DRUG DEVELOPMENT--IN VITRO AND IN VIVO THERAPY EVALUATION

药物开发——体外和体内治疗评估

• 批准号: 6236030
• 负责人: RALPH James BERNACKI
• 金额: $ 0.83万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1997-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236030
• 关键词: MCF7 cell; antineoplastic antibiotics; antineoplastics; athymic mouse; biological response modifiers; breast neoplasms; cell growth regulation; colon neoplasms; combination chemotherapy; disease /disorder model; doxorubicin; drug design /synthesis /production; drug metabolism; drug screening /evaluation; enzyme inhibitors; human tissue; immunofluorescence technique; laboratory mouse; lung neoplasms; methionine; neoplasm /cancer chemotherapy; neoplasm /cancer transplantation; neoplastic cell; nonhuman therapy evaluation; nucleoside analog; ovary neoplasms; radiotracer; tissue /cell culture

The overall goal of this study is to evaluate inappropriate tumor model systems the biological and therapeutic activity of potential antitumor agents and biological response modifiers, derived from within this program or if relevant to its goals, obtained from outside sources. Based on information on the activity and mode of action of new compounds, combinations of agents or treatments will also be assessed. Initial cytotoxicity screening of all agents is performed using a panel of human and murine tumor cell lines including human MCF7 mammary ca., A121 ovarian ca., WiDr colon ca., DMS114 small cell lung ca., H125 non small cell lung ca. and murine L1210 leukemia. IC50 and IC90 (growth inhibitory concentrations) are established for each drug in vitro using a semiautomated colorimetric assay. Promising new agents, having a unique structure or biological activity, are further evaluated for therapeutic activity in mice, syngeneic and nude athymic, transplanted with murine or human tumor, respectively. Studies are also proposed to evaluate in vitro drug sensitivity using freshly isolated human tumor cells grown on bovine corneal endothelial cell extracellular matrix (ECM). Endpoint analysis will include the measurement of cellular fluorescence generated by specific fluorescent tumor marker (FITC-conjugated monoclonal antibodies) using a Pandex FCA to quantitate tumor cell number and response to drug treatment. These studies are aimed at the development of a fresh human tumor model system for the evaluation of new antitumor agents and treatments. Finally, compounds that demonstrate antiproliferative or therapeutic activity are routinely evaluated for their ability to inhibit the incorporation of various labeled precursors into tumor cell nucleic acids, protein and glycoconjugates, and for their effects on intracellular pool sizes and tumor cell ultrastructure. These studies contribute to the rational development of new treatments of cancer.

本研究的总体目标是评估不合适的肿瘤模型 系统潜在抗肿瘤的生物和治疗活性 制剂和生物反应调节剂，源自该程序 或者如果与其目标相关，则从外部来源获得。 基于 有关新化合物的活性和作用方式的信息， 还将评估药物或治疗的组合。 最初的 所有药物的细胞毒性筛选均由一组人类进行 和鼠肿瘤细胞系，包括人 MCF7 乳腺细胞、A121 卵巢细胞 ca.、WiDr 结肠 ca.、DMS114 小细胞肺 ca.、H125 非小细胞肺 约和鼠L1210白血病。 IC50 和 IC90（生长抑制 浓度）是使用体外建立的每种药物 半自动比色测定。 有前途的新型代理，具有独特的 结构或生物活性，进一步评估其治疗作用 小鼠中的活性，同基因和裸无胸腺，移植有小鼠或 分别是人类肿瘤。 还建议进行体外评估研究 使用在牛上生长的新鲜分离的人肿瘤细胞进行药物敏感性 角膜内皮细胞细胞外基质（ECM）。 终点分析 将包括测量由以下物质产生的细胞荧光 特异性荧光肿瘤标记物（FITC 偶联单克隆抗体） 使用 Pandex FCA 定量肿瘤细胞数量和对药物的反应 治疗。 这些研究旨在培养新的人类 用于评估新型抗肿瘤药物和药物的肿瘤模型系统 治疗。 最后，具有抗增殖或抗增殖作用的化合物 常规评估治疗活性的抑制能力 将各种标记的前体掺入肿瘤细胞核酸中 酸、蛋白质和糖复合物及其对细胞内的影响 池大小和肿瘤细胞超微结构。 这些研究有助于 合理开发癌症新疗法。