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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. |
- Behndig, A, et al.
(författare)
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Superoxide dismutase isoenzymes in the normal and diseased human cornea.
- 2001
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 42:10, s. 2293-6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy.METHODS: The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry.RESULTS: The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation.CONCLUSIONS: Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.
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| 4. |
- 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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| 7. |
- Eklund, Anders, et al.
(författare)
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An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement
- 2003
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:7, s. 3017-24
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring intraocular pressure (IOP). The purpose of this study was to develop a new applanation method for IOP measurement that uses combined continuous force and area measurement and to develop and evaluate an applanation resonator sensor (ARS) tonometer based on that method. METHODS: The tonometer was developed and evaluated in an in vitro porcine eye model, in which enucleated eyes were pressurized with a saline column. A model assuming that the applanation principle is valid over a certain interval of contact area was proposed. Continuous contact area was measured with a resonator sensor device, and contact force was measured with a force transducer, both mounted together in one probe. Reference IOP was measured in the vitreous chamber (IOP(VC)) with a standard fluid pressure transducer. RESULTS: An optimization algorithm determined the applanation interval that was optimal for calculating IOP(ARS). The corresponding time interval was 30 +/- 3 to 77 +/- 4 ms (mean +/- SD, n = 418) after initial contact. The proposed model showed a degree of explanation of R(2 [supi]) = 0.991 (n = 410, six eyes), corresponding to a correlation of r = 0.995 (n = 410) between IOP(ARS) and IOP(VC). The within-eyes precision (i.e., 95% confidence interval for the residuals between IOP(ARS) and IOP(VC)) was +/- 1.8 mm Hg (n = 410, six eyes). CONCLUSIONS: In this study, the ARS method for measuring IOP was evaluated in an in vitro porcine eye model and showed high precision. The ARS method is, to the authors' knowledge, the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle: force and area. Consequently, there is a potential for reducing errors in clinical IOP tonometry.
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