BIOCHEMICAL STUDIES

这一研究计划的总体目标是建立一种理性的 癌症联合化疗基金会。这个 方法的基础是使用组合的概念 调节生化的代谢物和抗代谢物 从最大限度地损害癌细胞的角度出发的途径 同时保护正常宿主细胞免受药物的伤害 毒性。许多基本信息都是基于这些信息的 一种特定的药物组合是基于体外实验的 对他人的研究。然而，由于一种药物的最终效用 组合取决于有选择地实现 体内生化途径的适当调制(S)，研究 在研究项目2将被设计来确定 特定调节剂对最终产物的生化影响 主要效应剂在体内的活性。因此，具有治疗作用 从特定的药物操作中获得的结果，如预期的 在生化信息的基础上促使 操纵，将在生化水平上进行确认，以确保 生物学结果与预测的结果相关 生化变化。意想不到的治疗结果将是 在生化水平上探索，以提供新的信息 将被用来改变药物组合(或时间表)，从而 以达到预期的治疗进展。(必须强调的是) 生化研究将在组织中进行 从正在接受体内治疗方案的小鼠获得 问题)。 非常重要的是，这些体内生化和 药理学研究将为比较研究提供指南 临床药理和生化研究(研究 项目4，临床研究)，将用于调整前景看好的 用于动物模型翻译的治疗性药物方案 给癌症患者。 结合体内生物学和生化的发现，项目 1和2，导致特定临床试验的指南；反馈 来自项目4，临床研究，可能会建议新的实验 研究和改进。

The overall goal of this research program is to establish a rational foundation for the combination chemotherapy of cancer. The approach is based on the concept of employing combinations of metabolites and antimetabolites to modulate biochemical pathways with the view of achieving maximal cancer cell damage while simultaneously protecting normal host cells from drug toxicity. Much of the basic information upon which a rationale for a particular drug combination is based comes from in vitro studies of others. However, since the ultimate utility of a drug combination depends upon the selective achievement of the appropriate modulation(s) of biochemical pathways in vivo, studies in Research Project 2 will be designed to determine the biochemical effect of a given modulating agent on the final activity of the primary effector agent in vivo. Thus, therapeutic results from a particular drug manipulation, obtained as expected on the basis of the biochemical information that prompted that manipulation, will be confirmed on a biochemical level to insure that the biological results are related to the predicted biochemical changes. Unexpected therapeutic results will be explored at the biochemical level to provide new information that will be utilized to alter the drug combination (or schedule) so as to achieve the desired therapeutic advance. (It must be stressed that the biochemical studies will be performed with tissues obtained from mice undergoing the in vivo therapeutic regimen in question). Of great importance, these in vivo biochemical and pharmacological studies will provide guidelines for comparative pharmacological and biochemical studies in the clinic (Research Project 4, Clinical Studies) which will be used to adjust promising therapeutic drug regimens for translations from the animal model to cancer patients. The combined in vivo biological and biochemical findings, Projects 1 and 2, lead to guidelines for specific clinical trails; feedback from Project 4, Clinical Studies, may suggest new experimental studies and refinements.