Magnetic resonance spectroscopy detectable metabolomic fingerprint of response to antineoplastic treatment.
Magnetic resonance spectroscopy detectable metabolomic fingerprint of response to antineoplastic treatment.
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DOI：
10.1371/journal.pone.0026155
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ronen SM
中科院分区：
文献类型：
--
作者：
Lodi A;Ronen SM
靶向治疗方法越来越多地在临床中实施，但早期检测反应经常带来挑战，因为许多新疗法导致抑制肿瘤生长而不是肿瘤缩小。因此，需要开发新的非侵入性方法来监测对治疗的反应。磁共振波谱（MRS）和磁共振波谱成像是可用于监测代谢的非侵入性成像方法，并且先前的研究表明，这些方法可用于监测与早期药物靶向调节相关的治疗的代谢后果。然而，单一代谢物生物标志物通常对特定疗法没有特异性。在这里，我们使用了一个公正的1H MRS为基础的代谢组学方法来研究与磷酸肌醇3-激酶抑制剂LY 294002和热休克蛋白90抑制剂17 AAG治疗前列腺癌和乳腺癌细胞系的整体代谢后果。LY 294002处理导致细胞内乳酸、丙氨酸富马酸盐、磷酸胆碱和谷胱甘肽减少。在17 AAG处理后，还观察到细胞内乳酸、丙氨酸、富马酸和谷氨酰胺减少，但在每种情况下都有磷酸胆碱积累。此外，通常在正常前列腺组织中观察到但在肿瘤中未观察到的柠檬酸盐在前列腺细胞中的17 AAG处理后增加。这种方法可能会提供有关信号传导和代谢途径之间复杂相互作用的进一步信息。它还强调了基于MRS的代谢组学在识别代谢特征方面的潜力，这些代谢特征可以具体告知分子药物作用。
Targeted therapeutic approaches are increasingly being implemented in the clinic, but early detection of response frequently presents a challenge as many new therapies lead to inhibition of tumor growth rather than tumor shrinkage. Development of novel non-invasive methods to monitor response to treatment is therefore needed. Magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging are non-invasive imaging methods that can be employed to monitor metabolism, and previous studies indicate that these methods can be useful for monitoring the metabolic consequences of treatment that are associated with early drug target modulation. However, single-metabolite biomarkers are often not specific to a particular therapy. Here we used an unbiased 1H MRS-based metabolomics approach to investigate the overall metabolic consequences of treatment with the phosphoinositide 3-kinase inhibitor LY294002 and the heat shock protein 90 inhibitor 17AAG in prostate and breast cancer cell lines. LY294002 treatment resulted in decreased intracellular lactate, alanine fumarate, phosphocholine and glutathione. Following 17AAG treatment, decreased intracellular lactate, alanine, fumarate and glutamine were also observed but phosphocholine accumulated in every case. Furthermore, citrate, which is typically observed in normal prostate tissue but not in tumors, increased following 17AAG treatment in prostate cells. This approach is likely to provide further information about the complex interactions between signaling and metabolic pathways. It also highlights the potential of MRS-based metabolomics to identify metabolic signatures that can specifically inform on molecular drug action.
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影响因子：
5.7
作者：
Beloueche-Babari, M;Jackson, LE;Ronen, SM
通讯作者：
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