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Scientific reports
08 08, 2019;9 (1): 11515.

Field cancerization therapy with ingenol mebutate contributes to restoring skin-metabolism to normal-state in patients with actinic keratosis: a metabolomic analysis.

Valeria Righi, Elisabetta Tarentini, Adele Mucci, Camilla Reggiani, Maria Cecilia Rossi, Federica Ferrari, Alice Casari, Cristina Magnoni
Author Information
  1. Valeria Righi: Dipartimento di Scienze per la Qualità della Vita, Università di Bologna, Campus Rimini, Corso D'Augusto 237, 47921, Rimini, Italy. valeria.righi2@unibo.it. ORCID
  2. Elisabetta Tarentini: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. ORCID
  3. Adele Mucci: Dipartimento di Scienze Chimiche e Geologiche, Università di Modena e Reggio Emilia, via G. Campi 103, 41125, Modena, Italy. ORCID
  4. Camilla Reggiani: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.
  5. Maria Cecilia Rossi: Centro Interdipartimentale Grandi Strumenti, Università di Modena e Reggio Emilia, via G. Campi 213/A, 41125, Modena, Italy.
  6. Federica Ferrari: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.
  7. Alice Casari: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.
  8. Cristina Magnoni: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.
PMID: 31395965 DOI: 10.1038/s41598-019-47984-x

Abstract

Actinic keratosis (AK) is a skin premalignant lesion, which progresses into squamous cell carcinoma (SCC) if left untreated. Ingenol mebutate gel is approved for local treatment of non-hyperkeratotic, non-hypertrophic AK; it also has the potential to act as a field cancerization therapy to prevent the progression of AK to SCC. To gain better insights into the mechanisms of ingenol mebutate beyond the mere clinical assessment, we investigated, for the first time, the metabolome of skin tissues from patients with AK, before and after ingenol mebutate treatment, with high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. The metabolomic profiles were compared with those of tissues from healthy volunteers. Overall, we identified a number of metabolites, the homeostasis of which became altered during the process of tumorigenesis from healthy skin to AK, and was restored, at least partially, by ingenol mebutate therapy. These metabolites may help to attain a better understanding of keratinocyte metabolism and to unmask the metabolic pathways related to cell proliferation. These results provide helpful information to identify biomarkers with prognostic and therapeutic significance in AK, and suggest that field cancerization therapy with ingenol mebutate may contribute to restore skin metabolism to a normal state in patients with AK.

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MeSH Term

Biomarkers, Tumor
Case-Control Studies
Diterpenes
Humans
Keratosis, Actinic
Metabolomics
Proton Magnetic Resonance Spectroscopy
Skin

Chemicals

3-ingenyl angelate
Biomarkers, Tumor
Diterpenes
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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