title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Tongchun
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Guocan
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Luming
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Image-Guided Bio-Molecular Intervention Research, Department of Radiology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D006360:Heat-Shock Proteins; D013937:Thymidine Kinase
keywords: HSV-TK; drug resistance; gene therapy; heat shock protein promoter; radiofrequency hyperthermia