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Publikation: Zeitschriftenartikel
Tumor-preferential induction of immune responses and epidermal cell death in actinic keratoses by ingenol mebutate
Grunddaten
Abstract
Autoren
Einrichtung
Grunddaten
Titel
Tumor-preferential induction of immune responses and epidermal cell death in actinic keratoses by ingenol mebutate
Erscheinungsjahr
2016
Band
11
Heft-Nr.
9
Jahr
2016
Publikationsform
Elektronische Ressource
Publikationsart
Zeitschriftenartikel
Sprache
Englisch
DOI
10.1371/journal.pone.0160096
Letzte Änderung
11.01.2022 06:03:10
Bearbeitungsstatus
durch UB Rostock abschließend validiert
Dauerhafte URL
http://purl.uni-rostock.de/fodb/pub/67103
Links zu Katalogen
Abstract
The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate, against actinic keratosis (AK) has resulted in its recent approval. We conducted the first comprehensive analysis of the cellular and molecular mode of action of topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients in a phase I, single-center, open-label, within-patient comparison. As early as 1 day after application, ingenol mebutate induced profound epidermal cell death, along with a strong infiltrate of CD4+ and CD8+ T-cells, neutrophils, and macrophages. Endothelial ICAM-1 activation became evident after 2 days. The reaction pattern was significantly more pronounced in AK compared with uninvolved skin, suggesting a tumor-preferential mode of action. Extensive molecular analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated alterations in gene clusters functionally associated with epidermal development, inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals a unique mode of action linking directly to anti-tumoral effects. Trial Registration: ClinicalTrials.gov NCT01387711
Autoren
Emmert, Steffen
Hänßle, Holger
Einrichtung
UMR/Klinik und Poliklinik für Dermatologie und Venerologie (DUK)