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.

光动力疗法充分评估的障碍 （PDT）仍然缺乏有关PDT的基础知识 在细胞和体内水平诱导细胞毒性。 我们的PDT 耐药 RIF 肿瘤细胞是检查机制的有用工具 的行动。 我们假设分析 PDT 耐药性将提供 深入了解 PDT 诱导细胞毒性的基本机制 从而制定改善 PDT 的策略。 初始差异基因 表达研究已经确定了表达的独特转录本 特别是在亲本克隆或抗性克隆中。 这样的一位 转录本（仅在亲代细胞中发现）已被测序并且 鉴定为低密度脂蛋白受体相关蛋白（LRP）。 该受体也称为 α-2 巨球蛋白受体。 一个 LRP 的许多特性表明该分子可能参与 调节 PDT 敏感性。 分子和生化工具现在 可让我们确定 LRP 是否参与 PDT 敏感性。 共焦荧光显微镜将用于绘制图谱 抗性和抗性的光敏剂亚细胞定位特性 敏感细胞。 这项研究将提供明确的信息 亚细胞定位参数是否存在变化 光敏剂是 PDT 反应的决定因素。