患者来源的唾液腺恶性肿瘤类器官放疗模型的构建与应用评价  

Construction and application of organoid radiological model of patient-derived salivary gland malignant tumors

作　　者：徐凤 孟箭 陈霖[2,3] 陈寅瑜 王守鹏 XU Feng;MENG Jian;CHEN Lin;CHEN Yin-yu;WANG Shou-peng(Xuzhou Clinical College of Xuzhou Medical University,Xuzhou 221000;Department of Stomatology,Xuzhou Central Hospital,Xuzhou 221000;Affiliated Stomatological Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu Province,China)

机构地区：[1]徐州医科大学徐州临床学院,江苏徐州221000 [2]徐州市中心医院口腔科,江苏徐州221000 [3]徐州医科大学口腔医学院,江苏徐州221000

出　　处：《上海口腔医学》2025年第1期25-31,共7页Shanghai Journal of Stomatology

基　　金：国家口腔疾病临床医学研究中心开放课题(NCRCO-202101);江苏省老年健康科研项目(LKM2024031);徐州市重点研发计划(KC21187);徐州医科大学附属医院发展基金项目(XYFY202207)。

摘　　要：目的:构建患者来源的唾液腺恶性肿瘤类器官近距离放疗模型,评价^(125)I粒子干预对不同类器官活性的影响,探讨该模型指导唾液腺恶性肿瘤患者临床个性化治疗的可行性。方法:选取徐州市中心医院收治的唾液腺恶性肿瘤[黏液表皮样癌(mucoepidermoid carcinoma,MEC)、腺样囊性癌(adenoid cystic carcinoma,ACC)和腺泡细胞癌(acinic cell carcinoma,AciCC)]患者活检标本,运用3D培养法构建类器官模型,检测肿瘤组织标本与类器官样本免疫组织化学指标表达水平。构建近距离放疗模型,采用3D细胞微组织检测法检测不同剂量^(125)I粒子对类器官活性的影响,绘制活性曲线并计算IC_(50)值。采用GraphPad Prism 9.0软件对数据进行统计学分析。结果:H-E染色和免疫组织化学染色结果鉴定类器官与标本肿瘤具有同源性。^(125)I粒子对5例唾液腺恶性肿瘤类器官(1例ACC、2例AciCC和2例MEC)的IC_(50)均值分别为8508、6053、5203、10379和7743 cGy;AciCC对^(125)I粒子的敏感性更高,同种肿瘤的不同个体对^(125)I粒子的敏感性存在差异。结论:针对患者来源的唾液腺恶性肿瘤标本建立体外肿瘤类器官培养平台,检测其组织学结构、分子标志物表达符合原始患者肿瘤细胞的特征。类器官近距离放疗模型干预结果提示,该模型具有明显个体化差异,为^(125)I粒子应用于一些局部、复发、晚期、低分化或手术治疗意义不大的患者的有效性提供了依据。该模型建模时间短、价格低、可高通量检测,可在体外预测患者治疗反应,帮助恶性肿瘤的风险评估和建立个体化精准治疗方案。PURPOSE:To construct a brachytherapentic model of patient-derived salivary gland malignant tumor organoids,and evaluate the impact of ^(125)I radioactive seeds intervention on the activity of different organoids,and explore the feasibility of using this model to guide clinical personalized treatment of salivary gland malignant tumors.METHODS:Biopsy specimens from patients with malignant salivary gland tumors including mucoepidermoid carcinoma(MEC),adenoid cystic carcinoma(ACC)and acinic cell carcinoma(AciCC)from Xuzhou Central Hospital were collected,and 3D culture method was used to construct the organoid model.The expression levels of immunohistochemical indicators in salivary gland malignant tumor tissue samples and organoid samples were detected.Brachytherapentic model was constructed and the effect of different doses of ^(125)I seeds on organoid activity were detected using 3D cell viability assay.The activity curves were plotted and the IC_(50) values were calculated.The data were analyzed by GraphPad Prism 9.0 software.RESULTS:H-E staining results and immunohistochemical staining results identified homology between organoids and specimen tumors.The mean IC_(50) values of ^(125)I seeds on 5 cases of salivary gland malignant tumor organoids(1 case of ACC,2 cases of AciCC and 2 cases of MEC)were 8508,6053,5203,10379 and 7743 cGy,respectively.AciCC has a higher sensitivity to ^(125)I seeds,and the sensitivity of ^(125)I seeds varied among individuals of the same type of tumor.CONCLUSIONS:An in vitro tumor organoid culture platform has been established for specimens from patients with salivary gland malignant tumors,and its morphological,histological structure,and molecular marker expression are consistent with the characteristics of tumor cells in the original specimens.Intervention results indicated that the model has significant individualized differences,providing a theoretical basis and methodological reference for the effectiveness of ^(125)I seeds in some patients with local,recurrent,advanced,poorly dif

关 键 词：类器官 唾液腺恶性肿瘤 125I粒子 抗癌活性 

分 类 号：R739.87[医药卫生—肿瘤]