Synergistic interaction with arsenic trioxide and fractionated radiation in locally advanced murine tumor.
Synergistic interaction with arsenic trioxide and fractionated radiation in locally advanced murine tumor.
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发表时间：
2002-08
期刊：
影响因子：
11.2
通讯作者：
Y. Lew;A. Kolozsvary;Stephen Brown;J. H. Kim
中科院分区：
文献类型：
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作者：
Y. Lew;A. Kolozsvary;Stephen Brown;J. H. Kim
我们以前已经表明，三氧化二砷（ATO）优先关闭肿瘤血流，导致实体瘤中心部分的明显细胞死亡，对周围正常组织的影响最小。基于组织病理学和肿瘤灌注研究，我们假设ATO和放射联合治疗后局部晚期实体瘤的肿瘤控制率相对于放射或ATO单独治疗会增加。用甲基胆蒽诱导的BALB/c小鼠局部晚期纤维肉瘤进行了抗肿瘤作用和定量肿瘤灌注研究。南卡罗来纳用ATO单独（10 mg/kg）、放射单独（30戈伊）或药物加放射一起处理甲基胆蒽诱导的纤维肉瘤腿部肿瘤。与未经治疗的肿瘤相比，单独的放射和单独的药物延迟了肿瘤的生长几天。相比之下，当放射和药物一起给予时，肿瘤生长延迟长于1个月，导致局部肿瘤治愈55%。相对于单独药物或单独放射，分次放射与ATO组合显示出类似的显著肿瘤生长延迟。使用铷摄取方法测量的联合治疗后肿瘤血流量的持续减少证实了增强的肿瘤反应。药物治疗后，肿瘤组织中肿瘤坏死因子-α的产生立即增加10倍，伴随着肿瘤血流的迅速减少。目前的结果表明，联合治疗的肿瘤反应优于单独治疗，表明ATO有可能作为放疗的辅助治疗。
We have shown previously that arsenic trioxide (ATO) preferentially shutsdown tumor blood flow, leading to pronounced cell death in the central part of the solid tumor with a minimal effect on the surrounding normal tissues. On the basis of the histopathological and tumor perfusion studies, we hypothesized that the tumor control rate of locally advanced solid tumors would increase after the combined treatment of ATO and radiation relative to either radiation or ATO alone. The antitumor action and quantitative tumor perfusion studies were carried out with locally advanced methylcholanthrene-induced fibrosarcoma grown in BALB/c mice. The s.c. methylcholanthrene-induced fibrosarcoma leg tumors were treated with ATO alone (10 mg/kg), radiation alone (30 Gy), or drug plus radiation together. Radiation alone and drug alone delayed the growth of the tumor by a few days compared with untreated tumors. In contrast, when radiation and drug were given together, the tumor growth delay was longer than 1 month, resulting local tumor cure of 55%. The fractionated radiation combined with ATO showed a similar pronounced tumor growth delay relative to the drug alone or radiation alone. Sustained reduction in tumor blood flow after the combined treatment measured using a rubidium uptake method paralleled enhanced tumor response. There was an immediate 10-fold increase in the production of tumor necrosis factor-alpha in the tumor tissue after the drug treatment, concomitant with the onset of prompt reduction of the tumor blood flow. The present results indicate that tumor response was better with combined treatment than with either treatment alone, suggesting that ATO has potential as an adjuvant to radiotherapy.