Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers.

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers.
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DOI:
10.1186/1476-4598-9-66
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发表时间:
2010-03-23
期刊:
影响因子:
37.3
通讯作者:
Howe FA
Howe FA
中科院分区:
医学1区
文献类型:
--
作者:
Wright AJ;Fellows GA;Griffiths JR;Wilson M;Bell BA;Howe FA

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高分辨率魔角旋转(HRMAS)核磁共振波谱可以对整个活检样本进行详细的代谢分析,以研究肿瘤生物学和肿瘤分类。对“核磁共振可见”的小分子代谢物进行准确的生化分配将改善我们对HRMAS数据的解释,并将核磁共振肿瘤生物标记物转化为体内研究。用1D和2D 1H HRMAS核磁共振确定29种小分子代谢物和8种大分子信号占主要类型脑肿瘤(星形细胞瘤II级、脑胶质瘤III级、胶质母细胞瘤、转移瘤、脑膜瘤和淋巴瘤)HRMAS谱的大部分。在这些脑瘤类型之间,这些代谢物中的20种浓度的差异具有统计学意义。在扩展的2D数据采集过程中,HRMAS技术本身会影响样品分析:甘氨酸、谷胱甘肽和甘油磷胆碱都显示出微小的浓度变化;HRMAS后对样品的分析表明,结构损伤可能会影响后续的组织病理学分析。许多小分子代谢物已被确定为潜在的肿瘤类型的生物标志物,可能使开发更具选择性的体内1H核磁共振获取方法用于脑肿瘤的诊断和预后。
High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.
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