TECHNOLOGY FOR DRUG DISCOVERY AND CANCER PATIENT TESTING

药物发现和癌症患者测试技术

• 批准号: 6072044
• 负责人: W D HANKINS
• 金额: $ 10万
• 依托单位: ACADEMIC RESEARCH ENTERPRISES, LLC
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-29 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6072044
• 关键词: antineoplastics; apoptosis; bioassay; breast neoplasms; cell line; cell type; dosage; drug discovery /isolation; drug screening /evaluation; technology /technique development

A new cell biology technology, (called Kinetics Of Response, or KOR) was recently invented and validated on leukemia cells by one of the applicants. The technology- allows automated, real-time monitoring of the apoptosis-inducing effects of chemical and biological agents and makes feasible high throughput screening on live cells in culture. In addition, the assay can, m the same experimental culture well, discriminate and quantify proliferation, cytostasis; necrosis and apoptosis. Though still in its infancy, this new technology has already revealed heretofore unrecognized relationships between the drug exposure time, dose, cell viability, proliferation or apoptosis and generated characteristic response patterns of various cell types exposed chemotherapeutic drugs or biological agents. In brief, the bioassays derived from this technology provide continuous monitoring of subtle changes in optical density, in particular the side light scattering properties of cell population when they are exposed to various stimulatory or inhibitory agents. It is suggested that such automated in vitro measurements may allow a new approach to drug discovery, predictions of the in vivo efficacy of drug and more information about the drug's mechanism of action than is feasible with any other cell response assays. This innovative technology, its associated new concepts and medical informatics software will be covered under use, technology and software patents which are currently pending. Our studies suggest that in order to obtain an accurate picture of drug induced apoptosis one must assay at the time of maximal apoptosis. Since that time varies with drug, dose and cell type, a kinetic (as opposed to an endpoint) analysis the only, way to identify the time of maximum apoptosis. In sharp contrast, to all other existing apoptosis assays, the automated KOR assays are simple, inexpensive and provide live, continuous and kinetic monitoring of cell cultures during the entire period of drug exposure. This KOR assays have been validated for leukemia cells and our phase I objective is to test the feasibility of extending this assay to breast cancer and other solid tumors. PROPOSED COMMERCIAL APPLICATION: The automated new cell biology technology will be marketed as a new approach to: l) High throughput screening on cells for new drug leads 2) Chemosensitivity and Resistance pre-testing in patients contemplating chemotherapy 3) Academic research in apoptosis and related areas of cell biology 4) Medical informatics software to assist with clinical decisions

最近，一位申请者发明了一种新的细胞生物学技术(称为反应动力学，简称KOR)，并在白血病细胞上进行了验证。该技术-允许自动、实时监测化学和生物制剂的凋亡诱导效应，并对培养中的活细胞进行高通量筛选是可行的。此外，在相同的实验培养条件下，该方法能很好地区分和定量细胞的增殖、细胞停滞、坏死和凋亡。虽然这项新技术还处于初级阶段，但它已经揭示了药物暴露时间、剂量、细胞活力、增殖或凋亡之间的未知关系，并产生了各种细胞类型暴露于化疗药物或生物制剂时的特征反应模式。简而言之，从这项技术衍生出来的生物检测技术提供了对光密度的细微变化的连续监测，特别是当细胞暴露于各种刺激或抑制剂时，细胞群体的侧光散射特性。有人认为，这种自动化的体外测量可能会提供一种新的方法来发现药物，预测药物的体内疗效，并提供比任何其他细胞反应分析都可行的更多关于药物作用机制的信息。这项创新技术及其相关的新概念和医疗信息学软件将包括在目前正在申请的使用、技术和软件专利项下。我们的研究表明，为了获得药物诱导的细胞凋亡的准确图像，必须在最大凋亡率时进行检测。由于时间随药物、剂量和细胞类型的不同而不同，动力学(而不是终点)分析是确定最大凋亡时间的唯一方法。与现有的所有其他细胞凋亡检测方法形成鲜明对比的是，自动化的KOR检测方法简单、廉价，并在整个药物暴露期间提供对细胞培养的实时、连续和动态监测。这种KOR检测方法已经在白血病细胞中得到了验证，我们的第一阶段目标是测试将这种检测方法扩展到乳腺癌和其他实体肿瘤的可行性。拟议的商业应用：自动化的新细胞生物学技术将作为一种新的方法上市：L)对细胞进行高通量的新药筛选2)对考虑化疗的患者进行化疗敏感性和耐药性预测试3)细胞生物学的学术研究4)帮助临床决策的医学信息学软件