Document Detail


A novel Peptide to treat oral mucositis blocks endothelial and epithelial cell apoptosis.
MedLine Citation:
PMID:  22420966     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM.
METHODS AND MATERIALS: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer.
RESULTS: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-α-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-α, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction.
CONCLUSIONS: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.
Authors:
Xiaoyan Wu; Peili Chen; Stephen T Sonis; Mark W Lingen; Ann Berger; F Gary Toback
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-13
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  83     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-07-30     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e409-15     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Cell Line
Cricetinae
Cytoprotection / drug effects
Drug Evaluation, Preclinical / methods
Endothelial Cells / cytology,  drug effects,  radiation effects
Epithelial Cells / cytology,  drug effects*,  radiation effects
Humans
Mesocricetus
Peptide Fragments / pharmacology*
Peptide Hormones / pharmacology*
Radiation Injuries, Experimental / drug therapy*
Stomatitis / drug therapy*,  etiology
Tumor Necrosis Factor-alpha
Grant Support
ID/Acronym/Agency:
R21 DE018811/DE/NIDCR NIH HHS; R21 DE018811/DE/NIDCR NIH HHS; R21 DE018811-01A2/DE/NIDCR NIH HHS; R21 DE018811-02/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Peptide Hormones; 0/Tumor Necrosis Factor-alpha; 0/antrum mucosal protein peptide, human
Comments/Corrections

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