Skin and Connective Tissue Diseases Commons^™

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 …

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 …

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 …

Cutaneous Malignant Melanoma: A Synthesis On Updated Guidelines For The Primary Care Perspective, Seetha Venkateswaran, Nicholas D'Angelo

HCA Healthcare Journal of Medicine

Cutaneous malignant melanoma (CMM) is a condition wherein malignant cells form in the melanocytic cells. CMM is a potentially lethal form of skin cancer, commonly found in sun-exposed areas of the body. There are multiple risk factors for disease development, such as genetic mutation and UV radiation among others. Diagnosis and staging is important in determining disease morbidity and mortality. The United States Preventive Services Task Force (USPSTF) and the American Academy of Dermatology (AAD) have their respective guidelines and consensus on diagnosis, staging and treatment. It is imperative to delineate and educate primary care physicians on CMM, as they …

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Ivan P Gorlov, Christopher I Amos, Spiridon Tsavachidis, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Acral Lentiginous Melanoma: A Rare Variant With Unique Diagnostic Challenges, Taylor Gray, Brett Brazen, Maheera Farsi, Richard Miller

West Florida Division GME Research Day 2020

Acral lentiginous melanoma (ALM), named for its location and histological growth pattern, is a rare variant of melanoma. ALM presents on palms, soles, or in association with the nail unit.1 While ALM accounts for approximately 5% of melanomas diagnosed each year, it is the most commonly diagnosed subtype of melanoma in non-Caucasian patients.

End-Of-Life Healthcare Use Of Medicare Patients With Melanoma Based On Patient Characteristics And Year Of Death, Rebecca N. Hutchinson, F. Lee Lucas, Kathleen Fairfield

Journal of Maine Medical Center

Background: Many cancer patients receive overly-intensive care at end-of-life (EOL), despite recognition that this is a marker of poor quality. There is limited knowledge about care received by patients dying with melanoma.

Objective: We characterized healthcare utilization during EOL and patient characteristics associated with variations in care. We also described how utilization changed over time.

Methods: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify 9099 melanoma patients aged 65+ at diagnosis between 2000 and 2009, who died by 12/31/2010. We included patients enrolled in Medicare part A and B six-months prior to diagnosis and not in managed …

Treatment Of Basal Cell Carcinoma With Vismodegib, Sunitha Johns, Katlyn Brown, Emily Loudermilk, Crystal Zheng, Anh Dao Le, Sophocles Chrissobolis

Pharmacy and Wellness Review

The most prevalent nonmelanoma skin cancers are basal cell carcinoma (BCC) and locally advanced basal cell carcinoma (aBCC). Current, effective first-line treatments for BCC aim to remove and destroy cancerous skin cells through excision surgery, Mohs surgery, radiation therapy and cryotherapy, while treatment of aBCC remains limited. An emerging treatment option for aBCC that promotes tumor size reduction is vismodegib, a pharmaceutical product approved in 2012 by the U.S. Food and Drug Administration (FDA). Vismodegib was approved for the treatment of aBCC, metastasized HCC (mBCC) or recurrent BCC after surgery as well as for use in adults who are not …

Biological Pathway Involvement In Melanoma Heterogeneity And Drug-Induced Resistance, Sarah V. Pack

STAR Program Research Presentations

Tumors develop resistance to numerous drug therapies, and this remains a major obstacle in treating many types of non-surgical cancers. Melanoma provides a good model system for studying drug resistance in cancer due to its high propensity to incur resistance after a significant initial response to a drug. Genes that are highly expressed in melanoma cancer cells have been studied, but in order to further understand the collective function of these highly expressed genes we must analyze gene sets, or pathways. A single gene’s function is rarely independent of other genes, and pathway analysis takes this into account.

Our objective …

Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes

LSU Doctoral Dissertations

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …

Micromelanomas Identified With Time-Lapse Total Body Photography And Dermoscopy, Elizabeth D. Drugge, Elgida R. Volpicelli, Rebecca M. Sarac, Sophie R. Strang, Dirk M. Elston, Rhett J. Drugge

NYMC Faculty Publications

No abstract provided.

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations and Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Skin Cancer: Causes, Prevention, And Treatment, Lauren Queen

Senior Honors Theses

The purpose of this thesis is to analyze the causes, prevention, and treatment of skin cancer. Skin cancers are defined as either malignant or benign cells that typically arise from excessive exposure to UV radiation. Arguably, skin cancer is a type of cancer that can most easily be prevented; prevention of skin cancer is relatively simple, but often ignored. An important aspect in discussing the epidemiology of skin cancer is understanding the treatments that are available, as well as the prevention methods that can be implemented in every day practice. It is estimated that one in five Americans will develop …

Convolutional Neural Networks For Predicting Skin Lesions Of Melanoma, Anuruddha Jayasekara Pathiranage

Regis University Student Publications (comprehensive collection)

Diagnosis of an unknown skin lesion is crucial to enable proper treatments. While curable with early diagnosis, only highly trained dermatologists are capable of accurately recognize melanoma skin lesions. Expert dermatologist classification for melanoma dermoscopic images is 65-66%. As expertise is in limited supply, systems that can automatically classify skin lesions as either benign or malignant melanoma are very useful as initial screening tools. Towards this goal, this study presents a convolutional neural network model, trained on features extracted from a highway convolutional neural network pretrained on dermoscopic images of skin lesions. This requires no lesion segmentation nor complex preprocessing. …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

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

Dissertations and 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 …