Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model
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- Hiroaki Fujino
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
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- Emiko Sonoda-Fukuda
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
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- Lisa Isoda
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
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- Ayane Kawabe
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
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- Toru Takarada
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
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- Noriyuki Kasahara
- Departments of Neurological Surgery and Radiation Oncology, University of California, San Francisco, CA 94143, USA
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- Shuji Kubo
- Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
書誌事項
- 公開日
- 2023-10-02
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.3390/ijms241914823
- 公開者
- MDPI AG
説明
<jats:p>Retroviral replicating vectors (RRVs) selectively replicate and can specifically introduce prodrug-activating genes into tumor cells, whereby subsequent prodrug administration induces the death of the infected tumor cells. We assessed the ability of two distinct RRVs generated from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which infect cells via type-III sodium-dependent phosphate transporters, PiT-2 and PiT-1, respectively, to infect human gastric cancer (GC) cells. A quantitative RT-PCR showed that all tested GC cell lines had higher expression levels of PiT-2 than PiT-1. Accordingly, AMLV, encoding a green fluorescent protein gene, infected and replicated more efficiently than GALV in most GC cell lines, whereas both RRVs had a low infection rate in human fibroblasts. RRV encoding a cytosine deaminase prodrug activator gene, which converts the prodrug 5-flucytosine (5-FC) to the active drug 5-fluorouracil, showed that AMLV promoted superior 5-FC-induced cytotoxicity compared with GALV, which correlated with the viral receptor expression level and viral spread. In MKN-74 subcutaneous xenograft models, AMLV had significant antitumor effects compared with GALV. Furthermore, in the MKN-74 recurrent tumor model in which 5-FC was discontinued, the resumption of 5-FC administration reduced the tumor volume. Thus, RRV-mediated prodrug activator gene therapy might be beneficial for treating human GC.</jats:p>
収録刊行物
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 24 (19), 14823-, 2023-10-02
MDPI AG
