Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model.
Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model.
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DOI：
10.7863/jum.2012.31.11.1759
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Saini R
中科院分区：
文献类型：
--
作者：
Hoyt K;Sorace A;Saini R
本研究的目的是确定体积超声造影（US）成像是否可以在临床前三阴性乳腺癌动物模型中检测抗死亡受体5抗体（TRA-8）单独治疗或与化疗联合治疗的早期肿瘤反应。动物实验获得了机构动物护理和使用委员会的批准。在第0、3、7、10、14和17天，向30只携带乳腺肿瘤的小鼠施用Abraxane（紫杉醇; Celgene Corporation，Summit，NJ）、TRA-8、TRA-8 + Abraxane或盐水作为对照。在给药前第0、1、3和7天进行体积对比增强US成像。将肿瘤灌注参数图的变化与肿瘤体积和免疫组织学结果进行比较。在给药后7天内使用参数体积对比增强US成像检测治疗效果。与对照肿瘤相比，在TRA-8单独给药和TRA-8 + Abraxane给药的动物中观察到肿瘤灌注减少（分别为P = 0.17; P = 0.001）。在TRA-8 + Abraxane组中观察到的灌注减少与同期肿瘤大小的相应消退相匹配。存活曲线表明，与单独施用的相同药物相比，TRA-8 + Abraxane的组合改善了药物功效。免疫组织学分析显示TRA-8给药的肿瘤中细胞凋亡活性水平增加，证实了增强的抗肿瘤作用。初步结果是令人鼓舞的，体积对比增强的基于US的肿瘤灌注成像可能被证明在临床上是可行的，用于检测和监测TRA-8 + Abraxane联合治疗的早期抗肿瘤作用。
The objective of this study was to determine whether volumetric contrast-enhanced ultrasound (US) imaging could detect early tumor response to anti–death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor–bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone– and TRA-8 + Abraxane–dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy.
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DOI：
10.7863/jum.2010.29.4.577
发表时间：
2010-04
期刊：
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
影响因子：
--
作者：
Hoyt K;Warram JM;Umphrey H;Belt L;Lockhart ME;Robbin ML;Zinn KR
通讯作者：
Zinn KR
影响因子：
32.4
作者：
Chaudhary, PM;Eby, M;Hood, L
通讯作者：
Hood, L
DOI：
10.2217/14796694.2.4.493
发表时间：
2006-08-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Buchsbaum, Donald J;Zhou, Tong;Lobuglio, Albert F
通讯作者：
Lobuglio, Albert F
影响因子：
2.3
作者：
Gauthier, Thomas P.;Wasan, Harpreet S.;Leen, Edward L. S.
通讯作者：
Leen, Edward L. S.
影响因子：
6.7
作者：
Hoyt K;Sorace A;Saini R
通讯作者：
Saini R