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使用直线加速器建立辐射诱导的口腔黏膜炎仓鼠模型可增强临床前研究在治疗策略研究中的相关性。

Radiation-induced oral mucositis hamster model using a linear accelerator enhances clinical relevance of preclinical studies for treatment strategy investigation.

机构信息

Department of Chemical and Materials Engineering University of Kentucky Lexington KY USA.

Department of Internal Medicine University of Kentucky Lexington KY USA.

出版信息

Animal Model Exp Med. 2021 Jan 26;4(1):47-53. doi: 10.1002/ame2.12148. eCollection 2021 Mar.

Abstract

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory-initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation-induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro-inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

摘要

用于模拟和评估人类口腔粘膜炎(OM)的生物临床效应和反应的动物转化模型是必要的。这些模型应模拟导致氧化应激和炎症引发组织变化的高水平辐射暴露。已经广泛研究了仓鼠模型以观察辐射暴露的病理效应,并有助于开发有效的治疗方法。为了成功地评估具有一致性和相关性的治疗方案的潜力,开发了一种使用癌症患者每天使用的临床线性加速器对孤立的、外翻的颊囊进行辐射诱导的 OM 仓鼠模型。对仓鼠颊囊的隔离、外翻进行剂量暴露,以及损伤、促炎标志物、组织学和弹性分析的进展,以验证损伤模型的可重复性和再现性。该模型的研究结果表明,它能够在 28 天内使用 60Gy 的急性剂量持续诱导损伤和愈合。该模型的开发增强了评估潜在有效治疗方法的临床相关性,现在可以在功效研究中用于更好地在一种易于转化为临床研究的临床前模型中评估开发的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b6/7954840/905b97df37cd/AME2-4-47-g003.jpg

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