Rivenzon-Segal Dalia, Margalit Raanan, Degani Hadassa
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E623-30. doi: 10.1152/ajpendo.00050.2002.
Enhanced glycolysis represents a striking feature of cancers and can therefore serve to indicate a malignant transformation. We have developed a noninvasive, quantitative method to characterize tumor glycolysis by monitoring (13)C-labeled glucose and lactate with magnetic resonance spectroscopy. This method was applied in MCF7 human breast cancer implanted in the mammary gland of female CD1-NU mice and was further employed to assess tumor response to hormonal manipulation with the antiestrogen tamoxifen. Analysis of the kinetic data based on a unique physiological-metabolic model yielded the rate parameters of glycolysis, glucose perfusion, and lactate clearance in the tumor, as well as glucose pharmacokinetics in the plasma. Treatment with tamoxifen induced a twofold reduction in the rate of glycolysis and of lactate clearance but did not affect the other parameters. This metabolic monitoring can thus serve to evaluate the efficacy of new selective estrogen receptor modulators and may be further extended to improve diagnosis and prognosis of breast cancer.
增强的糖酵解是癌症的一个显著特征,因此可用于指示恶性转化。我们开发了一种非侵入性定量方法,通过磁共振波谱监测¹³C标记的葡萄糖和乳酸来表征肿瘤糖酵解。该方法应用于植入雌性CD1-NU小鼠乳腺的MCF7人乳腺癌,并进一步用于评估肿瘤对抗雌激素他莫昔芬激素处理的反应。基于独特的生理代谢模型对动力学数据进行分析,得出肿瘤中糖酵解、葡萄糖灌注和乳酸清除的速率参数,以及血浆中的葡萄糖药代动力学。他莫昔芬治疗使糖酵解速率和乳酸清除率降低了两倍,但不影响其他参数。因此,这种代谢监测可用于评估新型选择性雌激素受体调节剂的疗效,并可能进一步扩展以改善乳腺癌的诊断和预后。