CELL BIOLOGY

程序3-细胞生物学是名为：DNA拓扑异构酶- I-结肠癌的靶向治疗“。该计划将使用3-4张纸巾 人类结肠癌的培养系，由它们的DNA很好地确定 赤潮藻的拓扑异构酶I含量、生长方式和形态 针对TOPO-I测试新的类似物。TOPO-I和TOPO-I水平 对1)样品的形态进行了评价和比较 2)异种移植结肠癌和正常结肠黏膜 (3)结肠癌组织培养系和代表性系 选择了。这项研究将有助于该项目选择最有效的 以及用于体内测试的具有良好特性的化合物。我们的目标是 以下是： 1.通过无细胞体系中的筛子选择的化合物将是 通过克隆形成试验检测细胞毒性，以及形成 TOPO-I-DNA可裂解复合体。这些研究将通过测试来扩大 抗‘静止’或正氧/缺氧细胞，并通过测量 药物摄取和新陈代谢，比较有效的亲脂和水- 可溶的同系物。 2.多药耐药类似物对结肠癌细胞系的作用 表型将被确定，并对初始获得的抗性 研究了有效的类似物。 3.将使用(A)评估综合治疗的优点 临床有效的化疗药物，或(B)放射治疗， 或者顺序地与Topo-I的抑制剂一起或与之同时进行。 相加与协同或拮抗对细胞杀伤力的影响 被建立起来。

PROGRAM 3-CELL BIOLOGY is part of the project entitled: 'DNA Topoisomerase- I-Targeted Therapy of colonic Cancer'. The program will use 3-4 tissue culture lines of human colon cancer, well defined by their DNA topoisomerase I (topo-I) content, growth pattern and morphology for the testing of new analogs directed against topo-I. The level of topo-I and morphology has been evaluated and compared among 1) the specimens of colonic carcinoma and normal mucosa obtained from patients, 2) xenograft and 3) tissue-culture lines, and representative lines of colonic cancer chose. The research will aid the Project in selecting the most effective and well characterized compounds for in-vivo testing. the aims are the following: 1. The compounds, selected by screens in the cell-free system, will be tested for cytotoxicity by the clonogenic assay, and for the formation of topo-I-DNA cleavable complexes. The studies will be expanded by tests against 'quiescent' or euoxic/hypoxic cells, and by the measurement of drug-uptake and metabolism, comparing effective lipophilic and water- soluble congeners. 2. The efficacy of analogs against lines of colonic cancer with the mdrl phenotype will be determined, and an acquired resistance to initially effective analogs studied. 3. The merits of combination treatments will be evaluated, using (a) clinically effective chemotherapeutic agents, or (b) radiation treatment, either sequentially to or concomitantly with an inhibitor of topo-I. Additive versus synergistic versus antagonistic effects on cell kill will be established.