Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice

Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice
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DOI:
10.1097/01.mlg.0000240185.14224.7d
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发表时间:
2006-11-01
期刊:
影响因子:
2.6
通讯作者:
Welling, D. Bradley
Welling, D. Bradley
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Long-Sheng;Abraham, Jacob;Welling, D. Bradley

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目标。前庭神经鞘瘤新治疗选择的发展模式。(VS)缺乏治疗。本研究的目的是建立一种可量化的人与小鼠异种移植模型。研究设计与方法。都是大鼠恶性神经鞘瘤。将KE-F11和RT4细胞和人恶性神经鞘瘤细胞(HMS-97)接种于严重联合免疫缺陷(SCID)小鼠的大腿坐骨神经附近。此外,人类良性VS样本被植入另一组SCID小鼠。在接下来的6个月中,根据磁共振图像计算三维肿瘤体积。结果。植入恶性神经鞘瘤细胞的小鼠在2周内出现可见的肿瘤。使用4.7特斯拉磁共振成像和免疫组织病理学检查发现所有KE-F11和HMS-97异种移植瘤均为实体瘤,而RT4异种移植瘤始终发展为囊性神经鞘瘤。VS异种移植的生长速度表现出与人类VS相似的可变性。大多数VS异种移植物没有生长,但在整个研究过程中持续存在,而15个异种移植物中有两个显著生长。组织病理学和免疫组织化学检查证实,VS异种移植物在长时间植入后仍保持其原有的显微和免疫组织化学特征。结论。这项研究描述了第一个囊性神经鞘瘤的动物模型。此外,我们还展示了使用高场磁共振成像来量化VS异种移植物随时间的生长。VS异种移植代表了一种补充Nf2转基因和基因敲除小鼠进行翻译VS研究的模型。
Objectives. Models for the development of new treatment options in vestibular schwannoma. (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. Study Design and Methods. Both rat malignant schwannoma. cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. Results. Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. Conclusions. This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.