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Extensive astrocyte metabolism of γ-aminobutyric acid (GABA) sustains glutamine synthesis in the mammalian cerebral cortex.γ-氨基丁酸(GABA)在星形胶质细胞中的广泛代谢维持了哺乳动物大脑皮层中的谷氨酰胺合成。
Glia. 2020 Dec;68(12):2601-2612. doi: 10.1002/glia.23872. Epub 2020 Jun 25.
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Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism.雷公藤红素通过 Nrf2 驱动的谷胱甘肽代谢抑制 IDH1 突变恶性肿瘤。
Proc Natl Acad Sci U S A. 2020 May 5;117(18):9964-9972. doi: 10.1073/pnas.1913633117. Epub 2020 Apr 20.
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Blockade of Glutathione Metabolism in -Mutated Glioma.阻断 - 突变型神经胶质瘤中的谷胱甘肽代谢。
Mol Cancer Ther. 2020 Jan;19(1):221-230. doi: 10.1158/1535-7163.MCT-19-0103. Epub 2019 Sep 23.
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Simultaneous editing of GABA and GSH with Hadamard-encoded MR spectroscopic imaging.使用 Hadamard 编码磁共振波谱成像同时编辑 GABA 和 GSH。
Magn Reson Med. 2019 Jul;82(1):21-32. doi: 10.1002/mrm.27702. Epub 2019 Feb 22.
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Multi-vendor standardized sequence for edited magnetic resonance spectroscopy.多供应商标准化编辑磁共振波谱序列。
Neuroimage. 2019 Apr 1;189:425-431. doi: 10.1016/j.neuroimage.2019.01.056. Epub 2019 Jan 22.
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Validation of in vivo MRS measures of metabolite concentrations in the human brain.体内 MRS 测量人类大脑代谢物浓度的验证。
NMR Biomed. 2019 Mar;32(3):e4058. doi: 10.1002/nbm.4058. Epub 2019 Jan 21.
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GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas.人神经胶质瘤中 GABA、谷氨酰胺、谷氨酸氧化和琥珀酸半醛脱氢酶的表达。
J Exp Clin Cancer Res. 2018 Nov 7;37(1):271. doi: 10.1186/s13046-018-0946-5.
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Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate.通过对 2-羟戊二酸的体内 3D MRS 成像探测胶质母细胞瘤患者中突变 IDH1 抑制剂的药效动力学。
Nat Commun. 2018 Apr 16;9(1):1474. doi: 10.1038/s41467-018-03905-6.
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In vivo characterization of brain metabolism by H MRS, C MRS and FDG PET reveals significant glucose oxidation of invasively growing glioma cells.通过 H MRS、C MRS 和 FDG PET 对脑代谢进行体内特征分析,揭示了侵袭性生长的神经胶质瘤细胞有显著的葡萄糖氧化作用。
Int J Cancer. 2018 Jul 1;143(1):127-138. doi: 10.1002/ijc.31299. Epub 2018 Feb 21.
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Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux and Sensitizes Cells to Oxidative Stress.消耗 NADPH 合成 2-HG 会增加戊糖磷酸途径通量,并使细胞对氧化应激敏感。
Cell Rep. 2018 Jan 9;22(2):512-522. doi: 10.1016/j.celrep.2017.12.050.

体内 3T 下 HERMES 谱编辑检测到 IDH1 突变型低级别胶质瘤中 GSH 和 GABA 减少。

GSH and GABA decreases in IDH1-mutated low-grade gliomas detected by HERMES spectral editing at 3 T in vivo.

机构信息

Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Jinan Blood Center, Jinan, Shandong, China.

出版信息

Neurochem Int. 2020 Dec;141:104889. doi: 10.1016/j.neuint.2020.104889. Epub 2020 Oct 22.

DOI:10.1016/j.neuint.2020.104889
PMID:33115694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7704685/
Abstract

Isocitrate dehydrogenase 1 (IDH1) mutational status is an important prognostic biomarker in gliomas. γ-aminobutyric acid (GABA) and reduced glutathione (GSH) play an important role in energy production, which is related to tumor progression. Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES) is able to detect GABA and GSH in healthy controls. This study aims to examine GABA and GSH alterations in IDH1-mutated low-grade gliomas using HERMES. We prospectively enrolled 14 suspected low-grade gliomas and 6 healthy control patients in this study, all cases underwent a 3 T MRI scan, including T1-weighted imaging and HERMES acquisition with a volume of interest 3 × 3 × 3 cm. HERMES detects a "GABA+" signal that includes contributions from macromolecules and homocarnosine. GABA+ and GSH in tumor foci (group 1), contralateral cerebral regions (group 2) and healthy controls (group 3) were quantified using Gannet. The fitting errors and SNR of HERMES for GABA+ and GSH were analyzed; FWHM of the unsuppressed water signal was also recorded. The Wilcoxon signed-rank test was performed to test for differences between contralateral GABA+ and GSH levels, and differences in GABA+, GSH and fitting errors/SNR between the three groups were analyzed using analysis of variance (ANOVA). Eleven IDH1-mutant low-grade gliomas (5 Female and 6 Male, age 33-69) and 6 healthy subjects (2 Female and 4 Male, age 35-60) were finally enrolled this study. The mean water linewidth across all subjects was 9.67 ± 2.28 Hz. The Wilcoxon signed-rank test revealed that GABA+ and GSH were decreased significantly in glioma foci compared with contralateral regions, whereas no differences were seen between the left and right regions in healthy controls. ANOVA showed that GABA+ and GSH levels in tumor were lower than contralaterally and in healthy controls, while no differences were observed between the contralateral healthy tissue and healthy controls. No differences of fitting errors or SNR were found between tumors, contralateral regions or healthy controls. Our results suggest that HERMES is a reliable tool to simultaneously measure GABA and GSH alterations in low-grade gliomas with IDH1 mutations.

摘要

异柠檬酸脱氢酶 1(IDH1)突变状态是胶质瘤的重要预后生物标志物。γ-氨基丁酸(GABA)和还原型谷胱甘肽(GSH)在能量产生中发挥重要作用,与肿瘤进展有关。Hadamard 编码和 Mega-Edited 光谱重建(HERMES)能够在健康对照中检测 GABA 和 GSH。本研究旨在使用 HERMES 检查 IDH1 突变的低级别胶质瘤中 GABA 和 GSH 的变化。我们前瞻性地招募了 14 名疑似低级别胶质瘤患者和 6 名健康对照患者,所有患者均接受了 3T MRI 扫描,包括 T1 加权成像和 HERMES 采集,感兴趣区为 3×3×3cm。HERMES 检测到一个包含大分子和同型瓜氨酸贡献的“GABA+”信号。使用 Gannet 定量测定肿瘤灶(第 1 组)、对侧大脑区域(第 2 组)和健康对照组(第 3 组)中的 GABA+和 GSH。分析了 HERMES 检测 GABA+和 GSH 的拟合误差和 SNR,还记录了未抑制水信号的 FWHM。使用 Wilcoxon 符号秩检验检验对侧 GABA+和 GSH 水平的差异,并用方差分析(ANOVA)分析三组之间 GABA+、GSH 和拟合误差/SNR 的差异。最终纳入了 11 例 IDH1 突变的低级别胶质瘤患者(5 名女性和 6 名男性,年龄 33-69 岁)和 6 名健康受试者(2 名女性和 4 名男性,年龄 35-60 岁)。所有受试者的平均水线宽为 9.67±2.28Hz。Wilcoxon 符号秩检验显示,与对侧区域相比,肿瘤灶中的 GABA+和 GSH 显著降低,而健康对照组中左侧和右侧区域之间无差异。ANOVA 显示肿瘤中的 GABA+和 GSH 水平低于对侧和健康对照组,而对侧健康组织与健康对照组之间无差异。肿瘤、对侧区域或健康对照组之间的拟合误差或 SNR 无差异。我们的研究结果表明,HERMES 是一种可靠的工具,可同时测量 IDH1 突变的低级别胶质瘤中 GABA 和 GSH 的变化。