APOPTOSIS IN COLON CANCER CHEMOPREVENTION

这个项目要研究的一般问题是癌症 化学预防我们工作的具体重点将是 结肠直肠癌的化学预防，这是第二大原因 美国癌症死亡人数的一半。长期目标 这个项目的目的是确定结肠癌化学预防的策略 这将降低结肠炎的发病率和/或死亡率， 癌我们的一般做法是进一步确定 结肠癌的发生，并确定抑制这一过程的方法。 在这个程序中要检验的总体假设是， 在人类中的致癌作用与基底细胞的减少有关， 结肠粘膜细胞凋亡诱导率。我们还将 测试相关的假设，某些癌症化学预防剂 通过刺激肿瘤细胞凋亡抑制结肠癌发生 结肠组织 这项基础科学研究计划旨在补充现有的 亚利桑那州癌症中心正在进行的临床癌症化学预防试验 加州大学参与的中心和合作研究- 旨在帮助我们的小组回答关键问题 与未来的结肠癌化学预防试验有关。的统一 这项计划拨款的主题是结肠癌的发生和结肠 癌症化学预防和该计划的具体重点将是 凋亡过程。该计划的目标将是确定 如果a）凋亡在结肠息肉形成和随后的结肠 癌症的发展，和B）潜在的化学预防策略的工作， 除了它们对细胞增殖的作用之外，还促进细胞凋亡。 在此背景下，我们打算确定饮食和 细胞因子在正常和肿瘤细胞凋亡发生中的作用 结肠组织在这些拟议研究的过程中，我们计划使用 多种细胞培养模型和来自两种实验动物的组织 结肠癌发生模型和来自人类患者的活组织检查 参与正在进行的癌症化学预防试验。程序 申请包括4个独立但相互关联的研究项目 由3个科学核心支持。

The general problem to be studied in this program is cancer chemoprevention. The specific focus of our work will be the chemoprevention of colorectal cancers, which are the second leading cause of cancer deaths in the United States of America. The long term objective of this program is to identify strategies of colon cancer chemoprevention that will reduce the incidence of, and/or the mortality due to, colon cancer. Our general approach will be to further define the mechanisms of colon carcinogenesis and identify methods that will inhibit this process. The overall hypothesis to be tested in this program is that colon carcinogenesis in humans is associated with a decrease in either the basal rate of inducibility of apoptosis in colonic mucosal cells. We will also test the related hypothesis that certain cancer chemopreventive agents inhibit colon carcinogenesis by stimulating apoptosis in neoplastic colonic tissues. This basic science research program is intended to complement existing clinical cancer chemoprevention trials ongoing at the Arizona Cancer Center and collaborative studies involving the University of California- Irvine and is intended to help our group answer critical questions relevant to future colon cancer chemoprevention trials. The unifying themes of this proposed program grant are colon carcinogenesis and colon cancer chemoprevention and the specific focus of the program will be the process of apoptosis. The objectives of the program will be to determine if a) apoptosis plays a role in colon polyp formation and subsequent colon cancer development, and b) potential chemopreventive strategies work by promoting apoptosis in addition to their effects on cell proliferation. Within this context, we intend to determine the roles of dietary and cellular factors in the occurrence of apoptosis in normal and neoplastic colonic tissues. In the course of these proposed studies, we plan to use a variety of cell culture models and tissues from both experimental animal models of colon carcinogenesis and biopsies from human patients participating in ongoing cancer chemoprevention trials. The program application includes 4 independent, but interrelated, research projects supported by 3 scientific cores.