DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma.
DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma.
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DOI：
10.1371/journal.pone.0035857
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ross BD
中科院分区：
文献类型：
--
作者：
Galbán S;Lemasson B;Williams TM;Li F;Heist KA;Johnson TD;Leopold JS;Chenevert TL;Lawrence TS;Rehemtulla A;Mikkelsen T;Holland EC;Galbán CJ;Ross BD
在小鼠胶质瘤中评价了放射增敏剂吉西他滨（GEM）的有效性，并结合成像生物标志物扩散加权磁共振成像（DW-MRI）对治疗效果进行了早期检测。用吉西他滨（GEM）、替莫唑胺（TMZ）+/−电离辐射（IR）处理基因工程改造的鼠GBM模型[Ink 4a-Arf −/− PtenloxP/loxP/Ntv-a RCAS/PDGF（+）/Cre（+）]。通过对比增强MRI和DW-MRI分别对生长速率和肿瘤细胞构成进行量化治疗效果。用GEM、TMZ和辐射处理的小鼠早在处理开始后三天就显示出生长速率的显著降低。两种联合治疗（GEM/IR和TMZ/IR）均导致生存率高于单一治疗。在给予治疗后肿瘤体积生长速率出现可检测变化之前，肿瘤扩散值增加。伴随的GEM/IR和TMZ/IR在该GBM模型中是活性的并且耐受良好，并且类似地延长了荷瘤小鼠的中位生存期。DW-MRI提供了放射增敏治疗的早期变化，并在临床试验中对该成像生物标志物进行了评估。
The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials.
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影响因子：
4.8
作者：
Moffat, Bradford A.;Chenevert, Thomas L.;Ross, Brian D.
通讯作者：
Ross, Brian D.
影响因子：
8
作者：
Fisher, GH;Orsulic, S;Varmus, HE
通讯作者：
Varmus, HE
影响因子：
3.9
作者：
Fabi, Alessandra;Mirri, Alessandra;Carapella, Carmine Maria
通讯作者：
Carapella, Carmine Maria
影响因子：
10.5
作者：
Dai, C;Celestino, JC;Holland, EC
通讯作者：
Holland, EC
影响因子：
45.3
作者：
MACDONALD, DR;CASCINO, TL;CAIRNCROSS, JG
通讯作者：
CAIRNCROSS, JG