Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?
Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?
复制标题
DOI：
10.1016/j.eplepsyres.2011.06.017
复制
发表时间：
2012-07-01
影响因子：
2.2
通讯作者：
Mukherjee, Purna
中科院分区：
文献类型：
--
作者：
Seyfried, Thomas N.;Marsh, Jeremy;Mukherjee, Purna
恶性脑癌一直是发病率和死亡率最高的疾病。未能认识到脑癌是一种能量代谢疾病，在很大程度上导致了管理的失败。只要脑肿瘤细胞能够获得葡萄糖和谷氨酰胺，疾病就会进展。目前的标准治疗为脑肿瘤提供了获得葡萄糖和谷氨酰胺的途径。高脂肪低碳水化合物生酮饮食（KD）将以葡萄糖利用率为目标，当以严格限制的量给药时，可能还有谷氨酰胺的利用率，以减少总热量摄入和葡萄糖循环水平。限制性KD（RKD）靶向与葡萄糖和谷氨酰胺代谢相关的主要信号传导途径，包括IGF-1/PI 3 K/Akt/Hif途径。在患有恶性脑癌的小鼠中评价时，RKD具有抗血管生成、抗侵袭、抗炎和促凋亡作用。当与也靶向葡萄糖和谷氨酰胺的药物组合时，限制性KD的治疗功效可以增强。在人类病例报告中也观察到RKD对恶性胶质瘤的治疗效果。因此，RKD可以是当前标准治疗的有效无毒治疗选择，用于抑制恶性脑癌的生长和侵袭性。(C)2011 Elsevier B. V.保留所有权利。
Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As tong as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer. (C) 2011 Elsevier B.V. All rights reserved.