosenberg lab developed YUMMER, an immunogenic mouse melanoma line that forms tumors when injected into mice. This and other immunogenic murine cancer models were used to demonstrate that B cell depletion does not impair the anti-PD-1-induced anti-tumor immune response in mice. In addition, supplementing immune checkpoint inhibition with therapies targeting myeloid …