Hoffman Robert M, Kokkinakis Demetrius M, Frenkel Eugene P
AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.
Methods Mol Biol. 2019;1866:163-171. doi: 10.1007/978-1-4939-8796-2_13.
This chapter reviews how total methionine (MET) restriction (MR) of a human brain tumor xenograft, effected by the combination of recombinant L-methionine-α-deamino-γ-lyase (rMETase) and a MET-free diet, greatly potentiates standard chemotherapy for brain tumors in mouse models. The growth of human brain tumor Daoy, SWB77, and D-54 xenografts in nude mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of an MR diet and rMETase and homocysteine to rescue normal cells and tissues. MET was depleted to below 5 μm by this treatment. MR for 10-12 days inhibited tumor growth, but did not prevent tumor regrowth after treatment cessation. A single dose of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was ineffective alone, was administered at the end of the MR regimen, and caused a more than 80-day growth delay for Daoy and D-54 and a 20-day growth delay for SWB77. The total MR treatment regimens also increased the efficacy of temozolomide (TMZ) against the SWB77 xenograft when administered at the end of the MET regimen.
本章回顾了重组L-蛋氨酸-α-脱氨基-γ-裂解酶（rMETase）与无蛋氨酸饮食相结合对人脑肿瘤异种移植模型进行蛋氨酸（MET）全限制（MR），如何极大地增强小鼠模型中脑肿瘤的标准化疗效果。通过MR饮食和rMETase联合使用使小鼠血浆蛋氨酸（MET）耗竭，并补充同型半胱氨酸以挽救正常细胞和组织后，人脑肿瘤Daoy、SWB77和D-54异种移植瘤在裸鼠体内的生长受到抑制。经此处理后，MET降至5μm以下。进行10 - 12天的MR可抑制肿瘤生长，但在停止治疗后不能阻止肿瘤复发。在MR方案结束时给予单剂量的N,N'-双（2-氯乙基）-N-亚硝基脲（BCNU），其单独使用无效，但导致Daoy和D-54的生长延迟超过80天，SWB77的生长延迟20天。当在MET方案结束时给予时，总的MR治疗方案也提高了替莫唑胺（TMZ）对SWB77异种移植瘤的疗效。
