Breast Cancer Brain Metastasis Response to Radiation After Microbubble Oxygen Delivery in a Murine Model
Breast Cancer Brain Metastasis Response to Radiation After Microbubble Oxygen Delivery in a Murine Model
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DOI：
10.1002/jum.15031
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发表时间：
2019-12-01
影响因子：
2.3
通讯作者：
Eisenbrey, John R.
中科院分区：
文献类型：
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作者：
Delaney, Lauren J.;Ciraku, Lorela;Eisenbrey, John R.
低氧癌细胞已被证明比常氧细胞对放射治疗更有抵抗力。因此，本研究探讨超声（US）诱导的载氧微泡（mb）破裂是否会增强乳腺癌转移灶对放疗的反应。方法15只裸鼠右半球立体定向注射寻脑MDA-MB-231乳腺癌细胞。将动物随机分为5个治疗组：不干预、使用小动物辐射研究平台进行10 Gy辐射、10 Gy辐射前携带氮的MBs合并us介导的MB破裂、10 Gy辐射前携带氧的MBs、10 Gy辐射前携带氧的MBs合并us介导的MB破裂。用三维超声监测肿瘤进展，并记录总生存率。结果除载氧MB破裂和放射治疗组外，其余组治疗后肿瘤继续快速生长。仅放射治疗的肿瘤在治疗后一周内，体积+/- SD平均增加337% +/- 214%。经载氧MB和放射线治疗而无MB破裂的肿瘤体积增加383% +/- 226%。携带氧的MBs破裂后立即放射治疗的肿瘤体积仅增加41% +/- 1% (P = 0.045)，该组的生存时间也增加了1周。结论：在转移性乳腺癌小鼠模型中，在放射治疗中加入us破裂携带氧的MBs似乎可以延缓肿瘤进展并提高生存率。
Objectives Hypoxic cancer cells have been shown to be more resistant to radiation therapy than normoxic cells. Hence, this study investigated whether ultrasound (US)-induced rupture of oxygen-carrying microbubbles (MBs) would enhance the response of breast cancer metastases to radiation. Methods Nude mice (n = 15) received stereotactic injections of brain-seeking MDA-MB-231 breast cancer cells into the right hemisphere. Animals were randomly assigned into 1 of 5 treatment groups: no intervention, 10 Gy radiation using a small-animal radiation research platform, nitrogen-carrying MBs combined with US-mediated MB rupture immediately before 10 Gy radiation, oxygen-carrying MBs immediately before 10 Gy radiation, and oxygen-carrying MBs with US-mediated MB rupture immediately before 10 Gy radiation. Tumor progression was monitored with 3-dimensional US, and overall survival was noted. Results All groups except those treated with oxygen-carrying MB rupture and radiation had continued rapid tumor growth after treatment. Tumors treated with radiation alone showed a mean increase in volume +/- SD of 337% +/- 214% during the week after treatment. Tumors treated with oxygen-carrying MBs and radiation without MB rupture showed an increase in volume of 383% +/- 226%. Tumors treated with radiation immediately after rupture of oxygen-carrying MBs showed an increase in volume of only 41% +/- 1% (P = 0.045), and this group also showed a 1 week increase in survival time. Conclusions Adding US-ruptured oxygen-carrying MBs to radiation therapy appears to delay tumor progression and improve survival in a murine model of metastatic breast cancer.