Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.
J Neurosurg. 2010 Aug;113(2):234-9. doi: 10.3171/2009.11.JNS091314.
Glioblastoma (GB) tumors typically exhibit regions of hypoxia. Hypoxic areas within the tumor can make tumor cells less sensitive to chemotherapy and radiation therapy. Trans-sodium crocetinate (TSC) has been shown to transiently increase oxygen to hypoxic brain tumors. The authors examined whether this improvement in intratumor oxygenation translates to a therapeutic advantage when delivering standard adjuvant treatment to GBs.
The authors used C6 glioma cells to create a hypoxic GB model. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Fifteen days later, MR imaging was used to confirm the presence of a glioma. The animals were randomly assigned to 1 of 3 groups: 1) temozolomide alone (350 mg/m(2)/day for 5 days); 2) temozolomide and radiation therapy (8 Gy); or 3) TSC (100 microg/kg for 5 days), temozolomide, and radiation therapy. Animals were followed through survival studies, and tumor response was assessed on serial MR images obtained at 15-day intervals during a 2-month period.
Mean survival (+/- SEM) of the temozolomide-alone and the temozolomide/radiotherapy groups was 23.2 +/- 0.9 and 29.4 +/- 4.4 days, respectively. Mean survival in the TSC/temozolomide/radiotherapy group was 39.8 +/- 6 days, a statistically significant improvement compared with either of the other groups (p < 0.05). Although tumor size was statistically equivalent in all groups at the time of treatment initiation, the addition of TSC to temozolomide and radiotherapy resulted in a statistically significant reduction in the MR imaging-documented mean tumor size at 30 days after tumor implantation. The mean tumor size in the TSC/temozolomide/radiotherapy group was 18.9 +/- 6.6 mm(2) compared with 42.1 +/- 2.7 mm(2) in the temozolomide-alone group (p = 0.047) and 35.8 +/- 5.1 mm(2) in the temozolomide/radiation group (p = 0.004).
In a hypoxic GB model, TSC improves the radiological and clinical effectiveness of temozolomide and radiation therapy. Further investigation of this oxygen diffusion enhancer as a radiosensitizer for hypoxic brain tumors seems warranted.
胶质母细胞瘤（GB）肿瘤通常表现为缺氧区域。肿瘤内的缺氧区域会使肿瘤细胞对化疗和放疗的敏感性降低。转钠克罗酸盐（TSC）已被证明可使缺氧脑肿瘤的氧含量短暂增加。作者研究了在对 GB 进行标准辅助治疗时，这种肿瘤内氧合作用的改善是否转化为治疗优势。
作者使用 C6 神经胶质瘤细胞创建了一个缺氧的 GB 模型。将 C6 神经胶质瘤细胞立体定向注射到大鼠脑内以创建肿瘤。15 天后，使用磁共振成像（MRI）确认存在神经胶质瘤。动物被随机分配到 3 组中的 1 组：1）单独替莫唑胺（350mg/m2/天，连续 5 天）；2）替莫唑胺和放射治疗（8Gy）；或 3）TSC（100μg/kg，连续 5 天），替莫唑胺和放射治疗。对动物进行了生存研究，并在 2 个月期间每 15 天通过连续 MRI 图像评估肿瘤反应。
单独使用替莫唑胺和替莫唑胺/放射治疗组的平均生存时间（+/- SEM）分别为 23.2 +/- 0.9 和 29.4 +/- 4.4 天。TSC/替莫唑胺/放射治疗组的平均生存时间为 39.8 +/- 6 天，与其他两组相比具有统计学显著改善（p <0.05）。尽管在开始治疗时所有组的肿瘤大小在统计学上是等效的，但在替莫唑胺和放射治疗中添加 TSC 可导致在肿瘤植入后 30 天时 MRI 记录的平均肿瘤大小的统计学显著减少。TSC/替莫唑胺/放射治疗组的平均肿瘤大小为 18.9 +/- 6.6mm2，与单独使用替莫唑胺组的 42.1 +/- 2.7mm2（p = 0.047）和替莫唑胺/放射治疗组的 35.8 +/- 5.1mm2（p = 0.004）相比。
在缺氧的 GB 模型中，TSC 提高了替莫唑胺和放射治疗的放射学和临床效果。作为缺氧脑肿瘤的增敏剂，进一步研究这种氧扩散增强剂似乎是合理的。
