| 1. |
- Andersson, Eva, 1946-, et al.
(författare)
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Differential effects of UV irradiation on nuclear retinoid receptor levels in cultured keratinocytes and melanocytes
- 2003
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 12:5, s. 563-71
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Tidskriftsartikel (refereegranskat)abstract
- A major risk factor for skin cancer is UV irradiation, which not only damages DNA and other photosensitive compounds like vitamin A, but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to examine the effects of UV irradiation on the expression of the predominant retinoid receptors in the human skin (RARalpha, RARgamma and RXRalpha) and the AP-1 protein c-Jun; mRNA levels were studied by real-time PCR and protein levels by Western blot. In keratinocytes, a single dose of UVB (50 mJ/cm2) caused a rapid drop in the expression of all three receptors (mRNA levels minus 35-50% after 4 h; protein levels minus 20-45% after 8 h), which was followed over the next 40 h by a variable response, leading to full normalization for RARalpha only. In contrast, the levels of c-Jun did not change significantly after UV exposure. In melanocytes, UVB caused a similar drop of the retinoid receptor levels as in keratinocytes but this was soon followed by an increased expression leading to a complete normalization of all receptor levels within 1-3 days. The c-Jun levels in melanocytes increased 1 day after UV exposure and remained high (plus 50%) thereafter. In both cell types, a approximately 3-fold increase in apoptosis (measured by DNA fragmentation) was observed 8-48 h after UVB irradiation. In conclusion, a depletion of vitamin A and retinoid receptors by UV irradiation, together with unchanged or even increased c-Jun levels, might seriously interfere with retinoid signaling and thus promote future tumor development, especially in keratinocytes.
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| 2. |
- Andersson, Eva, 1946-, et al.
(författare)
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Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes
- 1999
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 9:4, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans [3H]retinoic acid in cultured human keratinocytes and melanocytes exposed to UVR, using high performance liquid chromatography. Before UVR the retinoid content was similar in keratinocytes and melanocytes, but the uptake of [3H]retinol was three-fold higher and the uptake of [3H]retinoic acid was 10-fold higher in the melanocytes. In both cell types, UVR (UVA 360 mJ/cm2 plus UVB 140 mJ/cm2) instantaneously reduced the concentration of retinol by about 50% and that of 3,4-didehydroretinol by about 20%. The retinoid concentrations returned to normal within 1-2 days post-irradiation, despite there being no overt increase in the uptake of [3H]retinol or the biosynthesis of 3,4-didehydroretinol. However, in both types of irradiated cells, the accumulation of the biologically most active metabolite, all-trans [3H]retinoic acid, was about 60% higher than in control cells. Furthermore, the metabolism of authentically supplied [3H]retinoic acid was reduced, especially in irradiated keratinocytes, which probably contributed to the restoration of retinoid levels after UV exposure.
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| 3. |
- Augustsson, A, et al.
(författare)
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Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 518-24
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Tidskriftsartikel (refereegranskat)abstract
- Common naevi, dysplastic naevi (DN) and other phenotypic features were evaluated as melanoma risk factors in a Swedish case-control study. One-hundred and twenty-one prevalent melanoma cases and 378 randomly selected controls participated. The mean total body naevus count was 115 in the cases and 67 in the controls. Fifty-six per cent of the cases and 18% of the controls had clinical DN. The corresponding figures for histologically diagnosed DN were 40% and 8% respectively. Clinical DN was as good as histologically diagnosed DN in identifying individuals at risk for melanoma. Subjects with sun-sensitive skin, greater than or equal to 150 naevi and presence of DN have 50 times higher melanoma risk than those without these characteristics.
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| 4. |
- Augustsson, A, et al.
(författare)
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Melanocytic naevi in sun-exposed and protected skin in melanoma patients and controls.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 512-7
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Tidskriftsartikel (refereegranskat)abstract
- The possible link between exposure to ultraviolet light and naevus development was studied in 121 melanoma patients and 310 controls by comparing the number of naevi in a sun-exposed area on the back with that in a sun-protected area on the buttocks. Both patients and controls had a four-fold increase in the number of naevi in the exposed compared with the protected area, p less than 0.001. The difference in naevus count between the exposed and the protected area was larger in patients than in controls, p less than 0.001. Subjects with dysplastic naevi, melanoma patients as well as controls, had a larger difference in the number of naevi between the two areas than subjects without dysplastic naevi, p less than 0.001. These results support the idea that sunlight plays an important role in naevus development and may explain why a high naevus count is a risk marker for malignant melanoma.
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| 5. |
- Augustsson, A, et al.
(författare)
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Prevalence of common and dysplastic naevi in a Swedish population.
- 1991
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Ingår i: The British journal of dermatology. - 0007-0963. ; 124:2, s. 152-6
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Tidskriftsartikel (refereegranskat)abstract
- The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001.
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| 6. |
- Augustsson, A, et al.
(författare)
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Regional distribution of melanocytic naevi in relation to sun exposure, and site-specific counts predicting total number of naevi.
- 1992
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 72:2, s. 123-7
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Tidskriftsartikel (refereegranskat)abstract
- The role of exposure to ultraviolet light in the formation of melanocytic naevi was analysed by investigating the regional naevus distribution in 310 subjects (30-50 years) from a Swedish census file. The lateral aspect of the arms and the back had the largest concentration of naevi. The mean naevus count per unit surface area was higher in intermittently exposed than in rarely exposed skin (p less than 0.001), while the lowest mean count was found in chronically exposed skin. These results support the idea that intermittent exposure to ultraviolet light has a "naevogenic" effect while chronic exposure might be protective. Dysplastic naevi had a distribution pattern quite different from common naevi. Considering the distribution pattern solely, dysplastic naevi seem to develop independently of exposure to ultraviolet light. The numbers of naevi in different skin areas were tested for their power in predicting the total body naevus count. The strongest correlations were found between total counts and counts on the anterior surface of the thighs and the lateral aspect of the arms. Counts from any of these areas will provide a practical and satisfactory estimate of the total number of naevi.
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| 7. |
- Berglind, Mari, 1953-, et al.
(författare)
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Uppskattning av antal patienter med basalcellscancer i Sverige under 2003 samt kostnader för diagnostik och behandling
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SSI:s vetenskapliga UV-råd skall ge myndigheten råd om det vetenskapliga underlaget beträffande sambandet UV-strålning och biologiska effekter. Vidare ligger i uppdraget att ge vägledning inför SSI:s ställningstagande i frågor av policykaraktär. Rådet har under året haft följande ledamöter: docent Harry Beitner, docent Yvonne Brandberg, meteorolog Weine Josefsson, professor Olle Larkö, professor Ulrik Ringborg (ordförande), docent Bernt Lindelöf, professor Per Söderberg, professor Rune Toftgård, docent Johan Hansson och docent Johan Westerdahl. Till rådet har adjungerats myndighetsspecialist Lars-Erik Paulsson.Alla tre hudcancerformer - malignt melanom, skivepitelcancer och basalcellscancer – ökar i Sverige och internationellt. Gemensamt för alla tre formerna är att ökningen sammanhänger med exposition av solens UV-strålning, den viktigaste yttre riskfaktorn. Av detta följer att modifiering av UV-exposition, framför allt genom ändrade solvanor i befolkningen, bör kunna leda till en minskning av förekomsten av hudcancer. Primär prevention genom förebyggande insatser med syfte minskad UV-exposition, bedöms vara ett betydelsefullt sätt att motverka uppkomsten av alla tre formerna av hudcancer.Ett annat gemensamt drag hos dessa tre tumörformer är nyttan av tidig diagnostik. Ett tidigt avlägsnande av en hudcancer innebär mindre sjukvårdsinsatser och, för framför allt malignt melanom, minskad risk för tumörspridning. Tumörutvecklingen sker ofta via förstadier och ökad kunskap om dessa leder till möjligheter att avlägsna förstadier innan dessa har hunnit bli elakartade tumörer. Denna form av tidigdiagnostik gränsar till den primära preventionen.Av de tre formerna hudcancer är det i första hand malignt melanom som kan förorsaka död i sjukdomen. Ett väsentligt mål med förebyggande insatser är därför att minska dödligheten. För alla tre formerna kan insjuknande förorsaka betydande besvär för patienten. På grund av den rikliga förekomsten av maligna hudtumörer är sjukvårdskostnader betydande. Därför är mål för förebyggande insatser också minskad morbiditet och sjukvårdskostnader. Förutom hudcancer orsakar solens UV-strålning betydande problem i form av ögonskador.I årets rapport redovisas (1) epidemiologiska aspekter av malignt hudmelanom, som under senare år uppvisar en stegrad ökningstakt; (2) maligna melanom hos barn och ungdomar; (3) förslag till studier av skivepitelcancer och yrke; (4) förekomst och kostnader för medicinsk handläggning av patienter med basalcellscancer, som visar höga incidenssiffror och höga kostnader; (5) lymfom och UV-strålning; (6) UV-strålning och katarakt, betydelsefullt med förebyggande åtgärder; (7) förslag till workshop om cellulära effekter av UV-strålning; (8) rekommendation att använda den uppgraderade versionen av European Code Against Cancer; (9) UV-strålning och vitamin D, viss UV-dos är av nytta; (10) dosrat och fraktioner av UV-strålning i relation till utveckling av hudcancer och hos möss, påverkar ej preventiva strategier; (11) debatt om ökad solexposition eventuellt skulle leda till förbättrad överlevnad för melanompatienter ändrar ej preventiva strategier; (12) synpunkter på primär prevention från 6th World Conference on Melanoma, Vancouver, 2005.
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| 8. |
- Bu, H, et al.
(författare)
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Significance of glutathione S-transferases M1, T1 and P1 polymorphisms in Swedish melanoma patients.
- 2007
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 17:4, s. 859-864
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.
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| 9. |
- Ericson, Marica, 1974, et al.
(författare)
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Photodynamic therapy of actinic keratosis at varying fluence rates : Assessment of photobleaching, pain and primary clinical outcome
- 2004
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 151, s. 1204-1212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm-2, and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm-2. The total cumulative light dose was 100 J cm-2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photo-bleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 ± 1.0 J cm -2 at 30 mW cm-2, to 7.3 ± 0.7 J cm-2 at 75 mW cm-2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm-2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm-2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm-2. Conclusions: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm-2) seems preferable when performing PDT of AK using noncoherent light sources.
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| 10. |
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