PMID- 14649886
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20190911
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 65
IP  - 1
DP  - 2003 Oct
TI  - Targeting the over-expressed urokinase-type plasminogen activator receptor on 
      glioblastoma multiforme.
PG  - 63-75
AB  - A recombinant fusion protein targeting the urokinase-type plasminogen activator 
      receptor (uPAR) and delivering a potent catalytic toxin has the advantage of 
      simultaneously targeting both over-expressed uPAR on glioblastoma cells and on 
      the tumor neovasculature. Such a hybrid protein was synthesized consisting of the 
      noninternalizing amino-terminal fragment (ATF) of urokinase-type plasminogen 
      activator (uPA) for binding, and the catalytic portion of diphtheria toxin (DT) 
      for killing, and the translocation enhancing region (TER) of DT for 
      internalization. The protein was highly selective for human glioblastoma in vitro 
      and in vivo. In vivo, this DT/ATF hybrid called DTAT caused the regression of 
      small subcutaneous uPAR-expressing tumors with minimal toxicity to critical 
      organs. In vitro, DTAT killed only uPAR-positive glioblastoma cell lines and 
      human endothelial cells in the form of the HUVEC cell line. Killing was selective 
      and blockable with specific antibody. DTAT was highly effective against tumor 
      cells cultured from glioblastoma multiforme patients and in vitro mixing 
      experiments combining DTAT with DTIL13 another highly effective anti-glioblastoma 
      agent showed that the mixture was as toxic as the most potent immunotoxin. In 
      this article, we review our progress to date with DTAT.
FAU - Rustamzadeh, Edward
AU  - Rustamzadeh E
AD  - Department of Neurosurgery, University of Minnesota Cancer Center, Minneapolis, 
      MN 55455, USA.
FAU - Li, Chunbin
AU  - Li C
FAU - Doumbia, Sekou
AU  - Doumbia S
FAU - Hall, Walter A
AU  - Hall WA
FAU - Vallera, Daniel A
AU  - Vallera DA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Diphtheria Toxin)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*drug therapy/metabolism
MH  - Diphtheria Toxin/*therapeutic use
MH  - Drug Delivery Systems
MH  - Glioblastoma/*drug therapy/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Receptors, Cell Surface/*antagonists & inhibitors
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Recombinant Fusion Proteins/*therapeutic use
MH  - Urokinase-Type Plasminogen Activator/*therapeutic use
RF  - 143
EDAT- 2003/12/03 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/12/03 05:00
PHST- 2003/12/03 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/12/03 05:00 [entrez]
AID - 10.1023/a:1026238331739 [doi]
PST - ppublish
SO  - J Neurooncol. 2003 Oct;65(1):63-75. doi: 10.1023/a:1026238331739.