Imiquimod treatment of papilloma virus and DMBA /TPA-induced cutaneous skin cancer in Mastomys coucha: an unique animal model system useful for preclinical studies.
BACKGROUND
Immune response modifiers including imiquimod can be topically applied for the treatment of both genital warts and benign and malignant skin tumours (e.g. actinic keratosis). In an initial pilot study, we examined the response of spontaneously papillomavirus caused skin lesions (e.g. papillomas, keratoacanthomas) vs. chemically induced skin tumours of Mastomys coucha to imiquimod.


METHODS
Fourteen spontaneously and 16 chemically [initiation with 7,12-dimethylbenzanthracene (DMBA) followed by repeated 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications] induced skin tumours were treated two to three times per week with 5% imiquimod or placebo.


RESULTS
Notably, significant higher regression or growth arrest rates of imiquimod treated animals were observed in chemically vs. spontaneously induced skin tumours [9/14 (64%) vs. 2/11 (18%), P < 0.05]. Regression or growth arrest of both skin tumours from placebo treated animals were similar (1/2 vs. 1/3). Tumour growth of nonresponders was lowest in imiquimod treated animals compared to the placebo or untreated group.


CONCLUSIONS
Imiquimod was able to reduce skin tumour growth particularly in chemically induced lesions of Mastomys coucha. The different clearance rates are most likely due to lower differentiation status of the DMBA/TPA-induced tumours, allowing a better uptake of imiquimod than spontaneously induced papillomas or keratoacanthomas, known to be highly keratinized.
Nafz
J
J
Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Ohnesorge
M
M
Stockfleth
E
E
Rösl
F
F
Nindl
I
I
D015127:9,10-Dimethyl-1,2-benzanthracene; D000634:Aminoquinolines / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000077271:Imiquimod; D051189:Murinae; D010212:Papilloma / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D013755:Tetradecanoylphorbol Acetate; D016896:Treatment Outcome
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate; D000077271:Imiquimod