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建立并鉴定患者肿瘤衍生的头颈部鳞状细胞癌异种移植物。

Establishment and characterization of patient tumor-derived head and neck squamous cell carcinoma xenografts.

机构信息

Departments of Cancer Biology and Dentistry and Maxillofacial Prosthetics, Roswell Park Cancer Institute, Buffalo, NY, USA.

出版信息

Cancer Biol Ther. 2009 Dec;8(23):2275-83. doi: 10.4161/cbt.8.23.10137. Epub 2009 Dec 19.

Abstract

The overall purpose of this study was to establish human head and neck squamous cell carcinoma (HNSCC) xenografts in mice by transplantation of surgical tumor tissue and to characterize the growth, histologic and vascular properties of these xenografts. Primary surgical specimens of HNSCC were xenografted into eight-to-twelve week old severe combined immunodeficiency (SCID) mice. Histologic features of primary HNSCC specimens, initial and established xenografts were compared for tumors established from three different head and neck subsites, namely, oral cavity, larynx and base of tongue (one tumor per site). Growth rates of xenografts were compared along with magnetic resonance imaging (MRI) measures of tumor vascularity and correlative CD31-immunostaining. Initial and established xenografts from all three sites demonstrated a squamous phenotype similar to the original patient tumor histology. Established xenografts of oral cavity and larynx exhibited increased keratinization (H&E) compared to initial xenografts and the primary tumor. No differences in tumor growth rates were observed between established xenografts from the different subsites. Xenografts established from SCC of the larynx exhibited increased microvessel density and lumen area (CD31 staining) along with enhanced permeability to the MR contrast agent compared to oral cavity and base of tongue tumors. Our results show that the combination of non-invasive imaging along with histologic evaluation of patient tumor xenografts offers a valuable platform for preclinical investigations in head and neck cancer. However, it is important to recognize the influence of tumor-host interactions on the histologic phenotype of transplanted tumors.

摘要

本研究的总体目的是通过移植手术肿瘤组织在小鼠中建立人头颈部鳞状细胞癌(HNSCC)异种移植物,并对这些异种移植物的生长、组织学和血管特性进行特征描述。将 HNSCC 的原发性手术标本异种移植到 8 至 12 周龄的严重联合免疫缺陷(SCID)小鼠中。比较了来自三个不同头颈部部位(口腔、喉部和舌根部)的肿瘤建立的原发性 HNSCC 标本、初始和已建立的异种移植物的组织学特征(每个部位一个肿瘤)。比较了异种移植物的生长速度以及磁共振成像(MRI)测量的肿瘤血管生成和相关的 CD31 免疫染色。来自所有三个部位的初始和已建立的异种移植物均表现出与原始患者肿瘤组织学相似的鳞状表型。与初始异种移植物和原发性肿瘤相比,口腔和喉部的已建立异种移植物显示出更高的角化(H&E)。在不同部位建立的已建立异种移植物之间未观察到肿瘤生长速度的差异。与口腔和舌根部肿瘤相比,喉 SCC 的已建立异种移植物显示出更高的微血管密度和管腔面积(CD31 染色),以及对 MR 对比剂的通透性增强。我们的研究结果表明,结合非侵入性成像和患者肿瘤异种移植物的组织学评估为头颈部癌症的临床前研究提供了一个有价值的平台。然而,重要的是要认识到肿瘤-宿主相互作用对头颈部移植肿瘤组织学表型的影响。

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