Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months: Results from an observational multicenter study.

BACKGROUND/PURPOSE: Narrowband UVB phototherapy is a common treatment modality in psoriasis and atopic dermatitis, but evidence of its actual effect in clinical setting is sparse. Our aim was to assess the effectiveness and costs of narrowband UVB phototherapy in psoriasis and atopic dermatitis in clinical setting. METHODS: We observed 207 psoriasis patients and 144 atopic dermatitis patients in eight centers. SAPASI, PO-SCORAD, and VAS measures were used at baseline, at the end, and 3 months after the narrowband UVB phototherapy course. Quality of life was measured using Dermatology Life Quality Index (DLQI), and costs were assessed using a questionnaire. RESULTS: In both psoriasis and atopic dermatitis, the DLQI and Self-Administrated PASI (SAPASI)/Patient-Oriented SCORAD (PO-SCORAD) improved significantly and the results remained improved for at least 3 months in both groups. Alleviation of pruritus correlated with better quality of life in both patient groups. We reported slight redness and burning side effects which were due to lack of MED testing. Self-administered tools proved to be useful in evaluating pruritus and severity of the disease in psoriasis and atopic dermatitis. Mean patient costs were 310 € and 21 hours of time, and mean costs for the healthcare provider were 810 €. CONCLUSION: In psoriasis, narrowband UVB is a very efficient treatment in clinical setting, whereas in atopic dermatitis, more studies are needed to determine the best dosage.

Effects of ultraviolet radiation on skin cell proteome.

Ultraviolet (UV) radiation is known to cause both positive and negative health effects for humans. The synthesis of vitamin D is one of the rare beneficial effects of UV. The negative effects, such as sunburn and premature photoaging of the skin, increase the risk of skin cancer, which is the most detrimental health consequence of UV radiation. Although proteomics has been extensively applied in various areas of the biomedical field, this technique has not been commonly used in the cutaneous biology. Proteome maps of human keratinocytes and of murine skin have been established to characterize the cutaneous responses and the age-related differences. There are very few publications, in which proteomic techniques have been utilized in photobiology and hence there is no systematic research data available of the UV effects on the skin proteome. The proteomic studies have mainly focused on the UV-induced photoaging, which is the consequence of the long-term chronic UV exposure. Since the use of proteomics has been very narrow in the photobiology, there is room for new studies. Proteomics would offer a cost-effective way to large-scale screen the possible target molecules involved in the UV-derived photodamage, especially what the large-scale effects are after the acute and chronic exposure on the different skin cell populations.

In vivo UVA irradiation of mouse is more efficient in promoting pulmonary melanoma metastasis than in vitro.

BACKGROUND: We have previously shown in vitro that UVA increases the adhesiveness of mouse B16-F1 melanoma cells to endothelium.We have also shown in vivo that UVA exposure of C57BL/6 mice, i.v. injected with B16-F1 cells, increases formation of pulmonary colonies of melanoma. The aim of the present animal study was to confirm the previously observed in vivo UVA effect and to determine whether in vitro UVA-exposure of melanoma cells, prior the i.v. injection, will have an enhancing effect on the pulmonary colonization capacity of melanoma cells. As a second aim, UVA-derived immunosuppression was determined. METHODS: Mice were i.v. injected with B16-F1 cells into the tail vein and then immediately exposed to UVA. Alternatively, to study the effect of UVA-induced adhesiveness on the colonization capacity of B16-F1 melanoma, cells were in vitro exposed prior to i.v. injection. Fourteen days after injection, lungs were collected and the number of pulmonary nodules was determined under dissecting microscope. The UVA-derived immunosuppression was measured by standard contact hypersensitivity assay. RESULTS AND DISCUSSION: Obtained results have confirmed that mice, i.v. injected with B16-F1 cells and thereafter exposed to UVA, developed 4-times more of melanoma colonies in lungs as compared with the UVA non-exposed group (p < 0.01). The in vitro exposure of melanoma cells prior to their injection into mice, led only to induction of 1.5-times more of pulmonary tumor nodules, being however a statistically non-significant change. The obtained results postulate that the UVA-induced changes in the adhesive properties of melanoma cells do not alone account for the 4-fold increase in the pulmonary tumor formation. Instead, it suggests that some systemic effect in a mouse might be responsible for the increased metastasis formation. Indeed, UVA was found to induce moderate systemic immunosuppression, which effect might contribute to the UVA-induced melanoma metastasis in mice lungs.

Imaging leukocyte trafficking in vivo with two-photon-excited endogenous tryptophan fluorescence.

We describe a new method for imaging leukocytes in vivo by exciting the endogenous protein fluorescence in the ultraviolet (UV) spectral region where tryptophan is the major fluorophore. Two-photon excitation near 590 nm allows noninvasive optical sectioning through the epidermal cell layers into the dermis of mouse skin, where leukocytes can be observed by video-rate microscopy to interact dynamically with the dermal vascular endothelium. Inflammation significantly enhances leukocyte rolling, adhesion, and tissue infiltration. After exiting the vasculature, leukocytes continue to move actively in tissue as observed by time-lapse microscopy, and are distinguishable from resident autofluorescent cells that are not motile. Because the new method alleviates the need to introduce exogenous labels, it is potentially applicable for tracking leukocytes and monitoring inflammatory cellular reactions in humans.

Reliability and validity of a bioimpedance measurement device in the assessment of UVR damage to the skin.

Ultraviolet radiation (UVR) is the primary cause of skin cancers. However, it is difficult to evaluate the amount of UVR absorbed into the skin retrospectively. Therefore, objective and non-invasive quantitative method would be valuable for epidemiological UVR exposure assessment. Photodamage reduces the amount of bound water in the skin, and thus, measuring the skin's dielectric constant can provide an opportunity for assessing the cumulative UVR exposure. The purpose of the study was to assess the reliability and validity of the bioimpedance device, Moisture Meter-D. The measurements were performed on 100 subjects at three separate measurement times. A questionnaire was used to obtain information on the host factors and on the past UVR exposure. The biological samples, to determine the elastin proportion of the dermis, were collected. Some long-term as well as seasonal variations in the dielectric constants were detected. Also, a weak relationship between the dielectric constant and the UVR exposure indicators and host factors was observed. The MoistureMeter-D appears not to measure structural alterations in the skin caused by photodamage, and thus it is not a valid instrument for the assessment of photodamage, i.e., past UVR exposure.

Ultraviolet-A radiation induces changes in cyclin G gene expression in mouse melanoma B16-F1 cells.

BACKGROUND: We have previously shown that ultraviolet-A (UVA) radiation enhances metastatic lung colonization capacity of B16-F1 melanoma cells. The aim of this study was to examine changes in expression profile of genes in mouse melanoma B16-F1 cells exposed to UVA radiation. RESULTS: B16-F1 melanoma cells were exposed to a single UVA radiation dose of 8 J/cm2 and mRNA was isolated 4 h after the end of UVA exposure. Atlas Mouse Cancer 1.2 cDNA expression arrays were used for the large-scale screening to identify the genes involved in the regulation of carcinogenesis, tumor progression and metastasis. Physiologically relevant UVA dose induced differential expression in 9 genes in the UVA exposed melanoma cells as compared to the unexposed control cells. The expression of seven genes out of nine was upregulated (HSC70, HSP86, alpha-B-crystallin, GST mu2, Oxidative stress induced protein OSI, VEGF, cyclin G), whereas the expression of two genes was down-regulated (G-actin, non-muscle cofilin). The gene expression of cyclin G was mostly affected by UVA radiation, increasing by 4.85-folds 4 hour after exposure. The analysis of cyclin G protein expression revealed 1.36-fold increase at the 6 hour time point after UVA exposure. Cell cycle arrest in G2/M phase, which is known to be regulated by cyclin G, occurred at 4-h hour time-point, peaking 8 hours after the end of UVA irradiation, suggesting that cyclin G might play a role in the cell cycle arrest. CONCLUSION: Our results suggest that UVA radiation-induces changes in the expression of several genes. Some of these changes, e.g. in expression of cyclin G, possibly might affect cell physiology (cell cycle arrest).

Ultraviolet A exposure alters adhesive properties of mouse melanoma cells.

BACKGROUND: We have examined whether ultraviolet A (UVA) irradiation could alter adhesive properties of melanoma cells. As an experimental in vitro model, we have used C57BL/6 mouse-derived B16- F1 and B16-F10 melanoma cell lines and the syngeneic MS-1 endothelial cell line. METHOD/RESULT: The melanoma cells were exposed to different doses of UVA irradiation. We have determined that a single dose of UVA at 8 and 12 J/cm(2) causes an 88% (P<0.001) and a 32% (P<0.05) increase in B16-F1 melanoma cell adhesiveness to the non-irradiated endothelial monolayer, respectively. The peak of the response was 24 h after the irradiation. The UVA dose of 8 J/cm(2) delivered in four doses separated by 1 h intervals (4 x 2 J/cm(2)) had led to a caused 149% (P<0.001) increase of B16-F1 melanoma adhesiveness already at 1 h after the last dose of UVA. Besides the induction of increase in the melanoma-endothelial cell adhesion, UVA exposure has induced a rapid decline (1 h after exposure) in homotypic melanoma-melanoma cell adhesion (clustering). The clustering decline of B16-F1 cells with a single dose of UVA at 8 J/cm(2) was by 61% (P<0.05) and by 35% (P<0.05) with 4 x 2 J/cm(2). Pilot experiments have shown that the changes of the adhesive properties of melanoma cells were accompanied by an increase in N-cadherin expression and a decline in E-cadherin expression. Such a change in cadherin expression profile has been shown to be an indicator of the increased metastatic potential. CONCLUSION: Our results suggest that UVA radiation appears to alter the adhesive properties of melanoma cells in vitro, by diminishing the melanoma-melanoma adhesion and by increasing melanoma adhesion to the endothelium. This suggests that UVA exposure might increase the metastatic capability of the melanoma cells.

Ultraviolet A exposure might increase metastasis of mouse melanoma: a pilot study.

BACKGROUND: The major sources of long-wave ultraviolet A radiation (UVA; 320-400 nm) exposure are extensive sunbathing and tanning in solaria. While the carcinogenic effects of mid-wave ultraviolet B radiation (UVB; 280-320 nm) are well recognized, the potentially hazardous effects of UVA are less understood. Several studies have shown that a variety of physiological processes in the cell are modified by UVA exposure, some of which might be involved in the regulation of tumor metastasis. In this study we suggest that UVA radiation could lead to the increase of metastatic capability of melanoma cells in mice. METHOD/RESULT: A pilot in vivo study was executed using C57BL/6 mice and syngeneic B16 melanoma cell lines. Mice were intravenously (i.v.) injected with either B16-F1 or B16-F10 melanoma cells into the tail vein and then immediately exposed to UVA. Fourteen days after melanoma injection, lungs were collected and the quantity and quality of metastases were determined under a dissecting microscope. As an outcome of the pilot study we observed that i.v. injected melanoma cells formed more lung metastases in the UVA-exposed mice in comparison with the control mice. CONCLUSION: This result suggests that the UVA exposure of mice, with melanoma cells present in blood circulation, increases the formation of melanoma metastases in lungs. Further studies should determine whether a similar pro-metastatic effect, as observed in mice, could occur in humans and whether other than melanoma tumors might be susceptible.