CANCER THERAPY WITH BIOCHEMICAL MODULATORS AND CSFS

生化调节剂和 CSFS 的癌症治疗

• 批准号: 2087407
• 负责人: DANIEL S MARTIN
• 金额: $ 127.45万
• 依托单位: CATHOLIC MEDICAL CTR OF BKLYN & QUEENS
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2087407
• 关键词: antineoplastics; combination cancer therapy; drug adverse effect; drug interactions; drug screening /evaluation; neoplasm /cancer pharmacology

The ultimate goal of the proposed research program is the development of both safer and more effective combination therapy for cancer. Based on principles of biochemical modulation, drug combinations, or drug- metabolite combinations, selected on the basis of known or potential biochemical interaction, will be utilized to manipulate relevant biochemical pathways in a therapeutically beneficial manner to either potentiate selective cytotoxicity in tumor cells, and/or to selectively diminish toxicity in normal host cells. the control of serious host toxicity is viewed as essential to the achievement of chemotherapeutic cure, because the resulting operational increase in drug selectivity will allow both a quantitative and a qualitative intensification of chemotherapy. In addition to the specific "rescue" approach for antimetabolite toxicity with the corresponding normal metabolite, attempts will be made to prevent drug-induced toxicity by stimulating more rapid hematopoietic recovery between drug treatment courses with hematopoietic growth factors; also, selected agents with potential for sparing, or for stimulating more rapid recovery in drug-damaged intestinal epithelium will be evaluated. the goal is to increase both the power and selectivity of the therapeutic attack, hopefully to the level of cure of advanced, spontaneous solid cancer, first in a murine model and then ultimately in patients. This approach requires the integration of 3 projects: Project 1, Experimental Therapy; Project 2, Biochemical Studies; Project 3, Clinical Studies. Preclinical therapy studies (Project 1) will be performed entirely in vivo murine tumor models. Therapeutic results from a particular drug manipulation, obtained as expected on the basis of the basis of the biochemical information that prompted that manipulation, will be confirmed on a biochemical level (Project 2) to insure that the chemotherapeutic results are related to the predicted biochemical changes. Biochemical analysis of human tumors, before and after treatment, determine (and establish) that the employed clinical dose is reproducing the same biochemical changes that were responsible for the successful preclinical results. Thus, the preclinical combined in vivo biological and biochemical findings, Projects 1 and 2, lead to guidelines for Project 3's very specific clinical trials.

拟议的研究计划的最终目标是开发 更安全，更有效的癌症结合疗法。 基于 生化调制，药物组合或药物的原理 - 代谢物组合，根据已知或潜力选择 生化互动将用于操纵相关 以治疗方式有益的生化途径 在肿瘤细胞中的增强选择性细胞毒性和/或选择性 正常宿主细胞中的毒性降低。 严重主机的控制 毒性被认为对于实现化学治疗至关重要 治愈，因为药物选择性的运营提高将 允许定量和定性强化 化学疗法。 除了具体的“救援”方法 抗代谢物毒性具有相应的正常代谢产物， 尝试通过刺激来防止药物引起的毒性 药物治疗课程之间的造血恢复更快 造血生长因素；此外，选定的代理有潜力 保留或刺激药物损害的更快恢复 将评估肠上皮。 目标是增加两者 治疗攻击的力量和选择性，希望能够 先进的自发固体癌的治愈水平，首先是在鼠 模型，然后最终在患者中。 这种方法需要 3个项目的整合：项目1，实验疗法；项目2， 生化研究；项目3，临床研究。 临床前治疗 研究（项目1）将完全在体内鼠肿瘤中进行 型号。 特定药物操纵的治疗结果， 根据生化的基础，如预期的 促使操纵的信息将在 生化水平（项目2）确保化学治疗结果 与预测的生化变化有关。 生化分析 治疗前后人类肿瘤的确定（并确定） 使用的临床剂量正在再现相同的生化 导致成功的临床前结果的变化。 因此，临床前的体内生物学和生化合并 调查结果（项目1和2）导致项目3的准则非常 具体的临床试验。