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 化学预防结直肠癌，这是第二大原因 在美国的癌症死亡人数中所占比例。长期目标 这项计划的目的是确定结肠癌的化学预防策略 这将降低结肠癌的发病率和/或死亡率。 癌症。我们的总体方法将是进一步定义 结肠癌的发生并找出抑制这一过程的方法。 在本程序中要测试的总体假设是冒号 人类的癌症发生与基底膜的减少有关。 结肠粘膜细胞的凋亡率。我们还将 检验某些癌症化学预防药物的相关假设 通过促进肿瘤细胞凋亡抑制结肠癌的发生 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癌症化学预防临床试验 中心和加州大学参与的合作研究- 欧文，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相关。一元化 这项计划拨款的主题是结肠癌和结肠癌。 癌症的化学预防和该计划的具体重点将是 细胞凋亡的过程。该计划的目标将是确定 如果a)细胞凋亡在结肠息肉形成和随后的结肠中起作用 癌症的发展，以及b)潜在的化学预防策略通过 除了对细胞增殖的影响外，还促进细胞凋亡。 在这一背景下，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。在这些拟议的研究过程中，我们计划使用 两种实验动物的各种细胞培养模型和组织 人类结肠癌发生和活检模型的建立 参与正在进行的癌症化学预防试验。该计划 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.