NATURAL INHIBITORS OF CARCINOGENESIS

癌症是一种具有巨大社会经济意义的顽固性疾病。 尽管治疗取得了显著的进展，但最终的治疗方法 是很少实现的。因此，解决这一困境的替代方法 都是值得探索的。基于我们目前对人类的理解 癌变，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。主要 预防策略(例如，停止吸烟、减少吸烟 接触化学致癌物)、早期诊断、饮食 修饰和癌症培训计划都至关重要。 然而，除此之外，癌症的潜在健康益处 化学预防)(即通过以下方式预防人类癌症 摄入化学制剂)现在被普遍认识到。帮助…… 这一努力，这一延续申请的主要目标是 红曲霉菌抗癌化学预防药物的发现及性质 自然资源。对科学文献的概述揭示了 一些癌症化学预防药物的结构和活性， 其中许多存在于饮食材料中。尽管如此，几乎所有的 其中一些是通过(半)经验方法发现的，而不是 系统调查，而且可以肯定的是，另外 化学预防药物尚未被发现。在上一次 在此期间，我们能够动员所有必要的组成部分 在以下领域实施成功的药物发现方案 癌症化学预防。这需要五个人的协调努力 多学科综合研究方案：(1)选择和 提供来源材料，(2)分离和鉴定活性物质 原理，(3)直接分级的短期体外生物测定和 研究分离株，(4)体内评估以确定疗效，以及(5) 化学合成、半合成和结构修饰以辅助 体制、机制、效能的建立。这项实验 方法导致了各种积极原则的采购，这些原则是 目前被认为是更高级测试的可行候选者 发展。此外，所有后勤挑战都已取消， 计划项目已经简化，并有一些有希望的线索 已被确认，目前正在接受调查。因此，这一点 永续建立在我们在这一独特领域积累的经验之上 并总结了我们在这一领域取得进展的能力。 我们的总体目标与我们鼓吹的预防战略是一致的 国家癌症研究所、美国癌症协会和其他机构。 具体地说，该项目将提供化学物质和活动 具有足够深度的剖面以允许博学地考虑 作为干预试验的候选药物。要充分宣传这一点 Goal，我们将与专业知识超过该目标的调查人员合作 包含在计划项目中。

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.