Abstract
PurposeTo investigate the mechanistic background of the muco-protective effect of systemic heparin treatment on the development of radiation-induced oral mucositis in mice.Materials and methodsFractionated irradiation was given to the snouts of male C3H/Neu mice over 2 weeks (10 × 3 Gy), either alone or in combination with daily subcutaneous application of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively). Over this course of 14 days, groups of mice (n = 3) were sacrificed every second day, their tongues excised and processed for histological analysis. The epithelial radiation response with and without heparin treatment was evaluated in terms of tissue morphology, proliferation and expression of cell contact molecules.ResultsSystemic treatment with heparins significantly reduced the cellular effects of irradiation to the oral epithelium. Heparin treated animals showed significantly higher total epithelial cell numbers and thickness throughout the study course. Bromodeoxyuridine (BrdU) incorporation analyses revealed that markedly more epithelial cells retained their proliferative capacity in the beginning of the first treatment week, but the proliferation of the mucosa was not stimulated during the rest of the study course. The expression of the adherens junction protein β‑catenin was slightly elevated in heparin treated animals, on day 2 the increase was statistically significant. The expression of e‑cadherin and occludin was mostly unaffected by the concomitant heparin treatment.ConclusionThe findings of this study indicate an interplay of additional heparin treatment with the repopulation processes, leading to an earlier onset of this adaptive radiation response in oral mucosa. Importantly, we could demonstrate that the protective potential of heparin did not rely on stimulation of normal tissue proliferation. Since both heparin preparations are already approved for clinical use, they are considered as promising candidates for future clinical studies.
Highlights
Oral mucositis is the most frequently occurring early side effect of radiotherapy in patients treated for head-and-neck cancers
Die Expression von e-Cadherin und Occludin wurde durch die begleitende Heparinbehandlung nicht beeinflusst
Da beide Heparine bereits in der Klinik zugelassen sind, stellen sie geeignete Kandidaten für weiterführende klinische Studien dar
Summary
Oral mucositis is the most frequently occurring early side effect of radiotherapy in patients treated for head-and-neck cancers. Oral mucositis significantly reduces the patient’s quality of life due to mucositis-associated pain and speaking and swallowing difficulties, which often necessitate parenteral nutrition. Radiation-induced oral mucositis often leads to local and systemic infections because of disturbed mucosal barrier function. Besides the socio-economic factor due to mucositis-associated hospitalizations [2], these radiation-induced complications might lead to treatment interruptions significantly lowering the tumor control probability. Being a recombinant human keratinocyte growth factor (KGF), the question regarding the proliferation stimulating effect on the malignant cells is still of concern and, in combination with its high costs, prevents the use of palifermin in head-and-neck patients [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
