Sheehan Jason, Sherman Jonathan, Cifarelli Christopher, Jagannathan Jay, Dassoulas Kasandra, Olson Claire, Rainey Jessica, Han Shaojie
Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.
J Neurosurg. 2009 Aug;111(2):226-9. doi: 10.3171/2009.3.JNS081339.
Glioblastoma multiforme tumors typically exhibit regions of hypoxia. Hypoxic regions within the tumor make cells less sensitive to radiosurgery and radiation therapy. Trans sodium crocetinate (TSC) has been shown to be a radiosensitizer. The goal of this research was to elucidate the underlying mechanism of TSC's radiosensitizing effect.
A rat C6 glioma model was used. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Two weeks later, MR imaging was used to confirm the presence of a glioma. Following demonstration on MR imaging of a brain tumor, animals were randomized into 1 of 2 groups: 1) TSC alone (100 microg/kg), or 2) saline control. Licox probes were inserted into the brain tumor and contralateral cerebral hemisphere. Tissue oxygenation measurements were recorded before and after intravenous infusion of either TSC or saline.
Not surprisingly, tissue oxygenation measurements revealed that the brain tumor was hypoxic relative to the contralateral cerebral hemisphere brain tissue. Two to 8 minutes after TSC was infused, tissue oxygenation measurements in the brain tumor increased above baseline by as much as 60%. After this temporary elevation following TSC infusion, tumor oxygenation measurements returned to baseline. No significant elevations in tissue oxygenation were seen on the contralateral side. Similarly, the saline vehicle was not observed to increase tissue oxygenation in either the brain tumor or the contralateral brain tissue.
Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.
多形性胶质母细胞瘤肿瘤通常表现出缺氧区域。肿瘤内的缺氧区域会使细胞对放射外科手术和放射治疗的敏感性降低。反式金盏花素(TSC)已被证明是一种放射增敏剂。本研究的目的是阐明TSC放射增敏作用的潜在机制。
使用大鼠C6胶质瘤模型。将C6胶质瘤细胞立体定向注射到大鼠脑内以形成肿瘤。两周后,采用磁共振成像(MR)确认胶质瘤的存在。在MR成像显示脑肿瘤后,将动物随机分为2组中的1组:1)单独使用TSC(100微克/千克),或2)生理盐水对照组。将Licox探头插入脑肿瘤和对侧脑半球。在静脉输注TSC或生理盐水之前和之后记录组织氧合测量值。
不出所料,组织氧合测量显示,相对于对侧脑半球脑组织,脑肿瘤处于缺氧状态。输注TSC后2至8分钟,脑肿瘤中的组织氧合测量值比基线升高多达60%。在TSC输注后的这种暂时升高之后,肿瘤氧合测量值恢复到基线。对侧未观察到组织氧合有明显升高。同样,未观察到生理盐水载体增加脑肿瘤或对侧脑组织中的组织氧合。
给予TSC可短暂改善缺氧胶质瘤中的组织氧合。这种作用是先前添加TSC后观察到的放射增敏作用的一种潜在机制。