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原位小鼠脑肿瘤模型的代谢

Metabolism of orthotopic mouse brain tumor models.

作者信息

Rosol Michael, Harutyunyan Ira, Xu Jingying, Melendez Elizabeth, Smbatyan Goar, Finlay Jonathan L, Krieger Mark D, Gonzalez-Gomez Ignacio, Reynolds C Patrick, Nelson Marvin D, Erdreich-Epstein Anat, Blüml Stefan

机构信息

Department of Radiology, Division of Hematology-Oncology, Saban Research Institute at Children's Hospital Los Angeles, USA.

出版信息

Mol Imaging. 2009 Jul-Aug;8(4):199-208.

Abstract

We used magnetic resonance spectroscopy to determine whether orthotopic mouse brain tumors grown as xenografts in immunocompromised mice either from human brain tumor cells implanted immediately after surgery or from cultured human tumor lines show metabolic profiles comparable to those of the original tumors. Using a 7 T scanner, spectra were acquired from mice with a human atypical teratoid/rhabdoid tumor (AT/RT) either implanted directly from the surgical specimen or first grown in culture, directly implanted choroid plexus carcinoma (CPC), and two medulloblastoma cell lines. The results were compared with spectra from these same tumors or tumor types in patients and with controls. Metabolic variability of tumors from a single cell line was also evaluated using the medulloblastoma lines. The main metabolic features of human tumors were qualitatively replicated in xenografts. AT/RTs in mice exhibited choline, creatine, and myo-inositol levels comparable to those observed in the patient. As in patients, choline was prominent in experimental CPC. Tumors from a single cell line were comparable. Significant correlations were found with key metabolites in humans and mice; however, differences including lower lipids in the implanted AT/RTs than in patient spectra and taurine observed in all animal spectra were also noted. The causes of these dissimilarities warrant further investigation.

摘要

我们使用磁共振波谱来确定,在免疫缺陷小鼠体内作为异种移植生长的原位小鼠脑肿瘤,无论是来自术后立即植入的人脑肿瘤细胞还是来自培养的人肿瘤细胞系,其代谢谱是否与原始肿瘤相当。使用7 T扫描仪,从患有人类非典型畸胎样/横纹肌样肿瘤(AT/RT)的小鼠获取波谱,这些肿瘤要么直接从手术标本植入,要么先在培养物中生长后再直接植入,还有直接植入的脉络丛癌(CPC)以及两种髓母细胞瘤细胞系。将结果与来自这些相同肿瘤或肿瘤类型的患者波谱以及对照进行比较。还使用髓母细胞瘤细胞系评估了来自单一细胞系的肿瘤的代谢变异性。人肿瘤的主要代谢特征在异种移植中得到了定性复制。小鼠体内的AT/RTs显示出与患者中观察到的胆碱、肌酸和肌醇水平相当。与患者一样,胆碱在实验性CPC中很突出。来自单一细胞系的肿瘤具有可比性。在人和小鼠中发现关键代谢物之间存在显著相关性;然而,也注意到了一些差异,包括植入的AT/RTs中的脂质低于患者波谱中的脂质,以及在所有动物波谱中都观察到了牛磺酸。这些差异的原因值得进一步研究。

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