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Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment

Authors Tian D , Sun, Yang, Lei, Ding, Han R

Received 21 December 2012

Accepted for publication 17 February 2013

Published 18 April 2013 Volume 2013:6 Pages 419—426


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Dawei Tian,1–4 Yan Sun,3 Yang Yang,2,3 Mingde Lei,3 Na Ding,3 Ruifa Han2,3

1Tianjin Medical University, Tianjin, People's Republic of China; 2Department of Urinary Surgery, 3Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China; 4Tianjin Nankai Hospital, Tianjin, People's Republic of China

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.

Keywords: hTERT promoter, HSV-TK/GCV, renal cell carcinoma, adenovirus

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