Discovery/Development of Anticancer Agents from Plants

超出所提供的空间-该项目的目标是从植物中获得的铅元素中发现和开发具有实体肿瘤活性的新型抗癌药物。鉴于对人类主要实体肿瘤有活性的抗癌药物的缺乏，这一需求是非常重要的。在过去的5年里，来自亚利桑那大学约瑟夫·霍夫曼博士实验室的近4000种粗植物提取物被Fred Valeriote博士评估为实体肿瘤选择性。现在在约瑟芬·福特癌症中心这些研究的结果为该项目提供了30个优先的，主要的目标，以便在未来5年内继续从这些植物中分离（通过生物测定-定向分离）和鉴定活性化合物。将根据需要进行大量收集，或在试验田中种植植物，为体外和体内的扩展测试提供足够的材料。额外的材料将通过气培/水培系统产生，特别是当根材料是活性化合物的主要来源时。每年将收集200种新植物，每年将优先考虑新旧先导物，每年将有6种优先植物完成，以产生至少6种用于体外和体内测试的活性化合物。将更加重视新化合物，而不是具有新的或已知抗癌活性的已知化合物。抗癌药物开发部分将在约瑟芬·福特癌症中心进行。体内药理学试验有三个基本组成部分：开发新化合物化学分析的分析方法；通过生物制药措施开发合适的静脉注射制剂；药物清除和分布的初步药理学试验将在体外建立剂量和靶药浓度小鼠在开始给药前将携带的双侧肿瘤生长到100 ~ 300 ram3，每种药物在0.2 ml体积内用于肠外给药的剂量将根据传统的剂量需求和根据体外药理学结果调整的剂量来估计化合物,最大耐受剂量,在小鼠肿瘤——轴承(同系的小鼠肿瘤或异种移植智慧网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED -The goal of this project is the discovery and development of new anticancer agents with solid tumor activity from leads obtained from plants The need for this is significant given the paucity of anticancer agents active against the major solid tumors of man During the past 5 years, nearly 4000 crude plant extracts, from the laboratory of Dr Joseph Hoffmann at the University of Arizona, have been evaluated for solid tumor selectivity by Dr Fred Valeriote, now at the Josephine Ford Cancer Center The results of these studies have provided this project with 30 prioritized, primary hits to continue with isolation (through bioassay- directed fractionation) and identification of the active compound(s) from these plants over the next 5 years In order to accomplish the objectives, bulk collections will be made as needed or plants will be grown in experimental field plots to provide sufficient material for expanded testing both in vitro and in vivo Additional material will be generated through aeroponic/hydroponic systems, especially when root material is the primary source of the active compound(s) Also, 200 new plants will be collected each year with the new and old leads prioritized annually Six priority plants will be targeted for completion each year to generate at least 6 active compounds for both in vitro and in vivo testing Greater emphasis will be placed on novel compounds over known compounds with either new or known anticancer activity The anticancer drug development component will be carried out at the Josephine Ford Cancer Center The pure compound moves into formulation, pharmacology and therapeutic assessment There are three essential components to in vivo pharmacology testing development of analytical methods for chemical analysis of the new compounds, development of a suitable IV formulation through biopharmaceutical measures, and preliminary pharmacology testing for drug clearance and distribution Doses and target drug concentrations will be established in vitro Mice will bear bilateral tumors that have grown to 100 to 300 ram3 prior to initiation of dosing Doses of each agent contained in 0 2 ml volume for parenteral administration will be estimated from traditional dosage demands and dosages adjusted for in vitro pharmacology results The methodology for the study on therapeutic efficacy to test doses of compound, up to the maximum tolerated dose, in tumor- bearing mice (syngeneic with a murine tumor or xenografted wit PERFORMANCE SITE ========================================Section End===========================================