核磁共振光谱鉴定胶质母细胞瘤肿瘤干细胞对靶向治疗无反应的代谢物生物标志物。,Journal of Proteome Research

当前位置： X-MOL 学术 › J. Proteome Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

核磁共振光谱鉴定胶质母细胞瘤肿瘤干细胞对靶向治疗无反应的代谢物生物标志物。
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-04-18 , DOI: 10.1021/acs.jproteome.8b00801
Ingvild Comfort Hvinden _{1,

2} , Henriette Engen Berg ₁ , Daniel Sachse ₁ , Erlend Skaga _{3,

4} , Frøydis Sved Skottvoll _{1,

5} , Elsa Lundanes ₁ , Cecilie J Sandberg ₃ , Einar O Vik-Mo ₃ , Frode Rise ₁ , Steven Ray Wilson _{1,

5}

Affiliation

胶质母细胞瘤是最常见和最恶性的脑肿瘤，目前的疗法只能带来适度的生存益处。一个主要障碍是我们监测肿瘤治疗效果的能力。目前的成像方式不明确，不鼓励重复活检。为了寻找治疗反应的标志物，我们使用核磁共振波谱来研究生存素抑制剂对原发性胶质母细胞瘤癌症干细胞代谢组的影响。对每个样品仅 300 万个细胞应用高分辨率 NMR 光谱（1H 共振频率：800.03 MHz），我们实现了对氨基酸、核苷和柠檬酸循环成分等的灵敏和高分辨率测定。对于在不同日期培养、制备和测量的对照样品，峰面积相对标准偏差为 15-20%。使用 COLMAR 和 HMDB 数据库对未分级裂解物进行分析，以便直接进行化合物鉴定。主成分分析显示柠檬酸盐水平在无反应细胞中明显上调，而乳酸水平在反应和无反应细胞治疗后显着降低。因此，乳酸和柠檬酸盐可能分别是药物成功吸收和对生存素抑制剂反应不佳的潜在标志物。与基于光谱的蛋白质组学相比，我们的代谢组学方法提供了替代的生物标志物候选物，强调了互补方法的好处。这些初步发现为探索脑肿瘤的体内 MR 光谱 (MRS) 奠定了基础，因为柠檬酸盐和乳酸是 MRS 可见的。总之，NMR 代谢组学是解决胶质母细胞瘤的工具。

"点击查看英文标题和摘要"

Nuclear Magnetic Resonance Spectroscopy to Identify Metabolite Biomarkers of Nonresponsiveness to Targeted Therapy in Glioblastoma Tumor Stem Cells.

Glioblastoma is the most common and malignant brain tumor, and current therapies confer only modest survival benefits. A major obstacle is our ability to monitor treatment effect on tumors. Current imaging modalities are ambiguous, and repeated biopsies are not encouraged. To scout for markers of treatment response, we used NMR spectroscopy to study the effects of a survivin inhibitor on the metabolome of primary glioblastoma cancer stem cells. Applying high resolution NMR spectroscopy (1H resonance frequency: 800.03 MHz) to just 3 million cells per sample, we achieved sensitive and high resolving determinations of, e.g., amino acids, nucleosides, and constituents of the citric acid cycle. For control samples that were cultured, prepared, and measured at varying dates, peak area relative standard deviations were 15-20%. Analyses of unfractionated lysates were performed for straightforward compound identification with COLMAR and HMDB databases. Principal component analysis revealed that citrate levels were clearly upregulated in nonresponsive cells, while lactate levels substantially decreased following treatment for both responsive and nonresponsive cells. Hence, lactate and citrate may be potential markers of successful drug uptake and poor response to survivin inhibitors, respectively. Our metabolomics approach provided alternative biomarker candidates compared to spectrometry-based proteomics, underlining benefits of complementary methodologies. These initial findings make a foundation for exploring in vivo MR spectroscopy (MRS) of brain tumors, as citrate and lactate are MRS-visible. In sum, NMR metabolomics is a tool for addressing glioblastoma.

更新日期：2019-04-20

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南