Velafermin (rhFGF-20) reduces the severity and duration of hamster cheek pouch mucositis induced by fractionated radiation

Autor:	Stephen T. Sonis, Brynmor A. Watkins, William J. Larochelle, Cyrus Karkaria, Gulshan Ara, Thomas R Hawthorne, Haihong Zhong
Rok vydání:	2008
Předmět:	Male medicine.medical_specialty NF-E2-Related Factor 2 medicine.medical_treatment Gastroenterology Epithelium Cheek pouch Cricetinae Internal medicine medicine Mucositis Animals Humans Radiology Nuclear Medicine and imaging Radiation Injuries Stomatitis Syrian hamsters Fractionated radiation Inflammation Chemotherapy Radiological and Ultrasound Technology Interleukin-6 Tumor Necrosis Factor-alpha business.industry Mouth Mucosa NF-kappa B Cheek medicine.disease Surgery Fibroblast Growth Factors medicine.anatomical_structure business Velafermin
Zdroj:	International Journal of Radiation Biology. 84:401-412
ISSN:	1362-3095 0955-3002
Popis:	Velafermin (recombinant human fibroblast growth factor-20, rhFGF-20) has been shown to reduce the severity and duration of mucositis in preclinical acute (single dose) radiation and chemotherapy/radiation models of oral mucositis. Our present study assessed the impact of velafermin on the severity and duration of oral mucositis that occurred as a consequence of fractionated radiation.Male Golden Syrian hamsters were exposed to eight doses of radiation (7.5 Gy/dose) to the cheek pouch on days 0, 1, 2, 3, 6, 7, 8 and 9 that resulted in severe mucositis. Velafermin (4 mg/kg intraperitoneally) was administered on days 3 and 9; days 2, 3, 8 and 9; days 3, 4, 9 and 10; or days 4, 5, 10 and 11.Although all velafermin-treated groups showed some reduction in the degree of mucositis relative to the vehicle control, the most significant reduction (p0.001) was observed in the groups treated on days 3 and 9 or on days 4, 5, 10 and 11. Further histological analysis of resected buccal mucosa revealed improvements in epithelial tissue degradation, connective tissue degradation and inflammation severity after velafermin treatment. Most notably, velafermin treatment reduced inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) production possibly through nuclear factor-kappaB (NF-kappaB) mediation. The detection of increased NF-E2-related factor-2 (NRF-2) expression in the early onset stage of mucositis in the buccal mucosa suggested additional protective benefits from reactive oxygen species (ROS) generated as a consequence of fractionated radiation treatment.Thus, velafermin provided therapeutic benefit in a hamster model of oral mucositis induced by fractionated radiation therapy.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af83fa3fe450f96030be8864b9518f41 https://doi.org/10.1080/09553000802007601 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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