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鸡胚绒毛尿囊膜(CAM)作为一种用于精准医学和临床前研究的多功能患者来源异种移植(PDX)平台。

The chick chorioallantoic membrane (CAM) as a versatile patient-derived xenograft (PDX) platform for precision medicine and preclinical research.

作者信息

DeBord Logan C, Pathak Ravi R, Villaneuva Mariana, Liu Hsuan-Chen, Harrington Daniel A, Yu Wendong, Lewis Michael T, Sikora Andrew G

机构信息

Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine Houston, TX 77030, USA.

The University of Texas Health Science Center at Houston, School of Dentistry, Department of Diagnostic and Biomedical Sciences Houston, TX 77054, USA.

出版信息

Am J Cancer Res. 2018 Aug 1;8(8):1642-1660. eCollection 2018.

Abstract

Patient-derived xenografts (PDX) are an increasingly valuable tool in oncology, providing biologically faithful models of many different cancer types, and potential platforms for the development of precision oncology approaches. However, PDX have primarily been established in immunodeficient rodent models, with accompanying cost and efficiency constraints that pose barriers to more widespread adoption. The chicken egg chorioallantoic membrane (CAM) is an alternative PDX model. We provide here a comprehensive review of studies that grafted primary human tissue, as opposed to cell lines, onto the CAM. Twenty publications met our criteria of having inoculated patient-derived tumor tissue onto the CAM. Successful engraftment has been reported for over a dozen tumor subtypes, supporting the appropriateness of the CAM as a PDX platform. Resemblance of xenografts to the original patient tumor, increased vascularity of the CAM following engraftment, and micrometastasis into the chick mesenchyme were frequently reported. Application of standard or experimental cancer therapies to xenografts has also been undertaken, with the discovery of both synergistic drug effects and positive associations between the assay and clinical outcome. The CAM provides opportunities for RNA and DNA based sequencing of patient tumors, and the ability to efficiently (in 5-10 days) test multiple targeted therapies on fragments derived from the same tumor. While routine use of the CAM-based PDX model would benefit from a more-complete understanding of the stromal environment of CAM xenografts and interaction with the developing avian immune system, current literature supports the model's potential as an efficient, scalable precision medicine platform.

摘要

患者来源的异种移植物(PDX)在肿瘤学中是一种越来越有价值的工具,它能提供多种不同癌症类型的生物学忠实模型,也是开发精准肿瘤学方法的潜在平台。然而,PDX主要是在免疫缺陷啮齿动物模型中建立的,随之而来的成本和效率限制成为了其更广泛应用的障碍。鸡胚绒毛尿囊膜(CAM)是一种替代的PDX模型。我们在此全面综述了将原发性人体组织(而非细胞系)移植到CAM上的研究。有二十篇出版物符合我们将患者来源的肿瘤组织接种到CAM上的标准。已有超过十二种肿瘤亚型的成功移植报道,这支持了CAM作为PDX平台的适用性。经常有报道称异种移植物与原始患者肿瘤相似、移植后CAM血管增多以及出现向鸡间充质的微转移。也已对异种移植物应用标准或实验性癌症疗法,发现了协同药物效应以及该检测与临床结果之间的正相关关系。CAM为患者肿瘤的基于RNA和DNA的测序提供了机会,并且能够在5至10天内高效地对来自同一肿瘤的片段测试多种靶向疗法。虽然基于CAM的PDX模型的常规使用将受益于对CAM异种移植物的基质环境以及与发育中的禽类免疫系统相互作用的更全面理解,但当前文献支持该模型作为高效、可扩展的精准医学平台的潜力。

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