| Exposure of oral mucosa to bioactive milk factors reduces severity of chemotherapy-induced mucositis in the hamster. | |
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MedLine Citation:
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PMID: 12110343 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Julie Clarke; Ross Butler; Gordon Howarth; Leanna Read; Geoff Regester |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oral oncology Volume: 38 ISSN: 1368-8375 ISO Abbreviation: Oral Oncol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-11 Completed Date: 2002-09-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9709118 Medline TA: Oral Oncol Country: England |
Other Details:
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Languages: eng Pagination: 478-85 Citation Subset: IM |
Affiliation:
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Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia 5006, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antimetabolites, Antineoplastic / adverse effects* Cell Division / drug effects Cheek Cricetinae Dose-Response Relationship, Drug Epithelial Cells / drug effects Fluorouracil / adverse effects* Mesocricetus Milk Proteins / pharmacology, therapeutic use* Mouth Mucosa / cytology, drug effects Stomatitis / chemically induced, drug therapy, pathology, prevention & control* |
| Chemical | |
Reg. No./Substance:
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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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