Gene therapy of carcinoma using ultrasound-targeted microbubble destruction.

Gene therapy of carcinoma using ultrasound-targeted microbubble destruction.
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DOI:
10.1016/j.ultrasmedbio.2010.11.011
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发表时间:
2011-03
影响因子:
2.9
通讯作者:
Villanueva, Flordeliza S.
Villanueva, Flordeliza S.
中科院分区:
医学3区
文献类型:
--
作者:
Carson, Andrew R.;McTiernan, Charles F.;Lavery, Linda;Hodnick, Abigail;Grata, Michelle;Leng, Xiaoping;Wang, Jianjun;Chen, Xucai;Modzelewski, Ruth A.;Villanueva, Flordeliza S.

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当微泡造影剂负载基因并系统注射时,超声靶向微泡破坏(UTMD)有助于将基因集中输送到靶组织。用小鼠鳞状细胞癌模型验证了UTMD在单纯疱疹病毒胸苷激酶(TK)和更昔洛韦治疗时能特异性转导肿瘤组织和减缓肿瘤生长的假说。UTMD介导的报告基因传递导致肿瘤血管周围区域和单个肿瘤细胞中荧光素酶和绿色荧光蛋白(GFP)的表达高于对照肿瘤(p=0.02)。TK组肿瘤细胞倍增时间长于GFP组(p=0.02),且TK组肿瘤细胞凋亡率增加(p=0.04),细胞脱落面积增加(p=0.03)。这些数据表明,UTMD基因治疗可以转导实体瘤,并介导治疗效果。UTMD是一种很有前途的非病毒靶向基因治疗方法,可能在一系列肿瘤中有用。
When microbubble contrast agents are loaded with genes and systemically injected, ultrasound-targeted microbubble destruction (UTMD) facilitates focused delivery of genes to target tissues. A mouse model of squamous cell carcinoma was used to test the hypothesis that UTMD would specifically transduce tumor tissue and slow tumor growth when treated with herpes simplex virus thymidine kinase (TK) and ganciclovir. UTMD-mediated delivery of reporter genes resulted in tumor expression of luciferase and green fluorescent protein (GFP) in perivascular areas and individual tumor cells that exceeded expression in control tumors (p = 0.02). The doubling time of TK-treated tumors was longer than GFP-treated tumors (p = 0.02), and TK-treated tumors displayed increased apoptosis (p = 0.04) and more areas of cellular drop-out (p = 0.03). These data indicate that UTMD gene therapy can transduce solid tumors and mediate a therapeutic effect. UTMD is a promising nonviral method for targeting gene therapy that may be useful in a spectrum of tumors.
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