- 作者：Xiaoyan Wu ; M.D. ; Ph.D.&lowast ; ; Peili Chen ; M.D. ; Ph.D.&lowast ; ; Stephen T. Sonis ; D.M.D. ; D.M.Sc.&Dagger ; ; § ; ; Mark W. Lingen ; D.D.S. ; Ph.D.&dagger ; ; Ann Berger ; Ph.D.鈥?/sup> ; F. Gary Toback ; M.D. ; Ph.D.&lowast ; ; gtoback@medicine.bsd.uchicago.edu
- 关键词：Oral mucositis ; Apoptosis ; Endothelial cells ; Epithelial cells ; Gastrokine 1
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2012
- 期刊代码：136_03603016
- 类别：med
- 出版时间：1 July, 2012
- 卷：83
- 期：3
- 页码：e409-e415
- 文件大小：970 K
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-伪-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-伪, 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.