Sensitization of chordoma cell lines to ionizing radiation

我们已签署必要的材料转让协议，以便我们从NCGC获得27种化合物。 根据我们与NCGC的协议，每次将不超过10种化合物发送给我们进行盲态检测。 NCGC还向我们提供了参考的50%致死剂量（LD 50）值，由其测定。 使用细胞内ATP含量的定量测定（类似于NCGC最初使用的那些），我们已经证实了我们在LD 50药物浓度下用前10种化合物在培养物中复制大约50%细胞毒性的能力。 我们已经完成了前10个化合物的放射增敏剂筛选，这表明，10个化合物之一作为一个放射增敏剂在文化。 在验证性试验证实了这一发现后，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作用的化合物。 这一发现与已知的脉络膜细胞中的mTOR通路（雷帕霉素作用于该通路）是有意义的。 目前正在进行实验，以阐明辐射致敏的确切水平和机制。 我们已经从NCGC收到了下一组10种化合物，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.