O câncer de pele pode ser do tipo melanoma ou não melanoma, sendo comum em pessoas acima de 40 anos, de pele clara ou com doenças cutâneas prévias. A incidência do melanoma é baixa, porém, é considerado o mais agressivo e mortal devido ao seu alto poder metastático. A cirurgia ainda é a forma de tratamento mais empregada para a doença, sendo muito invasiva e, portanto, terapias coadjuvantes estão sendo empregadas a fim de melhorar a qualidade de vida dos pacientes, como o laser de baixa potência (LBP). Sabe-se que o LBP pode desencadear efeito bioestimulatório em culturas celulares crescidas sob déficit nutricional, porém em linhagens tumorais sua ação é controversa. Dessa forma, o objetivo desse estudo consiste em investigar os efeitos inibitórios do LBP no comportamento de células de melanoma murino B16F10 e humano SKMEL 37 utilizando um laser de emissão infravermelha (λ = 780 nm) com diferentes densidades de energia. Foram adotados 4 grupos experimentais: G0 (grupo controle), G30 (30 J.cm-2), G90 (90 J.cm-2) e G150 (150 J.cm-2) a fim de verificar a viabilidade celular, através do ensaio de MTT e vermelho neutro; o comportamento de invasão celular, obtido através do ensaio de invasão transwell; e o papel do LBP na expressão do fator de crescimento endotelial vascular (VEGF), verificado através do ensaio imunoenzimático ELISA. Os resultados mostraram que a densidade de energia de 30 J.cm-2 estimulou o comportamento de invasão da linhagem celular B16F10. Por outro lado, o LBP não exerceu influência na expressão do fator de crescimento endotelial vascular, na viabilidade celular, e na atividade mitocondrial de ambas as linhagens celulares, em nenhuma das densidades de energia utilizadas, em comparação ao controle. / Skin cancer can be melanoma or non-melanoma type, being usual in people over 40 years of age, caucasian and with previous skin diseases. Its incidence is low, however, it is considered the most aggressive and fatal due to its great capacity of metastasis. Surgery is the most commonly treatment, nonetheless is highly invasive and therefore coadjuvant therapies, such as low level light (LLL) are being employed to improve patients quality of life. It is known that LLL has a biostimulatory effect in cell cultures growing in nutritional deficit, however in tumor cell lines its effects remain controversial. Thus, the aim of this study is to evaluate the inhibitory effect of LLL on the behavior of murine and human melanoma cells using an infrared LLL (λ = 780nm) delivering different energy densities. For this purpose, four experimental groups were designed: G0 (control group), G30 (30J/cm2), G90 (90J/cm2), G150 (150J/cm2) to verify cell viability by MTT and neutral red assay; the cell invasion behavior, obtained through the transwell invasion assays; and the role of LLL in the vascular endothelial growth factor expression, as verified by the enzyme-linked immunosorbent assay. The results showed that the lowest energy density stimulated the invasion behavior of B16F10 cells. On the other hand, LLL had no influence in the vascular endothelial growth factor expression, cell viability or in the metabolic activity of both cell lines in any energy density used when compared to control group.

Abstract Background: Despite the rise in the occurrence of skin cancer, primary care nurse practitioners are reluctant to perform skin cancer assessments during patient visits. Melanoma is almost always curable if detected in the early stages, but invasive disease accounts for 9,000 deaths per year (American Cancer Society, 2013). Changing knowledge, attitudes and practice regarding skin cancer assessments potentially leads to early detection and treatment of skin cancers and impacts patient outcomes. However, in order to change knowledge and attitudes, we must first assess them. Purpose: The purpose of this research was to validate a new skin cancer assessment tool instrument called KAP-SCA to measure knowledge, attitude, and practice in primary care NPs. Methods: Sequential mixed methods were used. First, focus group interviews with 14 primary care nurse practitioners were conducted during Phase I. Interviews were audio-recorded then transcribed verbatim and imported into ATLAS.ti. Phase II involved instrument development from a blueprint and calculation of content validity indexes (CVI) for items and subscales. Phase III of this study included testing the validity and reliability of a KAP instrument using quantitative methods. This new instrument assesses primary care nurse practitioner knowledge, attitudes, and practice regarding skin cancer assessment. Results: Content validity for the subscales was evaluated by CVI ranged from .90 to .95. The Cronbach's alpha was highest for the practice subscale (alpha =.89) while the lowest was seen with the knowledge subscales (alpha =.50). Construct validity assessed by exploratory factor analysis indicated the presence of three underlying factors, confidence in practice, confidence relating to education and NP role in practice. Implications for Practice: Interventions need to be developed based on the knowledge deficits and barriers to practice identified by these NPs including educational programs that focus on increasing primary care NPs' knowledge and confidence levels regarding skin cancer assessments and identification of malignant lesions. Conclusion: Beginning evidence of validity and reliability were found for the Knowledge, Attitudes and Practice-Skin Cancer Assessments (KAP-SCA), however further studies are warranted.

Understanding the motives for sunbathing and indoor tanning is an extremely important public health issue. 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 in understanding motives to UV expose 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 (Thompson et al., 1999), as well as those from the theory of reasoned action (Ajzen & Fishbein, 1980), health belief model (Rosenstock, 1974), revised protection motivation theory (Rogers, 1983), and a proposed integration of several health behavior models (Fishbein, 2000). 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 yield important information relevant to the understanding of motives to UV expose, which can useful to the development of novel prevention and early intervention programs geared toward the reduction of skin cancer risk.

Over four years from 2002 to 2006, a series of concomitant studies were undertaken to explore the complications and outcomes of skin cancer surgery. Specifically: 1. Through prospective studies, to identify risk factors for bleeding and infectious complications following skin surgery. 2. To determine through a randomized controlled trial whether mupirocin ointment versus paraffin ointment versus no ointment on a wound following skin closure affords the patient benefit. 3. To determine whether patients are at increased post operative bleeding risk should they remain on warfarin and / or aspirin prior to skin surgery. 4. To develop and then trial a novel approach (reducing opposed multilobed [ROM] flap) for below knee wound closures that may reduce the incidence of skin surgery complications on the leg and foot. 5. To investigate whether patients who suffer surgical complications are less likely to be satisfied with the service provision.

Doctor of Philosophy(PhD) / BCC is the commonest cancer in European-derived populations and Australia has the highest recorded incidence in the world, creating enormous individual and societal cost in management of this disease. The incidence of this cancer has been increasing internationally, with evidence of a 1 to 2% rise in incidence in Australia per year over the last two decades. The main four epidemiological risk factors for the development of BCC are ultraviolet radiation (UVR) exposure, increasing age, male sex, and inability to tan. The pattern and timing of UVR exposure is important to BCC risk, with childhood and intermittent UVR exposure both associated with an increased risk. The complex of inherited characteristics making up an individual’s ‘sun sensitivity’ is also important in determining BCC risk. Very little is known about population genetic susceptibility to BCC outside of the rare genodermatosis Gorlin syndrome. Mutations in the tumour suppressor gene patched (PTCH) are responsible for this BCC predisposition syndrome and the molecular pathway and target genes of this highly conserved pathway are well described. Derangments in this pathway occur in sporadic BCC development, and the PTCH gene is an obvious candidate to contribute to non-syndromic susceptibility to BCC. The melanocortin 1 receptor (MC1R) locus is known to be involved in pigmentary traits and the cutaneous response to UVR, and variants have been associated with skin cancer risk. Many other genes have been considered with respect to population BCC risk and include p53, HPV, GSTs, and HLAs. There is preliminary evidence for specific familial aggregation of BCC, but very little known about the causes. 56 individuals who developed BCC under the age of 40 in the year 2000 were recruited from the Skin and Cancer Foundation of Australia’s database. This represents the youngest 7 – 8% of Australians with BCC from a database that captures approximately 10% of Sydney’s BCCs. 212 of their first degree relatives were also recruited, including 89 parents and 123 siblings of these 56 probands. All subjects were interviewed with respect to their cancer history and all reports of cancer verified with histopathological reports where possible. The oldest unaffected sibling for each proband (where available) was designated as an intra-family control. All cases and control siblings filled out a questionnaire regarding their pigmentary and sun sensitivity factors and underwent a skin examination by a trained examiner. Peripheral blood was collected from these cases and controls for genotyping of PTCH. All the exons of PTCH for which mutations have been documented in Gorlin patients were amplified using PCR. PCR products were screened for mutations using dHPLC, and all detectable variants sequenced. Prevalence of BCC and SCC for the Australian population was estimated from incidence data using a novel statistical approach. Familial aggregation of BCC, SCC and MM occurred within the 56 families studied here. The majority of families with aggregation of skin cancer had a combination of SCC and BCC, however nearly one fifth of families in this study had aggregation of BCC to the exclusion of SCC or MM, suggesting that BCCspecific risk factors are also likely to be at work. Skin cancer risks for first-degree relatives of people with early onset BCC were calculated: sisters and mothers of people with early-onset BCC had a 2-fold increased risk of BCC; brothers had a 5-fold increased risk of BCC; and sisters and fathers of people with early-onset BCC had over four times the prevalence of SCC than that expected. For melanoma, the increased risk was significant for male relatives only, with a 10-fold increased risk for brothers of people with early-onset BCC and 3-fold for fathers. On skin examination of cases and controls, several phenotypic factors were significantly associated with BCC risk. These included increasing risk of BCC with having fair, easyburning skin (ie decreasing skin phototype), and with having signs of cumulative sun damage to the skin in the form of actinic keratoses. Signs reflecting the combination of pigmentary characteristics and sun exposure - in the form of arm freckling and solar lentigines - also gave subjects a significantly increased risk BCC. Constitutive red-green reflectance of the skin was associated with decreased risk of BCC, as measured by spectrophotometery. Other non-significant trends were seen that may become significant in larger studies including associations of BCC with propensity to burn, moderate tanning ability and an inability to tan. No convincing trend for risk of BCC was seen with the pigmentary variables of hair or eye colour, and a non-significant reduced risk of BCC was associated with increasing numbers of seborrhoeic keratoses. Twenty PTCH exons (exons 2, 3, 5 to 18, and 20 to 23) were screened, accounting for 97% of the coding regions with published mutations in PTCH. Nine of these 20 exons were found to harbour single nucleotide polymorphisms (SNPs), seen on dHPLC as variant melting curves and confirmed on direct sequencing. SNPs frequencies were not significantly different to published population frequencies, or to Australian general population frequencies where SNP database population data was unavailable. Assuming a Poisson distribution, and having observed no mutations in a sample of 56, we can be 97.5% confident that if there are any PTCH mutations contributing to early-onset BCC in the Australian population, then their prevalence is less than 5.1%. Overall, this study provides evidence that familial aggregation of BCC is occurring, that first-degree relatives are at increased risk of all three types of skin cancer, and that a combination of environmental and genetic risk factors are likely to be responsible. The PTCH gene is excluded as a major cause of this increased susceptibility to BCC in particular and skin cancer in general. The weaknesses of the study design are explored, the possible clinical relevance of the data is examined, and future directions for research into the genetics of basal cell carcinoma are discussed.

Understanding the motives for sunbathing and indoor tanning is an extremely important public health issue. Skin cancer rates have increased dramatically in recent years and UV exposure via sunbathing and utilization of sun lamps and tanning beds are considered important risk factors. Motives for sunbathing and tanning salon use have been thought to be related to appearance concerns, yet little research has examined the specific tan appearance attitudes that may contribute to use of these behaviors. Two studies were conducted with the aim of assessing distinct attitudes related to a tan appearance. In the first study items were created based on a review of the tanning literature and incorporation of constructs developed in the body image field, which were subsequently subject to exploratory factor analysis on 149 female university student sunbathers/tanning salon users.

Malignant cells increase glycolysis and down regulate mitochondrial respiration for ATP production. Mechanisms for respiratory impairment in cancerous cells and their importance for carcinogenesis are not well defined. We found that expression of the respiration-inducing uncoupling protein 3 (UCP3) was normally expressed in murine skin and was greatly decreased in cutaneous malignancies. To better understand the significance of UCP3 in epidermal biology and to test the importance of respiratory changes in cancer development, we generated hemizygous mice expressing a keratin-5 promoter-UCP3 transgene (K5-UCP3). Compared to wild type, K5-UCP3 mice exhibited increased cutaneous mitochondrial respiration, had decreased mitochondrial membrane potential in isolated keratinocytes, and were completely resistant to chemically-induced skin carcinogenesis. We showed that the mechanism of UCP3-dependent cancer protection is most likely not due to increased intracellular heat production or ATP depletion in pre-cancerous cells. Therefore, because hair follicle "bulge" stem cells (bSC) are K5⁺ and progenitors of cutaneous carcinomas, we hypothesized that K5-UCP3 animals were protected from skin carcinogenesis due to alterations in their bSC population. Unlike WT, most (85%) hair follicle bulge regions in K5-UCP3 mice lost biochemical markers of quiescent bSC, but bSC functions were fully intact. Supporting our hypothesis that increased skin turnover protected K5-UCP3 mice from skin cancer; we showed that basal keratinocyte cell cycling was increased 3% in K5-UCP3 skin compared to WT. Moreover, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced similar proliferative responses in both WT and K5-UCP3 skin, but the magnitude of TPA-induced skin thickening was greatly decreased in K5-UCP3 versus WT mice. Together with microarray, histochemical and in vitro morphologic analyses showing that keratinocyte differentiation was sharply increased in K5-UCP3 skin, this implies that UCP3 may increase keratinocyte transit from stem to differentiated daughter cells. Thus, the cancer resistance mechanism in K5-UCP3 mice likely stems from UCP3-induced mitochondrial respiration, which promotes the differentiation and abrogates the tumorigenicity of progenitor keratinocytes. This is the first demonstration in any context that UCP3 blocks carcinogenesis and promotes cellular differentiation. These observations support Warburg's contention that respiratory dysfunction promotes cancer development, and suggest that mitochondrial uncoupling may be a novel target for cancer prevention and treatment. / text

Mutation or inactivation of RB occurs in most human tumors and results in the deregulation of several E2F family transcription factors. Among the E2F family, E2F3 has been implicated as a key regulator of cell proliferation and E2f3 gene amplification and overexpression is detected in some human tumors. To study the role of E2F3a in tumor development, we established a transgenic mouse model expressing E2F3a in a number of epithelial tissues via a keratin 5 (K5) promoter. Transgenic expression of E2F3a leads to hyperproliferation, hyperplasia and increased levels of p53-independent apoptosis in transgenic epidermis. Consistent with data from human cancers, the E2f3a transgene is found to have a weak oncogenic activity on its own and to enhance the response to a skin carcinogenesis protocol. While E2F3a induces apoptosis in the absence of p53, the inactivation of both p53 and p73, but not p73 alone, significantly impairs apoptosis induced by E2F3a. This suggests that both p53 and p73 contribute to E2F3a induced apoptosis but that their function is compensatory. Even though data suggest that E2F3a carries out its unique apoptotic activity in part through another E2F family member E2F1, unlike E2F1, the ARF tumor suppressor is required for E2F3a-induced apoptosis. While both E2F3a and E2F1 require ATM for apoptosis, E2F3a activates ATM through a distinct mechanism from E2F1. The overexpression of E2F3a results in the accumulation of DNA damage in K5 transgenic keratinocytes and normal human fibroblasts (NHFs). In response to this, the DNA damage checkpoint kinase ATM is activated, and phosphorylation of the downstream targets p53 and the histone variant H2AX are significantly increased. Additional studies show that increased Cdk activity and aberrant DNA replication contributes to DNA damage, ATM activation and apoptosis in response to deregulated E2F3a, which suggest that aberrant replication imposed by deregulated E2F3a plays an important role in the activation of the ATM DNA damage response pathway. Activation of ATM by E2F3a is not affected by loss of ARF or E2F1. Meanwhile, E2F3a-induced ARF upregulation is not affected by E2F1 loss. The above results indicate that E2F3a engages several parallel pathways involving E2F1, ARF and the ATM kinase, and these pathways cooperate to promote apoptosis.

No description available.

Background: Skin cancer is one of the most preventable forms of cancer yet for certain types of skin cancers, it can be fatal if it goes untreated. While ultraviolet radiation is the main cause of skin cancer, there are several other risk factors, including sunburn history, smoking, environmental pollutants, family history, personal history, and skin color. Practicing sun protection behaviors and receiving regular skin cancer screenings can prevent the cancer from ever developing. This study examines the demographic and socioeconomic status risk factors for skin cancer. Methods: The Health Information National Trends Survey data was used from 2005. Using this secondary dataset, chi-square analysis was performed to determine the prevalence of skin cancer within the demographic categories of age and race/ethnicity as well as socioeconomic status indicators educational attainment, annual household income, employment status, and marital status. Univariate and multivariate analyses were performed to determine the correlations of the variables with skin cancer. A p-value of 0.05 and a 95% confidence interval were maintained throughout the analyses to determine any statistical significance. Results: Of the 3,804 respondents who answered the question related to cancer diagnosis, 226 indicated they had a positive skin cancer diagnosis, which was 5.94% of the total sample. Skin cancer and increased age were consistently associated (χ2 (2) = 171.5, p<.001). The skin cancer peak prevalence was for all those respondents aged 65 and older. Higher educational attainment and higher annual household income were associated with greater likelihood of skin cancer. Conclusions: This study revealed that skin cancer is significantly associated with increased age, higher educational attainment, and higher annual household income. Implementing consistent screening practices and targeted behavioral interventions are important areas for health focus in the future.