Complementary and alternative therapies in skin cancer a literature review of biologically active compounds.

Complementary and alternative medicine or therapies (CAM) are frequently used by skin cancers patients. Patient's self-administration of CAM in melanoma can reach up to 40%-50%. CAMs such as botanical agents, phytochemicals, herbal formulas ("black salve") and cannabinoids, among others, have been described in skin cancer patients. The objective of this review article was to acknowledge the different CAM for skin cancers through the current evidence, focusing on biologically active CAM rather than mind-body approaches. We searched MEDLINE database for articles published through July 2022, regardless of study design. Of all CAMs, phytochemicals have the best in vitro evidence-supporting efficacy against skin cancer including melanoma; however, to date, none have proved efficacy on human patients. Of the phytochemicals, Curcumin is the most widely studied. Several findings support Curcumin efficacy in vitro through various molecular pathways, although most studies are in the preliminary phase. In addition, the use of alternative therapies is not exempt of risks physicians should be aware of their adverse effects, interactions with standard treatments, and possible complications arising from CAM usage. There is emerging evidence for CAM use in skin cancer, but no human clinical trials support the effectiveness of any CAM in the treatment of skin cancer to date. Nevertheless, patients worldwide frequently use CAM, and physicians should educate themselves on currently available CAMs.

Bee pollen in zebrafish diet affects intestinal microbiota composition and skin cutaneous melanoma development.

Bee pollen is recommended as dietary supplement due to immunostimulating functions including antioxidant, anti-inflammatory and anti-carcinogenic properties. Nevertheless, the effectiveness of such properties is still not well understood. As diet can be associated with animal performance, microbiota modulation and potentially factor for cancer, this study aimed to analyze if bee pollen could influence growth, gut microbial and skin cutaneous melanoma development in zebrafish. Control diets based on commercial flakes and Artemia were compared with the same diet supplemented with bee pollen. Fish weight gain, increased length, intestinal bacteria metagenomics analysis, serum amyloid A gene expression and cutaneous melanoma transplantation assays were performed. Bee pollen affected microbiota composition and melanoma development. Differential abundance revealed higher abundance in the control group for Aeromonadaceae family, Aeromonas and Pseudomonas genus, A. sobria, A. schubertii, A. jandaei and P. alcaligenes species compared with pollen diet group. Pollen group presented higher abundance for Chromobacterium genus and for Gemmobacter aquaticus, Flavobacterium succinicans and Bifidobacterium breve compared with control group. Unexpectedly, fish fed with bee pollen showed higher tumor growth rate and larger tumor size than control group. This is the first study to report intestinal microbial changes and no protective cancer properties after bee pollen administration.

Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis.

Melanoma is the most aggressive and fatal type of skin cancer due to being highly proliferative. Acetylsalicylic acid (ASA; Aspirin) and salicylic acid (SA) are ancient drugs with multiple applications in medicine. Here, we showed that ASA and SA present anticancer effects against a murine model of implanted melanoma. These effects were also validated in 3D- and 2D-cultured melanoma B16F10 cells, where the drugs promoted pro-apoptotic effects. In both in vivo and in vitro models, SA and ASA triggered endoplasmic reticulum (ER) stress, which culminates with the upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). These effects are initiated by ASA/SA-triggered Akt/mTOR/AMPK-dependent activation of nitric oxide synthase 3 (eNOS), which increases nitric oxide and reactive oxygen species production inducing ER stress response. In the end, we propose that ASA and SA instigate anticancer effects by a novel mechanism, the activation of ER stress.

The molecular clock in the skin, its functionality, and how it is disrupted in cutaneous melanoma: a new pharmacological target?

The skin is the interface between the organism and the external environment, acting as its first barrier. Thus, this organ is constantly challenged by physical stimuli such as UV and infrared radiation, visible light, and temperature as well as chemicals and pathogens. To counteract the deleterious effects of the above-mentioned stimuli, the skin has complex defense mechanisms such as: immune and neuroendocrine systems; shedding of epidermal squamous layers and apoptosis of damaged cells; DNA repair; and pigmentary system. Here we have reviewed the current knowledge regarding which stimuli affect the molecular clock of the skin, the consequences to skin-related biological processes and, based on such knowledge, we suggest some therapeutic targets. We also explored the recent advances regarding the molecular clock disruption in melanoma, its impact on the carcinogenic process, and its therapeutic value in melanoma treatment.

Skin cancer incidence in rural workers at a reference hospital in western Paraná.

BACKGROUND: Skin cancer is common in Brazil and is related to sun exposure, among other risk factors. There are no data on the incidence of malignant skin neoplasm in rural workers in western Paraná. OBJECTIVE: To analyze the incidence and profile of rural workers who were diagnosed with skin cancer at a reference service in Cascavel, western Paraná, in the last five years (2011-2016). METHODS: This retrospective cross-sectional study was carried out through a review of the anatomopathological reports of rural workers diagnosed with skin cancer at Cascavel Oncology Center (CEONC), in Cascavel. The following variables were collected: year of diagnosis, age, gender, injury location and histological subtype. RESULTS: A total of 681 cases of malignant epithelial neoplasia were identified, with a higher frequency in the 61-70 age group. Data analysis showed an increase of about 210% in the occurrence of skin cancers in the last 5 years. The cephalic region was the most affected, and the most common histological subtype was nodular basal cell carcinoma. There was no association between gender and location. STUDY LIMITATIONS: This is a retrospective study and analysis of a secondary data bank. CONCLUSION: This study is a regional estimation of the incidence of cutaneous neoplasms and provides evidence of a considerable increase in the number of diagnoses in rural workers from western Paraná, Brazil. Moreover, it is possible to conclude that the sample group studied is at risk of developing skin cancer.

Skin cancer incidence in rural workers at a reference hospital in western Paraná

Abstract BACKGROUND: Skin cancer is common in Brazil and is related to sun exposure, among other risk factors. There are no data on the incidence of malignant skin neoplasm in rural workers in western Paraná. OBJECTIVE: To analyze the incidence and profile of rural workers who were diagnosed with skin cancer at a reference service in Cascavel, western Paraná, in the last five years (2011-2016). METHODS: This retrospective cross-sectional study was carried out through a review of the anatomopathological reports of rural workers diagnosed with skin cancer at Cascavel Oncology Center (CEONC), in Cascavel. The following variables were collected: year of diagnosis, age, gender, injury location and histological subtype. RESULTS: A total of 681 cases of malignant epithelial neoplasia were identified, with a higher frequency in the 61-70 age group. Data analysis showed an increase of about 210% in the occurrence of skin cancers in the last 5 years. The cephalic region was the most affected, and the most common histological subtype was nodular basal cell carcinoma. There was no association between gender and location. STUDY LIMITATIONS: This is a retrospective study and analysis of a secondary data bank. CONCLUSION: This study is a regional estimation of the incidence of cutaneous neoplasms and provides evidence of a considerable increase in the number of diagnoses in rural workers from western Paraná, Brazil. Moreover, it is possible to conclude that the sample group studied is at risk of developing skin cancer.

Ultraviolet radiation induces Melan-A-expressing cells in interfollicular epidermis in wild-type mice.

Adult wild-type mice are not supposed to be proper models for ultraviolet radiation (UVR)-induced melanoma since melanocytes are confined to hair follicles and cannot be sufficiently reached by UVR. On the other hand, in mutated mouse models used for melanoma research limitations, including an altered immune system and selection of affected pathways, lead to tumors phenotypically quite different from naturally occurring melanomas. We compared the distribution of epidermal melanocytes in UVR and not-UVR-exposed wild-type C57BL/6 mice. Starting at the age of 8 weeks, mice were exposed to physiologic doses of UVR three times weekly over 16 weeks. Back skin biopsies were taken 4, 8, 12 and 16 weeks after initiation of exposure, and stained for Melan-A, representing a highly selective marker for melanocytes. Surprisingly, after exposure to UVR, Melan-A positive cells were detected also in the interfollicular epidermis of C57BL/6 mice. We conclude that UVR is capable of inducing interfollicular epidermal melanocytes in wild-type mice.

Use of sunscreen and risk of melanoma and non-melanoma skin cancer: a systematic review and meta-analysis.

The use of sunscreen is a key component of public health campaigns for skin cancer prevention, but epidemiological studies have raised doubts on its effectiveness in the general population. This systematic review and meta-analysis aimed to assess the association between risk of skin cancer and sunscreen use. We searched PubMed, BIREME and Google Scholar from inception to May 17, 2017, to identify observational studies and controlled trials. We used a random-effects model for conventional and cumulative meta-analyses. We included 29 studies (25 case-control, two cohort, one cross-sectional, and one controlled trial) involving 313,717 participants (10,670 cases). The overall meta-analysis did not show a significant association between skin cancer and sunscreen use (odds ratio (OR) = 1.08; 95% CI: 0.91-1.28, I2 = 89.4%). Neither melanoma (25 studies; 9,813 cases) nor non-melanoma skin cancer (five studies; 857 cases) were associated with sunscreen use, with a pooled OR (95% CI) of 1.10 (0.92-1.33) and 0.99 (0.62-1.57), respectively. The cumulative evidence before the 1980s showed a relatively strong positive association between melanoma and sunscreen use (cumulative OR: 2.35; 95% CI: 1.66-3.33). The strength of the association between risk of skin cancer and sunscreen use has constantly decreased since the early 1980s, and the association was no longer statistically significant from the early 1990s. While the current evidence suggests no increased risk of skin cancer related to sunscreen use, this systematic review does not confirm the expected protective benefits of sunscreen against skin cancer in the general population.

A skin cancer prevention photoageing intervention for secondary schools in Brazil delivered by medical students: protocol for a randomised controlled trial.

INTRODUCTION: The incidence of melanoma is increasing faster than any other major cancer both in Brazil and worldwide. The Southeast of Brazil has especially high incidences of melanoma, and early detection is low. Exposure to UV radiation represents a primary risk factor for developing melanoma. Increasing attractiveness is a major motivation for adolescents for tanning. A medical student-delivered intervention that harnesses the broad availability of mobile phones as well as adolescents' interest in their appearance may represent a novel method to improve skin cancer prevention. METHODS AND ANALYSIS: We developed a free mobile app (Sunface), which will be implemented in at least 30 secondary school classes, each with 21 students (at least 30 classes with 21 students for control) in February 2018 in Southeast Brazil via a novel method called mirroring. In a 45 min classroom seminar, the students' altered three-dimensional selfies on tablets are 'mirrored' via a projector in front of their entire class, showing the effects of unprotected UV exposure on their future faces. External block randomisation via computer is performed on the class level with a 1:1 allocation. Sociodemographic data, as well as skin type, ancestry, UV protection behaviour and its predictors are measured via a paper-pencil questionnaire before as well as at 3 and 6 months postintervention. The primary end point is the group difference in the 30-day prevalence of daily sunscreen use at a 6-month follow-up. Secondary end points include (1) the difference in daily sunscreen use at a 3-month follow-up, (2) if a self-skin examination in accordance with the ABCDE rule was performed within the 6-month follow-up and (3) the number of tanning sessions. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committee of the University of Itauna. Results will be disseminated at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03178240; Pre-results.

Uso de cámaras de bronceado y cáncer de piel / Indoor tanning and skin cancer

ResumenEl cáncer de piel es la neoplasia más frecuente en Costa Rica.La constante exposición a luz ultravioleta es un factor de riesgo ampliamente reconocido para este cáncer.Las cámaras de bronceado que emiten radiación UV fueron clasificadas por un grupo de investigadores, IARC “International Agency for Research on Cáncer” como Grupo 1 “Cancerígeno para humanos”.El riesgo de melanoma aumenta en un 75% cuando las cámaras de bronceado son utilizadas en edades tempranas.Las campañas de salud enfocadas en foto protección han tenido un importante impacto en la prevención del cáncer de piel. Sin embargo, aún es necesario dar a conocer a la población general sobre la relación directa que existe entre el uso de fuentes artificiales de radiación ultravioleta (como cámaras de bronceado) con la aparición de cáncer de piel melanoma y no melanoma.

AbstractSkin cancer is the most common malignancy in Costa Rica.Constant exposure to ultraviolet light is a widely recognized risk factor for this neoplasm. Indoor tanning chambers that emit UV radiation were classified as Group 1 "Carcinogenic for humans" by the “International Agency for Research on Cancer” (IARC).The risk of melanoma increases in a 75% when the tanning beds are used in early ages.Health campaigns focused photo protective measures have had an important impact on skin cancer prevention.However, it is still necessary to inform general population about the direct relationship between the use of artificial sources of ultraviolet radiation like in tanning beds, with the development of melanoma and non-melanoma cancer.

A prospective study of patients with large congenital melanocytic nevi and the risk of melanoma.

BACKGROUND:: Large congenital melanocytic nevus (LCMN) is considered a risk factor for melanoma, although the magnitude of this risk is controversial. OBJECTIVE:: To evaluate the risk of melanoma development in patients with LCMN seen at a dermatology referral center in Brazil during a twelve-year period. To the best of our knowledge, there are no published similar studies on large congenital melanocytic nevus in South America. METHODS:: Our prospective cohort included only patients with congenital nevi ≥20cm. The cumulative risk of developing melanoma and the standardized morbidity ratio were calculated for patients followed up prospectively for at least 1 month. RESULTS:: Sixty-three patients were enrolled in this study. One patient who developed melanoma prior to enrollment was excluded, and five were eliminated because of insufficient follow-up time. Mean follow-up for the remaining 57 patients was 5.5 years (median 5.2 years). Median age of entry into the study was 2.6 years. Most patients (75.4%) underwent only clinical observation. Melanomas occurred in 2 (3.5%) patients. Five-year cumulative risk for melanoma was 4.8% (95% CI: 1.9-11.5%). Standardized morbidity ratio was 1584 (95% CI: 266-5232, p<0.001). STUDY LIMITATIONS:: The small sample size reduces the accuracy of risk estimates. CONCLUSIONS:: This study analyzed prospectively for the first time data from South America demonstrating that patients with LCMN have a higher risk of developing melanoma than the general population (p<0.001).

A prospective study of patients with large congenital melanocytic nevi and the risk of melanoma

Abstract: Background: Large congenital melanocytic nevus (LCMN) is considered a risk factor for melanoma, although the magnitude of this risk is controversial. Objective: To evaluate the risk of melanoma development in patients with LCMN seen at a dermatology referral center in Brazil during a twelve-year period. To the best of our knowledge, there are no published similar studies on large congenital melanocytic nevus in South America. Methods: Our prospective cohort included only patients with congenital nevi ≥20cm. The cumulative risk of developing melanoma and the standardized morbidity ratio were calculated for patients followed up prospectively for at least 1 month. Results: Sixty-three patients were enrolled in this study. One patient who developed melanoma prior to enrollment was excluded, and five were eliminated because of insufficient follow-up time. Mean follow-up for the remaining 57 patients was 5.5 years (median 5.2 years). Median age of entry into the study was 2.6 years. Most patients (75.4%) underwent only clinical observation. Melanomas occurred in 2 (3.5%) patients. Five-year cumulative risk for melanoma was 4.8% (95% CI: 1.9-11.5%). Standardized morbidity ratio was 1584 (95% CI: 266-5232, p<0.001). Study limitations: The small sample size reduces the accuracy of risk estimates. Conclusions: This study analyzed prospectively for the first time data from South America demonstrating that patients with LCMN have a higher risk of developing melanoma than the general population (p<0.001).

Cutaneous melanoma attributable to solar radiation in Cali, Colombia.

Estimating the population attributable fraction (PAF) of melanomas due to sun exposure is challenging as there are no unexposed population nor reliable exposure data. In high incidence countries, a historic cohort of the South Thames cancer registry was used as a minimally exposed population using the formula PAF = (observed incidence-incidence in minimally exposure)/observed incidence. In this study, we apply this method, constructing a minimally exposed cohort for Colombia and also using the historical South Thames data, using melanoma incidence data from the population-based cancer registry of Cali, Colombia for the period 1967-2012. The historic cohort incidence rates were very similar to those of Thames, but cohort effects were smaller for women and nonexistent for men. Age-specific incidence rates of these minimally exposed cohorts were applied to recent population numbers. For females, PAFs were 19% using the historic Thames cohort and 25% using the historic Cali cohort, corresponding numbers for males were 62% (vs. Thames) and 0% (vs. Cali). Taking into account the incidence rates of acral melanomas, which are not sun related, the PAF increased in women to 26% (vs. Thames) and 34% (vs. Cali) and for men 77% (vs. Thames). This exercise shows the modest contribution of exposure to ultraviolet radiation in the burden of melanoma in low-incidence countries, as well as the importance to take into consideration the acral lentiginous melanomas.

Medium-sized congenital melanocytic nevus of the forehead, glabella and temple – surgical treatment and long-term follow-up.

Congenital melanocytic nevi can be stigmatising for the patient. Larger nevi bear an increased risk for melanoma development. Large congenital melanocytic nevi may be a symptom of neurocutaneous melanosis. We report on a 5-year-old boy with an extensive hair-bearing facial congenital melanocytic nevus, covering forehead, glabella and temple region associated with unilateral brow and blepharoptosis. The lesion was excised en bloc. The resulting defect had been closed by full thickness skin graft. Healing was unremarkable and long-term follow-up over 13 years demonstrated a satisfying esthetic and functional outcome. There was no evidence of melanoma development. Surgery is an option for disfiguring larger congenital melanocytic nevi as long as esthetics and function can be preserved. Long-term follow-up is recommended due to the increased risk of melanoma.

Occupational skin cancer: Systematic review.

OBJECTIVE: To analyze the epidemiological profile, risk factors in the workplace environment and prevention methods for professionals at risk of skin cancer. METHOD: A systematic review of articles on occupational skin cancer, published in the Lilacs, Scielo, Medline and Cochrane Library from January 1st, 2008, to December 31st, 2013, was performed. The search included the following terms: "neoplasias cutâneas" (DeCS), "exposição ocupacional" (DeCS), "epidemiologia" (DeCS) as well as the keyword "prevenção", and their equivalents in English. RESULTS: After analyzing the titles and summaries of articles, the search strategy resulted in 83 references, of which 22 articles met the eligibility criteria. DISCUSSION: We found that sun exposure is the main occupational risk factor for skin cancer, causing outdoor workers to be the most vulnerable to developing occupational skin cancer. Professionals with low levels of education and European descent are at increased risk of developing this cancer. CONCLUSION: Outdoor workers are more vulnerable to developing occupational skin cancer, estimating that professionals with low level of education and European descent are at increased risk of developing this cancer. Therefore, companies need to invest more in the health of workers by providing protective equipment and thus preventing occupational skin cancer.

Occupational skin cancer: Systematic review / Câncer de pele ocupacional: revisão sistemática

SUMMARY Objective: To analyze the epidemiological profile, risk factors in the workplace environment and prevention methods for professionals at risk of skin cancer. Method: A systematic review of articles on occupational skin cancer, published in the Lilacs, Scielo, Medline and Cochrane Library from January 1st, 2008, to December 31st, 2013, was performed. The search included the following terms: “neoplasias cutâneas” (DeCS), “exposição ocupacional” (DeCS), “epidemiologia” (DeCS) as well as the keyword “prevenção”, and their equivalents in English. Results: After analyzing the titles and summaries of articles, the search strategy resulted in 83 references, of which 22 articles met the eligibility criteria. Discussion: We found that sun exposure is the main occupational risk factor for skin cancer, causing outdoor workers to be the most vulnerable to developing occupational skin cancer. Professionals with low levels of education and European descent are at increased risk of developing this cancer. Conclusion: Outdoor workers are more vulnerable to developing occupational skin cancer, estimating that professionals with low level of education and European descent are at increased risk of developing this cancer. Therefore, companies need to invest more in the health of workers by providing protective equipment and thus preventing occupational skin cancer.

RESUMO Objetivo: analisar o perfil epidemiológico, os fatores de risco no ambiente de trabalho e os métodos de prevenção dos profissionais de risco para câncer de pele. Método: foi realizada uma revisão sistemática de artigos sobre o câncer de pele ocupacional, publicados entre 1 de janeiro de 2008 e 31 de dezembro de 2013, nas bases de dados Lilacs, Scielo, Medline e Biblioteca Cochrane. A pesquisa baseou-se na intersecção dos seguintes termos: “neoplasias cutâneas” (DeCS), “exposição ocupacional” (DeCS), “epidemiologia” (DeCS) e a palavra-chave “prevenção” e seus equivalentes em inglês. Resultados: após a análise dos títulos e resumos dos artigos, a estratégia de busca resultou em 83 referências, das quais 22 artigos preencheram os critérios de elegibilidade. Discussão: a exposição solar é o principal fator de risco ocupacional para câncer de pele e os trabalhadores ao ar livre são os mais vulneráveis a desenvolvê-lo. Aqueles com baixo nível de escolaridade e ascendência europeia apresentam maior risco de desenvolver a neoplasia. Conclusão: os trabalhadores ao ar livre são mais vulneráveis a desenvolver câncer de pele ocupacional. Os profissionais com baixo nível de escolaridade e ascendência europeia apresentam maior risco de desenvolver a neoplasia. São necessários mais investimentos das empresas na saúde dos trabalhadores por meio de fornecimento de equipamentos de proteção, a fim de prevenir o câncer de pele ocupacional.

Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.

OBJECTIVE: The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders. METHODS: A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. RESULTS: Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). CONCLUSIONS: The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II.

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed?