| First Author | Korsisaari N | Year | 2008 |
| Journal | Clin Cancer Res | Volume | 14 |
| Issue | 1 | Pages | 249-58 |
| PubMed ID | 18172277 | Mgi Jnum | J:134086 |
| Mgi Id | MGI:3784937 | Doi | 10.1158/1078-0432.CCR-07-1552 |
| Citation | Korsisaari N, et al. (2008) 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. Clin Cancer Res 14(1):249-58 |
| abstractText | 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. |
