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Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032103/ https://www.ncbi.nlm.nih.gov/pubmed/29882770 http://dx.doi.org/10.3390/ijms19061684 |
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author | Gruber, Sylvia Arnold, Marlene Cini, Nilsu Gernedl, Victoria Hetzendorfer, Sabine Kowald, Lisa-Marie Kuess, Peter Mayer, Julia Morava, Susanne Pfaffinger, Stephanie Rohorzka, Andreas Dörr, Wolfgang |
author_facet | Gruber, Sylvia Arnold, Marlene Cini, Nilsu Gernedl, Victoria Hetzendorfer, Sabine Kowald, Lisa-Marie Kuess, Peter Mayer, Julia Morava, Susanne Pfaffinger, Stephanie Rohorzka, Andreas Dörr, Wolfgang |
author_sort | Gruber, Sylvia |
collection | PubMed |
description | Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation. |
format | Online Article Text |
id | pubmed-6032103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60321032018-07-13 Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation Gruber, Sylvia Arnold, Marlene Cini, Nilsu Gernedl, Victoria Hetzendorfer, Sabine Kowald, Lisa-Marie Kuess, Peter Mayer, Julia Morava, Susanne Pfaffinger, Stephanie Rohorzka, Andreas Dörr, Wolfgang Int J Mol Sci Article Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation. MDPI 2018-06-06 /pmc/articles/PMC6032103/ /pubmed/29882770 http://dx.doi.org/10.3390/ijms19061684 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gruber, Sylvia Arnold, Marlene Cini, Nilsu Gernedl, Victoria Hetzendorfer, Sabine Kowald, Lisa-Marie Kuess, Peter Mayer, Julia Morava, Susanne Pfaffinger, Stephanie Rohorzka, Andreas Dörr, Wolfgang Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title | Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title_full | Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title_fullStr | Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title_full_unstemmed | Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title_short | Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation |
title_sort | radioprotective effects of dermatan sulfate in a preclinical model of oral mucositis—targeting inflammation, hypoxia and junction proteins without stimulating proliferation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032103/ https://www.ncbi.nlm.nih.gov/pubmed/29882770 http://dx.doi.org/10.3390/ijms19061684 |
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