Sensitization of chordoma cell lines to ionizing radiation

我们已经签署了从NCGC获得27种化合物所需的材料转让协议。根据我们与NCGC的协议，每次不超过10种化合物将被发送给我们进行盲法测试。NCGC还为我们提供了50%致死剂量（LD50）的参考值，这是由他们的分析确定的。通过对细胞内ATP含量的定量分析（类似于NCGC最初使用的方法），我们证实了我们能够在LD50药物浓度下复制大约50%的细胞毒性，并提供前10种化合物。我们已经完成了前10种化合物的辐射致敏剂筛选，这表明10种化合物中的一种在培养中具有辐射致敏剂的作用。在验证性分析证实了这一发现后，NCGC合作者对数据进行了审查，他们发现雷帕霉素是表现出致敏性的化合物。这一发现对脊索瘤细胞中已知的mTOR通路（雷帕霉素作用的途径）是有意义的。实验正在进行中，以阐明辐射致敏的精确水平和机制。我们已经收到来自NCGC的下一组10个化合物，用于盲法筛选。

We have executed the Materials Transfer Agreements necessary for us to obtain the 27 compounds from the NCGC. Per our agreement with NCGC, no more than 10 compounds will be sent to us at a time for testing in a blinded fashion. NCGC has also provided us with the reference 50% lethal dose (LD50) values, as determined by their assays. Using quantitative assays of intracellular ATP content (similar to those used initially by NCGC), we have confirmed our ability to replicate roughly 50% cytotoxicity at LD50 drug concentrations in culture with the first 10 compounds supplied. We have completed screening the first 10 compounds for radiation sensitizers, and this revealed that one of the 10 compounds acted as a radiosensitizer in culture. After confirmatory assays confirmed this finding, the data were reviewed with NCGC collaborators, who revealed that rapamycin was the compound exhibiting sensitization. This finding makes sense with what is known about the mTOR pathway (upon which rapamycin acts) in chordoma cells. Experiments are ongoing to elucidate the precise level and mechanism of radiation sensitization. We have received the next set of 10 compouds from NCGC for screening in blinded fashion.