Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP
Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP
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DOI：
10.1016/j.bbrc.2004.09.047
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发表时间：
2004-11-05
影响因子：
3.1
通讯作者：
Pedersen, PL
中科院分区：
文献类型：
--
作者：
Ko, YH;Smith, BL;Pedersen, PL
许多晚期癌症的一个共同特征是他们将葡萄糖代谢成乳酸的能力增强。在一项旨在评估这种癌症是否可以减弱的挑战性研究中，我们将表达高度糖酵解表型的肝细胞癌细胞接种到幼鼠的两个不同位置。晚期癌症(2-3厘米)发生，并用烷化剂3-溴丙酮酸治疗，3-溴丙酮酸是乳酸盐/丙酮酸类似物，选择性地消耗ATP并诱导细胞死亡。在所有19只接受治疗的动物中，晚期癌症被根除，没有明显的毒性或复发。这些发现证明了完全摧毁晚期高度糖酵解癌症的可行性。(C)2004 Elsevier Inc.保留所有权利。
A common feature of many advanced cancers is their enhanced capacity to metabolize glucose to lactic acid. In a challenging study designed to assess whether such cancers can be debilitated, we seeded hepatocellular carcinoma cells expressing the highly glycolytic phenotype into two different locations of young rats. Advanced cancers (2-3 cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death. In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence. These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers. (C) 2004 Elsevier Inc. All rights reserved.