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1.
J Eur Acad Dermatol Venereol ; 34(5): 926-931, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32107848

RESUMEN

According to the guidelines for the treatment of psoriasis, phototherapy is given in courses of UVB exposure starting at 50-70% of the minimal erythema dose, MED, with subsequently incremental dosages, but keeping erythemal skin reactions to a minimum by restraining the dosages when necessary. In this review, this classical principle of short-term near erythematogenic UVB therapy without further UVB maintenance therapy is challenged as it is evidently not optimal for psoriasis as a chronic condition. There is old experimental evidence supplemented with growing knowledge on the mode of action of phototherapy and more recent data on low-level UVB regimens as maintenance therapy that should urge us to revisit our guidelines on phototherapy to address psoriasis for what it is: a chronic condition.


Asunto(s)
Psoriasis , Terapia Ultravioleta , Eritema , Humanos , Fototerapia , Psoriasis/radioterapia
2.
Photochem Photobiol Sci ; 18(3): 641-680, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30810559

RESUMEN

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.


Asunto(s)
Oftalmopatías/etiología , Inmunidad/efectos de la radiación , Neoplasias Cutáneas/etiología , Ozono Estratosférico/análisis , Rayos Ultravioleta , Deficiencia de Vitamina D/etiología , Cambio Climático , Daño del ADN/efectos de la radiación , Oftalmopatías/prevención & control , Salud , Humanos , Enfermedades de la Piel/etiología , Enfermedades de la Piel/prevención & control , Neoplasias Cutáneas/prevención & control , Luz Solar , Rayos Ultravioleta/efectos adversos , Vitamina D/análisis , Deficiencia de Vitamina D/prevención & control
3.
Photochem Photobiol Sci ; 17(2): 127-179, 2018 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-29404558

RESUMEN

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

4.
Br J Dermatol ; 175(6): 1320-1328, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27411377

RESUMEN

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.


Asunto(s)
Daño del ADN/efectos de la radiación , Estaciones del Año , Luz Solar , Vitamina D/biosíntesis , 8-Hidroxi-2'-Desoxicoguanosina , Adolescente , Adulto , Asia Sudoriental/etnología , Biomarcadores/sangre , Biomarcadores/orina , Reparación del ADN/fisiología , Reparación del ADN/efectos de la radiación , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Dieta , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dímeros de Pirimidina/orina , Piel/metabolismo , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/orina , Pigmentación de la Piel/efectos de la radiación , Vitamina D/administración & dosificación , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/etnología , Deficiencia de Vitamina D/orina , Adulto Joven
6.
Br J Dermatol ; 173(1): 201-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25645571

RESUMEN

BACKGROUND: Solar ultraviolet radiation (UVR) is recognized as the principal environmental cause of skin cancer. In particular, the risk of induction of squamous cell carcinoma (SCC) has been shown to increase with cumulative exposure to UVR. Models of risk of SCC induction have been developed but these do not include the use of sunbeds. OBJECTIVES: To explore the links between sunbed exposure and risk of SCC induction. METHODS: To this end, the values of published on-site UVR levels emitted from sunbeds were used to provide real measured sunbed exposure levels to inform the model. The model incorporated three conditions of exposure: day-to-day, holiday and sunbed exposure. The risks associated with different exposure scenarios were implemented in the model. Baseline exposure comprised day-to-day and holiday exposure. Relative risk (RR) was defined as the risk of SCC induction from (sunbed + baseline dose)/baseline dose. RESULTS: The RR of SCC induction from estimated median sunbed exposure output [176 standard erythemal dose (SED) per year; 20-35 years of age] in addition to median baseline sun exposure level (166 SED year + 85.5 SED per year holiday) was 1.9 (90% risk increase) up to 55 years of age. A higher sunbed exposure (302 SED per year; 20-35 years of age) produced an RR value of 2.8 (180% increase) at 55 years of age. CONCLUSIONS: This is the first time that a risk model for SCC of the skin has been developed that includes estimated sunbed doses derived from measured irradiance data. The model demonstrates that the additional risk associated with sunbed use may be significant, particularly when high-output, fast-tan sunbeds are used.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Neoplasias Cutáneas/etiología , Baño de Sol , Rayos Ultravioleta/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Industria de la Belleza , Exposición a Riesgos Ambientales/efectos adversos , Vacaciones y Feriados , Humanos , Persona de Mediana Edad , Neoplasias Inducidas por Radiación , Factores de Riesgo , Luz Solar/efectos adversos , Adulto Joven
7.
Photochem Photobiol Sci ; 14(1): 53-87, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25383760

RESUMEN

Due to the implementation of the Montreal Protocol, which has limited, and is now probably reversing, the depletion of the stratospheric ozone layer, only modest increases in solar UV-B radiation at the surface of the Earth have occurred. For many fair-skinned populations, changing behaviour with regard to exposure to the sun over the past half century - more time in the sun, less clothing cover (more skin exposed), and preference for a tan - has probably contributed more to greater levels of exposure to UV-B radiation than ozone depletion. Exposure to UV-B radiation has both adverse and beneficial effects on human health. This report focuses on an assessment of the evidence regarding these outcomes that has been published since our previous report in 2010. The skin and eyes are the organs exposed to solar UV radiation. Excessive solar irradiation causes skin cancer, including cutaneous malignant melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma, and contributes to the development of other rare skin cancers such as Merkel cell carcinoma. Although the incidence of melanoma continues to increase in many countries, in some locations, primarily those with strong sun protection programmes, incidence has stabilised or decreased over the past 5 years, particularly in younger age-groups. However, the incidence of non-melanoma skin cancers is still increasing in most locations. Exposure of the skin to the sun also induces systemic immune suppression that may have adverse effects on health, such as through the reactivation of latent viral infections, but also beneficial effects through suppression of autoimmune reactivity. Solar UV-B radiation damages the eyes, causing cataracts and pterygium. UV-B irradiation of the skin is the main source of vitamin D in many geographic locations. Vitamin D plays a critical role in the maintenance of calcium homeostasis in the body; severe deficiency causes the bone diseases, rickets in children and osteomalacia in adults. Although many studies have implicated vitamin D deficiency in a wide range of diseases, such as cancer and cardiovascular disease, more recent evidence is less compelling, with meta-analyses of supplementation trials failing to show a beneficial effect on the health outcomes that have been tested. It continues to be difficult to provide public health messages to guide safe exposure to the sun that are accurate, simple, and can be used by people with different skin types, in different locations, and for different times of the year or day. There is increasing interest in relating sun protection messages to the UV Index. Current sun protection strategies are outlined and assessed. Climatic factors affect the amount of UV radiation received by the skin and eyes, separately from the effect of ozone depletion. For example, cloud cover can decrease or increase the intensity of UV radiation at Earth's surface and warmer temperatures and changes in precipitation patterns may alter the amount of time people spend outdoors and their choice of clothing. The combination of changes in climate and UV radiation may affect the number of pathogenic microorganisms in surface waters, and could have an impact on food security through effects on plant and aquatic systems. It remains difficult to quantify these effects and their possible importance for human health.


Asunto(s)
Pérdida de Ozono , Ozono Estratosférico/química , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Cambio Climático , Ambiente , Ojo/efectos de la radiación , Oftalmopatías/diagnóstico , Oftalmopatías/etiología , Humanos , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , Salud Pública , Piel/efectos de la radiación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/etiología , Rayos Ultravioleta , Vitamina D/metabolismo
8.
J Eur Acad Dermatol Venereol ; 27(1): 67-72, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22142537

RESUMEN

BACKGROUND: An effective prophylactic treatment of patients with polymorphic light eruption (PLE) consists of repeated low, gradually increasing exposures to UVB radiation. This so-called UV(B) hardening induces better tolerance of the skin to sunlight. OBJECTIVE: SunshowerMedical company (Amsterdam) has developed an UV (B) source that can be used during taking shower. The low UV fluence of this apparatus makes it an interesting device for UV hardening. In a group of PLE patients, we compared the effectiveness of the irradiation with SunshowerMedical at home with that of the UVB treatment in the hospital. METHODS: The PLE patients were randomized for one of the treatments. The hospital treatment consisted of irradiations with broad-band UVB (Waldmann 85/UV21 lamps) twice a week during 6 weeks. The home UV-device was used each day with the maximal irradiation time of 6 min. The outcome assessment was based on the information obtained from patients' dermatological quality of life (DLQI) questionnaires, the ability of both phototherapies to reduce the provocation reaction and from the patients' evaluation of the long-term benefits of their phototherapies. RESULTS: Sixteen patients completed treatment with SunshowerMedical and thirteen completed treatment in hospital. Both types of phototherapy were effective. There was a highly significant improvement in DLQI with either treatment. In most cases, the hardening reduced or even completely suppressed clinical UV provocation of PLE. The patients using SunshowerMedical at home were, however, much more content with the treatment procedure than the patients visiting the dermatological units. CONCLUSIONS: Both treatments were equally effective in the induction of skin tolerance to sunlight in PLE patients. However, the home treatment was much better accepted than the treatment in the hospital.


Asunto(s)
Dermatitis Fotoalérgica/radioterapia , Piel/efectos de la radiación , Terapia Ultravioleta/instrumentación , Terapia Ultravioleta/métodos , Adolescente , Adulto , Anciano , Intervalos de Confianza , Dermatitis Fotoalérgica/diagnóstico , Diseño de Equipo , Seguridad de Equipos , Femenino , Estudios de Seguimiento , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/radioterapia , Dosis de Radiación , Índice de Severidad de la Enfermedad , Piel/patología , Resultado del Tratamiento , Adulto Joven
9.
Carcinogenesis ; 33(3): 714-20, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22227037

RESUMEN

Chronic ultraviolet (UV) exposure induces clones of cells overexpressing mutant p53 in the interfollicular (IF) epidermis and subsequently squamous cell carcinomas (SCCs) with similar p53 mutations. Mutated p53 may give cells growth advantage over neighbouring cells by impaired apoptosis. We tested this by UV overexposure of skin laden with p53-mutant clones and assessed the impact on subsequent tumour development. P53-mutant clones were induced in two groups of hairless SKH1 mice by daily exposures (500 J/m(2) UV from TL12 lamps) for 28 days. On day 29, one group was overexposed (to 10 kJ/m(2) UV), whereas the control group received the regular daily dose. After 1 week of recovery, the daily exposures were resumed in both groups to induce SCCs. UV overexposure forced the entire IF basal layer into caspase-3-driven apoptosis while leaving overlying layers with sunburn cells intact. No apparent regions were spared from apoptosis. Pulse-chase BrdU labelling showed the IF epidermis to be repopulated from the hair follicles (remaining p63 positive). One week after overexposure, the p53-mutant clones had virtually disappeared (0.6, 95% confidence interval 0.5-0.8 per mouse versus 102, 59-179, without overexposure). Tumour development was significantly delayed after UV overexposure (P < 0.0001) by an average of 27 days (standard error of the mean 3); a period matching that of daily exposures preceding the overexposure. Thus, we found that UV-induced ablation of the IF epidermal basal layer eliminates p53-mutant clones and resets UV carcinogenesis. Furthermore, and in contrast with earlier reports, our data show that UV-induced p53-mutant clones and SCCs originate from the IF epidermis.


Asunto(s)
Carcinoma de Células Escamosas/patología , Epidermis/efectos de la radiación , Genes p53 , Neoplasias Inducidas por Radiación/patología , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/metabolismo , Rayos Ultravioleta/efectos adversos , Animales , Apoptosis , Carcinoma de Células Escamosas/genética , Caspasa 3/genética , Caspasa 3/metabolismo , Transformación Celular Neoplásica , Daño del ADN , Epidermis/metabolismo , Epidermis/patología , Femenino , Masculino , Ratones , Ratones Pelados , Neoplasias Cutáneas/genética , Quemadura Solar/patología , Proteína p53 Supresora de Tumor/genética
10.
Int J Cancer ; 131(6): 1267-76, 2012 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-22161643

RESUMEN

Because of its antitumor effect, the immunosuppressant rapamycin holds great promise for organ transplant recipients in that it may lower their cancer risk. In a mouse model, we showed previously that rapamycin inhibits the outgrowth of primary skin carcinomas induced by UV radiation. However, the tumors that did grow out showed an altered p53 mutation spectrum. Here, we investigated whether this shift in p53 mutations already occurred in the smallest tumors, which were not affected in onset. We found that rapamycin did not alter the mutational spectrum in small tumors and in preceding microscopic clusters of cells expressing mutant-p53. However, rapamycin did reduce the number of these cell clusters. As this reduction did not affect tumor onset, we subsequently investigated whether rapamycin merely suppressed expression of mutated p53. This was not the case, as we could demonstrate that switching from a diet with rapamycin to one without, or vice versa, did not affect the number of existing mutant-p53 expressing cell clusters. Hence, rapamycin actually reduced the formation of mutant-p53 cell clusters. In wild-type and p53-mutant mice, we could not measure a significant enhancement of UV-induced apoptosis, but we did observe clear enhancement in human skin equivalents. This was associated with a clear suppression of HIF1α accumulation. Thus, we conclude that rapamycin reduces the formation of mutant-p53-expressing cell clusters without affecting tumor onset, suggesting that tumors grow out of a minor subset of cell clusters, the formation of which is not affected by rapamycin.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Genes p53 , Mutación , Neoplasias Inducidas por Radiación/prevención & control , Sirolimus/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/análisis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Ratones , Ratones Pelados , Neoplasias Inducidas por Radiación/genética , Rayos Ultravioleta
11.
Photochem Photobiol Sci ; 10(2): 199-225, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21253670

RESUMEN

Depletion of the stratospheric ozone layer has led to increased solar UV-B radiation (280-315 nm) at the surface of the Earth. This change is likely to have had an impact on human exposure to UV-B radiation with consequential detrimental and beneficial effects on health, although behavioural changes in society over the past 60 years or so with regard to sun exposure are of considerable importance. The present report concentrates on information published since our previous report in 2007. The adverse effects of UV radiation are primarily on the eye and the skin. While solar UV radiation is a recognised risk factor for some types of cataract and for pterygium, the evidence is less strong, although increasing, for ocular melanoma, and is equivocal at present for age-related macular degeneration. For the skin, the most common harmful outcome is skin cancer, including melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma. The incidence of all three of these tumours has risen significantly over the past five decades, particularly in people with fair skin, and is projected to continue to increase, thus posing a significant world-wide health burden. Overexposure to the sun is the major identified environmental risk factor in skin cancer, in association with various genetic risk factors and immune effects. Suppression of some aspects of immunity follows exposure to UV radiation and the consequences of this modulation for the immune control of infectious diseases, for vaccination and for tumours, are additional concerns. In a common sun allergy (polymorphic light eruption), there is an imbalance in the immune response to UV radiation, resulting in a sun-evoked rash. The major health benefit of exposure to solar UV-B radiation is the production of vitamin D. Vitamin D plays a crucial role in bone metabolism and is also implicated in protection against a wide range of diseases. Although there is some evidence supporting protective effects for a range of internal cancers, this is not yet conclusive, but strongest for colorectal cancer, at present. A role for vitamin D in protection against several autoimmune diseases has been studied, with the most convincing results to date for multiple sclerosis. Vitamin D is starting to be assessed for its protective properties against several infectious and coronary diseases. Current methods for protecting the eye and the skin from the adverse effects of solar UV radiation are evaluated, including seeking shade, wearing protective clothing and sunglasses, and using sunscreens. Newer possibilities are considered such as creams that repair UV-induced DNA damage, and substances applied topically to the skin or eaten in the diet that protect against some of the detrimental effects of sun exposure. It is difficult to provide easily understandable public health messages regarding "safe" sun exposure, so that the positive effects of vitamin D production are balanced against the negative effects of excessive exposure. The international response to ozone depletion has included the development and deployment of replacement technologies and chemicals. To date, limited evidence suggests that substitutes for the ozone-depleting substances do not have significant effects on human health. In addition to stratospheric ozone depletion, climate change is predicted to affect human health, and potential interactions between these two parameters are considered. These include altering the risk of developing skin tumours, infectious diseases and various skin diseases, in addition to altering the efficiency by which pathogenic microorganisms are inactivated in the environment.


Asunto(s)
Cambio Climático , Ozono/análisis , Salud Pública , Animales , Humanos , Ozono/química , Protección Radiológica , Rayos Ultravioleta/efectos adversos , Vitamina D/biosíntesis , Vitamina D/metabolismo
12.
Int J Cancer ; 127(4): 796-804, 2010 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19998342

RESUMEN

Increased skin cancer risk in organ transplant recipients has been experimentally emulated with enhanced UV carcinogenesis from administering conventional immunosuppressants. However, newer generation immunosuppressive drugs, rapamycin (Rapa) and mycophenolate mofetil (MMF), have been shown to impair angiogenesis and outgrowth of tumor implants. To ascertain the overall effect on UV carcinogenesis, Rapa and MMF were admixed into the food pellets of hairless SKH1 mice receiving daily sub-sunburn UV dosages. With immunosuppressive blood levels neither of the drugs affected onset of tumors (<2 mm), but in contrast to MMF, Rapa significantly increased latency of large tumors (>or=4 mm, medians of 190 vs 125 days) and reduced their multiplicity (1.6 vs 4.5 tumors per mouse at 200 days). Interestingly, tumors (>2 mm) from the Rapa-fed group showed a reduction in UV-signature p53 mutations (39% vs 90%) in favor of mutations from putative base oxidation. This shift in mutation spectrum was not essentially linked to the reduction in large tumors because it was absent in large tumors similarly reduced in number when feeding Rapa in combination with MMF, possibly owing to an antioxidant effect of MMF. Significantly fewer tumor cells were Vegf-positive in the Rapa-fed groups, but a correspondingly reduced expression of Hif1alpha target genes (Vegf, Ldha, Glut1, Pdk1) that would indicate altered glucose metabolism with increased oxidative stress was not found. Remarkably, we observed no effect of the immunosuppressants on UV-induced tumor onset, and with impaired tumor outgrowth Rapa could therefore strongly reduce skin carcinoma morbidity and mortality rates in organ transplant recipients.


Asunto(s)
Inmunosupresores/administración & dosificación , Ácido Micofenólico/análogos & derivados , Neoplasias Inducidas por Radiación/tratamiento farmacológico , Sirolimus/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Proteínas Angiogénicas/genética , Animales , Western Blotting , Dieta , Femenino , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Pelados , Mutación/genética , Ácido Micofenólico/administración & dosificación , Neoplasias Inducidas por Radiación/irrigación sanguínea , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Neovascularización Patológica/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Irradiación Corporal Total
13.
Exp Dermatol ; 18(3): 212-7, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19046297

RESUMEN

Polymorphic light eruption (PLE) is a putative delayed-type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB-induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro-inflammatory and chemotactic cytokines are differentially expressed in UVB-irradiated skin of UVB-provocable PLE patients (n = 6) and age- and gender-matched healthy controls (n = 6). Interstitial interleukin-1alpha (IL-1alpha), IL-1beta, IL-1Ra, IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein 1-alpha (MIP-1alpha), MIP-1beta and monocyte chemotactic protein-1 (MCP-1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL-1Ra levels were significantly lower in the PLE patients than in controls (P < 0.05). IL-8 and TNF-alpha levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose-trend analyses showed that UVB irradiation caused significant increases in IL-1alpha in both groups, and that the levels of IL-1alpha and IL-1beta were on average twofold higher in the PLE group (P = 0.03 and P = 0.004, respectively.). Accordingly, the ratios of IL-1Ra over IL-1alpha and over IL-1beta were overall lower in the skin of PLE patients (P = 0.015 and P < 0.001, respectively.). This shift in cytokines in UVB-irradiated skin of PLE patients reveals an amplified early pro-inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.


Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Interleucina-1/metabolismo , Trastornos por Fotosensibilidad/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta , Adulto , Estudios de Casos y Controles , Movimiento Celular/efectos de la radiación , Femenino , Humanos , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Células de Langerhans/patología , Células de Langerhans/efectos de la radiación , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Neutrófilos/efectos de la radiación , Trastornos por Fotosensibilidad/patología , Factor de Necrosis Tumoral alfa/metabolismo
14.
Am J Transplant ; 8(11): 2205-11, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18801025

RESUMEN

The increased risk for the development of malignancies in transplant recipients is generally attributed to the debilitated immune system that results from chronic exposure to potent immunosuppressive drugs required to prevent graft rejection. While impaired immunity is clearly a key determinant, there is strong evidence that a constellation of other factors contribute to the pathogenesis of posttransplant cancers. In this article we discuss the underlying molecular and immunologic mechanisms that contribute to the development of de novo malignancies in transplant recipients, with particular focus on the two leading posttransplant neoplasia, skin cancer and Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD).


Asunto(s)
Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/patología , Neoplasias/etiología , Neoplasias/patología , Trasplante de Órganos/efectos adversos , Animales , Antineoplásicos/uso terapéutico , Reparación del ADN , Herpesvirus Humano 4/inmunología , Humanos , Sistema Inmunológico , Inmunosupresores/efectos adversos , Modelos Biológicos , Recurrencia , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología
16.
Tsitologiia ; 48(11): 958-66, 2006.
Artículo en Ruso | MEDLINE | ID: mdl-17233481

RESUMEN

Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of peripheral lymphocytes after their UVC-irradiation and cultivation, we have found that within the first four hours of cultivation the CPD-specific fluorescent signal from cell nuclei increased. Earlier, a similar increase in binding of antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured DNA isolated from UV-irradiated Chinese hamster ovary cells was reported (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair enzyme might induce such of DNA modification in lymphocyte nuclei that increased specific antibody binding to DNA fragments with lesions. We suggest that enzymatic formation of open structures in DNA predominated qualitatively over dual-incision and excision of these fragments, and resulted in the enhanced exposure of the pyrimidine dimers in nuclei to specific antibodies. The results evidence that nucleotid excision repair in unstimualted human lymphocytes being deficient in dual incision and removal of UV-induced DNA lesions appear to be capable of performing chromatin relaxation and pre-incision uncoiling of DNA fragments with lesions.


Asunto(s)
Daño del ADN/efectos de la radiación , Linfocitos/metabolismo , Dímeros de Pirimidina/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Reparación del ADN , Citometría de Flujo , Humanos , Immunoblotting , Linfocitos/efectos de la radiación , Dímeros de Pirimidina/análisis , Factores de Tiempo , Rayos Ultravioleta
17.
Cancer Res ; 51(3): 979-84, 1991 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-1988142

RESUMEN

The development of skin tumors (mainly squamous cell carcinomas) in hairless Skh-HR1 mice after discontinuation of a course of daily UV irradiations (wavelengths, 280-370 nm) is compared to that when the daily irradiations are continued. Under conditions of continued daily exposures 50% of 22 animals contracted tumors with diameters of at least 4 mm in 135 days. With exposures stopped after 35 or 19 days (2 groups with 24 and 23 mice) this time interval increased to 280 and 645 days, respectively; the rate at which multiple tumors developed on the mice was correspondingly lower. A mathematical model, derived from a larger experiment (223 mice) with different levels of chronic UV exposure, successfully predicts the tumor development after discontinuation of UV exposure. This model is similar to those used in risk assessments for skin cancers in human populations, e.g., in relation to stratospheric ozone depletion, sunbeds, etc. The model separates UV-driven processes from purely time-dependent processes. These stochastic processes, described by Weibull statistics, form stages in the tumorigenesis. This interpretation of the data indicates that a late, UV-independent stage occurs between the smallest observable tumors and larger ones with diameters of over 4 mm. This could be a simple growth stage, but histopathology suggests that it may also entail a transition from actinic keratosis to squamous cell carcinoma.


Asunto(s)
Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/etiología , Animales , Ratones , Ratones Pelados , Neoplasias Inducidas por Radiación/patología , Dosis de Radiación , Neoplasias Cutáneas/patología , Factores de Tiempo
18.
Cancer Res ; 53(18): 4212-7, 1993 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-8364916

RESUMEN

The rate of tumor induction by UV-A radiation rises more slowly with time and accumulated dose than that by UV-B radiation. It has recently been shown that this difference disappears when frank papillomas are excluded from the analysis. Thus, the rate of development of "nonpapillomas" (mainly squamous cell carcinomas and precursors) can be fully characterized by a typical tumor induction time, e.g., the time until 50% of the mice bear tumors. This has opened the possibility to investigate how UV-A and UV-B exposures add up in the induction of squamous cell carcinomas, which is an important issue in risk assessments of artificial UV-A sources for cosmetic or medical purposes. We present the results of an experiment in which 6 groups of 24 albino SKH:HR1 mice were treated daily for 600 days with either effective UV-A radiation, effective UV-B radiation, or combinations of both. The observed times it took for 50% of the mice to bear tumors in the combination groups were compared with those calculated on the basis of arithmetical addition of effective UV-A and effective UV-B doses. We did not find a statistically significant (P < 0.05) deviation from additivity.


Asunto(s)
Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/etiología , Rayos Ultravioleta , Animales , Carcinoma de Células Escamosas/etiología , Femenino , Masculino , Ratones , Ratones Pelados , Papiloma/etiología
19.
Cancer Res ; 57(4): 581-4, 1997 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-9044829

RESUMEN

Although xeroderma pigmentosum (XP) patients are rare, carriers of XP genes (heterozygotes) are much more common. Whether such carriers have an increased skin cancer risk is unknown. Recently developed mouse models for XP have opened up the possibility of determining the skin cancer risk of heterozygotes relative to wild types. Therefore, the XPA knockout trait has been crossed into hairless mice, and squamous cell carcinomas of the skin have been induced by low daily UVB exposures for 500 days in all three genotypes (-/-, +/-, and +/+). The carcinogenic response of the heterozygotes did not significantly differ from that of their wild-type littermates. Tumors in the XPA -/- animals appeared with a latency time that was decreased by a factor of 4.2. From this, we estimate that a functional XPA gene provides a "protection factor" of 60 (95% confidence interval, 15-250) against UV carcinogenesis, which is greater protection than that against acute UV effects, such as erythema and edema (protection factor between 7 and 16). Deficient nucleotide excision repair appears to have a more dramatic impact on skin cancer susceptibility than on sensitivity to acute UV effects.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Inducidas por Radiación/genética , Neoplasias Cutáneas/genética , Xerodermia Pigmentosa/genética , Animales , Carcinoma de Células Escamosas/patología , Susceptibilidad a Enfermedades , Genotipo , Ratones , Ratones Pelados , Ratones Noqueados/genética , Neoplasias Inducidas por Radiación/patología , Papiloma/genética , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Dosis de Radiación , Piel/efectos de la radiación , Neoplasias Cutáneas/patología
20.
Cancer Res ; 53(1): 53-60, 1993 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-8416751

RESUMEN

Information on the variation in carcinogenicity with wavelength is crucial in risk assessments for skin cancers induced by UV radiation. Until recently the wavelength (lambda) dependencies of other detrimental UV effects, such as sunburn, have been used as substitutes. Direct information on the lambda dependency can only be obtained from animal experiments. To this end we accumulated a large data set on skin tumors induced by chronic UV exposure of albino SKH:HR1 mice (14 different broadband UV sources and about 1100 mice); the data come from the Photobiology Unit of the former Skin and Cancer Hospital in Philadelphia and from the Department of Dermatology of the University of Utrecht. The lambda dependency was extracted from this data set (a statistically satisfactory description with chi 2 = 13.4, df = 7) and represented by the Skin Cancer Utrecht-Philadelphia action spectrum, i.e., a set of factors to weight the exposures at different wavelengths according to their respective effectiveness (inversely proportional to the daily exposure required for a median tumor induction time of 300 days). The fits obtained with other already available action spectra proved to be poor (chi 2 > 60, df = 11). The maximum effectiveness was found at 293 nm, and above 340 nm the effectiveness showed a shoulder at about 10(-4) of the maximum. A sensitivity analysis of the final solution for the lambda dependency showed a large margin of uncertainty above 340 nm and an information gap below 280 nm. The large variation in tumor responses in the present data set can be transformed to a coherent, common dose-response relationship by proper spectral weighting with this single action spectrum.


Asunto(s)
Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversos , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Masculino , Cómputos Matemáticos , Ratones , Ratones Pelados , Modelos Biológicos , Espectrofotometría Ultravioleta/métodos
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