PDF(Pubmed)
Abstract：
High-grade gliomas (HGG) are aggressive brain tumors associated with short median patient survival and limited response to therapies, driving the need to develop tools to improve patient outcomes. Patient-derived xenograft (PDX) models, such as mouse PDX, have emerged as potential Avatar platforms for personalized oncology approaches, but the difficulty for some human grafts to grow successfully and the long time required for mice to develop tumors preclude their use for HGG.
We used a rapid and efficient ex-ovo chicken embryo chorioallantoic membrane (CAM) culture system to evaluate the efficacy of oncologic drug options for HGG patients.
Implantation of fresh glioma tissue fragments from 59 of 60 patients, that include difficult-to-grow IDH-mutated samples, successfully established CAM tumor xenografts within 7 days, with a tumor take rate of 98.3%. These xenografts faithfully recapitulate the histological and molecular characteristics of the primary tumor, and the ability of individual fragments to form tumors was predictive of poor patient prognosis. Treatment of drug-sensitive or drug-resistant xenografts indicates that the CAM-glioma assay enables testing tumor sensitivity to temozolomide and carboplatin at doses consistent with those administered to patients. In a proof-of-concept study involving 14 HGG patients, we observed a correlation of 100% between the CAM xenograft response to temozolomide or carboplatin and the clinical response of patients.
The CAM-glioma model is a fast and reliable assay that has the potential to serve as a complementary model to drug discovery and a real-time Avatar platform to predict the best treatment for HGG patients.
We used a rapid and efficient ex-ovo chicken embryo chorioallantoic membrane (CAM) culture system to evaluate the efficacy of oncologic drug options for HGG patients.
Implantation of fresh glioma tissue fragments from 59 of 60 patients, that include difficult-to-grow IDH-mutated samples, successfully established CAM tumor xenografts within 7 days, with a tumor take rate of 98.3%. These xenografts faithfully recapitulate the histological and molecular characteristics of the primary tumor, and the ability of individual fragments to form tumors was predictive of poor patient prognosis. Treatment of drug-sensitive or drug-resistant xenografts indicates that the CAM-glioma assay enables testing tumor sensitivity to temozolomide and carboplatin at doses consistent with those administered to patients. In a proof-of-concept study involving 14 HGG patients, we observed a correlation of 100% between the CAM xenograft response to temozolomide or carboplatin and the clinical response of patients.
The CAM-glioma model is a fast and reliable assay that has the potential to serve as a complementary model to drug discovery and a real-time Avatar platform to predict the best treatment for HGG patients.
摘要：
背景：高级别胶质瘤（HGG）是侵袭性脑肿瘤，与患者中位生存期短和对治疗反应有限有关，推动需要开发工具来改善患者的治疗效果。患者来源的异种移植（PDX）模型，比如鼠标PDX，已经成为个性化肿瘤学方法的潜在阿凡达平台，但是某些人类移植物难以成功生长，并且小鼠发展肿瘤所需的时间很长，因此无法将其用于HGG。
方法：我们使用了一种快速有效的外卵鸡胚绒毛尿囊膜（CAM）培养系统来评估肿瘤药物选择对HGG患者的疗效。
结果：60例患者中有59例植入新鲜神经胶质瘤组织碎片，其中包括难以生长的IDH突变样品，在7天内成功建立CAM肿瘤异种移植物，肿瘤的取出率为98.3%。这些异种移植物忠实地概括了原发性肿瘤的组织学和分子特征，个体片段形成肿瘤的能力预示着患者预后不良。药物敏感性或耐药性异种移植物的治疗表明CAM-神经胶质瘤测定能够以与给予患者的剂量一致的剂量测试肿瘤对替莫唑胺和卡铂的敏感性。在一项涉及14名HGG患者的概念验证研究中，我们观察到对替莫唑胺或卡铂的CAM异种移植反应与患者的临床反应之间有100%的相关性.
结论：CAM-神经胶质瘤模型是一种快速可靠的检测方法，有可能作为药物发现的补充模型和实时阿凡达平台来预测HGG患者的最佳治疗方法。
方法：我们使用了一种快速有效的外卵鸡胚绒毛尿囊膜（CAM）培养系统来评估肿瘤药物选择对HGG患者的疗效。
结果：60例患者中有59例植入新鲜神经胶质瘤组织碎片，
结论：CAM-神经胶质瘤模型是一种快速可靠的检测方法，有可能作为药物发现的补充模型和实时阿凡达平台来预测HGG患者的最佳治疗方法。
