Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.
Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.
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肿瘤代谢，生酮饮食和β-羟基丁酸：辅助脑肿瘤疗法的新方法。
DOI：
10.3389/fnmol.2016.00122
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发表时间：
2016
影响因子：
4.8
通讯作者：
Scheck AC
中科院分区：
文献类型：
--
作者：
Woolf EC;Syed N;Scheck AC
恶性脑瘤是毁灭性的，尽管积极的治疗，如手术切除，化疗和放疗。新诊断的胶质母细胞瘤患者的平均预期寿命约为18个月。很明显，提高脑肿瘤患者的生存率需要设计新的治疗方式，特别是那些加强现有治疗和/或限制肿瘤生长的治疗方式。一个新的治疗领域是代谢失调，导致肿瘤细胞对葡萄糖的需求增加。这一现象表明，肿瘤生长的减少可以通过降低葡萄糖供应来实现，这可以通过药物手段或通过使用高脂肪、低碳水化合物的生酮饮食（KD）来实现。KD，顾名思义，也提供更多的血酮来支持正常组织的能量需求。来自许多实验室的临床前工作表明，KD确实可以减少肿瘤在体内的生长。此外，KD已被证明可以减少血管生成、炎症、肿瘤周围水肿、迁移和侵袭。此外，这种饮食可以增强胶质瘤小鼠模型的放疗和化疗活性，从而提高生存率。另外的体外研究表明，在没有葡萄糖还原的情况下，增加β-羟基丁酸（βHB）等酮类也可以抑制细胞生长并增强化疗和放疗的作用。因此，虽然我们才刚刚开始了解KD影响肿瘤生长和对常规疗法反应的多能性机制，但新出现的数据为使用KD治疗恶性胶质瘤提供了强有力的支持。这导致研究KD在原发性和复发性胶质瘤患者中的应用的临床试验数量有限。
Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.
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影响因子：
11.4
作者：
Allen, Bryan G.;Bhatia, Sudershan K.;Anderson, Carryn M.;Eichenberger-Gilmore, Julie M.;Sibenaller, Zita A.;Mapuskar, Kranti A.;Schoenfeld, Joshua D.;Buatti, John M.;Spitz, Douglas R.;Fath, Melissa A.
通讯作者：
Fath, Melissa A.
影响因子：
28.2
作者：
Cantor JR;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
2.8
作者：
Courtnay, Rupert;Ngo, Darleen C.;Karagiannis, Tom C.
通讯作者：
Karagiannis, Tom C.
影响因子：
3.9
作者：
Boele, Florien W.;Heimans, Jan J.;Klein, Martin
通讯作者：
Klein, Martin
影响因子：
21.3
作者：
Boroughs LK;DeBerardinis RJ
通讯作者：
DeBerardinis RJ