PHOTOSENSITIZER LOCALIZATION IN PDT RESISTANT & PDT SENSITIVE CELLS

PDT 抗性中的光敏剂定位

• 批准号: 6308184
• 负责人: CHARLES Joseph GOMER
• 金额: $ 2.46万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6308184
• 关键词: biological products; biomedical resource; drug /agent; human tissue; lasers; neoplasm /cancer; proteins; technology /technique

An obstacle to the adequate assessment of Photodynamic Therapy (PDT) continues to be the lack of basic knowledge regarding PDT induced cytotoxicity at the cellular and in-vivo levels. Our PDT resistant RIF tumor cells are a useful tool for examining mechanisms of action. We hypothesize that analyzing PDT resistance will provide insights into the basic mechanisms of PDT induced cytotoxicity and thereby lead to strategies to improve PDT. Initial differential gene expression studies have identified unique transcripts expressed specifically in either the parental or resistant clones. One such transcript (found only in the parental cells) has been sequenced and identified as low density lipoprotein receptor related protein (LRP). This receptor is also known as alpha-2 macroglobulin receptor. A number of LRP properties suggest that this molecule may be involved in modulating PDT sensitivity. Molecular and biochemical tools are now available to allow us to determine whe ther LRP is involved in PDT sensitivity. Confocal fluorescence microscopy will be used to map photosensitizer subcellular localization properties for resistant and sensitive cells. This study will provide definitive information on whether variations in subcellular localization parameters of photosensitizers are determinants in PDT responses.

充分评估光动力疗法的障碍 （PDT）继续是缺乏有关PDT的基本知识 在细胞和体内水平上诱导的细胞毒性。 我们的PDT 抗性RIF肿瘤细胞是检查机制的有用工具 行动。 我们假设分析PDT抗性将提供 对PDT诱导的细胞毒性的基本机制的见解和 从而导致改善PDT的策略。 初始差异基因 表达研究已经确定了表达的独特成绩单 特别是在父母或抗性克隆中。 一个这样的 转录本（仅在父母细胞中发现）已被测序，并且 被鉴定为低密度脂蛋白受体相关蛋白（LRP）。 该受体也称为α-2大球蛋白受体。 一个 LRP特性的数量表明该分子可能参与 调节PDT灵敏度。 现在正在分子和生化工具 可让我们确定lrp参与PDT 灵敏度。 共聚焦荧光显微镜将用于映射 耐药性和 敏感细胞。 这项研究将提供有关的明确信息 是否存在亚细胞定位参数的变化 光敏剂是PDT响应中的决定因素。