{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T07:49:02Z","timestamp":1781423342264,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research B from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)","award":["21H03012"],"award-info":[{"award-number":["21H03012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<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>","DOI":"10.3390\/ijms241914823","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:17:19Z","timestamp":1696220239000},"page":"14823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Hiroaki","family":"Fujino","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"},{"name":"Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo 669-1330, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Sonoda-Fukuda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Isoda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"},{"name":"Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo 669-1330, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayane","family":"Kawabe","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"},{"name":"Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo 669-1330, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-4433","authenticated-orcid":false,"given":"Toru","family":"Takarada","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"},{"name":"Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, Hyogo 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-9082","authenticated-orcid":false,"given":"Noriyuki","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and Radiation Oncology, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-4835","authenticated-orcid":false,"given":"Shuji","family":"Kubo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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