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Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma

机译:靶向表达Fas的腺病毒结合γδT细胞在人卵巢癌小鼠模型中的治疗作用

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摘要

The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with γδ T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, γδ T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and γδ T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and γδ T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and γδ T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the γδ T cell group, the adenovirus and γδ T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and γδ T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and γδ T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and γδ T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts.
机译:本研究旨在调查表达Fas的腺病毒与γδT细胞介导的杀伤结合使用在BALB / c小鼠中治疗人卵巢癌异种移植物的治疗效果和安全性。构建了包含人类端粒酶逆转录酶启动子控制元件和两步转录扩增系统的穿梭质粒,并将其包装到腺病毒5载体中,以表达外源Fas基因。构建了人类卵巢癌的小鼠异种移植模型。将总共​​35只BALB / c小鼠随机分为五组,分别注射PBS,γδT细胞,表达Fas的腺病毒,紫杉醇或表达Fas的腺病毒和γδT细胞。监测每组小鼠中肿瘤的重量和体积。比较表达Fas的腺病毒和γδT细胞组与PBS组的小鼠各种组织的组织切片,以评估表达Fas的腺病毒和γδT细胞在治疗人卵巢癌异种移植肿瘤中的安全性。本研究的结果表明,所有治疗组中的小鼠在治疗过程结束时仍存活。 PBS组的肿瘤重量和体积最高,其次是腺病毒组,γδT细胞组,腺病毒和γδT细胞组以及紫杉醇组。腺病毒和γδT细胞组的体重和体积抑制率明显高于PBS组(P <0.05)。对组织样品的病理观察表明,与健康对照相比,腺病毒和γδT细胞组中的重要器官在治疗过程中均未出现任何明显的形态学变化。总之,与表达Fas的腺病毒和γδT细胞的联合疗法对于治疗小鼠人卵巢癌异种移植物是有效和安全的。

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