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Induction of cell fusion/apoptosis in anaplastic thyroid carcinoma in orthotopic mouse model by urokinase-specific oncolytic Sendai virus.
Head & Neck 2019 April 11
BACKGROUND: This study was designed to assess the therapeutic effect of urokinase-targeted recombinant oncolytic Sendai virus, termed "BioKnife," on anaplastic thyroid carcinoma (ATC).
METHODS: Urokinase activity was investigated in human ATC cell lines, and BioKnife cytotoxicity against the cell lines was evaluated in vitro. Orthotopic mouse models of ATC were treated with three intratumoral injections of BioKnife, control virus, or phosphate-buffered saline (PBS) and were observed daily until >20% weight loss occurred.
RESULTS: All three ATC cell lines showed a high level of urokinase activity. BioKnife induced urokinase-dependent cell fusion and cytotoxicity in all cell lines. Orthotopic models treated with BioKnife showed significantly prolonged survival compared with models treated with control virus or PBS (BioKnife 41.6 ± 15.0, control virus 17.0 ± 2.9, PBS 17.7 ± 6.3 days).
CONCLUSIONS: BioKnife exerted therapeutic effects in orthotopic ATC mouse models. Thus, BioKnife represents a possible treatment option for ATC.
METHODS: Urokinase activity was investigated in human ATC cell lines, and BioKnife cytotoxicity against the cell lines was evaluated in vitro. Orthotopic mouse models of ATC were treated with three intratumoral injections of BioKnife, control virus, or phosphate-buffered saline (PBS) and were observed daily until >20% weight loss occurred.
RESULTS: All three ATC cell lines showed a high level of urokinase activity. BioKnife induced urokinase-dependent cell fusion and cytotoxicity in all cell lines. Orthotopic models treated with BioKnife showed significantly prolonged survival compared with models treated with control virus or PBS (BioKnife 41.6 ± 15.0, control virus 17.0 ± 2.9, PBS 17.7 ± 6.3 days).
CONCLUSIONS: BioKnife exerted therapeutic effects in orthotopic ATC mouse models. Thus, BioKnife represents a possible treatment option for ATC.
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