ENZYME PATTERN-TARGETED CHEMOTHERAPY

酶模式靶向化疗

• 批准号: 3479346
• 负责人: GEORGE WEBER
• 金额: $ 33.77万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479346
• 关键词: adenocarcinoma; alkylating agents; aminoacid metabolism; antimetabolites; combination chemotherapy; disease /disorder model; drug adverse effect; drug metabolism; drug resistance; enzyme therapy; human tissue; lymphocytic leukemia; molecular oncology; myelogenous leukemia; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplasm /cancer transplantation; neoplastic cell; purine /pyrimidine metabolism; serine

A comprehensive and integrated program is planned to test the molecular correlation concept in human cancer cells and the design of enzyme pattern-targeted chemotherapy. The long-term objective is to provide novel observations and creative ideas for an integrated, rational approach toward disease-oriented, enzyme- and biochemical-pattern-targeted chemotherapy. The specific aims are to elucidate linking of enzymic and metabolic features of malignant cells with transformation and progression in rat model systems and in human colon adenocarcinoma, hepatocellular carcinoma and myelogenous and lymphocytic leukemias. The following 4 related projects comprise the coordinated program. 1. Elucidation of the characteristic pattern of the biochemical strategy of cancer cells in purine, pyrimidine and serine metabolism. 2. Elucidation of the enzymic and biochemical determinants of selective toxicity and resistance to anti-metabolites (tiazofurin, selenazofurin, and acivicin) in tumors and normal tissue. 3. Investigation of chemotherapy with anti-metabolites and combination therapy with transport inhibitors and alkylating agents. 4. Study of biochemical impact of drugs in human myelogenous and lymphocytic leukemic cells and in human colon adenocarcinoma cells as a predicting system and as an indicator of sensitivity and resistance to the chemotherapeutic agents. The methods and procedures required for acccomplishing the research objectives are operative in this Laboratory. Other techniques are readily adapted from the literature. Understanding the stringency of linkage of enzymic and metabolic features of malignant cells with transformation and progression and the selective advantages these alterations confer to cancer cells should reveal strategic enzymic and biochemical alterations that should be sensitive targets in the design of selective chemotherapy in animals and in human neoplasia.

计划开展一项全面综合的计划来测试分子 人类癌细胞中的相关概念和酶的设计 模式靶向化疗。 长期目标是提供新颖的 观察和创造性的想法，以综合、合理的方法 以疾病为导向的酶和生化模式靶向化疗。 具体目标是阐明酶和代谢之间的联系 大鼠恶性细胞转化和进展的特点 模型系统和人类结肠腺癌、肝细胞癌 以及骨髓性和淋巴细胞性白血病。 以下 4 个相关项目构成了协调计划。 1. 生化策略特征模式的阐明 癌细胞中嘌呤、嘧啶和丝氨酸的代谢。 2. 说明 选择性毒性的酶学和生化决定因素以及 对抗代谢药物（噻唑呋林、硒唑呋林和阿西维星）的耐药性 肿瘤和正常组织。 3. 化疗的研究 抗代谢药物和转运抑制剂联合治疗 烷化剂。 4.药物对人体生化影响的研究 骨髓和淋巴细胞白血病细胞以及人类结肠中 腺癌细胞作为预测系统和指标 对化疗药物的敏感性和耐药性。 完成研究所需的方法和程序 目标在该实验室中有效。 其他技术很容易 改编自文献。 了解酶和代谢特征之间联系的严格性 恶性细胞的转化和进展以及选择性 这些改变赋予癌细胞的优势应该揭示战略意义 酶和生化改变应该是敏感目标 动物和人类肿瘤选择性化疗的设计。