PHOTO THERAPY OF BLADDER CANCER WITH HEMATOPORPHYRINS

该项目的总体目标是提高 光疗法治疗膀胱癌 我们已经取得了实质性进展 在过去的基础研究和临床前研究资助期间， 以及使用血卟啉治疗的临床发展 衍生物（HPD）作为光敏剂。 III期临床试验 目前正在进行HPD光疗。 我们现在集中精力 通过寻找更多的 有效的光敏剂。 我们打算从高肿瘤的方向进行研究- 对光敏性的选择性。 我们的目标是一群 相关染料已经证明，从早期和我们的 对一些系统进行初步工作，以便在 定位于肿瘤中。 我们能够提高光活性的 恶嗪购买修改其结构;高达65%的绝对 实现了单线态氧产率。 本课题 建议评估并进一步开发这些化合物， 用于肿瘤光疗的有效和选择性敏化剂。 这次调查的一个重要部分是我们努力 将发色团的分子结构与它们的 物理化学和光化学性质，并进一步与 它们在细胞中的选择性定位和光活性， 肿瘤的 本课题的具体目标是：（1）筛选、合成 并表征了一系列系统的恶嗪衍生物， 让我们能够确定结构与功能的关系 与选择性肿瘤定位、光动力活性有关。 (2)评价这些恶嗪衍生物对肿瘤的选择性 在动物肿瘤模型和培养细胞中的定位。 (3)到 评价和优化恶嗪类药物在 介导体外光细胞毒性，单， 浸润性、微观和转移性肿瘤，以及它们的 暗毒性 (4)为了研究决定 选择性肿瘤定位和发色团的光活性 研究分子结构、光化学 和生物物理性质，以及肿瘤选择性， 发色团的光活性。 该项目可能会导致改善光疗， 发现新的、有效的和肿瘤选择性的敏化剂。 这 可能会扩大这种疗法的效用，以治疗危及生命的 浸润性和转移性肿瘤。 我们的研究可以提供一个 更好地理解决定肿瘤的分子因素- 选择性和光反应性。 这将为以下方面提供指导 未来的发展，甚至更好的感光和更大的 利用光疗。 最后，我们希望这个项目 将获得有关这些染料的充分信息， for lunching午餐preclinical临床and clinical临床studies研究.

The overall goal of this project is to advance the technique of phototherapy for bladder cancer. We have made substantial progress during the past funding period in basic studies and in preclinical and clinical development of this treatment using hematoporphyrin derivative (HPD) as the photosensitizer. Phase III clinical trials for HPD-phototherapy are now underway. We now focus our efforts on improving and expanding this treatment by searching for more effective photosensitizers. We intend to approach this search from the direction of high tumor- selectivity for the photosensiti. Our target is a group of oxazine related dyes that have demonstrated, from early and from our preliminary work on a number of systems, to be highly selective in localizing in tumors. We are able to enhance the photoactivity of the oxazines buy modifying their structures; up to 65% absolute singlet oxygen yield has been achieved. In this project, we propose to evaluate and further develop these compounds into effective and selective sensitizers for phototherapy of tumors. An important part of this investigation is in our efforts to correlate molecular structures of chromophores with their physicochemical and photochemical properties, and further with their selective localization and photoactivity in cells and in tumors. The specific aims of this project are: (1) To select, synthesize and characterize a systematic series of oxazine derivatives chosen to allow us to determine structure-function relationships pertaining to selective-tumor localization, photodynamic activity. (2) To evaluate these oxazine derivatives for their selective tumor localization in animal tumor models and in cultured cells. (3) To evaluate and optimize the effectiveness of the oxazines in mediating photo-cytotoxicity in vitro, photodestruction of single, infiltrating, microscopic and metastatic tumors, as well as their dark toxicity. (4) To investigate molecular mechanisms dictating selective-tumor localization and photoactivity of chromophores by examining relationships between molecular structure, photochemical and photophysical properties, and tumor-selectivity and photoavtivity of chromophores. This project will likely lead to improvement of phototherapy by discovering new, effective and tumor-selective sensitizers. This may expand the utility of this therapy to treat life-threatening infiltrating and metastatic tumors. Our study could provide a better understanding for molecular factors dictating tumor- selective and photoreactivity. This will provide guidances for future development of even better photosensiti and greater utilizations of phototherapy. Finally, we expect that this project will obtain adequate information on these dyes to provide the basis for lunching preclinical and clinical studies.