title: A novel Peptide to treat oral mucositis blocks endothelial and epithelial cell apoptosis.
abstract: OBJECTIVE
  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
  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.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.forename: Peili
authors.initials: P
authors.lastname: Chen
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.forename: Ann
authors.initials: A
authors.lastname: Berger
authors.forename: F Gary
authors.initials: FG
authors.lastname: Toback
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D019610:Cytoprotection / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008647:Mesocricetus; D010446:Peptide Fragments / Q000494:pharmacology*; D036361:Peptide Hormones / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha
chemical_list: D010446:Peptide Fragments; D036361:Peptide Hormones; D014409:Tumor Necrosis Factor-alpha; C573936:antrum mucosal protein peptide, human