School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN, USA.
Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):1075-82. doi: 10.1016/j.ijrobp.2011.06.1984. Epub 2011 Dec 22.
Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model.
Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells.
The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation.
We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.
正常组织的损伤是临床放射治疗（RT）的一个限制因素。我们通过大鼠原位脑肿瘤模型，测试了肿瘤的存在改变正常组织对照射反应的假设。
使用大鼠颅窗的活体显微镜评估了大鼠 C6 神经胶质瘤对肿瘤周围组织的原位影响，包括有无 RT。RT 方案包括在肿瘤植入后第 5 天开始每天 8 Gy 给予 40 Gy。终点包括血脑屏障通透性、清除指数、白细胞-内皮相互作用和血管内皮生长因子（VEGF）、胶质纤维酸性蛋白和细胞凋亡染色。为了描述系统对 RT 的反应，测量了动物的存活率和肿瘤表面积和体积。在类似的植入了没有肿瘤细胞的基底膜基质的动物中进行了假手术实验。
仅肿瘤的存在就会增加通透性，但对白细胞-内皮相互作用和星形胶质细胞增生几乎没有影响。单独照射会增加组织通透性、白细胞-内皮相互作用和星形胶质细胞增生。在同时存在肿瘤和照射的模型中，通透性和细胞黏附的水平最高；然而，肿瘤的存在似乎减少了滚动白细胞的体积。未照射的肿瘤和肿瘤周围组织的清除率很差。照射的肿瘤和肿瘤周围组织的清除指数与照射和未照射的假植入动物相似。辐射减少了肿瘤周围正常组织中 VEGF 的存在，但对正常组织中的细胞凋亡没有影响。有或没有辐射的肿瘤组织都发生了细胞凋亡。
我们开发了一种新方法来证明肿瘤的存在改变了大鼠颅内模型中正常组织对照射的反应。
