Core--In Vivo Procedures Core

这一核心组成部分将评估该项目中开发的试剂的急性毒性和增强中等热疗对小鼠体内加热的异种肿瘤的放射增敏效果的能力。核心还将确定与热诱导放射增敏(HIR)和/或其体外增强(如项目中确定的)有关的参数是否也与HIR或其在体内的增强有关。这项工作的一个长期目标是开发非侵入性成像这些参数的方法。简而言之，这个核心将与项目研究人员合作，将他们的体外研究扩展到最初的临床前模型，利用裸鼠体内作为异种移植生长的人类肿瘤。 这个核心的建立将为评估项目3和项目4中开发的化合物的体内疗效和毒性提供一个有效和成本效益高的资源。此外，核心将与所有项目合作，以确认导致体外HIR增加的参数(即分子变化)也与HIR或其在体内的增强有关。

This Core Component will evaluate reagents developed in the Projects for acute toxicity and the ability to enhance the radiosensitizing effects of moderate hyperthermia in tumor xenografts heated in vivo in mice. The Core will also determine if the parameters that relate to heat-induced radiosensitization (HIR) and/or its enhancement in vitro (as established in the Projects) also relate to HIR or its enhancement in vivo. A long-range goal of this effort is to develo methods to image these parameters non-invasively. Briefly, this Core will collaborate with the Project researchers to extend their in vitro studies to initial pre-clinical models utilizing human tumors grown as xenografts in nude mice. The establishment of this Core will provide an efficient and cost effective resource for evaluating the in vivo efficacy and toxicity of compounds developed in Projects 3 and 4. In addition, the Core will collaborate with all of the Projects to confirm that the parameters (i.e. molecular alterations) that contribute to increased HIR in vitro are also related to HIR or its enhancement in vivo.