論文 - 詳細
| RRC ID | 78852 |
|---|---|
| 著者 | Fujino H, Sonoda-Fukuda E, Isoda L, Kawabe A, Takarada T, Kasahara N, Kubo S. |
| タイトル | Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model. |
| ジャーナル | Int J Mol Sci |
| Abstract |
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. |
| 巻・号 | 24(19) |
| 公開日 | 2023-10-2 |
| DOI | 10.3390/ijms241914823 |
| PII | ijms241914823 |
| PMID | 37834271 |
| PMC | PMC10573151 |
| MeSH | Animals Cell Line, Tumor Genetic Therapy Genetic Vectors / genetics Humans Leukemia Virus, Gibbon Ape / genetics Leukemia Virus, Gibbon Ape / metabolism Mice Prodrugs* / metabolism Prodrugs* / pharmacology Prodrugs* / therapeutic use Stomach Neoplasms* / drug therapy Stomach Neoplasms* / genetics |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HGC-27(RCB0500) Kato III(RCB2088) MKN-7 MKN45(RCB1001) MKN74(RCB1002) |