PMID- 37834271
OWN - NLM
STAT- MEDLINE
DCOM- 20231101
LR  - 20240304
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 19
DP  - 2023 Oct 2
TI  - Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a 
      Gastric Cancer Model.
LID - 10.3390/ijms241914823 [doi]
LID - 14823
AB  - 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.
FAU - Fujino, Hiroaki
AU  - Fujino H
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
AD  - Departments of Biomedical Chemistry, School of Science and Technology, Kwansei 
      Gakuin University, Hyogo 669-1330, Japan.
FAU - Sonoda-Fukuda, Emiko
AU  - Sonoda-Fukuda E
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
FAU - Isoda, Lisa
AU  - Isoda L
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
AD  - Departments of Biomedical Chemistry, School of Science and Technology, Kwansei 
      Gakuin University, Hyogo 669-1330, Japan.
FAU - Kawabe, Ayane
AU  - Kawabe A
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
AD  - Departments of Biomedical Chemistry, School of Science and Technology, Kwansei 
      Gakuin University, Hyogo 669-1330, Japan.
FAU - Takarada, Toru
AU  - Takarada T
AUID- ORCID: 0000-0001-9993-4433
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
AD  - Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, 
      Hyogo 658-8558, Japan.
FAU - Kasahara, Noriyuki
AU  - Kasahara N
AUID- ORCID: 0000-0002-6069-9082
AD  - Departments of Neurological Surgery and Radiation Oncology, University of 
      California, San Francisco, CA 94143, USA.
FAU - Kubo, Shuji
AU  - Kubo S
AUID- ORCID: 0000-0001-7384-4835
AD  - Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical 
      Science, Hyogo Medical University, Hyogo 663-8501, Japan.
LA  - eng
GR  - 21H03012/Grant-in-Aid for Scientific Research B from the Ministry of Education, 
      Culture, Sports, Science and Technology (MEXT)/
PT  - Journal Article
DEP - 20231002
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Prodrugs)
SB  - IM
MH  - Mice
MH  - Humans
MH  - *Stomach Neoplasms/drug therapy/genetics
MH  - *Prodrugs/pharmacology/therapeutic use/metabolism
MH  - Cell Line, Tumor
MH  - Genetic Therapy
MH  - Leukemia Virus, Gibbon Ape/genetics/metabolism
MH  - Genetic Vectors/genetics
MH  - Animals
PMC - PMC10573151
OTO - NOTNLM
OT  - gastric cancer
OT  - prodrug activator gene therapy
OT  - retroviral replicating vectors
COIS- NK is a former consultant of Tocagen Inc. This does not alter the authors' 
      adherence to all CGT policies on sharing data and materials. The other authors 
      declare no conflicts of interest.
EDAT- 2023/10/14 10:49
MHDA- 2023/11/01 12:45
PMCR- 2023/10/02
CRDT- 2023/10/14 01:03
PHST- 2023/08/04 00:00 [received]
PHST- 2023/09/29 00:00 [revised]
PHST- 2023/09/29 00:00 [accepted]
PHST- 2023/11/01 12:45 [medline]
PHST- 2023/10/14 10:49 [pubmed]
PHST- 2023/10/14 01:03 [entrez]
PHST- 2023/10/02 00:00 [pmc-release]
AID - ijms241914823 [pii]
AID - ijms-24-14823 [pii]
AID - 10.3390/ijms241914823 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Oct 2;24(19):14823. doi: 10.3390/ijms241914823.