title: In vitro analysis of photosensitizer accumulation for assessment of applicability of fluorescence diagnosis of squamous cell carcinoma of epidermolysis bullosa patients.
abstract: Epidermolysis bullosa (EB) is a group of inherited skin disorders characterized by blistering following mechanical trauma. Chronic wounds of EB patients often lead to tumors such as squamous cell carcinoma (SCC). Early diagnosis may prevent its invasive growth--frequently the reason of premature mortality of EB-patients. Early detection of tumors is achieved by fluorescence diagnosis (FD), where photosensitizers localize selectively in tumors and fluoresce upon illumination. Excessive accumulation of photosensitizers in inflamed areas, as occasionally found at chronic wounds and tumors due to inflammatory processes, leads to false-positive results in FD. This study analyzed accumulation kinetics of the photosensitizers hypericin and endogenous protoporphyrin IX (PpIX) in different skin cell lines including the three EB subtypes under normal and proinflammatory conditions (stimulated with TNF-alpha). The aim was to assess the applicability of FD of SCC in EB. All cell lines accumulate hypericin or PpIX mostly increasing with incubation time, but with different kinetics. SCC cells of recessive dystrophic EB (RDEB) accumulate less hypericin or PpIX than nonmalignant RDEB cells. Nevertheless, tumor selectivity in vivo might be existent. Non-EB cell lines are more active concerning photosensitizer enrichment. Proinflammatory conditions of skin cell lines seem to have no major influence on photosensitizer accumulation.
authors.affiliation: Division of Molecular Tumorbiology, Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Larisch
authors.forename: Thomas
authors.initials: T
authors.lastname: Verwanger
authors.forename: Kamil
authors.initials: K
authors.lastname: Onder
authors.forename: Barbara
authors.initials: B
authors.lastname: Krammer
mesh_terms: D000873:Anthracenes; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000175:diagnosis*; D045744:Cell Line, Tumor; D004820:Epidermolysis Bullosa / Q000150:complications / Q000175:diagnosis*; D005189:False Positive Reactions; D005347:Fibroblasts / Q000166:cytology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000166:cytology; D008856:Microscopy, Fluorescence / Q000379:methods*; D010569:Perylene / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000378:metabolism; D012878:Skin Neoplasms / Q000150:complications / Q000175:diagnosis*
chemical_list: D000873:Anthracenes; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D010569:Perylene; C004965:hypericin; C028025:protoporphyrin IX