PMID- 10326034
OWN - NLM
STAT- MEDLINE
DCOM- 19990602
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 5
IP  - 8
DP  - 1998 Aug
TI  - Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses 
      angiogenesis-dependent tumor growth and dissemination in mice.
PG  - 1105-13
AB  - AdmATF is a recombinant adenovirus encoding a secreted version of the 
      amino-terminal fragment (ATF) of murine urokinase (uPA). This defective 
      adenovirus was used in three murine models to assess the antitumoral effects 
      associated with local or systemic delivery of ATF, a broad cell invasion 
      inhibitor that antagonizes uPA binding to its cell surface receptor (uPAR). A 
      single intratumoral injection of AdmATF into pre-established MDA-MB-231 human 
      breast xenografts grown in athymic mice, or into pre-established C57/BL6 
      syngeneic Lewis lung carcinoma resulted in a specific arrest of tumor growth. 
      Neovascularization within and at the vicinity of the injection site was also 
      suppressed, suggesting that AdmATF inhibited primary tumor growth by targeting 
      angiogenesis. AdmATF also interfered with tumor cell establishment at distant 
      sites: (1) lung dissemination of Lewis lung carcinoma cells was significantly 
      reduced following intratumoral injection at the primary site; and (2) systemic 
      administration of AdmATF inhibited subsequent liver metastasis in a LS174T human 
      colon carcinoma xenograft model. These data outline the potential of using a 
      recombinant adenovirus directing the secretion of an antagonist of 
      cell-associated uPA for cancer gene therapy.
FAU - Li, H
AU  - Li H
AD  - CNRS-Rhone-Poulenc Rorer-IGR UMR 1582, Institut Gustave Roussy, Villejuif, 
      France.
FAU - Lu, H
AU  - Lu H
FAU - Griscelli, F
AU  - Griscelli F
FAU - Opolon, P
AU  - Opolon P
FAU - Sun, L Q
AU  - Sun LQ
FAU - Ragot, T
AU  - Ragot T
FAU - Legrand, Y
AU  - Legrand Y
FAU - Belin, D
AU  - Belin D
FAU - Soria, J
AU  - Soria J
FAU - Soria, C
AU  - Soria C
FAU - Perricaudet, M
AU  - Perricaudet M
FAU - Yeh, P
AU  - Yeh P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (PLAUR protein, human)
RN  - 0 (Plasminogen Inactivators)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Plaur protein, rat)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Breast Neoplasms/pathology/therapy
MH  - Female
MH  - Genetic Engineering/methods
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*administration & dosage
MH  - Humans
MH  - Injections, Intralesional
MH  - Injections, Intramuscular
MH  - Liver Neoplasms/secondary/therapy
MH  - Lung Neoplasms/pathology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - Neoplasms/*therapy
MH  - Neovascularization, Pathologic/*prevention & control
MH  - Plasminogen Inactivators/pharmacology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Receptors, Cell Surface/antagonists & inhibitors
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/antagonists & inhibitors/*genetics
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1038/sj.gt.3300742 [doi]
PST - ppublish
SO  - Gene Ther. 1998 Aug;5(8):1105-13. doi: 10.1038/sj.gt.3300742.