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


METHODS
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.


RESULTS
Although all velafermin-treated groups showed some reduction in the degree of mucositis relative to the vehicle control, the most significant reduction (p < 0.001) 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.


CONCLUSIONS
Thus, velafermin provided therapeutic benefit in a hamster model of oral mucositis induced by fractionated radiation therapy.
Ara
Gulshan
G
CuraGen Corporation, Branford, Connecticut, USA.
Watkins
Brynmor A
BA
Zhong
Haihong
H
Hawthorne
Thomas R
TR
Karkaria
Cyrus E
CE
Sonis
Stephen T
ST
Larochelle
William J
WJ
D000818:Animals; D002610:Cheek; D006224:Cricetinae; D004848:Epithelium / Q000528:radiation effects; D005346:Fibroblast Growth Factors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000532:radiotherapy; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D011832:Radiation Injuries / Q000188:drug therapy*; D013280:Stomatitis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C416003:FGF20 protein, human; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors