关键词: ex vivo mucositis oral mucosa personalized medicine radiosensitivity prediction

Mesh : Humans Mouth Mucosa / radiation effects X-Rays / adverse effects Radiation Injuries / etiology pathology Male Mucositis / etiology pathology Female Dose-Response Relationship, Radiation Stomatitis / etiology pathology Adult Middle Aged

来  源:   DOI:10.3390/ijms25137157   PDF(Pubmed)

Abstract:
Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.
摘要:
头颈部区域的放射治疗是主要的治疗选择之一。然而,这是以不同程度的正常组织毒性为代价的,影响高达80%的患者。粘膜炎会引起疼痛,体重减轻和治疗延迟,导致更差的结果和生活质量下降。因此,迫切需要一种在治疗前预测患者正常粘膜反应的方法.我们在这里描述了一种检测健康口腔粘膜组织中辐射反应的方法。手术切除后从口腔获得粘膜标本,切成薄片,照射和培养三天。七个样品用X射线照射,另外三个样品用X射线和质子照射。健康口腔粘膜组织切片维持正常形态和活力三天。我们测量了对X射线照射的剂量依赖性反应,并使用标准化的自动图像分析比较了同一粘膜样品中的X射线和质子照射。此外,照射后可以检测到炎症诱导因子水平的升高-粘膜炎发展的主要驱动因素。该模型可用于研究粘膜炎发展的机理方面,并可开发为预测正常粘膜中辐射诱导的毒性的测定法。
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