...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Linkage between cellular communications, energy utilization, and proliferation in metastatic neuroendocrine cancers
【24h】

Linkage between cellular communications, energy utilization, and proliferation in metastatic neuroendocrine cancers

机译：转移性神经内分泌癌中细胞通讯，能量利用和增殖之间的联系

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To identify metabolic features that support the aggressive behavior of human neuroenclocrine (NE) cancers, we examined metastatic prostate NE tumors and derived prostate NE cancer (PNEC) cell lines from a transgenic mouse model using a combination of magic angle spinning NMR spectroscopy, in silico predictions of biotransformations that observed metabolites may undergo, biochemical tests of these predictions, and electrophysiological/calcium imaging studies. Malignant NE cells undergo excitation and increased proliferation when their GABA(A), glutamate, and/or glycine receptors are stimulated, use glutamate and GABA as substrates for NADH biosynthesis, and produce propylene glycol, a precursor of pyruvate derived from glycine that increases levels of circulating free fatty acids through extra-NE cell effects. Treatment of nude mice containing PNEC tumor xenografts with (i) amiloride, a diuretic that inhibits Abpl, an enzyme involved in NE cell GABA metabolism, (ii) carbiclopa, an inhibitor of dopa decarboxylasewhich functions upstream of Abpl, plus (iii) flumazenil, a benzodiazepine antagonist that binds to GABAA receptors, leads to significant reductions in tumor growth. These findings may be generally applicable: GeneChip data sets from 471 human neoplasms revealed that components of GABA metabolic pathways, including ABP1, exhibit statistically significant increases in their expression in NE and non-NE cancers.
机译：为了确定支持人类神经营养素（NE）癌症侵略性行为的代谢特征，我们使用了幻角旋转NMR光谱技术，结合了转基因小鼠模型，检查了转移性前列腺NE肿瘤和衍生的前列腺NE癌（PNEC）细胞系。观察到的代谢物可能经历的生物转化的预测，这些预测的生化测试以及电生理/钙成像研究。当刺激其GABA（A），谷氨酸和/或甘氨酸受体时，恶性NE细胞会受到激发并增加增殖，使用谷氨酸和GABA作为NADH生物合成的底物，并产生丙二醇，丙二醇是丙酮酸的丙酮酸前体，会增加甘氨酸水平。 NE外细胞效应影响循环脂肪酸的含量。用（i）阿米洛利（一种抑制Abpl（一种参与NE细胞GABA代谢的酶）的利尿剂），（ii）Carbiclopa（一种在Abpl上游起作用的多巴脱羧酶的抑制剂）和（iii）氟米西尼治疗含有PNEC异种移植物的裸鼠。与GABAA受体结合的苯二氮卓拮抗剂会导致肿瘤生长显着减少。这些发现可能普遍适用：来自471个人类肿瘤的GeneChip数据集显示，包括ABP1在内的GABA代谢途径的成分在NE和非NE癌症中的表达均具有统计学上的显着增加。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号