PMID- 14681721
OWN - NLM
STAT- MEDLINE
DCOM- 20040804
LR  - 20131121
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 11
IP  - 1
DP  - 2004 Jan
TI  - hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes 
      cervical cancer cells to a low dose of cisplatin.
PG  - 1-7
AB  - Cervical cancers at advanced stages or with recurrent status are mainly treated 
      by platinum-based chemotherapy, such as cisplatin. However, a novel strategy to 
      reduce the minimally effective dose is required to prevent severe adverse effects 
      that limit the effectiveness of the treatment. Monocyte chemoattractant protein-1 
      (MCP-1) is a subtype of chemokines that can promote monocyte/macrophage 
      infiltration and enhance their phagocytosis at not only sites of inflammatory 
      lesions but also of tumors. The present study applies MCP-1-based gene therapy to 
      treat cervical cancers. To achieve tumor-specific expression of MCP-1, retroviral 
      expression vector was constructed using the human telomerase reverse 
      transcriptase gene (hTERT) promoter. Retroviral expression of MCP-1 into cervical 
      cancer ME180 cells did not affect their proliferation either in vitro or in vivo. 
      However, when combined with a suboptimal low dose of cisplatin, tumor formation 
      was obviously reduced in clones transduced with MCP-1, but not in control clones. 
      Histological examination revealed that a substantial number of macrophages 
      infiltrated the tumor sites of MCP-1-transduced cells, but not of controls. These 
      findings suggest that MCP-1 expression sensitizes cervical cancer cells to an 
      otherwise ineffective low dose of cisplatin, possibly by inducing the migration 
      of macrophages to eradicate tumor cells. This system may be a novel strategy for 
      chemotherapy combined with immunogene therapy against otherwise intractable 
      cervical cancers.
FAU - Nakamura, Mitsuhiro
AU  - Nakamura M
AD  - Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, 
      13-1, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
FAU - Kyo, Satoru
AU  - Kyo S
FAU - Kanaya, Taro
AU  - Kanaya T
FAU - Yatabe, Noriyuki
AU  - Yatabe N
FAU - Maida, Yoshiko
AU  - Maida Y
FAU - Tanaka, Masaaki
AU  - Tanaka M
FAU - Ishida, Yuko
AU  - Ishida Y
FAU - Fujii, Chifumi
AU  - Fujii C
FAU - Kondo, Toshikazu
AU  - Kondo T
FAU - Inoue, Masaki
AU  - Inoue M
FAU - Mukaida, Naofumi
AU  - Mukaida N
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - EC 2.7.7.49 (Telomerase)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*genetics/*metabolism
MH  - Cisplatin/administration & dosage/pharmacology/*therapeutic use/toxicity
MH  - DNA-Binding Proteins
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genetic Therapy
MH  - Humans
MH  - Macrophages/drug effects
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Promoter Regions, Genetic/*genetics
MH  - Telomerase/*genetics
MH  - Uterine Cervical Neoplasms/*drug therapy/genetics/metabolism/*pathology
EDAT- 2003/12/19 05:00
MHDA- 2004/08/05 05:00
CRDT- 2003/12/19 05:00
PHST- 2003/12/19 05:00 [pubmed]
PHST- 2004/08/05 05:00 [medline]
PHST- 2003/12/19 05:00 [entrez]
AID - 7700650 [pii]
AID - 10.1038/sj.cgt.7700650 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2004 Jan;11(1):1-7. doi: 10.1038/sj.cgt.7700650.