PHOTODYNAMIC THERAPY AND HYPEROXYGENATION

该项目之前的研究表明，关键的 影响肿瘤对光动力疗法(PDT)反应的参数包括 治疗过程中肿瘤内的氧合水平。基于 这一数据我们假设，肿瘤对光动力疗法的反应 随之而来的是正常组织毒性的增加，可以通过 各种高氧技术。我们进一步假设 这种增强的机制将增加对 肿瘤以前的缺氧区。最后，我们还假设 在反应方面的改善方面的差异在两个方面 将采用的移植模型系统将与 氧在这两个体系中扩散的理论模型。 C3H小鼠/MCA(乳腺腺癌)移植瘤系统的建立 腿部或侧翼将是所有人都采用的两个模型系统 学习。为了检验这些假设，以下具体目标将是 地址。首先，我们建议证明肿瘤内的氧合作用 可以通过让动物接受各种不同的 高氧状态。然后，我们建议展示增强的 肿瘤对PDT治疗的反应 氧合能力的改善。随后，对于这些条件集， 氧气和治疗变量，显示出改善的肿瘤反应，如 体外/体内测试系统将被用来证明 应答的增强可归因于增强的直接细胞杀伤。

Previous studies in this project have indicated that one of the critical parameters influencing tumor response to Photodynamic Therapy (PDT) is the level of oxygenation in the tumor during the treatment. Based upon this data we hypothesize that tumor response to PDT without a concomitant increase in normal tissue toxicity, can be improved by various hyperoxygenation techniques. We further hypothesize that the mechanism for this enhancement will increase direct cell killing in previous hypoxic regions of the tumor. Finally, we also hypothesize that the differences in improvement in response seen in the two transplant model systems to be employed will correlate with the theoretical models of oxygen diffusion in the two systems. The C3H mouse/MCA (mammary adenocarcinoma) tumor system implanted into either the leg or flank will be the two model systems employed for all studies. To test the hypotheses the following specific aims will be addressed. First we propose to demonstrate that intratumor oxygenation can be directly manipulated by subjecting the animals to various hyperoxygenation conditions. We then propose to demonstrate enhanced tumor response to PDT treatment for those treatment conditions showing improvement in oxygenation. Subsequently, for those sets of conditions, oxygen and treatment variables, showing improved tumor response, as in vitro/in vivo assay system will be employed to demonstrate that the enhancement of response is attributable to enhanced direct cell killing.