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    Improving Topical Non-Melanoma Skin Cancer Treatment:
    in vitro Efficacy of a Novel Guanosine-Analog Phosphonate (2014)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Ali-von Laue, C
    Zoschke, C
    Do, N
    Lehnen, D
    Küchler, S
    Mehnert, W
    Blaschke, T
    Kramer, K D
    Plendl, Johanna (WE 1)
    Weindl, G
    Korting, H C
    Hoeller Obrigkeit, D
    Merk, H-F
    Schäfer-Korting, M
    Quelle
    Skin pharmacology and physiology; 27(4) — S. 173–180
    ISSN: 1660-5535
    Sprache
    Englisch
    Verweise
    DOI: 10.1159/000354118
    Pubmed: 24503861
    Kontakt
    Institut für Veterinär-Anatomie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53555
    anatomie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ± 0.1%. For improved preclinical evaluation, we combined tissue engineering with clinically used keratin-18 quantification. Three doses of 10(-3) mol/l OxBu, dissolved in phosphate-buffered saline as well as loaded to SLN, were effective on reconstructed NMSC. Tumour response and apoptosis induction were evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7 activation as well as by reduced expression of matrix metallopeptidase-2 and Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and thus the drug should be subjected to the next step in preclinical evaluation. © 2014 S. Karger AG, Basel.