Generation of low-flux X-ray micro-planar beams and their biological effect on a murine subcutaneous tumor model.

Generation of low-flux X-ray micro-planar beams and their biological effect on a murine subcutaneous tumor model.
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DOI:
10.1093/jrr/rrv037
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发表时间:
2015-09
影响因子:
2
通讯作者:
Tsuboi K
Tsuboi K
中科院分区:
医学4区
文献类型:
--
作者:
Hong Z;Zenkoh J;Le B;Gerelchuluun A;Suzuki K;Moritake T;Washio M;Urakawa J;Tsuboi K

文献摘要

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我们使用实验室规模的工业X射线发生器(60 kV/20 mA)产生低通量X射线微平面束(MPB),该发生器具有三种不同峰/间距宽度(50/200 μm,100/400 μm,50/400 μm)的定制准直器。为了评价正常皮肤反应,将C3 H/HeN小鼠的大腿暴露于100和200戈伊MPB,并与宽束(20、30、40、50、60戈伊)进行比较。在具有皮下肿瘤(SCCVII)的C3 H/HeN小鼠中评价MPB的抗肿瘤作用。用100和200 Gy的戈伊MPB以及20和30 Gy的戈伊宽束照射肿瘤后,测量肿瘤大小并进行生存分析。此外,切除肿瘤并进行免疫化学检查以检测γ-H2 AX、ki 67和CD 34。结果表明,200戈伊的50/200 μm和100/400 μm的MPBs的抗肿瘤作用明显大于20戈伊束,与30戈伊束相当。γ-H2 AX阳性细胞在MPB照射后呈明显的条纹状,24 h后条纹逐渐消失并混杂。Ki 67阳性的时间变化在MPBs和宽束之间没有差异,而CD 34阳性面积在MPBs中比在宽束中显著减少。此外,研究表明,与达到相同肿瘤控制效果的等效剂量的宽束照射相比,MPB照射后的皮肤损伤明显更轻。旁观者效应和肿瘤血管损伤可能是MPBs疗效的机制。
We generated low-flux X-ray micro-planar beams (MPBs) using a laboratory-scale industrial X-ray generator (60 kV/20 mA) with custom-made collimators with three different peak/pitch widths (50/200 μm, 100/400 μm, 50/400 μm). To evaluate normal skin reactions, the thighs of C3H/HeN mice were exposed to 100 and 200 Gy MPBs in comparison with broad beams (20, 30, 40, 50, 60 Gy). Antitumor effects of MPBs were evaluated in C3H/HeN mice with subcutaneous tumors (SCCVII). After the tumors were irradiated with 100 and 200 Gy MPBs and 20 and 30 Gy broad beams, the tumor sizes were measured and survival analyses were performed. In addition, the tumors were excised and immunohistochemically examined to detect γ-H2AX, ki67 and CD34. It was shown that antitumor effects of 200 Gy MPBs at 50/200 μm and 100/400 μm were significantly greater than those of 20 Gy broad beams, and were comparable with 30 Gy broad beams. γ-H2AX-positive cells demonstrated clear stripe-patterns after MPB irradiation; the pattern gradually faded and intermixed over 24 h. The chronological changes in ki67 positivity did not differ between MPBs and broad beams, whereas the CD34-positive area decreased significantly more in MPBs than in broad beams. In addition, it was shown that skin injury after MPB irradiation was significantly milder when compared with broad-beam irradiation at equivalent doses for achieving the same tumor control effect. Bystander effect and tumor vessel injury may be the mechanism contributing to the efficacy of MPBs.