| 1. |
- Agnarsdóttir, Margrét, et al.
(författare)
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SOX10 expression in superficial spreading and nodular malignant melanomas
- 2010
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 20:6, s. 468-478
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Tidskriftsartikel (refereegranskat)abstract
- SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P = 0.008). The staining intensity was also inversely correlated with T-stage (Spearman's rho = -0.261, P = 0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (rho = -0.173, P = 0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P <= 0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn. Melanoma Res 20:468-478
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| 2. |
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| 3. |
- 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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| 4. |
- Andersson, Ronny, et al.
(författare)
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Effects of interferon-[alpha], verapamil and dacarbazine in the treatment of advanced malignant melanoma
- 2003
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 13:1, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-[alpha] (IFN[alpha]) as single drugs, or in combination, results in a response rate of approximately 15–20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFN[alpha]2b and verapamil (VPL). Thirty patients with disseminated metastatic melanoma received DTIC 250 mg/m2 on days 1–5 of a 4 week schedule, IFN[alpha]2b 3 MIU on days 1–5 each week, and VPL 80 mg three times a day throughout the cycle, until either disease progression or serious toxicity was observed. Among the 28 evaluable patients, there were four complete responses (CRs), five partial responses (PRs) and eight patients with stable disease (SD). The overall response rate (CR + PR) was 32%. Two patients with a CR were long-term survivors (45 and 34 months) and a third is still in complete remission after 49 months. The fourth CR patient relapsed and died with progressive brain metastases after 8 months. Among the eight patients with SD, one survived for 22 months and another for 34 months. Despite one toxic death, these results suggest that this treatment regimen is well tolerated and seems to be more effective than DTIC alone in a subset of patients. A controlled randomized study would be required to determine the value of adding VPL and IFN[alpha]2b to DTIC.
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| 5. |
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| 6. |
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| 7. |
- Bivik, Cecilia, et al.
(författare)
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Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
- 2005
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Ingår i: Melanoma Research. - : Ovid Technologies (Wolters Kluwer Health). - 0960-8931 .- 1473-5636. ; 15:1, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.
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| 8. |
- Bolander, Åsa, et al.
(författare)
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Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
- 2008
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 18:6, s. 412-419
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level
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| 9. |
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| 10. |
- Claeson, Magdalena, 1976, et al.
(författare)
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Incidence of cutaneous melanoma in Western Sweden, 1970-2007.
- 2012
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Ingår i: Melanoma research. - 1473-5636. ; 22:5, s. 392-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe the increasing incidence of cutaneous malignant melanoma (CMM) in Western Sweden during the period 1970-2007. A secondary aim was to show a geographical variation in incidence between coastal and inland areas, considering the effects of the local average duration of sunshine, and the sun exposure-related behavior in the populations. The Swedish Cancer Registry provided data on invasive melanomas during 1970-2007. Meteorological maps showed the annual average duration of sunshine during 1961-1990. A survey from 2007 with 2871 participants, carried out by the National Board of Health and Welfare, provided data on self-reported sun exposure. During the period studied, the age-standardized incidence for men in Western Sweden more than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to 27.1/100 000. Coastal areas, including Gothenburg city, had a high average duration of sunshine (1701-1900 h of sun/year), whereas inland areas had lower average duration of sunshine (≤1700 h). The incidence of CMM was higher in coastal areas and in Gothenburg city, compared with inland areas. This may be linked to ultraviolet radiation, a consequence of the higher average duration of sunshine. The sun exposure survey showed additional factors, which possibly led to the increased incidence, for example high sun exposure on holidays abroad. The alarming increase in the incidence of CMM in Western Sweden, during the period 1970-2007, shows the need for additional primary preventive measures, for example sun protection programs targeted at populations in this area.
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