Document Detail

Exposure of oral mucosa to bioactive milk factors reduces severity of chemotherapy-induced mucositis in the hamster.
MedLine Citation:
PMID:  12110343     Owner:  NLM     Status:  MEDLINE    
A biologically active extract containing bovine whey proteins, whey growth factor extract-A (WGFE-A) was administered topically to the oral mucosa of hamsters and its ability to prevent and treat chemotherapy-induced oral mucositis investigated. Oral mucositis was induced in Syrian golden hamsters through a combination treatment of the antimetabolite chemotherapy drug 5-fluorouracil (5-FU), and mild abrasion of the cheek pouch. WGFE-A administered to the oral mucosa via hydrogel and liquid treatments, pre and concurrent to 5-FU therapy, resulted in significantly reduced mucosal ulceration. The protective effect was dose dependent with greatest benefit from WGFE-A doses applied at 4.2 mg/ml gel and 14 mg/ml mouthwash (P<0.01). The protective activity of WGFE-A also appeared related to mode of delivery. Administration of WGFE-A from an alternate vehicle Orabase(R) did not alleviate mucositis compared to WGFE-A applied in hydrogel. When administered continuously after the chemotherapy schedule, WGFE-A failed to reduce ulcer area when applied over a 12-day period. In a separate study, cell cycle staining indicated that cheek pouch mucosal epithelial cells pre-exposed to WGFE-A in-vivo showed a reduced rate of proliferation, measured as a 21% reduction in the bromodeoxyuridine (BrdU) cell labelling index (P<0.04). This was consistent with a protective mode of WGFE-A action against anti-metabolites such as 5-FU which target rapidly dividing cells. The results were also consistent with recent in vitro data showing protective properties from WGFE-A administered to epithelial cells given pre/concurrent to chemotherapy exposure. WGFE-A is known to contain mitogens which stimulate cells of mesenchymal origin and inhibit epithelial cell growth in culture. Several WGFE-A constituents are likely to confer protective effects on the cheek mucosa, including anti-proliferative, anti-apoptotic and anti-microbial factors. WGFE-A provides a potentially valuable source of topically delivered proteins for clinical application in preventing severe oral mucositis caused by chemotherapy.
Julie Clarke; Ross Butler; Gordon Howarth; Leanna Read; Geoff Regester
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oral oncology     Volume:  38     ISSN:  1368-8375     ISO Abbreviation:  Oral Oncol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-11     Completed Date:  2002-09-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  478-85     Citation Subset:  IM    
Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia 5006, Australia.
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MeSH Terms
Antimetabolites, Antineoplastic / adverse effects*
Cell Division / drug effects
Dose-Response Relationship, Drug
Epithelial Cells / drug effects
Fluorouracil / adverse effects*
Milk Proteins / pharmacology,  therapeutic use*
Mouth Mucosa / cytology,  drug effects
Stomatitis / chemically induced,  drug therapy,  pathology,  prevention & control*
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Milk Proteins; 0/whey protein; 51-21-8/Fluorouracil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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