Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of esophageal squamous cancers.

Despite recent advances in surgical technique and treatment strategies for esophageal cancer (EC), to effectively manage the advanced (metastatic or disseminated) and recurrent EC still remain a great challenge. The aim of this study was to determine the feasibility of using intra-esophagus radiofrequency hyperthermia to enhance local HSV-TK/ganciclovir-mediated suicide gene therapy of an innovative animal models with orthotopic esophageal squamous cancers. Human esophageal squamous cancer (ESCa) cells were labeled with lentivirus/luciferase. ESCa cells and nude rats with orthotopic ESCa were divided into in four groups (n = 6/group) and treated with: i) combination therapy of MR imaging-heating-guidewire-mediated radiofrequency hyperthermia ((RFH, 42°C) plus local HSV-TK/GCV; ii) HSV-TK/GCV alone; iii) RFH alone; and (iv) phosphate-buffered saline (PBS). Bioluminescence optical imaging and transcutaneous ultrasound imaging were used to follow up bioluminescence signal and size changes of tumors among different groups over two weeks, which were correlated with subsequent histology. We demonstrated that combination therapy of RFH with gene therapy resulted in the lowest cell proliferation (37.5±8.6%, P<0.0001), rendered the smallest relative tumor volume (0.90±0.15, P<0.01), and relative bioluminescence optical imaging photon signal intensity (0.81±0.17, P<0.01) of orthotopic esophageal cancers, compared with groups treated with gene therapy alone, RFH alone and PBS. Our study indicated that intra-esophageal radiofrequency hyperthermia could enhance the HSV-TK-mediated effect on esophageal squamous cancers.