PMID- 12679798
OWN - NLM
STAT- MEDLINE
DCOM- 20031218
LR  - 20121115
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 10
IP  - 4
DP  - 2003 Apr
TI  - Enhanced antitumor effects of a bicistronic adenovirus vector expressing both 
      herpes simplex virus thymidine kinase and monocyte chemoattractant protein-1 
      against hepatocellular carcinoma.
PG  - 260-9
AB  - The efficacy of the suicide gene therapy using the herpes simplex virus thymidine 
      kinase/ganciclovir (HSV-tk/GCV) system for the treatment of cancer is limited 
      because of the insufficient gene transfer and the low killing activity. To 
      enhance the antitumor activity, we determined whether recombinant adenovirus 
      vector (rAd)s expressing both HSV-tk and monocyte chemoattractant protein-1 
      (MCP-1) genes could potentiate the destruction of hepatocellular carcinoma (HCC). 
      The rAd Ad-tk-MCP1 harboring HSV-tk and MCP-1 genes in sequence under the 
      universal CAG promoter was constructed with a bicistronic unit including the 
      encephalomyocarditis virus-internal ribosomal entry site. The levels of HSV-tk 
      expression and GCV-sensitive tumoricidal activity of Ad-tk-MCP1 were comparable 
      to those of rAd expressing HSV-tk alone. The growth of subcutaneous tumors in 
      athymic nude mice was markedly suppressed when tumors were treated with 
      Ad-tk-MCP1 as opposed to another bicistronic vector Ad-MCP1-tk, rAd expressing 
      either HSV-tk or MCP-1, or both of these vectors. The antitumor effects of 
      Ad-tkMCP1 may be dependent on the activation of macrophages, since the 
      recruitment of macrophages was observed tumor necrosis factor-alpha production 
      was enhanced in the tumor tissue. Furthermore, the enhanced antitumor effect was 
      abolished by inactivating macrophages with carrageenan treatment. These results 
      demonstrated that a bicistronic rAd harboring both suicide and chemokine genes in 
      sequence exerted the enhanced, macrophage-dependent, antitumor effects in a model 
      of HCC and support the use of this strategy for the treatment of HCC.
FAU - Tsuchiyama, Tomoya
AU  - Tsuchiyama T
AD  - Department of Gastroenterology, Graduate School of Medical Science, Kanazawa 
      University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
FAU - Kaneko, Shuichi
AU  - Kaneko S
FAU - Nakamoto, Yasunari
AU  - Nakamoto Y
FAU - Sakai, Yoshio
AU  - Sakai Y
FAU - Honda, Masao
AU  - Honda M
FAU - Mukaida, Naofumi
AU  - Mukaida N
FAU - Kobayashi, Kenichi
AU  - Kobayashi K
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA, Recombinant)
RN  - EC 2.7.1.21 (Thymidine Kinase)
SB  - IM
EIN - Cancer Gene Ther. 2003 Aug;10(8):647
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Chemokine CCL2/*genetics/metabolism
MH  - DNA, Recombinant/genetics
MH  - Genetic Therapy
MH  - *Genetic Vectors
MH  - Humans
MH  - Liver Neoplasms, Experimental/immunology/pathology/*therapy
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Simplexvirus/enzymology
MH  - Thymidine Kinase/*genetics/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2003/04/08 05:00
MHDA- 2003/12/19 05:00
CRDT- 2003/04/08 05:00
PHST- 2003/04/08 05:00 [pubmed]
PHST- 2003/12/19 05:00 [medline]
PHST- 2003/04/08 05:00 [entrez]
AID - 7700571 [pii]
AID - 10.1038/sj.cgt.7700571 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2003 Apr;10(4):260-9. doi: 10.1038/sj.cgt.7700571.