Hoffman Robert M
AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.
Methods Mol Biol. 2019;1866:273-278. doi: 10.1007/978-1-4939-8796-2_21.
The general cancer-specific metabolic defect of methionine (MET) dependence is due to MET overuse for aberrant transmethylation reactions. The excess use of MET for aberrant transmethylation reactions apparently diverts methyl groups from DNA. The resulting global DNA hypomethylation is also a general phenomenon in cancer and leads to unstable genomes and aneuploid karyotypes. The excessive and aberrant use of MET in cancer is readily observed in [C]-MET-PET imaging, where high uptake of [C]-MET results in a very strong and selective tumor signal compared to normal tissue background for brain cancer and possibly other cancers. [C]-MET is superior to [C]-fluorodeoxyglucose (FDG) for PET imaging, suggesting that MET overuse in cancer ("Hoffman effect") is greater than glucose overuse in cancer ("Warburg effect").
甲硫氨酸（MET）依赖这一普遍的癌症特异性代谢缺陷是由于MET过度用于异常的转甲基反应。MET过度用于异常转甲基反应显然会使甲基从DNA转移。由此产生的全基因组DNA低甲基化也是癌症中的普遍现象，会导致基因组不稳定和非整倍体核型。在[C]-MET-PET成像中很容易观察到癌症中MET的过度和异常使用，与脑癌及可能的其他癌症的正常组织背景相比，[C]-MET的高摄取会产生非常强烈且选择性的肿瘤信号。对于PET成像，[C]-MET优于[C]-氟脱氧葡萄糖（FDG），这表明癌症中MET的过度使用（“霍夫曼效应”）大于癌症中葡萄糖的过度使用（“瓦伯格效应”）。
