Prolactin-secreting @entity652 are the most frequent type among @entity977 , and pharmacological therapy with @entity935 agonists remains the mainstay of treatment. But some @entity652 are resistant, and a decrease in the number or function of @entity935 D2 receptors (D2Rs) has been described in these cases. D2R knockout [ @entity9767 (-/-)] @entity19 have chronic @entity4089 and @entity1373 and provide an experimental model for @entity935 agonist-resistant @entity2013 . We described previously that disruption of D2Rs increases @entity1611 ( @entity1611 ) expression. We therefore designed two strategies of antiangiogenesis using @entity2013 generated in @entity9767 (-/-) female @entity19 : direct intra-adenoma @entity9842 ( @entity9842 )/Fc chimera ( @entity1611 -TRAP) injection for 3 weeks [into subcutaneously transplanted pituitaries from @entity9767 (-/-) @entity19 ] and systemic @entity1611 neutralization with the specific monoclonal antibody G6-31. Both strategies resulted in substantial decrease of prolactin content and lactotrope area, and a reduction in @entity5 size was observed in in situ @entity2013 . There were significant decreases in vascularity, evaluated by cluster of differentiation molecule 31 vessel staining, and proliferation (proliferating cell nuclear antigen staining) in response to both anti- @entity1611 treatments. These data demonstrate that the antiangiogenic approach was effective in inhibiting the growth of in situ @entity935 -resistant @entity2013 as well as in the transplanted @entity652 . No differences in @entity1611 protein expression were observed after either anti- @entity1611 treatment, and, although serum @entity1611 was increased in G6-31-treated @entity19 , pituitary activation of the @entity11132 signaling pathway was reduced. Our results indicate that, even though the role of angiogenesis in @entity977 is contentious, @entity1611 might contribute to adequate vascular supply and represent a supplementary therapeutic target in @entity935 agonist-resistant @entity2013 .

Inhibitory effects of antivascular endothelial growth factor strategies in experimental @entity935 -resistant XXXX .

@entity4089 :: ('MESH:D006966', 'Disease') :: ['hyperprolactinemia'] @entity11132 :: ('16542(Tax:10090)', 'Gene') :: ['VEGF receptor 2'] @entity2013 :: ('MESH:D015175', 'Disease') :: ['prolactinomas'] @entity9842 :: ('14254(Tax:10090)', 'Gene') :: ['Flt-1', 'mVEGF R1'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['pituitary hyperplasia'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity977 :: ('MESH:D010911', 'Disease') :: ['pituitary adenomas', 'pituitary tumors'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['vascular endothelial growth factor', 'VEGF'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity9767 :: ('13489(Tax:10090)', 'Gene') :: ['Drd2']
@entity2013 :: (MESH:D015175,Disease) :: ['prolactinomas']
