The Journal of investigative dermatology
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J. Invest. Dermatol. · Feb 2004
Imatinib mesylate inhibits platelet-derived growth factor receptor phosphorylation of melanoma cells but does not affect tumorigenicity in vivo.
Platelet-derived growth factor (PDGF) and its cognate receptor are widely expressed on melanomas. Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms. Imatinib mesylate was previously reported to have specific activity in inhibiting select tyrosine kinase receptors, including PDGF and c-Kit. ⋯ Immunohistochemical studies demonstrated inhibition of PDGFR phosphorylation on the tumors from mice treated with imatinib mesylate but not from control mice, suggesting that the receptors were functional and that the concentration of drug used was appropriate. Our data demonstrated that imatinib mesylate blocked both PDGFR-alpha and PDGFR-beta in vivo. It did not, however, affect the growth of melanoma cells expressing PDGFR, regardless of whether the cells expressed c-Kit.
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J. Invest. Dermatol. · Jan 2004
Ultraviolet radiation-induced inflammation as a model for cutaneous hyperalgesia.
The effects of UVA-I and solar simulated radiation on skin sensitivity to thermal and mechanical stimuli were compared in normal volunteers. Individual minimal erythema doses (MED) for each source were determined and previously unexposed buttock skin was exposed to 1, 2 and 3 MED of each spectrum. Erythema, and mechanical and thermal pain thresholds were quantified from 3 to 72 hours post-irradiation. ⋯ These data demonstrate the usefulness of UVR-induced inflammation as a model of cutaneous hypersensitivity. This model has clinical relevance for the study of hyperalgesia in general and the abnormal sensitivity of sunburnt skin in particular. It is likely to be useful in the assessment of peripherally acting analgesic drugs.
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J. Invest. Dermatol. · Dec 2003
Case ReportsA novel loss-of-function mutation (N48K) in the PTEN gene in a Spanish patient with Cowden disease.
Cowden disease, also known as multiple hamartoma syndrome, is a rare disease inherited in an autosomal dominant pattern, which confers a high risk of developing breast and thyroid carcinomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with Cowden disease. In this work, the direct sequencing of all coding regions of the PTEN gene led us to the identification of N48K, a new germline PTEN missense mutation, in a patient suffering from Cowden disease. ⋯ Moreover, by functional analysis we found that the ability of PTEN N48K mutant protein to inhibit the activation of the proto-oncogene PKB/Akt was impaired, supporting the involvement of N48K mutation in Cowden disease. Loss of heterozygosity using three microsatellites (D10S215, D10S541, and D10S564) and the complete sequence analysis of PTEN exons in breast and endometrial tumor samples from the same patient were also carried out in an attempt to identify additional PTEN somatic mutations. The lack of loss of heterozygosity or additional mutations in tumor samples suggests that abnormalities of the regulatory regions of the PTEN gene or haplo-insufficiency might occur in tumors from Cowden disease patients.
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J. Invest. Dermatol. · Dec 2003
Perceptual matching for assessment of itch; reliability and responsiveness analyzed by a rank-invariant statistical method.
The aim of this study was to evaluate the reliability and responsiveness of a new device-perceptual matching by Matcher (Cefar Medical AB, Lund, Sweden)-in the assessment of the progress of experimentally induced itch as well as determine the reliability of the method in patients with skin disease and itch. The perceptual matching unit electrically stimulates the skin of the fingers in the left hand. When the amplitude of the sensation corresponded to that of the experienced itch, the subject was instructed to halt the stimulation and a value was automatically saved in the electronic device. ⋯ The augmented rank order coefficient was high (0.98). In conclusion, Matcher measures itch intensity via perceptual matching with a high reliability and excellent responsiveness. The method is stable and can be recommended as an assessment tool for itch intensity both in experimental conditions as well as in patients with skin disease and itch.
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J. Invest. Dermatol. · Nov 2003
A novel role of fibrin in epidermal healing: plasminogen-mediated migration and selective detachment of differentiated keratinocytes.
Recent studies have shown that fibrin promotes epidermal regeneration in vitro and maintains the stem cell population after transplantation of keratinocytes in vivo. As epidermal keratinocytes do not express integrin alpha(v)beta3, the receptor for fibrin and fibrinogen, the mechanism through which fibrin affects epidermal cells remains elusive. To investigate the role of fibrin in epidermal wound healing, we developed an in vitro model in which fibrin was added to the top of wounded keratinocyte monolayers grown on collagen. ⋯ Our results suggest a novel dual role of fibrin in epidermal healing. First, fibrin promotes keratinocyte migration indirectly by exposing plasminogen to migrating cells, and second, fibrin selectively disrupts adhesion of differentiated keratinocytes. Our data are novel and may have important implications in understanding wound healing and in the use of fibrin as a biomaterial for protein and gene delivery.