Evaluation of continuous low dose rate versus acute single high dose rate radiation combined with oncolytic viral therapy for prostate cancer.
Evaluation of continuous low dose rate versus acute single high dose rate radiation combined with oncolytic viral therapy for prostate cancer.
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DOI：
10.3109/09553000903419338
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发表时间：
2010-03
影响因子：
2.6
通讯作者：
Rodriguez R
中科院分区：
文献类型：
--
作者：
Liu C;Zhang Y;Liu MM;Zhou H;Chowdhury W;Lupold SE;Deweese TL;Rodriguez R
先前已证明，连续复制腺病毒（CRAd）可增强放射活性，从而产生细胞杀伤的协同作用。然而，以前的模型结合辐射与CRAD没有集中在辐射输送的方法。我们模拟了一种新的前列腺特异性CRAd，Ad 5 PSE/PBN E1 A-AR（Ad 5：腺病毒5; PSE：前列腺特异性增强子; PBN：大鼠probasin启动子; E1 A：早期区域1A; AR：雄激素受体）与急性和连续递送的辐射的组合，以更好地模拟前列腺癌放射治疗的潜在临床模式。我们证明，在病毒感染前24小时用急性单次高剂量率（HDR）辐射预处理细胞，可显著增强病毒复制和病毒介导的细胞死亡。此外，这种组合导致γ-H2 AX（丝氨酸139上的磷酸化组蛋白H2 AX）水平增加，这是双链DNA损伤的标志物，也是核碎片的间接测量。相比之下，连续低剂量率（LDR）辐射感染后立即相同的CRAd的结果在没有增强病毒复制，和病毒介导的细胞死亡中只有累加效应。这些数据首次直接评估了放射对病毒复制的实时影响，并首次比较了放射递送对CRAd病毒疗法疗效的影响。我们的数据表明，CRAD疗效的基础上的辐射输送模式的实质性差异。
Conditionally Replicative Adenovirus (CRAd) has been previously demonstrated to augment the activity of radiation, resulting in synergy of cell kill. However, previous models combining radiation with CRAd have not focused on the methods of radiation delivery. We model the combination of a novel prostate-specific CRAd, Ad5 PSE/PBN E1A-AR (Ad5: adenovirus 5; PSE: prostate-specific enhancer; PBN: rat probasin promoter; E1A: early region 1A; AR: androgen receptor), with radiation delivered both acutely and continuously, in an effort to better mimic the potential clinical modes of prostate cancer radiotherapy. We demonstrate that pre-treatment of cells with acute single high dose rate (HDR) radiation 24 hours prior to viral infection results in significantly enhanced viral replication and virus-mediated cell death. In addition, this combination causes increased level of γ-H2AX (Phosphorylated histone protein H2AX on serine 139), a marker of double-stranded DNA damage and an indirect measure of nuclear fragmentation. In contrast, continuous low dose rate (LDR) radiation immediately following infection of the same CRAd results in no enhancement of viral replication, and only additive effects in virus-mediated cell death. These data provide the first direct assessment of the real-time impact of radiation on viral replication and the first comparison of the effect of radiation delivery on the efficacy of CRAd virotherapy. Our data demonstrate substantial differences in CRAd efficacy based on the mode of radiation delivery.
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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
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2.4
作者：
Teh, BS;Amosson, CM;Butler, EB
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Butler, EB
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11.2
作者：
Nagano, Satoshi;Perentes, Jean Yannis;Boucher, Yves
通讯作者：
Boucher, Yves
影响因子：
4.8
作者：
Hart, Lori S.;Ornelles, David;Koumenis, Constantinos
通讯作者：
Koumenis, Constantinos
影响因子：
5.7
作者：
Rajecki, Maria;Kanerva, Anna;Hemminki, Akseli
通讯作者：
Hemminki, Akseli