Cilengitide-induced temporal variations in transvascular transfer parameters of tumor vasculature in a rat glioma model: identifying potential MRI biomarkers of acute effects.
Cilengitide-induced temporal variations in transvascular transfer parameters of tumor vasculature in a rat glioma model: identifying potential MRI biomarkers of acute effects.
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DOI：
10.1371/journal.pone.0084493
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ewing JR
中科院分区：
文献类型：
--
作者：
Nagaraja TN;Aryal MP;Brown SL;Bagher-Ebadian H;Mikkelsen T;Yang JJ;Panda S;Keenan KA;Cabral G;Ewing JR
据报道，西仑吉肽治疗后4-8小时放疗（RT）的疗效增加。我们假设西仑吉肽对肿瘤经血管转移参数的影响可能是这种增强作用的基础，从而预测这种增强作用。采用动态对比增强（DCE）-MRI对植入后约21天的原位U251胶质瘤无胸腺大鼠进行了研究。血管参数，即：在肿瘤脉管系统中测定造影剂的血浆体积分数（Vp）、前向体积转移常数（Ktranss）和间质体积分数（Ve），在施用西仑吉肽（4 mg/kg; N = 31;每组6-7）之后，在组2、4、8、12和24小时之前测定一次，并再次测定。对灌注固定的脑切片进行血管性血友病因子染色，以使血管段可视化。治疗前和治疗后参数的比较显示，西仑吉肽治疗前后MR指数之间的差异围绕8 h时间点旋转，2和4 h组显示增加，12和24 h组显示降低，8 h时间点的值接近基线。2 h和4 h组与12 h和24 h组之间的血管参数差异有统计学意义，K trans（p = 0.0001）和v e（p = 0.0271）。西仑吉肽给药后，血管染色随时间变化不大。西仑吉肽治疗后8小时发生的血管正常化与之前类似的报告一致，即西仑吉肽治疗后8小时进行RT时治疗疗效增加。药理学正常化的血管有可能增加敏感性RT。评估急性时间反应肿瘤血管公认的抗血管生成药物可能有助于优化其与其他治疗方式的组合。
Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days after implantation using dynamic contrast-enhanced (DCE)-MRI. Vascular parameters, viz: plasma volume fraction (v p), forward volume transfer constant (K trans) and interstitial volume fraction (v e) of a contrast agent, were determined in tumor vasculature once before, and again in cohorts 2, 4, 8, 12 and 24 h after Cilengitide administration (4 mg/kg; N = 31; 6-7 per cohort). Perfusion-fixed brain sections were stained for von Willebrand factor to visualize vascular segments. A comparison of pre- and post-treatment parameters showed that the differences between MR indices before and after Cilengitide treatment pivoted around the 8 h time point, with 2 and 4 h groups showing increases, 12 and 24 h groups showing decreases, and values at the 8 h time point close to the baseline. The vascular parameter differences between group of 2 and 4 h and group of 12 and 24 h were significant for K trans (p = 0.0001 and v e (p = 0,0271). Vascular staining showed little variation with time after Cilengitide. The vascular normalization occurring 8 h after Cilengitide treatment coincided with similar previous reports of increased treatment efficacy when RT followed Cilengitide by 8 h. Pharmacological normalization of vasculature has the potential to increase sensitivity to RT. Evaluating acute temporal responses of tumor vasculature to putative anti-angiogenic drugs may help in optimizing their combination with other treatment modalities.
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影响因子：
4.7
作者：
Jacobs VL;Valdes PA;Hickey WF;De Leo JA
通讯作者：
De Leo JA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1097/00005072-199611000-00005
发表时间：
1996-11-01
影响因子：
3.2
作者：
Gladson, CL
通讯作者：
Gladson, CL
影响因子：
3.7
作者：
Kawataki, Tomoyuki;Yamane, Tetsu;Patarroyo, Manuel
通讯作者：
Patarroyo, Manuel
影响因子：
3.3
作者：
Bagher-Ebadian, Hassan;Jain, Rajan;Nejad-Davarani, Siamak P.;Mikkelsen, Tom;Lu, Mei;Jiang, Quan;Scarpace, Lisa;Arbab, Ali S.;Narang, Jayant;Soltanian-Zadeh, Hamid;Paudyal, Ramesh;Ewing, James. R.
通讯作者：
Ewing, James. R.