{"title":"在阿特金斯类饮食中补充酮酯可延长胶质母细胞瘤正位异种移植模型的存活时间。","authors":"Hassan Azari, Angela Poff, Dominic D'Agostino, Brent Reynolds","doi":"10.5115/acb.23.158","DOIUrl":null,"url":null,"abstract":"<p><p>Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.</p>","PeriodicalId":7831,"journal":{"name":"Anatomy & Cell Biology","volume":" ","pages":"97-104"},"PeriodicalIF":1.4000,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10968192/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ketone ester supplementation of Atkins-type diet prolongs survival in an orthotopic xenograft model of glioblastoma.\",\"authors\":\"Hassan Azari, Angela Poff, Dominic D'Agostino, Brent Reynolds\",\"doi\":\"10.5115/acb.23.158\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.</p>\",\"PeriodicalId\":7831,\"journal\":{\"name\":\"Anatomy & Cell Biology\",\"volume\":\" \",\"pages\":\"97-104\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-03-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10968192/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anatomy & Cell Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5115/acb.23.158\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anatomy & Cell Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5115/acb.23.158","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/9 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
胶质母细胞瘤(GBM)严重依赖葡萄糖代谢,而利用酮体的能力却很低,因此很有希望成为酮基疗法的候选对象。众所周知,生酮饮食(KD)在控制胶质母细胞瘤肿瘤生长方面具有良好的效果。此外,合成酮酯(KE)在转移性 VM-M3 小鼠肿瘤模型中已被证明能提高血液酮体水平并提高动物存活率。在此,我们比较了阿特金斯类膳食(ATD-KE)与传统酮酯在临床相关的正位患者异种移植 GBM 模型中控制肿瘤进展和提高存活率的功效。我们的研究结果表明,ATD-KE 能保持体重(与基线相比的百分比变化;112±2.99 vs. 116.9±2.52 和 104.8±3.67),降低血糖(80.55±0.86 vs. 118.6±9.51 和 52.35±3.89 mg/dl),增加血液中的酮体(1.15±0.03 mM vs. 0.55±0.04 和 2.66±0.21 mM)和脑肿瘤组织(3.35±0.30 mM vs. 2.04±0.3 和 4.25±0.25 mM)中的酮体含量与 KD 相当(结果分别为 ATD-KE vs. 标准饮食 [STD] 和 KD)。重要的是,与 STD 相比,ATD-KE 治疗显著提高了存活率,与 KD 的存活率相差无几(STD 为 47 天,KD 和 ATD-KE 为 56 天),这表明营养均衡的低碳水化合物 ATD 联合 KE 在减少脑肿瘤进展方面可能与单独的 KD 一样有效。总之,这些数据支持将补充 KE 的低碳水化合物饮食作为脑肿瘤患者辅助治疗方法进行临床测试的合理性。
Ketone ester supplementation of Atkins-type diet prolongs survival in an orthotopic xenograft model of glioblastoma.
Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.