Monitoring of singlet oxygen is useful for predicting the photodynamic effects in the treatment for experimental glioma

Monitoring of singlet oxygen is useful for predicting the photodynamic effects in the treatment for experimental glioma
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DOI:
10.1158/1078-0432.ccr-06-0786
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发表时间:
2006-12-01
影响因子:
11.5
通讯作者:
Namba, Hiroki
Namba, Hiroki
中科院分区:
医学1区
文献类型:
--
作者:
Yamamoto, Junkoh;Yamamoto, Seiji;Namba, Hiroki

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目的:光动力疗法(PDT)中产生的单线态氧(O-1(2))在杀死肿瘤细胞方面发挥着非常重要的作用。使用新型近红外光电倍增管系统,我们监测了PDT过程中O-1(2)的实时产生,从而研究了O-1(2)产生与光动力效应之间的关系。实验设计:我们使用5-氨基乙酰丙酸和纳秒脉冲染料激光在体外9L胶质肉瘤细胞和体内实验肿瘤模型中进行了PDT。在此期间,我们使用该系统监控 O-1(2)。此外,基于O-1(2)监测,我们设置不同的激光照射条件并研究它们是否会影响肿瘤细胞死亡。结果:我们可以详细观察PDT过程中O-1(2)产生的时间变化。在低注量率下,O-1(2) 信号逐渐下降并出现低峰,而在高注量率下,O-1(2) 信号立即下降并出现高峰。因此,低注量率下的累积O-1(2)较高,从而产生强烈的光动力效应。因此,细胞凋亡与坏死的比例可能取决于 O-1(2) 信号的峰值和持续时间。低注量率容易引起细胞凋亡变化,而高注量率则容易引起坏死性变化。结论:本研究结果表明,O-1(2)的监测使我们能够预测光动力效应,使我们能够为每个患者选择最佳的激光条件。
Purpose: Singlet oxygen (O-1(2)) generated in photodynamic therapy (PDT) plays a very important role in killing tumor cells. Using a new near-IR photomultiplier tube system, we monitored the real-time production of O-1(2) during PDT and thus investigated the relationship between the O-1(2) production and photodynamic effects.Experimental Design: We did PDT in 9L gliosarcoma cells in vitro and in an experimental tumor model in vivo using 5-aminolevulinic acid and nanosecond-pulsed dye laser. During this time, we monitored O-1(2) using this system. Moreover, based on the O-1(2) monitoring, we set the different conditions of laser exposure and investigated whether they could affect the tumor cell death.Results: We could observe the temporal changes of O-1(2) production during PDT in detail. At a low fluence rate the O-1(2) signal gradually decreased with a low peak, whereas at a high fluence rate it decreased immediately with a high peak. Consequently, the cumulative O-1(2) at a low fluence rate was higher, which thus induced a strong photodynamic effect. The proportion of apoptosis to necrosis might therefore be dependent on the peak and duration of the O-1(2) signal. A low fluence rate tended to induce apoptotic change, whereas a high fluence rate tended to induce necrotic change.Conclusions:The results of this study suggested that the monitoring of O-1(2) enables us to predict the photodynamic effect, allowing us to select the optimal laser conditions for each patient.