PURPOSE: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo. METHODS: The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. RESULTS: TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. CONCLUSIONS: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.
PURPOSE: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on humanosteosarcoma both in vitro and in vivo. METHODS: The anti-tumor effects of Telomelysin were evaluated on humanosteosarcoma cell lines in vitro and in a mouse xenograft model of humanosteosarcoma in vivo. The replication efficiencies of Telomelysin in humanosteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. RESULTS: TelomeScan and Telomelysin were efficiently replicated in humanosteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the humanosteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. CONCLUSIONS: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of humanosteosarcoma.
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Authors: M Meyerson; C M Counter; E N Eaton; L W Ellisen; P Steiner; S D Caddle; L Ziaugra; R L Beijersbergen; M J Davidoff; Q Liu; S Bacchetti; D A Haber; R A Weinberg Journal: Cell Date: 1997-08-22 Impact factor: 41.582
Authors: C Heise; T Hermiston; L Johnson; G Brooks; A Sampson-Johannes; A Williams; L Hawkins; D Kirn Journal: Nat Med Date: 2000-10 Impact factor: 53.440
Authors: Allen M Goorin; Douglas J Schwartzentruber; Meenakshi Devidas; Mark C Gebhardt; Alberto G Ayala; Michael B Harris; Lee J Helman; Holcombe E Grier; Michael P Link Journal: J Clin Oncol Date: 2003-04-15 Impact factor: 44.544
Authors: Juan Martín Liberal; Laura Lagares-Tena; Miguel Sáinz-Jaspeado; Silvia Mateo-Lozano; Xavier García Del Muro; Oscar M Tirado Journal: Sarcoma Date: 2012-06-03