Publication Database

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

Bandzählung: 27

Heftzählung: 4

Seiten: 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 75784
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.