PHOTO THERAPY OF BLADDER CANCER WITH HEMATOPORPHYRINS

卟啉敏化光放射治疗(PSPT)是一种很有前途的治疗方法 多种恶性肿瘤的治疗方法，目前是 在多个研究所积极研究和开发。的总目标是 我们的项目是开发用于膀胱癌的PSPT。我们已经做出了 在过去的筹资期间，在基础研究方面取得了重大进展 在这种治疗方法的发展中。当前应用程序将 使我们能够继续努力实现这一目标。 在这一应用中，我们打算将我们的临床研究集中在 “全膀胱壁照射”治疗浅表性膀胱炎的研究进展 肿瘤，包括原位癌(CIS)，在用 血卟啉衍生物(Hpd)。光辐射将会完成 通过通过光纤传输的514 nm激光 弥散尖端，当位于膀胱中心时，将 分配灯光以照亮整个膀胱壁。基础研究 将以阐明PSPT的一些机制为基础 以提高治疗水平。这些将围绕以下理论展开： 分子侵袭和解聚在卟啉中起主要作用 摄取、保留和光敏化，以及“不可交换” 卟啉(NEP)可能是HPD的“体内活性成分”。研究将会 进行了卟啉组成和物理性质的研究。 NEP的状态、HPD活性成分与 NEP的形成及其与亚细胞的可能联系 网站。还需要研究的是血浆和细胞之间的相互作用。 蛋白质与卟啉的结合；蛋白质结合对卟啉的影响 NEP和胞内蛋白的摄取、保留和形成 与NEP相关联。还将开展几项临床前研究。 探索PSPT的新途径。其中包括与 热疗，使用其他类型的激光和其他波长的光 而不是纳米。 该项目为治疗复发提供了一种新的方法。 和耐药膀胱癌，其中一些无法治疗 目前是令人满意的。从基础研究中获得的信息 将有助于更好地理解卟啉摄取的机制， 在肿瘤细胞中的滞留和光敏化，从而为 在增效减毒中提高治疗水平 效果。开发和信息也可以在 其他肿瘤的PSPT治疗。

Porphyrin-sensitized photoradiation therapy (PSPT) is a promising treatment modality for a variety of malignant tumors, and is currently a subject of active research and development in many institutes. The overall goal of our project is to develop PSPT for bladder carcinoma. We have made substantial progress during the past funding period, both in basic studies and in the development of this treatment. The current application will enable us to continue our efforts in achieving this goal. In this application, we intend to concentrate our clinical studies on the development of "whole bladder wall photoradiation" to treat superficial tumors including carcinoma-in-situ (CIS), after sensitizing the tumor with hermatoporphyrin derivative (HpD). The photoradiation will be accomplished by a 514 nm laser light delivered through an optical fiber with a dispersion tip, which when situated at the center of the bladder will distribute the light to illuminate the entire bladder wall. Basic studies will be carried out to elucidate some of the mechanisms of PSPT as a basis for improving the treatment. These will be centered around the theory that molecular aggression and deaggregation play major parts in porphyrin uptake, retention and photosensitization, and the "non-exchangeable" porphyrin (NEP) may be an "in vivo active component" of HpD. Studies will be carried out to investigate the porphyrin composition and the physical state of NEP, the relationship between active HpD component and the formation of NEP, and the possible association of NEP with subcellular sites. Also to be studied are the interactions of plasma and cellular proteins with the porphyrins; the effect of protein binding on porphyrin uptake, retention and formation of NEP, and intracellular proteins associated with NEP. Several pre-clinical studies will also be carried out to explore new approaches of PSPT. These include combination with hyperthermia, use of other types of lasers and light at wavelengths other than nm. This project offers the potential for a new modality in treating recurrent and resistant bladder cancer, some of these cannot be treated satisfactorily at the present. Information gained form the basic studies will provide a better understanding for mechanisms of porphyrin uptake, retention and photosensitization in tumor cells, thus providing a basis for improving the treatment by increasing the efficacy and reducing the side effects. The development and the information can also be useful in the treatment of other tumors by PSPT.