Anybody watching the SID meeting? Ligand did a PR relating to this abstract:
>>ABSTRACT FINAL ID: 212 ;
CONTROL ID: 4474
CONTACT (NAME ONLY): J.V. Smit
Abstract Details
CATEGORY: Clinical Research
PRESENTATION TYPE: Poster
KEYWORDS: Keratins; Psoriasis; Retinoid;
Abstract TITLE:
Immunohistochemistry and flow cytometry of psoriatic skin before and after oral
bexarotene treatment.
AUTHORS (ALL): Smit, J.V. 1; Franssen, M.E.J. 1; de Jong, E.M.G.J. 1; Stevens,
V. J. 2; van de Kerkhof, P.C.M. 1
INSTITUTIONS (ALL): 1. Dermatology, University Medical Center, Nijmegen, ,
NL;
2. Medical Research, Ligand Pharmaceuticals Inc., San Diego, CA, USA;
ABSTRACT BODY:
Abstract Body: Patients with moderate to severe psoriasis were treated with
bexarotene, an RXR-selective retinoid, at doses of 0.5, 1, 2, and 3 mg/kg/day for
12 wks. Baseline and post-treatment evaluations were made on 30 pts for severity
of clinical signs and symptoms (mPASI), immunohistochemistry (IHC) markers of
the epidermis, and for flow cytometry of epidermal cells dispersed from biopsies.
Lesion biopsies before and after 12 wks of treatment were embedded in paraffin,
sectioned and stained for IHC analysis for the following markers: Ki67 associated
proliferation, keratin 10, keratin 13, keratin 16, keratin 19, transglutaminase, dermal
T-cells, CD4+ and CD8+. Lesional epidermis was also analyzed by flow cytometry
using thermolysin split skin dispersed into single epidermal cell suspensions for
assessment of keratin 10 and keratin 6. The overall response was a reduction in
the mean PASI score of 28% from 16.3 to 11.8 (p<0.001). A dose-response trend
was not observed. Analysis by IHC indicated that bexarotene decreased the
number of proliferating keratinocytes (p<0.001) and hyperproliferation-associated
keratin 16 expression (p<0.01). Significant improvements were observed in keratin
10 expression (p<0.01), transglutaminase (p=0.01), dermal infiltrate (p<0.001), and
CD4+ T-cells (p=0.001). Retinoid stimulated keratins 13 and 19 were not
expressed. Flow cytometry demonstrated a significant increase of 43% in the
keratin 10+ keratinocytes without a significant change in either keratin 6+
keratinocytes or the number of epidermal cells in the SG2M-phase. Analysis of
keratin 6 and 10 co-expressing cells indicated an increase of 77% of K10+K6-
(p<0.05) and a 33% decrease in K10-K6+ cells (p<0.01), but K10+K6+ cells were
unchanged. The data suggest that bexarotene treatment affects keratinocyte
compartments to increase cells in normal keratinization at the expense of
proliferation-associated keratinization. IHC data also indicate a reduction in
proliferating keratinocytes and dermal CD4+ T-cells.<<
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If only ASCO was this easy.
Cheers, Tuck |
