Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker

Abstract The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical...

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Autores principales: Skaidre Jankovskaja, Johan Engblom, Melinda Rezeli, György Marko-Varga, Tautgirdas Ruzgas, Sebastian Björklund
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/adb075fb242b4491a8d2ced12964cc68
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spelling oai:doaj.org-article:adb075fb242b4491a8d2ced12964cc682021-12-02T14:01:22ZNon-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker10.1038/s41598-020-79903-w2045-2322https://doaj.org/article/adb075fb242b4491a8d2ced12964cc682021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79903-whttps://doaj.org/toc/2045-2322Abstract The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.Skaidre JankovskajaJohan EngblomMelinda RezeliGyörgy Marko-VargaTautgirdas RuzgasSebastian BjörklundNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Skaidre Jankovskaja
Johan Engblom
Melinda Rezeli
György Marko-Varga
Tautgirdas Ruzgas
Sebastian Björklund
Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
description Abstract The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.
format article
author Skaidre Jankovskaja
Johan Engblom
Melinda Rezeli
György Marko-Varga
Tautgirdas Ruzgas
Sebastian Björklund
author_facet Skaidre Jankovskaja
Johan Engblom
Melinda Rezeli
György Marko-Varga
Tautgirdas Ruzgas
Sebastian Björklund
author_sort Skaidre Jankovskaja
title Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
title_short Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
title_full Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
title_fullStr Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
title_full_unstemmed Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
title_sort non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/adb075fb242b4491a8d2ced12964cc68
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