title: Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma.
abstract: OBJECTIVE
  To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in vitro confirmation and in vivo validation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology.
  
  
  RESULTS
  In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29 ± 6% vs. 56 ± 9%, 93 ± 4%, and 100 ± 5%, p < .05). Ultrasound imaging of treated animal xenografts showed smaller relative tumour volume in combination therapy group than those in three control groups (0.74 ± 0.19 vs. 1.79 ± 0.24, 3.14 ± 0.49 and 3.22 ± 0.52, p < .05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumours in the combination therapy group, compared to those in three control groups (1.2 ± 0.1 vs. 1.9 ± 0.2% vs. 3.3 ± 0.6% vs. 3.5 ± 0.4%, p < .05). These imaging findings were correlated well with histologic confirmation.
  
  
  CONCLUSIONS
  RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy.
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.|b Department of Radiology , Chaoyang Hospital, Capital Medical University , Beijing , China.
authors: Jianfeng
authors: J
authors: Wang
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.|c Department of Interventional Oncology, Renji Hospital , School of Medicine, Shanghai Jiaotong University , Shanghai , China.
authors: Yaoping
authors: Y
authors: Shi
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Zhibin
authors: Z
authors: Bai
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Yonggang
authors: Y
authors: Li
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Longhua
authors: L
authors: Qiu
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Guy
authors: G
authors: Johnson
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Feng
authors: F
authors: Zhang
authors: a Image-Guided Biomolecular Intervention Research, Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.
authors: Xiaoming
authors: X
authors: Yang
keywords: Hepatocellular carcinoma; gene therapy; herpes simplex virus-thymidine kinase; radiofrequency hyperthermia