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.

光动力疗法的充分评估的障碍 (PDT)仍然是缺乏关于PDT的基本知识 在细胞和体内水平上诱导细胞毒性。我们的PDT 耐药RIF肿瘤细胞是研究机制的有用工具 行动的一部分。我们假设，分析光动力疗法的耐药性将提供 光动力疗法诱导细胞毒性的基本机制及意义 从而得出改善PDT的策略。初始差异基因 表达研究已经确定了独特的转录本 特别是在亲本或抗性克隆中。这样的一个 转录本(只在亲本细胞中发现)已经测序， 鉴定为低密度脂蛋白受体相关蛋白(LRP)。 这种受体也被称为α-2巨球蛋白受体。一个 LRP的一些性质表明，这个分子可能参与了 调节光动力疗法的灵敏度。分子和生化工具现在 可用于确定PDT中是否涉及LRP 敏感度。共聚焦荧光显微镜将被用来绘制 抗癌药物光敏剂的亚细胞定位特性 敏感细胞。这项研究将为以下方面提供明确的信息 亚细胞定位参数的变化是否 光敏剂是光动力反应的决定因素。