Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Sci Rep. 2018 Oct 18;8(1):15410. doi: 10.1038/s41598-018-33747-7.
Radiation therapy is one of the main treatment options for many cancer patients. Although high doses of radiation may maximize tumor cell killing, dose escalation is limited by toxicity to neighboring normal tissues. This limitation applies particularly to the small intestine, the second most radiosensitive organ in the body. Identifying small intestinal (SI) radioprotectors could enable dose escalation in the treatment of abdominopelvic malignancies. However, the only assay currently available to identify effects of radiomodulating drugs on the regenerating capacity of SI stem cells is the Withers-Elkind microcolony assay, which requires large numbers of mice, making it a costly and low throughput method. Here, we describe a novel spheroid formation assay (SFA) that utilizes SI stem cell-enriched three-dimensional epithelial spheroid cultures to identify gastrointestinal radiomodulators ex vivo. The SFA is scalable for high throughput screening and can be used to identify both radioprotectors and radiosensitizers.
放射治疗是许多癌症患者的主要治疗选择之一。尽管高剂量的辐射可以最大限度地杀死肿瘤细胞，但剂量的增加受到邻近正常组织毒性的限制。这种限制尤其适用于小肠，它是体内第二敏感的器官。鉴定小肠（SI）辐射防护剂可以使腹部和骨盆恶性肿瘤的治疗剂量增加。然而，目前唯一可用于鉴定调节放射药物对 SI 干细胞再生能力的检测方法是 Withers-Elkind 微集落检测法，该方法需要大量的小鼠，因此成本高、通量低。在这里，我们描述了一种新的球体形成检测法（SFA），它利用富含 SI 干细胞的三维上皮球体培养物来鉴定胃肠道辐射调节剂。SFA 可进行高通量筛选，并可用于鉴定辐射防护剂和辐射增敏剂。
