PHOTOSENSITIZER LOCALIZATION IN PDT RESISTANT & PDT SENSITIVE CELLS

充分评估光动力疗法的障碍 (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， 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转录本， 特别是在亲本或抗性克隆中。 一个这样 转录物（仅在亲本细胞中发现）已被测序， 被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 LRP的一些性质表明，这种分子可能参与 调节PDT敏感性。 分子和生物化学工具现在 可用于确定LRP是否参与PDT 灵敏度 共聚焦荧光显微镜将用于映射 光敏剂的亚细胞定位特性， 敏感细胞 这项研究将提供明确的信息， 是否在亚细胞定位参数的变化， 光敏剂是PDT反应的决定因素。

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.