PMID- 22402625
OWN - NLM
STAT- MEDLINE
DCOM- 20121023
LR  - 20131121
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 19
IP  - 5
DP  - 2012 May
TI  - Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor 
      effects of suicide gene therapy in a model of hepatocellular carcinoma.
PG  - 312-9
LID - 10.1038/cgt.2012.3 [doi]
AB  - Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir 
      (HSV-tk/GCV) system combined with monocyte chemoattractant protein-1 (MCP-1) 
      provides significant antitumor efficacy. The current study was designed to 
      evaluate the antitumor immunity of a newly developed membrane-bound form of MCP-1 
      (mMCP-1) in an immunocompetent mouse model of hepatocellular carcinoma (HCC). A 
      recombinant adenovirus vector (rAd) harboring the human MCP-1 gene and the 
      membrane-spanning domain of the CX3CL1 gene was used. Large amounts of MCP-1 
      protein were expressed and accumulated on the tumor cell surface. The growth of 
      subcutaneous tumors was markedly suppressed when tumors were treated with mMCP-1, 
      as compared with soluble MCP-1, in combination with the HSV-tk/GCV system 
      (P<0.01). The numbers of Mac-1-, CD4- and CD8a-positive cells were significantly 
      higher in tumor tissues (P<0.05), and tumor necrosis factor (TNF) mRNA expression 
      levels with mMCP-1 were almost five-fold higher than those with soluble MCP-1. 
      These results indicate that the delivery of the mMCP-1 gene greatly enhanced 
      antitumor effects following the apoptotic stimuli by promoting the recruitment 
      and activation of macrophages and T lymphocytes, suggesting a novel strategy of 
      immune-based gene therapy in the treatment of patients with HCC.
FAU - Marukawa, Y
AU  - Marukawa Y
AD  - Department of Disease Control and Homeostasis, Graduate School of Medical 
      Science, Kanazawa University, Kanazawa, Japan.
FAU - Nakamoto, Y
AU  - Nakamoto Y
FAU - Kakinoki, K
AU  - Kakinoki K
FAU - Tsuchiyama, T
AU  - Tsuchiyama T
FAU - Iida, N
AU  - Iida N
FAU - Kagaya, T
AU  - Kagaya T
FAU - Sakai, Y
AU  - Sakai Y
FAU - Naito, M
AU  - Naito M
FAU - Mukaida, N
AU  - Mukaida N
FAU - Kaneko, S
AU  - Kaneko S
LA  - eng
PT  - Journal Article
DEP - 20120309
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Cx3cl1 protein, mouse)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/biosynthesis/*genetics/metabolism
MH  - Chemokine CX3CL1/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Ganciclovir/pharmacokinetics/pharmacology
MH  - *Genes, Transgenic, Suicide
MH  - Genetic Therapy/*methods
MH  - Herpes Simplex/enzymology/genetics
MH  - Humans
MH  - Liver Neoplasms, Experimental/genetics/metabolism/*therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Thymidine Kinase/biosynthesis/genetics/metabolism
EDAT- 2012/03/10 06:00
MHDA- 2012/10/24 06:00
CRDT- 2012/03/10 06:00
PHST- 2012/03/10 06:00 [entrez]
PHST- 2012/03/10 06:00 [pubmed]
PHST- 2012/10/24 06:00 [medline]
AID - cgt20123 [pii]
AID - 10.1038/cgt.2012.3 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2012 May;19(5):312-9. doi: 10.1038/cgt.2012.3. Epub 2012 Mar 9.