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- 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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| 2. |
- Dizdar (Dizdar Segrell), Nil, et al.
(författare)
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Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants
- 1997
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 7:4, s. 322.-328
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Tidskriftsartikel (refereegranskat)abstract
- Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.
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| 3. |
- Lambe, Mats, et al.
(författare)
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Malignant melanoma : reduced risk associated with early childbearing and multiparity
- 1996
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Ingår i: Melanoma research. - : Ovid Technologies (Wolters Kluwer Health). - 0960-8931 .- 1473-5636. ; 6:2, s. 147-153
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Tidskriftsartikel (refereegranskat)abstract
- Pigmentary changes during pregnancy and sex-specific differences in incidence patterns of cutaneous malignant melanoma (CMM) suggest that sex hormones may be involved in the development of CMM. We explored possible associations between childbearing and the risk of CMM in a case-control study "nested' in a nation-wide cohort. A total of 4,779 incident cases of CMM in women aged 24-65 were compared with 23,888 individually age-matched controls. Delayed childbearing was associated with an increased risk of CMM, corresponding to approximately 16% per 5 years. Parous women had a significantly lower risk of CMM compared with nulliparous women; in univariate analysis there was an 8% reduction in risk for each additional birth (odds ratio = 0.92; 95% confidence interval = 0.89-0.95). In multivariate analyses the risk of CMM was best explained by a model including both age at first birth and parity. Age at first birth was the most important variable. Time since most recent birth was unrelated to risk of CMM. These findings indicate that early childbearing and multiparity reduce the risk of CMM. Conceivable explanations are hormonal changes induced by childbearing, enhanced immunologic activity via exposure to fetal antigens during pregnancy, or long-lasting effects of pregnancy-associated hyperpigmentation. Our results need confirmation in studies with proper adjustment for confounding; less sun exposure in young mothers and high parity women may represent an alternative explanation but is unlikely to explain entirely the twofold difference in risk found between extreme categories of age at first birth and parity.
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| 4. |
- Rosdahl, Inger, et al.
(författare)
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Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells
- 1997
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Ingår i: Melanoma research. - : Ovid Technologies (Wolters Kluwer Health). - 0960-8931 .- 1473-5636. ; 7:4, s. 267-74
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo- and hyperpigmentation. Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation. We detected messenger RNA transcripts for the cellular retinol- and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes. In the melanoma cell lines the major transcript was CRABP II. Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells. The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]RA. Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.
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| 10. |
- Hanson, C, et al.
(författare)
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Sensitivity to extrinsically supplied interferon and the endogenous expression of interferon in melanoma cell lines.
- 1999
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Ingår i: Melanoma research. - 0960-8931. ; 9:5, s. 451-6
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Tidskriftsartikel (refereegranskat)abstract
- Interferons (IFNs) have been shown to Induce loss of growth potential in melanoma cell lines. However, human melanomas have shown limited responsiveness to clinical therapy with IFN. In a previous study on melanoma cell lines we found that greatest sensitivity to IFN was found in cell lines with the greatest number of copies of chromosome 9p, where the IFN gene family is located. In the present study the expression In melanoma cell lines of IFN genes, IFN receptor genes and standard control genes (beta-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA and cyclophilin) was investigated using the reverse transcription-polymerase chain reaction, together with an exogenous standard (cyclophllin armoured RNA). We found that the sensitivity to extrinsically supplied IFN seems to correlate with the expression of endogenous IFN genes. The two melanoma cell lines producing the highest relative amount of IFN mRNA transcripts also demonstrated the most marked response to extrinsically supplied IFN. We hypothesize that tumours with enhanced endogenous IFN production may respond more positively to IFN treatment.
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