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- All-Ericsson, Charlotta, et al.
(författare)
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c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?
- 2004
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 45:7, s. 2075-82
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma. METHODS: Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1. RESULTS: Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM. CONCLUSIONS: The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.
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| 2. |
- Ayala, Marcelo, et al.
(författare)
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p53 expression and apoptosis in the lens after ultraviolet radiation exposure
- 2007
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:9, s. 4187-4191
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To localize p53 protein and active caspase-3 in the albino rat lens and to compare p53 mRNA and active caspase-3 expression in ultraviolet radiation (UVR) 300 nm exposed lenses and their contralateral nonexposed controls. METHODS: Ten Sprague-Dawley albino rats were unilaterally exposed to 8 kJ/m(2) UVR, and the contralateral eyes were left nonexposed. In total, four exposed lenses and their respective contralateral nonexposed lenses were analyzed by immunohistochemistry to localize p53 and active caspase-3. In addition, six exposed and contralateral nonexposed lenses were analyzed by real-time RT-PCR. Quantified p53 and caspase-3 expression were compared between the in vivo UVR 300 nm exposed lenses and the contralateral nonexposed lenses. RESULTS: All lenses exposed to UVR developed cataract. Immunohistochemistry showed that p53 and active caspase-3 were localized in the lens epithelial cells. Quantified p53 and caspase-3 expression were significantly higher in lenses exposed to UVR than in nonexposed lenses. CONCLUSIONS: p53 and caspase-3 expression increase in lens epithelial cells after UVR exposure. In the lens, apoptosis induced by UVR may be associated with increased p53 expression.
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| 5. |
- Bergman, L, et al.
(författare)
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Uveal melanoma survival in Sweden from 1960 to 1998
- 2003
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:8, s. 3282-3287
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Tidskriftsartikel (refereegranskat)
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