Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model.
Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model.
复制标题
谷氨酰胺靶向抑制 VM-M3 小鼠肿瘤模型中的全身转移。
DOI：
10.1002/ijc.25431
复制
发表时间：
2010-11-15
影响因子：
6.4
通讯作者：
Seyfried, Thomas N.
中科院分区：
文献类型：
--
作者：
Shelton, Laura M.;Huysentruyt, Leanne C.;Seyfried, Thomas N.
转移性癌症是发病率和死亡率的主要原因。目前的治疗选择包括化疗、放疗或靶向治疗。然而，这些疗法往往是有毒的，对一小部分癌症类型有效，或者导致耐药性。因此，需要一种更全面、毒性更小的转移性癌症治疗策略。尽管大多数癌症表现出葡萄糖代谢增加，谷氨酰胺也是许多癌症的主要能量底物。我们利用新的VM小鼠全身转移模型，评估了谷氨酰胺类似物6-重氮-5-氧- l -去甲亮氨酸（DON）的抗转移潜力。我们发现，DON治疗小鼠的原发肿瘤生长比未治疗的对照组小鼠低约20倍。我们还发现，通过生物发光成像和组织学检测，DON治疗抑制了肝、肺和肾的转移。我们的研究结果证明了以谷氨酰胺代谢为目标的代谢疗法可以治疗全身转移性癌症。
Metastatic cancer is a major cause of morbidity and mortality. Current therapeutic options consist of chemotherapy, radiation, or targeted therapies. However, these therapies are often toxic, effective over a small range of cancer types, or result in drug resistance. Therefore, a more global, less toxic strategy for the management of metastatic cancer is required. Though most cancers display increased glucose metabolism, glutamine is also a major energy substrate for many cancers. We evaluated the anti-metastatic potential of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog, using the new VM mouse model of systemic metastasis. We found that primary tumor growth was approximately 20-fold less in DON treated mice than in untreated control mice. We also found that DON treatment inhibited metastasis to liver, lung, and kidney as detected by bioluminescence imaging and histology. Our findings provide proof of concept that metabolic therapies targeting glutamine metabolism can manage systemic metastatic cancer.
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影响因子：
4.5
作者：
Marsh J;Mukherjee P;Seyfried TN
通讯作者：
Seyfried TN
影响因子：
7.4
作者：
Carretero, J;Obrador, E;Estrela, JM
通讯作者：
Estrela, JM
影响因子：
6.4
作者：
Dyer, ES;Paulsen, MT;Ljungman, M
通讯作者：
Ljungman, M
影响因子：
6.2
作者：
Kauffman, H. Myron;Cherikh, Wida S.;Hanto, Douglas W.
通讯作者：
Hanto, Douglas W.
影响因子：
11.5
作者：
Li, XN;Parikh, S;Lau, CC
通讯作者：
Lau, CC