PHOTODYNAMIC THERAPY AND HYPEROXYGENATION

该项目的先前研究表明， 影响肿瘤对光动力学疗法（PDT）反应的参数是 治疗过程中肿瘤的氧合水平。 基于 根据这些数据，我们假设肿瘤对PDT的反应没有明显的 伴随正常组织毒性增加，可通过以下方法改善 各种高氧合技术。 我们进一步假设， 这种增强的机制将增加直接细胞杀伤， 肿瘤的缺氧区域。 最后，我们还假设 在两个实验中， 将采用的移植模型系统与 氧在两个系统中扩散的理论模型。 将C3 H小鼠/MCA（乳腺腺癌）肿瘤系统植入到 腿或侧翼将是两个模型系统， 问题研究 为了检验这些假设，将有以下具体目标： 处理。 首先，我们建议证明肿瘤内氧合 可以通过对动物进行各种 高氧合条件。 然后，我们建议展示增强的 对于那些治疗条件，肿瘤对PDT治疗的反应显示 氧合改善。 随后，对于这些条件， 氧和治疗变量，显示改善的肿瘤反应，如在 将采用体外/体内测定系统来证明 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.