Laboratory of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
Nutr Cancer. 2021;73(11-12):2315-2322. doi: 10.1080/01635581.2020.1822423. Epub 2020 Sep 21.
Glioblastoma multiforme (GBM) is considered the most malignant form of primary brain tumor. Despite multimodal treatment, prognosis remains poor. Ketogenic diet (KD) has been suggested for the treatment of GBM. In this study, the syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on the metabolic responses of the tumor using 7T magnetic resonance imaging/spectroscopy. GL261 cells were injected into the caudate nucleus of mice. Following implantation, animals were fed with standard chow or underwent a KD. 18 days after initiating the diet, mice fed with KD displayed significantly higher plasmatic levels of ketone bodies and survived longer than those fed with the standard diet. Decreased concentrations of gamma-aminobutyric acid, N-Acetyl-Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days into the KD, while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The accumulation of bHB in the tumor tissue in mice undergoing the KD, may suggest either elevated uptake/release of bHB by tumor cells, or the inability of tumor cells in this context to use it for mitochondrial metabolism.
胶质母细胞瘤（GBM）被认为是原发性脑肿瘤中最恶性的形式。尽管采用了多模式治疗，但预后仍然很差。生酮饮食（KD）已被提议用于治疗 GBM。在这项研究中，使用 7T 磁共振成像/光谱学，使用同基因原位 GL261 小鼠神经胶质瘤模型来评估 KD 对肿瘤代谢反应的影响。将 GL261 细胞注入小鼠尾状核。植入后，动物喂食标准饲料或进行 KD。在开始饮食 18 天后，喂食 KD 的小鼠表现出明显更高的血浆酮体水平，并且比喂食标准饮食的小鼠存活时间更长。在 KD 后 9 天，在肿瘤组织中发现γ-氨基丁酸、N-乙酰天冬氨酸和 N-乙酰天冬氨酸谷氨酸的浓度降低，而与正常脑组织相比，肿瘤组织中β-羟丁酸（bHB）的含量大大增加。在进行 KD 的小鼠的肿瘤组织中 bHB 的积累，可能表明肿瘤细胞对 bHB 的摄取/释放增加，或者在这种情况下肿瘤细胞无法将其用于线粒体代谢。
