Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma |
| |
Authors: | Jianfeng Wang Yaoping Shi Zhibin Bai Yonggang Li Longhua Qiu Guy Johnson |
| |
Institution: | 1. Image-Guided Biomolecular Intervention Research, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA;2. Department of Radiology, Chaoyang Hospital, Capital Medical University, Beijing, China;3. Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China |
| |
Abstract: | Purpose: 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).Materials and 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.Conclusion: 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. |
| |
Keywords: | Hepatocellular carcinoma radiofrequency hyperthermia gene therapy herpes simplex virus-thymidine kinase |
|
|