Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence.
Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence.
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DOI：
10.18632/oncotarget.12314
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发表时间：
2016-11-15
期刊：
影响因子：
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通讯作者：
Hoffman RM
中科院分区：
文献类型：
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作者：
Yano S;Takehara K;Miwa S;Kishimoto H;Tazawa H;Urata Y;Kagawa S;Bouvet M;Fujiwara T;Hoffman RM
我们之前已经开发出一种基因工程的表达GFP的端粒酶依赖型腺病毒OBP-401，它可以选择性地照亮癌细胞。在本报告中，我们证明了以OBP-401靶向三阴性高侵袭性人类乳腺癌在裸鼠体内原位生长能够实现根治性荧光引导手术(FGS)。由于病毒能够选择性地标记并随后杀死癌细胞，OBP-401实现了完全切除，防止了局部复发，并极大地抑制了淋巴结转移。相比之下，残留的乳腺癌细胞在强(白)光手术(BLS)后变得更具侵袭性。与传统的BLS相比，基于OBP-401的FGS也提高了总的存活率。因此，在临床相关的小鼠模型中，FGS可以预防高度侵袭性三阴性乳腺癌的转移。
We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.