PMID- 18172277
OWN - NLM
STAT- MEDLINE
DCOM- 20080327
LR  - 20080103
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 1
DP  - 2008 Jan 1
TI  - Blocking vascular endothelial growth factor-A inhibits the growth of pituitary 
      adenomas and lowers serum prolactin level in a mouse model of multiple endocrine 
      neoplasia type 1.
PG  - 249-58
LID - 10.1158/1078-0432.CCR-07-1552 [doi]
AB  - PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the 
      combined occurrence of multiple tumors, typically of the parathyroid glands, 
      pancreatic islet cells, and anterior pituitary gland. A mouse model with a 
      heterozygous deletion of the Men1 gene recapitulates the tumorigenesis of MEN1. 
      We wished to determine the role of vascular endothelial growth factor (VEGF)-A in 
      the vascularization and growth of MEN1-associated tumors, with an emphasis on 
      pituitary adenomas. EXPERIMENTAL DESIGN: To investigate whether tumor growth in 
      Men1(+/-) mice is mediated by VEGF-A dependent angiogenesis, we carried out a 
      monotherapy with the anti-VEGF-A monoclonal antibody (mAb) G6-31. We evaluated 
      tumor growth by magnetic resonance imaging and assessed vascular density in 
      tissue sections. We also measured hormone levels in the serum. RESULTS: During 
      the treatment with mAb G6-31, a significant inhibition of the pituitary adenoma 
      growth was observed, leading to an increased mean tumor doubling-free survival 
      compared with mice treated with a control antibody. Similarly, the growth of s.c. 
      pituitary adenoma transplants was effectively inhibited by administration of 
      anti-VEGF-A mAb. Serum prolactin was lowered by mAb G6-31 treatment but not by 
      control antibody, potentially providing a new therapeutic approach for treating 
      the hormonal excess in MEN1 patients. Additionally, the vascular density in 
      pancreatic islet tumors was significantly reduced by the treatment. CONCLUSIONS: 
      These results suggest that VEGF-A blockade may represent a nonsurgical treatment 
      for benign tumors of the endocrine system.
FAU - Korsisaari, Nina
AU  - Korsisaari N
AD  - Genentech, Inc., South San Francisco, California 94080, USA.
FAU - Ross, Jed
AU  - Ross J
FAU - Wu, Xiumin
AU  - Wu X
FAU - Kowanetz, Marcin
AU  - Kowanetz M
FAU - Pal, Navneet
AU  - Pal N
FAU - Hall, Linda
AU  - Hall L
FAU - Eastham-Anderson, Jeffrey
AU  - Eastham-Anderson J
FAU - Forrest, William F
AU  - Forrest WF
FAU - Van Bruggen, Nicholas
AU  - Van Bruggen N
FAU - Peale, Franklin V
AU  - Peale FV
FAU - Ferrara, Napoleone
AU  - Ferrara N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Adenoma/blood/*metabolism/pathology
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mice, Nude
MH  - Multiple Endocrine Neoplasia Type 1/blood/metabolism/*pathology
MH  - Neovascularization, Pathologic
MH  - Pituitary Neoplasms/blood/metabolism/*pathology
MH  - Prolactin/*blood
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors/drug effects
EDAT- 2008/01/04 09:00
MHDA- 2008/03/28 09:00
CRDT- 2008/01/04 09:00
PHST- 2008/01/04 09:00 [pubmed]
PHST- 2008/03/28 09:00 [medline]
PHST- 2008/01/04 09:00 [entrez]
AID - 14/1/249 [pii]
AID - 10.1158/1078-0432.CCR-07-1552 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Jan 1;14(1):249-58. doi: 10.1158/1078-0432.CCR-07-1552.