The incidence of melanoma and non‐melanoma skin cancer is continuing to increase worldwide. Melanoma is the sixth most common cancer in the United States, making skin cancer a significant public health issue. Photo chemoprevention with natural products is an effective strategy for the control of cutaneous neoplastic. Polyphenols from fruits have been shown to protect the skin from the adverse effects of solar UVR, cancer, and the growth of cancer stem cells. In particular, blueberries are known for their high concentration of phenolic compounds that have the high antioxidant capacity, and their effectiveness in reducing UV damage and, therefore, skin cancer. In Matar's lab, we have shown that Polyphenol-Enriched Blueberry Preparation (PEBP), derived from biotransformation of blueberry juice through fermentation, is effective for targeting skin cancer stem cell proliferation in different skin cancer cell lines. We predicted that PEBP affects melanoma skin cancer stem cells (MCSCs) epigenetically by targeting miRNA pathways. We observed the effects of PEBP on sphere growth and cell motility in vitro. We performed RT2-qPCR analyses to determine PEBP influence on miRNA in B16F10 spheres. We transfected B16F10 cells with miR-200b and performed western blotting analyses. Our results demonstrated that PEBP reduced sphere growth and cell migration, and up regulated miR-200b expression in different biological settings. Inhibition of miR-200b increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression. Consequently, PEBP may influence MCSCs through miRNA pathways. Elucidating the mechanisms by which PEBP modulates CSCs biological behavior by controlling miRNAs will enhance our understanding of the molecular mechanisms in skin cancer chemoprevention and might result in their use as natural photo-protectants in skin cancer.

Ultraviolet radiation (UVR) is a complete carcinogen, inducing skin cancer via DNA photodamage that can lead to mutagenesis, and promoting its growth via photoimmunosuppression (PI). The omega-3 polyunsaturated fatty acid (n-3 PUFA) eicosapentaenoic acid was shown in murine studies to protect against PI and UV-induced skin cancer although the mechanism is uncertain. The principal objectives of this thesis were to (i) examine whether n-3 PUFA can protect against a clinical model of PI in healthy humans and (ii) explore whether the underlying mechanism could be abrogation of UV-induced depletion of antigen-presenting Langerhans cells (LC) from the epidermis, and/or impact on immunomodulatory cytokines. Nickel (Ni) allergic females (n=79) were randomized to 3 months of daily supplementation with 5g n-3 PUFA (70% eicosapentaenoic acid, EPA; 10% docosahexaenoic acid, DHA) or the placebo medium chain triglyceride, GTCC. Local PI was clinically assessed post supplementation using the nickel contact hypersensitivity (Ni CHS) model. In each volunteer, Ni patches were applied to 3 skin sites that were irradiated for 3 consecutive days with UV-doses of 1.89, 3.82 & 7.59J/cm2 respectively. CHS responses were measured and compared to responses of control patches applied on unirradiated skin using a reflectance erythema meter. In the same subjects, assessments of cellular and biochemical mediators of PI were made pre and post supplementation. At 24hr post irradiation with an erythemal UV-dose (4 minimal erythemal doses) to upper buttock skin, half the subjects (n=39) had skin punch biopsies taken and the other half (n=40) had suction blisters raised on this irradiated skin and on unirradiated skin of the contralateral buttock. Epidermal sheets were prepared from the punch biopsies and immunohistochemically stained to assess UV-induced LC numbers. Levels of immunomodulatory cytokines were analysed in the suction blister fluid using Luminex multiplex assay kits. To evaluate compliance and bioavailability, blood samples were taken from all volunteers, pre and post supplementation and EPA% weight in red blood cell membranes was examined using gas chromatography. Post supplementation, EPA %wt was significantly higher in the active group compared to control: mean 3.61% ± 0.22% (SEM) vs. 0.93% ± 0.06% (p<0.001). 3 volunteers showed evidence of non-compliance and were excluded from further analysis. Compared to placebo, evidence for protection against local PI of Ni CHS was apparent post n-3 PUFA at all UV doses, reaching statistical significance at the UV-dose of 3.8J/cm2 (p<0.05). No significant difference in post-UV epidermal LC numbers after supplementation was seen between active and placebo groups, with a % fall following UV of 76.61 ± 3.39% (SEM) in the active group and 73.52 ± 5.24% (SEM) in the control group. When intragroup comparisons were made pre vs. post supplementation, a similar increase in UV-induced LC depletion from the epidermis was seen in both groups, reaching statistical significance following n-3 PUFA (p=0.018). Levels of interleukins IL-10 and IL-8, and of TNF-α, increased post-UVR in both active and control groups pre-supplementation, with no changes occurring following supplementation. In conclusion, supplemental EPA was bioavailable and evidence of protection against clinical PI of Ni CHS was seen in the actively treated group. However, no evidence was found that this abrogation of PI was mediated through a reduced effect of UV on migration of epidermal LC or the immunomodulatory cytokines examined. This original study gives the first evidence that dietary n-3 PUFA may protect against clinical PI, and potentially skin cancer promotion, in humans. Further research is needed to confirm this finding, and to examine the underlying mechanisms, which could involve other immunoregulatory cells of the skin, such as dermal dendritic cells and T regulatory cells and other mediators of UV-immunosuppression including the prostanoids, which may be modified by n-3 PUFA.

Non-melanoma skin cancer (NMSC) is the most common malignant tumor, representing more than a third of all malignant tumors combined and the incidence is increasing every year. Ultraviolet (UV) radiation from the sun is the most dominant factor contributing to tumor initiation and progression. The condition is most prevalent in populations with lighter skin and older age. Current pharmaceutical molecular research targets the inhibition of the Epidermal Growth Factor Receptor (EGFR), a receptor which is commonly over-expressed or dysregulated in skin malignancies. This study evaluates the content and location of the damage marker p21 within keratinocytes that were incubated in sphingomyelin (SM) and later exposed to UV. Confocal microscopy and automated image processing provided the tools to assess large populations of keratinocytes in the effort to accurately identify the photoprotective qualities of sphingomyelin. Classification of individual cells into subpopulations yielded results suggesting SM may be involved in the inhibition of EGFR, and could potentially be a more naturally derived treatment.

Skin cancer rates continue to rise affecting millions of individuals annually. While cutaneous malignant melanoma comprises a fraction of total skin cancers diagnosed, melanoma is associated with a poor prognosis and higher mortality rate when compared to other forms of skin cancer. The greatest risk factor for skin cancer is the amount of ultraviolet light exposure making skin cancer the most common preventable form of cancer. In conjunction with primary prevention, part of secondary prevention measures involves performing routine skin examinations. According to data from the National Health Interview Survey, only 8% of individuals who had seen a primary care provider in the previous 12 months had a skin examination performed (Johnson et al., 2017). A low rate of skin examination can largely be attributed to current professional guidelines from the United States Preventative Services Task Force (2016) not supporting routine skin screening of all patients. Despite the recommendation, primary care providers are consistently faced with the need to evaluate skin lesions. Other barriers identified include lack of training and practical screening methods. Dermoscopy is a noninvasive technique for identifying skin lesions. Based on the need for improved screening practices and identified barriers, a brief educational session and resource on skin cancer and dermoscopy was presented to primary care providers at an urban family practice clinic in eastern North Dakota. Following the educational session, a three-month implementation period provided time for providers to implement their knowledge and dermoscopy skills in practice. The purpose of the project was to increase knowledge, improve accuracy of identifying skin lesions, and increase provider confidence using dermoscopy. Evaluation using a pre-implementation survey of providers in the clinic found the primary care providers felt comfortable with their baseline knowledge of skin cancer but did not feel confident in their ability to use a dermoscope. Most of the participating providers deemed their level of knowledge regarding dermoscopy to be at a novice level. Results of the post-implementation found providers felt more comfortable using dermoscopy and knowledge in dermoscopy overall improved from novice to advanced beginner or competent.

Community health outreach workers (CHOWs) have been demonstrated to increase CRC screening patient education for vulnerable, medically underserved patients as well as increase CRC screening rates in rural populations.1,2 This project examined the effectiveness of CHOWs in increasing CRC screening rates among low-income, underserved ethnic minorities in Portland, Maine. Eligible patients were ages 50-75; due for CRC screening; enrolled in Medicaid or had no health insurance; and spoke Arabic, English, French, Kinyarwanda, Somali, Spanish or Vietnamese. Seven CHOWs were trained in CRC screening outreach and assigned to patients from their own ethnic communities where they employed culturally sensitive interventions to reduce barriers to CRC screening. CHOWs attempted contact with patients by phone four times prior to sending a language-specific letter to patients recommending CRC screening. CHOWs offered fecal immunochemical testing (FIT) or colonoscopy and provided tailored education and frequent reminders for colonoscopies, explanations about procedures for bowel preps, transportation to colonoscopies, reminders and instructions for FIT completion as well as assistance with health insurance and financial barriers. Upon completion of this session, participants should be able to: Define the role of a community health outreach worker (CHOW) in CRC screening. State three common sociocultural barriers patients experience for CRC screening. Identify the efficacy of CHOWs in increasing CRC screening rates.

This study examined cognitions relevant to sunbathing decision-making in college-aged subjects. Using Jaccard's (1981) theory of alternative behavior as a guiding model, 263 subjects were recruited from psychology classes and administered questionnaires assessing their sunbathing behavioral tendencies, attitudes toward sunbathing, attitudes toward reasonable behavioral alternatives to sunbathing, and cognitive variables underlying these attitudinal variables. The fits of models predicting sunbathing attitudes and sunbathing behavioral tendencies (evaluated using covariate structural equations modeling techniques; LISREL VIII) were good for all models tested. In contrast to previous work, the results of this study support the notion that young people will make their decisions regarding sunbathing based on the behavioral alternatives available to them (i.e., generally the one that they prefer most). Furthermore, the multivariate approach used clearly delineates the specific cognitive beliefs and orientations that might be targeted to change these attitudes. The relevance of these findings to skin cancer prevention interventions is discussed.

Sunbathing and sunscreen use, as well as related intentions, attitudes, beliefs, and knowledge, were assessed in 90 Southern Appalachian undergraduates. A large majority (75%) reported sunbathing; with more than half reporting sun lamp use. A slight majority (56.7%) reported some use of sunscreen. Subjects reporting an intention to tan spent more time sunbathing, both outside and under a sun lamp. Individuals reporting a sun protection intention had lighter tans and spent less time sunbathing. Sunbathing was predicted by perceptions of sunbathing as relaxing, while sun lamp use was predicted by more positive views of suntans. Sunscreen use was predicted by more positive sun protection attitudes and less negative sunscreen attitudes.

UV exposure via sunbathing and utilization of sun lamps and tanning beds are considered important risk factors for the development of skin cancer. Psychosocial models of UV exposure are often based on theories of health behavior, but theory from the body image field can be useful as well. The current study examines models that prospectively predict sunbathing and indoor tanning behaviors using constructs and interrelationships derived from the tripartite theory of body image, theory of reasoned action, health belief model, revised protection motivation theory, and a proposed integration of several health behavior models. The results generally support a model in which intentions mediate the relationship between appearance attitudes and tanning behaviors, appearance reasons to tan and intentions mediate the relationship between sociocultural influences and tanning behaviors, and appearance reasons not to tan and intentions mediate the role of perceived threat on behaviors. The implications of these findings are considered.

BACKGROUND. Skin cancer represents a significant health threat with over 1.3 million diagnoses, 8000 melanoma deaths, and more than $1 billion spent annually for skin cancer healthcare in the US. Despite findings from laboratory, case-control, and prospective studies that indicate a link between youthful indoor tanning (IT) and skin cancer, IT is increasing among US youth. Appearance-focused interventions represent a promising method to counteract these trends. METHODS. A total of 430 female indoor tanners were randomized into intervention or no intervention control conditions. Intervention participants received an appearance-focused booklet based on decision-theoretical models of health behavior. Outcome variables included self-reports of IT behavior and intentions, as well as measures of cognitive mediating variables. RESULTS. Normative increases in springtime IT rates were significantly lower (ie, over 35%) at 6-month follow-up in intervention versus control participants with similar reductions in future intentions. Mediation analyses revealed 6 cognitive variables (IT attitudes, fashion attitudes, perceived susceptibility to skin cancer and skin damage, subjective norms, and image norms) that significantly mediated change in IT behavior. CONCLUSIONS. The appearance-focused intervention demonstrated strong effects on IT behavior and intentions in young indoor tanners. Appearance-focused approaches to skin cancer prevention need to present alternative behaviors as well as alter IT attitudes. Mediational results provide guides for strengthening future appearance-focused interventions directed at behaviors that increase risk of skin cancer.

This study designed and implemented an appearance-based skin cancer prevention intervention in college-aged females. One hundred and forty-seven respondents were randomly assigned to treatment or control groups. Treatment respondents received a short workbook describing the appearance damaging effects of indoor tanning. At short-term follow-up (2 weeks later) treatment respondents had significantly more negative attitudes toward indoor tanning, and reported fewer intentions to indoor tan. At 2-month follow-up, treatment respondents reported indoor tanning one-half as much as control respondents in the previous 2 months. This appearance-based intervention was able to produce clinically significant changes in indoor tanning use tendencies that could have a beneficial effect on the future development of skin cancer.