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1.
JMIR Serious Games ; 9(1): e24652, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33764308

RESUMEN

BACKGROUND: Public health sun safety campaigns introduced during the 1980s have successfully reduced skin cancer rates in Australia. Despite this success, high rates of sunburn continue to be reported by youth and young adults. As such, new strategies to reinforce sun protection approaches in this demographic are needed. OBJECTIVE: This study aims to develop a virtual reality (VR) game containing preventive skin cancer messaging and to assess the safety and satisfaction of the design based on end user feedback. METHODS: Using a two-phase design approach, we created a prototype VR game that immersed the player inside the human body while being confronted with growing cancer cells. The first design phase involved defining the problem, identifying stakeholders, choosing the technology platform, brainstorming, and designing esthetic elements. In the second design phase, we tested the prototype VR experience with stakeholders and end users in focus groups and interviews, with feedback incorporated into refining and improving the design. RESULTS: The focus groups and interviews were conducted with 18 participants. Qualitative feedback indicated high levels of satisfaction, with all participants reporting the VR game as engaging. A total of 11% (2/8) of participants reported a side effect of feeling nauseous during the experience. The end user feedback identified game improvements, suggesting an extended multistage experience with visual transitions to other environments and interactions involving cancer causation. The implementation of the VR game identified challenges in sharing VR equipment and hygiene issues. CONCLUSIONS: This study presents key findings highlighting the design and implementation approaches for a VR health intervention primarily aimed at improving sun protection behaviors. This design approach can be applied to other health prevention programs in the future.

3.
JMIR Dermatol ; 4(1): e24653, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37632801

RESUMEN

BACKGROUND: Photography using a UV transmitting filter allows UV light to pass and can be used to illuminate UV blocking lotions such as sunscreens. OBJECTIVE: The aim of this study is to compare currently available UV photography cameras and assess whether these devices can be used as visualization tools for adequate coverage of sun protection lotions. METHODS: This study was conducted in 3 parts: in phase 1, 3 different UV cameras were tested; in phase 2, we explored whether UV photography could work on a range of sun protection products; and in phase 3, a UV webcam was developed and was field-tested in a beach setting. In phase 1, volunteers were recruited, and researchers applied 3 sun protection products (ranging from sun protection factor [SPF] 15 to 50+) to the participants' faces and arms. UV photography was performed using 3 UV cameras, and the subsequent images were compared. In phase 2, volunteers were recruited and asked to apply their own SPF products to their faces in their usual manner. UV photographs were collected in the morning and afternoon to assess whether the coverage remained over time. Qualitative interviews were conducted to assess the participants' level of satisfaction with the UV image. In phase 3, a small portable UV webcam was designed using a plug-and-play approach to enable the viewing of UV images on a larger screen. The developed webcam was deployed at a public beach setting for use by the public for 7 days. RESULTS: The 3 UV camera systems tested during phase 1 identified the application of a range of sun protection lotions of SPF 15 to 50+. The sensitivity of the UV camera devices was shown to be adequate, with SPF-containing products applied at concentrations of 2 and 1 mg/cm2 clearly visible and SPF-containing products applied at a concentration of 0.4 mg/cm2 having lower levels of coverage. Participants in phase 2 reported high satisfaction with the UV photography images, with 83% (29/35) of participants likely to use UV photography in the future. During phase 2, it was noted that many participants used tinted SPF-containing cosmetics, and several tinted products were further tested. However, it was observed that UV photography could not identify the areas missed for all tinted products. During phase 3, the electrical components of the UV webcam remained operational, and the camera was used 233 times by the public during field-testing. CONCLUSIONS: In this study, we found that UV photography could identify the areas missed by sun protection lotions with chemical filters, and participants were engaged with personalized feedback. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619000975190; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377089 ; Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619000145101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376672.

4.
JMIR Public Health Surveill ; 6(4): e22305, 2020 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-33006559

RESUMEN

BACKGROUND: Hand hygiene is one of the most effective ways to remove germs, prevent the spread of infectious pathogens, and avoid getting sick. Since the COVID-19 pandemic began, health authorities have been advocating good hand hygiene practices. OBJECTIVE: The primary aim of this study is to field test a prototype smart handwashing station deployed in a school setting during the COVID-19 pandemic. METHODS: We deployed a smart handwashing station and examined key technological considerations including connectivity, security, and data management systems, as well as the health and safety of users. RESULTS: The smart handwashing station was deployed for 10 days in a school setting in Australia during the COVID-19 pandemic. The smart handwashing station's electrical components remained operational during field testing and underwent robust cleaning protocols each day. The handwashing station was used 1138 times during the field test and there was no COVID-19 transmission at the school during the testing. CONCLUSIONS: This study demonstrates that a personalized feedback approach using technology can successfully be implemented at a school and can provide a platform to improve hand hygiene among school-aged children.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Desinfección de las Manos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Instituciones Académicas , Australia/epidemiología , COVID-19 , Niño , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología
5.
JMIR Mhealth Uhealth ; 8(9): e21243, 2020 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-32936083

RESUMEN

BACKGROUND: Australia and New Zealand have the highest skin cancer incidence rates worldwide, and sun exposure is the main risk factor for developing skin cancer. Sun exposure during childhood and adolescence is a critical factor in developing skin cancer later in life. OBJECTIVE: This study aims to test the effectiveness of wearable UV sensors to increase sun protection habits (SPH) and prevent sunburn in adolescents. METHODS: During the weeklong school leavers outdoor festival (November 2019) at the Gold Coast, Australia, registered attendees aged 15-19 years were recruited into the field study. Participants were provided with a wearable UV sensor and free sunscreen. The primary outcome was sun exposure practices using the SPH index. Secondary outcomes were self-reported sunburns, sunscreen use, and satisfaction with the wearable UV sensor. RESULTS: A total of 663 participants were enrolled in the study, and complete data were available for 188 participants (188/663, 28.4% response rate). Participants provided with a wearable UV sensor significantly improved their use of sunglasses (P=.004) and sunscreen use both on the face (P<.001) and on other parts of the body (P=.005). However, the use of long-sleeve shirts (P<.001) and the use of a hat (P<.001) decreased. During the study period, 31.4% (59/188) of the participants reported receiving one or more sunburns. Satisfaction with the wearable UV sensor was high, with 73.4% (138/188) of participants reporting the UV sensor was helpful to remind them to use sun protection. CONCLUSIONS: Devices that target health behaviors when outdoors, such as wearable UV sensors, may improve use of sunscreen and sunglasses in adolescents.


Asunto(s)
Vacaciones y Feriados , Dispositivos Electrónicos Vestibles , Adolescente , Femenino , Humanos , Masculino , Adulto Joven , Australia/epidemiología , Nueva Zelanda
6.
Prev Med Rep ; 19: 101166, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32714780

RESUMEN

Sunscreen is a popular form of sun protection and when applied sufficiently (2 mg/cm2) has been shown to block the harmful molecular effects of ultraviolet radiation (UV). This field study tested the effectiveness of UV detection stickers to improve sunscreen use. During a rugby league two-day sporting event (28-29 February 2020) in Queensland, Australia interested players 14-18 years old were provided with access to free sunscreen on DAY-1 and during the subsequent day (DAY-2) were provided with a free UV detection sticker and access to sunscreen. On DAY-2, one UV detection sticker was handed out to 550 attendees. The sunscreen bottles were weighted periodically by research staff throughout both event days. Primary outcomes were sunscreen usage. Overall, 868 g of sunscreen was used across both DAY-1 and DAY-2, with 19% (167 g) of sunscreen used on DAY-1 and 81% (701 g) of sunscreen used on DAY-2. This resulted in a >3-fold improvement in sunscreen use on DAY-2 when the UV detection stickers were provided. We found UV detection stickers may improve use of sunscreen in adolescents during sporting events in high UV environments.

7.
J Med Internet Res ; 22(5): e17079, 2020 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-32463378

RESUMEN

BACKGROUND: Skin cancer is the most prevalent but also most preventable cancer in Australia. Outdoor workers are at increased risk of developing skin cancer, and improvements in sun protection are needed. Sunscreen, when applied at the recommended concentration (2 mg/cm2), has been shown to block the harmful molecular effects of ultraviolet radiation in vivo. However, sunscreen is often not applied, reapplied sufficiently, or stored adequately to yield protection and reduce sunburns. OBJECTIVE: The primary aim of this study was to test an Internet of Things approach by deploying a smart sunscreen station to an outdoor regional mining site. METHODS: We deployed a smart sunscreen station and examined the key technological considerations including connectivity, security, and data management systems. RESULTS: The smart sunscreen station was deployed for 12 days at a mining workplace (Dalby, Australia). The smart sunscreen station's electrical components remained operational during field testing, and data were received by the message queuing telemetry transport server automatically at the end of each day of field testing (12/12 days, 100% connectivity). CONCLUSIONS: This study highlights that an Internet of Things technology approach can successfully measure sunscreen usage and temperature storage conditions.


Asunto(s)
Internet de las Cosas/normas , Neoplasias Cutáneas/prevención & control , Protectores Solares/uso terapéutico , Femenino , Humanos , Masculino , Prueba de Estudio Conceptual
8.
Prev Med ; 124: 67-74, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31077722

RESUMEN

Sunscreen when applied at the recommended concentration (2 mg/cm2) has been shown to block the harmful molecular effects of ultraviolet radiation (UVR) in vivo. In real world conditions, however, sunscreen is often not applied/reapplied sufficiently to yield protection. This field study tested the effectiveness of UV detection stickers to prevent sunburn and improve reapplication of sunscreen. During the Ashes Cricket Test match event (November 2017) in Brisbane, Australia interested spectators were recruited into the control group on DAY-1 and during subsequent days (DAY-2, DAY-3, DAY-4) new participants were recruited into the UV-Sticker group. Participants in both groups were provided with free sunscreen and participants in the UV-Sticker group were additionally provided with a UV detection sticker. Primary outcomes were self-reported sunburns and reapplication of sunscreen. Secondary endpoints included satisfaction with the UV detection stickers. 813 participants enrolled in the study, and complete data is available for 428 participants (52.6% response rate, n = 369 UV detection sticker, n = 59 control). Participants provided with a UV detection sticker were more likely to re-apply sunscreen than controls (80% vs 68%, p = 0.04); but do not reduce sunburn rates. UV detection stickers may improve sunscreen re-application in a high UV-environment. Trial registration: Australian and New Zealand clinical trials register (ACTRN12617001572358).


Asunto(s)
Promoción de la Salud , Melanoma/prevención & control , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control , Protectores Solares/uso terapéutico , Rayos Ultravioleta/efectos adversos , Adulto , Australia , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
9.
JMIR Mhealth Uhealth ; 6(11): e199, 2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-30487115

RESUMEN

BACKGROUND: Skin cancer is the most prevalent and most preventable cancer in Australia. Despite Australia's long-running public health campaigns, young Australian adults continue to report high levels of ultraviolet radiation (UVR) exposure and frequent sunburns. Young people are now increasingly turning away from traditional media, such as newspapers and TV, favoring Web-based streaming, which is challenging the health care sector to develop new ways to reach this group with targeted, personalized health promotion messages. Advances in technology have enabled delivery of time- and context-relevant health interventions. OBJECTIVE: The primary aim of this randomized controlled trial was to test the effect of UVR feedback from a smartphone app or a UVR dosimeter feedback device on sun protection habits, sun exposure behaviors, sunburn, and physical activity levels in young adults. METHODS: Young adults aged 18-35 years (n=124) were recruited from Queensland, Australia, between September 2015 and April 2016, via social or traditional media campaigns and outreach activities in the local community. Participants were randomized into 3 groups for a 4-week intervention: (1) no intervention control group; (2) UVR monitor group, who were asked to wear a UVR dosimeter feedback device set to their skin type; and (3) a SunSmart app group, who were asked to download and use the SunSmart phone app. Data were self-assessed through Web-based surveys at baseline and 1 week and 3 months postintervention. RESULTS: Complete data were available for 86.2% (107/124) of participants (control group, n=36; UVR monitor group, n=36; and SunSmart app group, n=35). Intervention uptake in the UVR monitor group was high, with 94% (34/36) of participants using the device all or some of the time when outdoors. All SunSmart app group participants downloaded the app on their smartphone. There was no significant difference in the change in the sun protection habits (SPH) index (main outcome measure) across the 3 groups. However, compared with the control group, a significantly greater proportion of the participants in the UVR monitor group reduced their time unprotected and exposed to UVR on weekends during the intervention compared with the baseline (odds ratio [OR]: 2.706, 95% CI 1.047-6.992, P=.04). This significant effect was sustained with greater reductions observed up to 3 months postintervention (OR: 3.130, 95% CI 1.196-8.190, P=.02). There were no significant differences between the groups in weekday sun exposure, sunscreen use, sunburn, suntan, or physical activity. CONCLUSIONS: Using technology such as apps and personal UVR monitoring devices may improve some sun exposure behaviors among young adults, but as the SPH index did not increase in this study, further research is required to achieve consistent uptake of sun protection in young people. TRIAL REGISTRATION: The Australian and New Zealand Clinical Trials register ACTRN12615001296527; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368458 (Archived by WebCite at http://www.webcitation.org/731somROx).

10.
JMIR Res Protoc ; 7(4): e102, 2018 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-29666044

RESUMEN

BACKGROUND: Skin cancer is the most prevalent cancer in Australia. Skin cancer prevention programs aim to reduce sun exposure and increase sun protection behaviors. Effectiveness is usually assessed through self-report. OBJECTIVE: It was the aim of this study to test the acceptance and validity of a newly developed ultraviolet radiation (UVR) exposure app, designed to reduce the data collection burden to research participants. Physical activity data was collected because a strong focus on sun avoidance may result in unhealthy reductions in physical activity. This paper provides lessons learned from collecting data from participants using paper diaries, a mobile app, dosimeters, and accelerometers for measuring end-points of UVR exposure and physical activity. METHODS: Two participant groups were recruited through social and traditional media campaigns 1) Group A-UVR Diaries and 2) Group B-Physical Activity. In Group A, nineteen participants wore an UVR dosimeter wristwatch (University of Canterbury, New Zealand) when outside for 7 days. They also recorded their sun exposure and physical activity levels using both 1) the UVR diary app and 2) a paper UVR diary. In Group B, 55 participants wore an accelerometer (Actigraph, Pensacola, FL, USA) for 14 days and completed the UVR diary app. Data from the UVR diary app were compared with UVR dosimeter wristwatch, accelerometer, and paper UVR diary data. Cohen kappa coefficient score was used to determine if there was agreement between categorical variables for different UVR data collection methods and Spearman rank correlation coefficient was used to determine agreement between continuous accelerometer data and app-collected self-report physical activity. RESULTS: The mean age of participants in Groups A (n=19) and B (n=55) was 29.3 and 25.4 years, and 63% (12/19) and 75% (41/55) were females, respectively. Self-reported sun exposure data in the UVR app correlated highly with UVR dosimetry (κ=0.83, 95% CI 0.64-1.00, P<.001). Correlation between self-reported UVR app and accelerometer-collected moderate to vigorous physical activity data was low (ρ=0.23, P=.10), while agreement for low-intensity physical activity was significantly different (ρ=-0.49, P<.001). Seventy-nine percent of participants preferred the app over the paper diary for daily self-report of UVR exposure and physical activity. CONCLUSIONS: This feasibility study highlights self-report using an UVR app can reliably collect personal UVR exposure, but further improvements are required before the app can also be used to collect physical activity data.

11.
Exp Dermatol ; 26(10): 875-882, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28191677

RESUMEN

The exposure of skin to ultraviolet (UV) radiation can have both beneficial and deleterious effects: it can lead, for instance, to increased pigmentation and vitamin D synthesis but also to inflammation and skin cancer. UVB may induce genetic and epigenetic alterations and have reversible effects associated with post-translational and gene regulation modifications. ß-catenin is a main driver in melanocyte development; although infrequently mutated in melanoma, its cellular localization and activity are frequently altered. Here, we evaluate the consequence of UVB on ß-catenin in the melanocyte lineage. We report that in vivo, UVB induces cytoplasmic/nuclear relocalization of ß-catenin in melanocytes of newborn mice and adult human skin. In mouse melanocyte and human melanoma cell lines in vitro, UVB increases ß-catenin stability, accumulation in the nucleus and cotranscriptional activity, leading to the repression of cell motility and velocity. The activation of the ß-catenin signalling pathway and its effect on migration by UVB are increased by an inhibitor of GSK3ß, and decreased by an inhibitor of ß-catenin. In conclusion, UVB represses melanocyte migration and does so by acting through the GSK3-ß-catenin axis.


Asunto(s)
Movimiento Celular/efectos de la radiación , Melanocitos/efectos de la radiación , Melanoma/metabolismo , Transporte de Proteínas/efectos de la radiación , Rayos Ultravioleta , beta Catenina/metabolismo , Animales , Línea Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Queratinocitos , Melanocitos/fisiología , Ratones , Fosforilación/efectos de la radiación , Transducción de Señal/efectos de la radiación , beta Catenina/antagonistas & inhibidores , beta Catenina/genética
12.
Prev Med ; 90: 121-32, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27374946

RESUMEN

OBJECTIVE: Print-based health promotion interventions are being phased out to bring forth more appealing and assessable new technology applications. This review aimed to evaluate the current literature on the use of mobile text messaging and similar electronic technology interventions in the area of skin cancer prevention. METHOD: A search of studies guided by Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) was conducted on mobile technology interventions for improving skin cancer prevention in the electronic databases PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO. RESULTS: Overall, 136 articles were screened for eligibility between 2001 (earliest relevant article found) and November 2015. Eight studies fulfilled the inclusion criteria and were reviewed according to the PRISMA guidelines. Of these, five were randomised controlled trials (RCTs), two were controlled clinical trials, and one was a cohort study. Five studies used text messages as an intervention, two used mobile phone applications, and another used electronic messages via email. All studies resulted in self-reported behaviour change in at least one of their outcome measures (e.g., sunscreen application, seeking shade). CONCLUSION: While the behaviour change outcomes are promising, the lack of change in more objective measures such as sunburn indicates a need to further improve mobile phone technology-delivered interventions in order to have a greater impact on skin cancer prevention. Future studies may consider the use of objective outcome measures (e.g., sunscreen weight), electronic diaries, or behavioural outcomes in social networks.


Asunto(s)
Teléfono Celular/estadística & datos numéricos , Aplicaciones Móviles , Neoplasias Cutáneas/prevención & control , Envío de Mensajes de Texto , Promoción de la Salud , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Int J Dermatol ; 55(10): 1096-105, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27126210

RESUMEN

BACKGROUND: There is some evidence that basal cell carcinomas (BCCs) arising on different anatomic sites and developing to different histological subtypes differ in their pathophysiology. The expression of a number of proteins, including PTCH1, COX-2, p53, and Ki-67, is frequently altered in BCC development. OBJECTIVES: This study sought to determine whether protein expression differs between BCCs at different anatomic sites and of different histological subtypes. METHODS: Expression of PTCH1, COX-2, p53, and Ki-67 proteins was compared between: (i) BCCs arising on the head (n = 55) and trunk (n = 53), and (ii) nodular (n = 52) and superficial (n = 43) BCCs. The intensity of immunohistochemistry (IHC) staining (low, moderate, strong, very strong) for PTCH1 and COX-2 proteins was measured and the proportions of p53- and Ki-67-positive cells quantified. RESULTS: The proportion of cells expressing Ki-67 was higher in tumor tissue than in non-malignant epidermis, whereas the opposite was found for PTCH1. The IHC staining intensity for PTCH1 was substantially greater in truncal BCCs than in BCCs on the head (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.63-8.96). The intensity of staining for PTCH1 was greater for superficial than for nodular BCCs (OR 3.70, 95% CI 1.53-8.97), and superficial BCCs showed a higher proportion of Ki-67-positive cells (OR 5.57, 95% CI 1.66-18.67). CONCLUSIONS: These differences suggest that the pathophysiology of BCC differs between lesions on the head and trunk and between nodular and superficial subtypes, perhaps indicating differences in their etiology.


Asunto(s)
Carcinoma Basocelular/química , Neoplasias de Cabeza y Cuello/química , Neoplasias Cutáneas/química , Torso , Anciano , Carcinoma Basocelular/patología , Ciclooxigenasa 2/análisis , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Receptor Patched-1/análisis , Piel/química , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/análisis
14.
J Invest Dermatol ; 136(4): 829-837, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26807515

RESUMEN

Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports.


Asunto(s)
Genes ras , Melanoma/metabolismo , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Receptor de Melanocortina Tipo 1/metabolismo , Neoplasias Cutáneas/metabolismo , Proteínas ras/genética , Adolescente , Adulto , Anciano , ADN de Neoplasias/genética , Salud de la Familia , Femenino , Genotipo , Humanos , Queratosis Actínica/genética , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Luz Solar/efectos adversos , Encuestas y Cuestionarios , Adulto Joven , Melanoma Cutáneo Maligno
15.
J Am Acad Dermatol ; 70(5): 858-62.e1-2, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24388723

RESUMEN

BACKGROUND: BRAF mutations are frequent in melanoma but their prognostic significance remains unclear. OBJECTIVE: We sought to further evaluate the prognostic value of BRAF mutations in localized cutaneous melanoma. METHODS: We undertook an observational retrospective study of 147 patients with localized invasive (stages I and II) cutaneous melanomas to determine the prognostic value of BRAF mutation status. RESULTS: After a median follow-up of 48 months, patients with localized melanomas with BRAF-mutant melanomas exhibited poorer disease-free survival than those with BRAF-wt genotype (hazard ratio 2.2, 95% confidence interval 1.1-4.3) even after adjustment for Breslow thickness, tumor ulceration, location, age, sex, and tumor mitotic rate. LIMITATIONS: The retrospective design and the small number of events are limitations. CONCLUSIONS: Our findings suggest that reappraisal of clinical treatment approaches for patients with localized melanoma harboring tumors with BRAF mutation might be warranted.


Asunto(s)
Melanoma/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Melanoma/patología , Mutación , Invasividad Neoplásica , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Cutáneas/patología
16.
Mol Cell ; 51(4): 409-22, 2013 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-23973372

RESUMEN

The individuals carrying melanocortin-1 receptor (MC1R) variants, especially those associated with red hair color, fair skin, and poor tanning ability (RHC trait), are more prone to melanoma; however, the underlying mechanism is poorly defined. Here, we report that UVB exposure triggers phosphatase and tensin homolog (PTEN) interaction with wild-type (WT), but not RHC-associated MC1R variants, which protects PTEN from WWP2-mediated degradation, leading to AKT inactivation. Strikingly, the biological consequences of the failure of MC1R variants to suppress PI3K/AKT signaling are highly context dependent. In primary melanocytes, hyperactivation of PI3K/AKT signaling leads to premature senescence; in the presence of BRAF(V600E), MC1R deficiency-induced elevated PI3K/AKT signaling drives oncogenic transformation. These studies establish the MC1R-PTEN axis as a central regulator for melanocytes' response to UVB exposure and reveal the molecular basis underlying the association between MC1R variants and melanomagenesis.


Asunto(s)
Regulación de la Expresión Génica/efectos de la radiación , Melanocitos/metabolismo , Melanoma Experimental/patología , Fosfohidrolasa PTEN/metabolismo , Receptor de Melanocortina Tipo 1/metabolismo , Pigmentación de la Piel/fisiología , Rayos Ultravioleta , Animales , Western Blotting , Células Cultivadas , Humanos , Técnicas para Inmunoenzimas , Melanocitos/efectos de la radiación , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Ratones , Mutación/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor de Melanocortina Tipo 1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Pigmentación de la Piel/efectos de la radiación , alfa-MSH/genética , alfa-MSH/metabolismo
17.
Pigment Cell Melanoma Res ; 26(6): 835-44, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23962207

RESUMEN

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.


Asunto(s)
Variación Genética , Melanocitos/efectos de los fármacos , Melanocitos/efectos de la radiación , Melanoma/patología , Receptor de Melanocortina Tipo 1/genética , Protectores Solares/farmacología , Rayos Ultravioleta , Adulto , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Caspasa 3/metabolismo , Recuento de Células , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Daño del ADN , Eritema/patología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Melanocitos/enzimología , Melanocitos/patología , Fenotipo , Dímeros de Pirimidina/metabolismo , Baño de Sol , Proteína p53 Supresora de Tumor/metabolismo
19.
J Invest Dermatol ; 133(4): 1027-33, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23096702

RESUMEN

There is increasing epidemiologic and molecular evidence that cutaneous melanomas arise through multiple causal pathways. To further define the pathways to melanoma, we explored the relationship between germline and somatic mutations in a series of melanomas collected from 134 Spanish and 241 Austrian patients. Tumor samples were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed clinical data were systematically collected from patients. We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk. We observed a nonsignificant association between germline MC1R status and somatic BRAF mutations in melanomas from trunk sites (odds ratio (OR) 1.8 (0.8-4.1), P=0.1), whereas we observed a significant inverse association between MC1R and BRAF for melanomas of the head and neck (OR 0.3 (0.1-0.8), P=0.02). This trend was observed in both the Spanish and Austrian populations.


Asunto(s)
GTP Fosfohidrolasas/genética , Melanoma/genética , Proteínas de la Membrana/genética , Proteínas Proto-Oncogénicas B-raf/genética , Receptor de Melanocortina Tipo 1/genética , Neoplasias Cutáneas/genética , Austria/epidemiología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Fenotipo , Neoplasias Cutáneas/epidemiología , España/epidemiología , Melanoma Cutáneo Maligno
20.
Pigment Cell Melanoma Res ; 24(3): 525-37, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21435193

RESUMEN

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Melanoma/metabolismo , MicroARNs/biosíntesis , Proteínas de Neoplasias/biosíntesis , Factores del Dominio POU/metabolismo , ARN Neoplásico/metabolismo , Diferenciación Celular/genética , Proteínas de Homeodominio/genética , Humanos , Melanocitos/metabolismo , Melanocitos/patología , Melanoma/genética , Melanoma/patología , MicroARNs/genética , Modelos Biológicos , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Factores del Dominio POU/genética , Biosíntesis de Proteínas/genética , ARN Neoplásico/genética , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Células Tumorales Cultivadas
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