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Development of a novel in-vivo drug/in-vitro light system to investigate mechanisms of cell killing with photodynamic therapy

机译:开发新型体​​内药物/体外光系统以研究光动力疗法杀死细胞的机制

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Abstract: Over the last decade considerable interest has developed in the use of exogenously administered chromophores in combination with visible light for the treatment of human tumors. Whether cells are killed directly, or indirectly as a result of disruption of the tissue, microvasculature is unknown. The authors have developed methods to assess in short term culture the effects of PDT on precision cut tissue slices. The use of these tissue slices provide an important link between in vivo studies and in vitro isolated cultured cells for the following reasons: 1) slices contain all of the normal cells in their proper in vivo architectural arrangement; 2) since slices can be obtained relatively easily and in a very short period of time (a few minutes), animals can be treated with compounds in vivo, the tissue can be removed, sliced and mechanistic studies performed in vitro (without the several hours delay required to produce cultured cells); 3) in vitro comparisons between species, including human, can be readily made; and 4) mechanisms of PDT-induced cell killing can be studied in the absence of a functioning vascular system. Using this in vivo drug/in vitro light system, the results presented will detail the findings using normal rat liver and a transplantable rat tumor model.!
机译:摘要:在过去的十年中,人们对将外源发色团与可见光相结合用于治疗人类肿瘤产生了浓厚的兴趣。无论是直接杀死细胞,还是由于组织破坏而间接杀死细胞,微脉管系统都是未知的。作者已经开发出了在短期培养中评估PDT对精确切割的组织切片的影响的方法。这些组织切片的使用提供了体内研究与体外分离的培养细胞之间的重要联系,其原因如下:1)切片包含所有处于正常体内结构安排的正常细胞; 2)由于可以相对容易地在很短的时间内(几分钟)获得切片,因此可以在体内用化合物对动物进行处理,可以将组织取出,切片并在体外进行机理研究(无需几个小时)产生培养细胞所需的延迟); 3)可以容易地进行包括人类在内的物种之间的体外比较;和4)可以在不存在正常血管系统的情况下研究PDT诱导的细胞杀伤机制。使用这种体内药物/体外照明系统,给出的结果将详细说明使用正常大鼠肝脏和可移植大鼠肿瘤模型的发现。

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