NATURAL INHIBITORS OF CARCINOGENESIS

癌症是一种具有巨大社会经济重要性的恶性疾病。 尽管已经取得了显著的治疗进展， 是很少实现的。 因此，解决这一困境的替代方法 值得探索 根据我们目前对人类的理解， 致癌，预计全面实施预防 这些策略可以将癌症的发病率降低70%或更多。 初级 预防策略（例如，戒烟，减少 暴露于化学致癌物），早期诊断，饮食 修改和癌症培训计划都是至关重要的。 此外，癌症的潜在健康益处 化学预防）（即，预防癌症在人群中， 化学药剂的摄入）现在被普遍认识到。 以帮助 为此，本延续申请的主要目标是 癌症化学预防剂的发现和表征 自然资源。 科学文献的概述揭示了 许多癌症化学预防剂的结构和活性， 其中许多存在于膳食材料中。 然而，几乎所有 这些代理人被发现（半）经验方法，而不是 系统的调查，而且可以肯定的是， 化学预防剂还有待发现。 前一 在此期间，我们能够调动所有必要的组成部分， 在以下领域实施成功的药物发现计划： 癌症化学预防 这需要五个国家的协调努力， 多学科综合研究计划：（1）选择和 提供源材料，（2）分离和鉴定活性 原则，（3）短期体外生物测定，以直接分馏， 研究分离株，（4）体内评价以确定疗效，和（5） 化学合成、半合成和结构修饰， 结构、机制和效能的建立。 本实验 这种方法导致了各种积极的原则， 目前被认为是更先进的测试的可行候选人， 发展 此外，所有后勤挑战都已消除， 该方案项目已经精简，一些有前途的线索， 目前正在调查中。 因此， 延续建立在我们在这一独特领域积累的经验之上 的研究，并总结了我们在这方面取得进展的能力。 我们的总体目标与预防战略是一致的， 国家癌症研究所，美国癌症协会和其他机构。 具体而言，该项目将提供化学实体和活动 有足够深度的剖面图，以便对 作为干预试验的候选人。 为了充分促进这一点， 我们将与专业知识超过这一目标的调查人员合作， 项目包含的项目。

Cancer is a recalcitrant disease of enormous socioeconomic importance. Although notable therapeutic progress has been made, definitive treatment is rarely achieved. Thus, alternative approaches to solving this dilemma are worth exploring. Based on our current understanding of human carcinogenesis, it is anticipated that full implementation of prevention strategies could reduce the incidence of cancer by 70% or more. Primary prevention strategies (e.g., cessation of cigarette smoking, reduction of exposure to chemical carcinogens), early diagnosis, dietary modification and cancer training programs are all of vital importance. In addition, however, the potential health benefit of cancer chemoprevention )(i.e., prevention of cancer in human populations by ingestion of chemical agents) is now generally recognized. To aid in this endeavor, the primary objective of this continuation application is the discovery and characterization of cancer chemopreventive agents from natural sources. An overview of the scientific literature reveals the structures and activities of a number of cancer chemopreventive agents, many of which are present in dietary materials. Nonetheless, nearly all of these agents were uncovered by (semi) empirical methods rather than systematic investigation, and it is certain that additional chemopreventive agents have yet to be discovered. During the previous period, we were able to mobilize all of the necessary components for the implementation of a successful drug discovery program in the area of cancer chemoprevention. This entailed the coordinated effort of five multidisciplinary, integrated research programs: (1) selection and provision of source materials, (2) isolation and identification of active principles, (3) short-term in vitro bioassays to direct fractionation and studies isolates, (4) in vivo evaluations to establish efficacy, and (5) chemical synthesis, semisynthesis and structural modification to aid in the establishment of structure, mechanism and efficacy. This experiment approach has led to the procurement of various active principles that are currently considered viable candidates for more advanced testing and development. In addition, all logistical challenges have been abrogated, the program project has been streamlined, and a number of promising leads have been identified and are currently under investigation. Thus, this continuation builds on our accumulated experience in this unique field of research and summarizes our ability to realize progress in this area. Our overall objective is consistent with prevention strategies touted by the National Cancer Institute, the American Cancer Society and others. Specifically, this project will provide chemical entities and activity profiles of sufficient depth to permit erudite consideration of the agents as candidates for intervention trials. To adequately promote this goal, we will cooperate with investigators whose expertise exceeds that encompassed by the program project.