Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study
| Autor: | Marieke M B Seyger, I.M.J.J. van Vlijmen-Willems, Annechien M. G. Langewouters, D.W.A. Van Rens, H.J. Bovenschen, M.E. Otero, P.C.M. van de Kerkhof |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Retinoic acid Administration Oral Tretinoin Dermatology Biology Auto-immunity transplantation and immunotherapy [N4i 4] Natural killer cell chemistry.chemical_compound Keratolytic Agents Internal medicine Psoriasis medicine Humans Benzothiazoles IL-2 receptor Cell Proliferation Chronic inflammation and autoimmunity [UMCN 4.2] Epidermis (botany) integumentary system Middle Aged Triazoles Natural killer T cell medicine.disease Immunohistochemistry Pathogenesis and modulation of inflammation [N4i 1] medicine.anatomical_structure Endocrinology chemistry Female Clinical Pharmacology and physiology [CTR 2] Dermatologic Agents CD8 |
| Zdroj: | British Journal of Dermatology, 156, 263-70 British Journal of Dermatology, 156, 2, pp. 263-70 |
| ISSN: | 0007-0963 |
| Popis: | Contains fulltext : 52014.pdf (Publisher’s version ) (Closed access) BACKGROUND: The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis. OBJECTIVES: The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial. METHODS: Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis. RESULTS: At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05). CONCLUSIONS: Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole. |
| Databáze: | OpenAIRE |
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