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Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades-Behçet's disease-like mouse model.

Authors
Sohn, S; Lutz, M; Kwon, HJ; Konwalinka, G; Lee, S; Schirmer, M
Citation
Experimental dermatology, 13(10):630-634, 2004
Journal Title
Experimental dermatology
ISSN
0906-67051600-0625
Abstract
The aim of this work was to study the effects and side effects of gemcitabine (2',2'-difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus (HSV)-induced Adamantiades-Behçet's disease (ABD)-like mouse model. For the dose-escalation study, ICR mice were treated intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were inoculated with HSV and classified as having ABD according to a revised Japanese classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or 0.12 microg of dFdC/day over 5 days. Serum levels of interleukin-4 (IL-4), IL-6, IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay. After application of 3 microg of dFdC over 5 days, alanine aminotransferase increased (P = 0.032), but all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC treatment with 0.06 or 0.12 microg of dFdC/day resulted in a dose-dependent improvement of cutaneous manifestations by more than 60% (P = 0.017). There was no significant change in cytokine levels, and none of the cytokine levels correlated with response to treatment. Moreover, dFdC shows promising effects to improve cutaneous lesions in the HSV-induced ABD-like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.
MeSH terms
Alanine Transaminase/analysisAnimalsBehcet Syndrome/*drug therapy/immunology/virologyCytokines/bloodDeoxycytidine/adverse effects/*analogs & derivatives/*therapeutic useDisease Models, AnimalDose-Response Relationship, DrugHerpes Simplex/complicationsImmunosuppressive Agents/adverse effects/*therapeutic useMiceMice, Inbred ICRSkin Ulcer/*drug therapy/immunology/virology
DOI
10.1111/j.0906-6705.2004.00210.x
PMID
15447723
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
손, 성향
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