Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy.
Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy.
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射频热疗联合热休克蛋白启动子控制的HSV-TK基因治疗可促进化疗耐药乳腺癌的治疗效果：走向影像引导介入基因治疗
DOI：
10.18632/oncotarget.11346
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发表时间：
2016-10-04
期刊：
影响因子：
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通讯作者：
Yang X
中科院分区：
文献类型：
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作者：
Luo J;Wu X;Zhou F;Zhou Y;Huang T;Liu F;Han G;Chen L;Bai W;Wu X;Sun J;Yang X
目的 基因治疗是现代医学的前沿领域。本研究充分结合影像引导微创介入肿瘤学、射频技术、直接瘤内基因治疗等多学科领域的优势，探索了一种有效治疗多重耐药（MDR）乳腺癌的新技术。结果 与对照组相比，PHSP-TK联合RFH联合治疗后TK基因转染/表达显着升高，细胞增殖率降低，细胞凋亡指数升高。 MRI 体内验证实验证实，与对照动物相比，联合治疗导致相对肿瘤体积显着减小，组织学和细胞凋亡分析的结果也支持了这一点。材料和方法热休克蛋白启动子（PHSP）用于精确控制胸苷激酶（TK）（PHSP-TK）的过表达。进行了一系列体外实验，以确认射频热疗 (RFH) 是否可以增强 MDR 乳腺癌细胞系 (MCF7/Adr) 中的 PHSP-TK 转染和表达。然后进行了一系列体内实验来验证新技术的可行性，该新技术被称为介入性 RFH 增强直接瘤内 PHSP-TK 基因治疗。通过MRI评估联合治疗的疗效，并通过随后的实验室相关性证实。结论 本研究为耐多药乳腺癌介入 RFH 增强局部基因治疗这一新技术建立了“原理验证”，该技术可能通过介入肿瘤学、射频技术和直接瘤内基因治疗的同时整合，为有效治疗耐多药乳腺癌开辟新途径。
Objective Gene therapy is a frontier in modern medicine. In the present study, we explored a new technique for the effective treatment of multidrug-resistant (MDR) breast cancer by combining fully the advantages of multidisciplinary fields, including image-guided minimally invasive interventional oncology, radiofrequency technology, and direct intratumoral gene therapy. Results Combination treatment with PHSP-TK plus RFH resulted in significantly higher TK gene transfection/expression, as well as a lower cell proliferation rate and a higher cell apoptosis index, than those of control groups. In vivo validation experiments with MRI confirmed that combination therapy resulted in a significant reduction of relative tumor volume compared with those of control animals, which was supported by the results of histologic and apoptosis analyses. Materials and methods The heat shock protein promoter (PHSP) was used to precisely control the overexpression of thymidine kinase (TK) (PHSP-TK). Serial in vitro experiments were performed to confirm whether radiofrequency hyperthermia (RFH) could enhance PHSP-TK transfection and expression in a MDR breast cancer cell line (MCF7/Adr). Serial in vivo experiments were then carried out to validate the feasibility of the new technique, termed interventional RFH-enhanced direct intratumoral PHSP-TK gene therapy. The therapeutic effect of combination therapy was evaluated by MRI and confirmed by subsequent laboratory correlation. Conclusions This study has established “proof-of-principle” of a new technique, interventional RFH-enhanced local gene therapy for MDR breast cancer, which may open new avenues for the effective management of MDR breast cancers via the simultaneous integration of interventional oncology, RF technology, and direct intratumoral gene therapy.
DOI：
10.1186/1756-9966-32-5
发表时间：
2013-01-26
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
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作者：
Wei F;Wang H;Zhang J;Chen X;Li C;Huang Q
通讯作者：
Huang Q