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建立和鉴定甲状腺未分化癌和头颈部鳞状细胞癌的患者来源异种移植模型。

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma.

机构信息

Precision Medicine Research Center, Sichuan Provincial Key Laboratory of Precision Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University; Sichuan Kangcheng Biotech Co.

Department of Thyroid Surgery, West China Hospital, Sichuan University.

出版信息

J Vis Exp. 2023 Jun 2(196). doi: 10.3791/64623.

DOI:10.3791/64623
PMID:37335092
Abstract

Patient-derived xenograft (PDX) models faithfully preserve the histological and genetic characteristics of the primary tumor and maintain its heterogeneity. Pharmacodynamic results based on PDX models are highly correlated with clinical practice. Anaplastic thyroid carcinoma (ATC) is the most malignant subtype of thyroid cancer, with strong invasiveness, poor prognosis, and limited treatment. Although the incidence rate of ATC accounts for only 2%-5% of thyroid cancer, its mortality rate is as high as 15%-50%. Head and neck squamous cell carcinoma (HNSCC) is one of the most common head and neck malignancies, with over 600,000 new cases worldwide each year. Herein, detailed protocols are presented to establish PDX models of ATC and HNSCC. In this work, the key factors influencing the success rate of model construction were analyzed, and the histopathological features were compared between the PDX model and the primary tumor. Furthermore, the clinical relevance of the model was validated by evaluating the in vivo therapeutic efficacy of representative clinically used drugs in the successfully constructed PDX models.

摘要

患者来源异种移植(PDX)模型忠实地保留了原发肿瘤的组织学和遗传学特征,并保持其异质性。基于 PDX 模型的药效学结果与临床实践高度相关。间变性甲状腺癌(ATC)是甲状腺癌中最恶性的亚型,具有很强的侵袭性、预后不良和治疗受限。尽管 ATC 的发病率仅占甲状腺癌的 2%-5%,但其死亡率高达 15%-50%。头颈部鳞状细胞癌(HNSCC)是最常见的头颈部恶性肿瘤之一,全球每年有超过 60 万例新发病例。本文详细介绍了建立 ATC 和 HNSCC PDX 模型的方案。在这项工作中,分析了影响模型构建成功率的关键因素,并比较了 PDX 模型与原发肿瘤的组织病理学特征。此外,通过评估在成功构建的 PDX 模型中代表性临床使用药物的体内治疗效果,验证了该模型的临床相关性。

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