| A novel Peptide to treat oral mucositis blocks endothelial and epithelial cell apoptosis. | |
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MedLine Citation:
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PMID: 22420966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiaoyan Wu; Peili Chen; Stephen T Sonis; Mark W Lingen; Ann Berger; F Gary Toback |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-03-13 |
Journal Detail:
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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:
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Created Date: 2012-05-28 Completed Date: 2012-07-30 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7603616 Medline TA: Int J Radiat Oncol Biol Phys Country: United States |
Other Details:
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Languages: eng Pagination: e409-15 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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R21 DE018811/DE/NIDCR NIH HHS; R21 DE018811-01A2/DE/NIDCR NIH HHS; R21 DE018811-02/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Peptide Fragments; 0/Peptide Hormones; 0/Tumor Necrosis Factor-alpha; 0/antrum mucosal protein peptide, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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