CASE FOR AMINOPTERIN IN THE TREATMENT OF LEUKEMIA

甲氨蝶呤(MTX)可能是治疗该疾病最重要的单一药物。 孩子们和所有人。它已经40年没有被取代过了。在此期间 时至今日，大量研究已经揭示了肿瘤的发病机制 抗药性(更适用于体外模型)和抗谱 叶酸毒性。过去几年的研究表明， MTX的淋巴母细胞代谢与长期生存之间的关系。主要目标 我们实验室的目的是提高抗叶酸的治疗效果。 这将通过获得更多关于肿瘤和宿主的信息来完成 新陈代谢。使用功能分析(放射性标记药物的代谢)作为 以及免疫印迹和核酸探针，我们正在寻找 患者和肿瘤细胞的差异，以确定哪些患者 很可能被治愈，反应不佳，和/或那些可能 体验过度的毒性。我们对氨基喋呤(AMT)的研究 分离的白血病原始细胞以及已建立的细胞系已经证实 AMT在体外具有更强的新陈代谢和药效。这样做的目的是 应用程序是利用我们的技术能力来测试 假设AMT有时是更好的药物。第一阶段，生物利用度 并将进行AMT的II/III期试验。加上额外的 我们在近50年中获得的知识和监测能力 在最初使用多年后，我们有更好的装备来预防、预测、 并减轻AMT的毒性。

Methotrexate (MTX) may be the single most important drug in the treatment of children with ALL. It has not been replaced in 4 decades. During this time, a great deal of research has revealed the mechanisms for tumor resistance (more applicable to models in vitro) and the spectrum of anti- folate toxicity. Studies in the last few years have shown an association between lymphoblast metabolism of MTX and long-term survival. A main goal of our laboratory is to increase the therapeutic efficacy of anti-folates. This will be done by obtaining more information about tumor and host metabolism. Using functional assays (metabolism of radio-labeled drug) as well as immunoblotting and nucleic acid probes, we are searching for differences in patients and tumor cells in order to identify patients who are likely to be cured, to be poor responders, and/or those who may experience excessive toxicity. Our studies with Aminopterin (AMT) in isolated leukemia blasts as well as established cell lines have confirmed AMT's greater metabolism and potency in vitro. The goal of this application is to utilize our technical capabilities to test the hypothesis that AMT is at times the better drug. Phase I, bioavailability and phase II/III trials of AMT will be done. With the additional knowledge and monitoring capabilities that we have gained in the nearly 50 years since its initial use, we are better equipped to prevent, predict, and ameliorate AMT toxicities.