References of "Weiner, Richard I"
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See detailNovel antiangiogenic peptide agents and their therapeutic and diagnostic use
Weiner, Richard I.; Martial, Joseph ULg; Struman, Ingrid ULg et al

Patent (2008)

The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormones, human placental lactogen ... [more ▼]

The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormones, human placental lactogen, human growth hormone variant hGH-V, and prolactin, and their use in inhibiting angiogenesis and in the diagnosis of diseases of human pregnancy involving abnormalities of placental vascularization. [less ▲]

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See detail16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of Ras in Capillary Endothelial Cells
D'Angelo, Gisela; Martini, Jean-François; Iiri, Taroh et al

in Molecular Endocrinology (Baltimore, Md.) (1999), 13(2), 692-704

Signaling pathways mediating the antiangiogenic action of 16K human (h)PRL include inhibition of vascular endothelial growth factor (VEGF)-induced activation of the mitogen-activated protein kinases (MAPK ... [more ▼]

Signaling pathways mediating the antiangiogenic action of 16K human (h)PRL include inhibition of vascular endothelial growth factor (VEGF)-induced activation of the mitogen-activated protein kinases (MAPK). To determine at which step 16K hPRL acts to inhibit VEGF-induced MAPK activation, we assessed more proximal events in the signaling cascade. 16K hPRL treatment blocked VEGF-induced Raf-1 activation as well as its translocation to the plasma membrane. 16K hPRL indirectly increased cAMP levels; however, the blockade of Raf-1 activation was not dependent on the stimulation of cAMP-dependent protein kinase (PKA), but rather on the inhibition of the GTP-bound Ras. The VEGF-induced tyrosine phosphorylation of the VEGF receptor, Flk-1, and its association with the Shc/Grb2/Ras-GAP (guanosine triphosphatase-activating protein) complex were unaffected by 16K hPRL treatment. In contrast, 16K hPRL prevented the VEGF-induced phosphorylation and dissociation of Sos from Grb2 at 5 min, consistent with inhibition by 16K hPRL of the MEK/MAPK feedback on Sos. The inhibition of Ras activation was paralleled by the increased phosphorylation of 120 kDa proteins comigrating with Ras-GAP. Taken together, these findings show that 16K hPRL inhibits the VEGF-induced Ras activation; this antagonism represents a novel and potentially important mechanism for the control of angiogenesis. [less ▲]

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See detailDesign and characterization of novel forms of human 16K prolactin, an antiangiogenic factor
Mainfroid, Véronique; Struman, Ingrid ULg; Weiner, Richard I. et al

Poster (1998, January)

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See detailThe 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis
Clapp, Carmen; Martial, Joseph ULg; Guzman, Raphaël C et al

in Endocrinology (1993), 133(3), 1292-9

The formation of a new blood supply, angiogenesis, is an essential component of carcinogenesis and unrestricted tumor growth. A substance capable of inhibiting angiogenesis would be of considerable ... [more ▼]

The formation of a new blood supply, angiogenesis, is an essential component of carcinogenesis and unrestricted tumor growth. A substance capable of inhibiting angiogenesis would be of considerable therapeutic potential in the treatment of cancer. We previously reported that the 16-kilodalton N-terminal fragment of rat PRL (16K rPRL) was a potent inhibitor of capillary endothelial cell proliferation via a novel receptor. We now report that the nanomolar concentrations of recombinant human 16K PRL inhibit basal and basic fibroblast growth factor- or vascular endothelial growth factor-stimulated growth of bovine brain capillary endothelial cells. 16K human (h) PRL also inhibits stimulation of human umbilical vein endothelial cell proliferation by basic fibroblast growth factor. The organization of endothelial cells into capillary-like structures in type I collagen gels is also prevented by 16K hPRL. Furthermore, in an in vivo assay, the chick embryo chorioallantoic membrane assay, 16K hPRL as well as 16K rPRL were potent inhibitors of capillary formation. 16K hPRL, like 16K rPRL, maintains its biological activity as a partial PRL agonist at PRL receptors on mammary gland epithelial cells. These data demonstrate for the first time that the biological activity of 16K rPRL is not unique and that similar fragments of hPRL are active. The antiangiogenic activity of these molecules is conserved across avian and mammalian species. That 16K hPRL is a potent antiangiogenic factor in in vitro and an in vivo assay raises the exciting potential of this peptide being capable of inhibiting tumor growth. [less ▲]

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See detailDecreased responsiveness of GH3 cells to the dopaminergic inhibition of prolactin
Faure, Nacia; Cronin, Michaël J; Martial, Joseph ULg et al

in Endocrinology (1980), 107(4), 1022-1026

The inhibitory regulation of PRL secretion by dopamine (DA) or the dopaminergic agonists bromergocryptine (CB-154) and apomorphine was studied in cultured GH3 cells, an established rat anterior pituitary ... [more ▼]

The inhibitory regulation of PRL secretion by dopamine (DA) or the dopaminergic agonists bromergocryptine (CB-154) and apomorphine was studied in cultured GH3 cells, an established rat anterior pituitary cell line which produces both PRL and GH. The basal release of PRL from GH3 cells was unaffected when incubated for 6 h with DA concentrations as high as 10(-4) M. The inability of DA to suppress PRL secretion could not be explained by the catabolism of DA or the presence of unknown inhibitors (e.g. estradiol) in the fetal calf serum present in the incubation media. Apomorphine and CB-154 were only partially effective in suppressing PRL release at high concentrations of 10(-4) and 10(-5) M, respectively. Various concentrations of the dopaminergic antagonist d-butaclamol did not reverse the inhibitory action of 10(-5) M CB-154, while equal concentrations (10(-5) M) of both d- and l-butaclamol significantly suppressed PRL release. The greatly lowered responsiveness of GH3 cells to dopaminergic inhibition of PRL is suggestive of some impairment of DA receptors. This hypothesis is supported by radioligand binding studies in which high affinity dopaminergic binding sites are absent in the same cell line used in this study. [less ▲]

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See detailAbsence of high affinity dopamine receptor in GH3 cells: a prolactin-secreting clone resistant to the inhibitory action of dopamine
Cronin, Michaël J; Faure, Nacia; Martial, Joseph ULg et al

in Endocrinology (1980), 106(3), 718-23

Dopamine (DA) and DA agonists bind with high affinity to anterior pituitary receptors which mediate the inhibition of PRL release. Spiperone (SPIP), a DA antagonist, has also been successfully used to ... [more ▼]

Dopamine (DA) and DA agonists bind with high affinity to anterior pituitary receptors which mediate the inhibition of PRL release. Spiperone (SPIP), a DA antagonist, has also been successfully used to characterize pituitary DA receptors with a dissociation constant (Kd) of less than 1 nM. We studied the binding of SPIP to GH3D6 cells which secrete only PRL and GH. This clone was derived from a radiation-induced tumor of the rat anterior pituitary. Equilibrium binding of [3H]SPIP to living GH3 cells showed no high affinity receptors, but a low affinity (Kd = 0.83 microM) and saturable (0.06 fmol/cell) population of sites was observed. In addition, saturable binding with a similar affinity (Kd = 0.57 microM) was noted in broken GH3 cells. The interaction was completely reversible and temperature dependent. The concentration of various ligands required to compete for half of the [3H]SPIP binding to whole cells were: chlorpromazine, 0.17 microM; haloperidol, 0.68 microM; pimozide, 0.77 microM; d-butaclamol, 1.16 microM; 1-butaclamol, 1.30 microM; SPIP, 1.49 microM; bromergocryptine, 4.98 microM; apomorphine, 13.9 microM; and DA, 100 microM. The absence of a high affinity site in GH3 cells is consistent with the decreased effectiveness of various agonists and antagonists on PRL secretion. It is possible that the low affinity interactions observed in GH3 cells are normally present in the anterior pituitary and brain and do not simply represent an alteration of receptor affinity. [less ▲]

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See detailStructure of cloned DNA complementary to rat prolactin messenger RNA
Cooke, Nancy E; Coit, Doris; Weiner, Richard I et al

in Journal of Biological Chemistry (1980), 255(13), 6502-6510

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