Rutkowski, D, Syed, F, Matthews, LC et al. (4 more authors) (2015) An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease. British Journal of Dermatology, 173 (3). pp. 690-700. ISSN 0007-0963
Abstract
Background: Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable sideeffects. Identifying patient responsiveness early could guide therapy. Methods: Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry. Results: At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a signifccant decrease in GAG at week 2 (P < 0 05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0 05) and a continued reduction in perfusion (P < 0 001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein. Conclusions: This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2015, The Authors. Published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Jun 2016 16:00 |
Last Modified: | 21 Jun 2016 16:00 |
Published Version: | http://dx.doi.org/10.1111/bjd.13752 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/bjd.13752 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99719 |