PMID- 18447716
OWN - NLM
STAT- MEDLINE
DCOM- 20080624
LR  - 20211020
IS  - 0022-3085 (Print)
IS  - 1933-0693 (Electronic)
IS  - 0022-3085 (Linking)
VI  - 108
IP  - 5
DP  - 2008 May
TI  - Successful inhibition of intracranial human glioblastoma multiforme xenograft 
      growth via systemic adenoviral delivery of soluble endostatin and soluble 
      vascular endothelial growth factor receptor-2: laboratory investigation.
PG  - 979-88
LID - 10.3171/JNS/2008/108/5/0979 [doi]
AB  - OBJECT: Glioblastoma multiforme (GBM) is characterized by neovascularization, 
      raising the question of whether angiogenic blockade may be a useful therapeutic 
      strategy for this disease. It has been suggested, however, that, to be useful, 
      angiogenic blockade must be persistent and at levels sufficient to overcome 
      proangiogenic signals from tumor cells. In this report, the authors tested the 
      hypothesis that sustained high concentrations of 2 different antiangiogenic 
      proteins, delivered using a systemic gene therapy strategy, could inhibit the 
      growth of established intracranial U87 human GBM xenografts in nude mice. 
      METHODS: Mice harboring established U87 intracranial tumors received intravenous 
      injections of adenoviral vectors encoding either the extracellular domain of 
      vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) 
      alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, 
      or immunoglobulin 1-Fc (Ad-Fc) as a control. RESULTS: Three weeks after 
      treatment, magnetic resonance imaging-based determination of tumor volume showed 
      that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with 
      Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent 
      monitoring of tumor growth revealed growth inhibition in the same treatment 
      groups to be 62, 74, and 72%, respectively. Staining with proliferating cell 
      nuclear antigen and with terminal deoxynucleotidyl transferase-mediated 
      deoxyuridine triphosphate nick-end labeling showed reduced tumor cell 
      proliferation and increased apoptosis in all antiangiogenic treatment groups. 
      CONCLUSIONS: These results suggest that systemic delivery and sustained 
      production of endostatin and soluble VEGFR2 can slow intracranial glial tumor 
      growth by both reducing cell proliferation and increasing tumor apoptosis. This 
      work adds further support to the concept of using antiangiogenesis therapy for 
      intracranial GBM.
FAU - Szentirmai, Oszkar
AU  - Szentirmai O
AD  - Department of Genetics, Harvard Institutes of Medicine and Harvard Medical 
      School, and Department of Pediatrics, Children's Hospital, Boston, MA, USA.
FAU - Baker, Cheryl H
AU  - Baker CH
FAU - Bullain, Szofia S
AU  - Bullain SS
FAU - Lin, Ning
AU  - Lin N
FAU - Takahashi, Masaya
AU  - Takahashi M
FAU - Folkman, Judah
AU  - Folkman J
FAU - Mulligan, Richard C
AU  - Mulligan RC
FAU - Carter, Bob S
AU  - Carter BS
LA  - eng
GR  - K08 CA082773/CA/NCI NIH HHS/United States
GR  - K08 CA082773-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Neurosurg
JT  - Journal of neurosurgery
JID - 0253357
RN  - 0 (Endostatins)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Apoptosis
MH  - Brain Neoplasms/*pathology
MH  - Endostatins/*administration & dosage/analysis/genetics
MH  - Genetic Vectors
MH  - Glioblastoma/*pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Neovascularization, Pathologic/drug therapy
MH  - Transplantation, Heterologous
MH  - Vascular Endothelial Growth Factor Receptor-2/*administration & 
      dosage/analysis/genetics
PMC - PMC4459889
MID - NIHMS327136
EDAT- 2008/05/02 09:00
MHDA- 2008/06/25 09:00
PMCR- 2015/06/08
CRDT- 2008/05/02 09:00
PHST- 2008/05/02 09:00 [pubmed]
PHST- 2008/06/25 09:00 [medline]
PHST- 2008/05/02 09:00 [entrez]
PHST- 2015/06/08 00:00 [pmc-release]
AID - 10.3171/JNS/2008/108/5/0979 [doi]
PST - ppublish
SO  - J Neurosurg. 2008 May;108(5):979-88. doi: 10.3171/JNS/2008/108/5/0979.