title: Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment.
abstract: New treatment strategies are required for renal cell carcinoma (RCC) due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT)-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tumor volume, weight, relative proliferation rate, and cell-apoptosis levels were examined in mice injected with adenovirus (Ad)-hTERT-HSV-TK and GCV. Increased cell death occurred following treatment with Ads carrying hTERT-HSV-TK/GCV or cytomegalovirus promoter-controlled (CMV)-HSV-TK/GCV for human RCC 786-0 and fibroblast MRC-5 cells. In mice, Ad-hTERT-HSV-TK/GCV more specifically inhibited tumor and RCC xenograft growth than Ad-CMV-HSV-TK/GCV (P < 0.05). Furthermore, Ad-hTERT-HSV-TK/GCV did not significantly damage normal fibroblasts or organ systems (heart, lung, liver, brain, kidney, and spleen). Thus, Ad-hTERT-HSV-TK/GCV is an effective RCC inhibitor in human cells in vitro and in vivo mouse models, indicating potential usefulness in RCC-targeted gene therapy.
authors.affiliation: Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Tian
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Mingde
authors.initials: M
authors.lastname: Lei
authors.forename: Na
authors.initials: N
authors.lastname: Ding
authors.forename: Ruifa
authors.initials: R
authors.lastname: Han
keywords: HSV-TK/GCV; adenovirus; hTERT promoter; renal cell carcinoma