CORE--DRUG EVALUATION

药物评价核心的总体目标是为以下方面提供支持： 研究者要求的常规程序、测定和分析 方案项目。一般来说，将使用现有的方法。新 方法，或已建立的方法的修改，将开发与 项目和核心根据需要。 核心使用的方法包括但不限于 以下内容： (i)药物亲脂性的测量，使用计算机估计， HPLC保留时间和油：缓冲液分配方法; (ii)细胞、组织和生物制品中药物水平的测定 使用吸光度、荧光和提取/溶解方法测定液体。 这些方法将用于培养的细胞、动物模型， 临床试验中的患者; (iii)光敏剂浓度的测定 非侵入性原位反射光谱法和荧光测定法。这些 将在临床试验中的动物模型和患者中进行测量。 审判; (iv)测量肿瘤对PDT的反应，包括维持 电子卡尺肿瘤测量的电子维护， 计算机化数据存储系统; （五） 使用荧光素测量血管对PDT的反应 排阻试验和专门构建的非侵入性原位 荧光计; (vi)使用孔测量正常组织对PDT的毒性 建立小鼠足反应模型; (vii)测量细胞对PDT的反应， 体内/离体（切除测定）模型; （viii）检测细胞、组织和细胞内的光敏剂和代谢物， 和液体中进行分析。 (ix)使用高灵敏度的光敏剂的白蛋白结合的测量 性能置换色谱法; （十） 确定光敏剂的组织和细胞部位 使用共聚焦荧光显微镜进行定位; (xi)组织学标本制备、组织学方法 发展 药物评价核心的活动将是必不可少的， 最大限度地从综合项目中获得有用的信息 和核心在这个项目中。核心人员将执行、指导或 监督这些例行程序，从而提高一致性， 以及规模经济;这种整合还将提高质量 控制，并将使项目之间的数据交换更加可行。

The overall aim of the Drug Evaluation Core is to provide support for routine procedures, assays and analyses required by the investigators of the Program Project. Generally, existing methodology will be used. New methods, or modifications of established methods, will be developed with the Projects and Cores as needed. Methods to be used by the Core include, but are not limited to, the following: (i) measurement of drug lipophilicity, using computer estimates, HPLC retention times and oil:buffer partitioning methods; (ii) determination of drug levels in cells, tissues and biological fluids using absorbance, fluorescence and extraction/dissolution methods. These methods will be performed for cultured cells, animal models, and patients in clinical trials; (iii) determination of photosensitizer concentrations using noninvasive in situ reflectance spectroscopy and fluorimetry. These measurements will be performed in animal models and patients in clinical trials; (iv) measurement of tumor response to PDT, including maintenance of electronic maintenance of electronic-caliper tumor measurement and computerized data storage systems; (v) measurement of vascular response to PDT using a fluorescein exclusion assay and specially constructed, non-invasive in situ fluorometer; (vi) measurement of normal tissue toxicity to PDT using the well established murine foot response model; (vii) measurement of cellular responses to PDT using in vitro and in vivo/ex vivo (excision assay) models; (viii)detection of photosensitizers and metabolites in cells, tissues and fluids using analytical HPLC. (ix) measurement of albumin binding of photosensitizers using high- performance displacement chromatography; (x) determine tissue and cellular sites of photosensitizer localization using confocal fluorescence microscopy; (xi) preparation of specimens for histology, histology method development. The activities of the Drug Evaluation Core will be essential for maximizing the yield of useful information from the integrated Projects and Cores in this Program Project. Core personnel will perform, direct or supervise these routine procedures, resulting in increased consistency as well as economy of scale; this consolidation will also improve quality control and will make it more feasible to exchange data between Projects.