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Abstract:

Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF-β1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF-β1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas. Copyright © 2012 by The Endocrine Society.

Registro:

Documento: Artículo
Título:Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1)
Autor:Recouvreux, M.V.; Camilletti, M.A.; Rifkin, D.B.; Becu-Villalobos, D.; Díaz-Torga, G.
Filiación:Instituto de Biología Y Medicina Experimental, Consejo Nacional de Investigaciones Cientificas Y Técnicas, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Department of Cell Biology, New York University Medical Center, New York, NY 10016, United States
Palabras clave:abt 898; angiogenesis inhibitor; n acetylsarcosylglycylvalyl dextro alloisoleucylthreonylnorvalylisoleucylarginylproline ethylamide; prolactin; thrombospondin 1; transforming growth factor beta1; unclassified drug; animal experiment; animal model; antiangiogenic activity; article; cell proliferation; controlled study; drug effect; female; hypophysis; nonhuman; priority journal; prolactin blood level; prolactinoma; rat; treatment duration; tumor growth; Animals; Diethylstilbestrol; Female; Oligopeptides; Prolactinoma; Rats; Rats, Sprague-Dawley; Thrombospondin 1; Transforming Growth Factor beta1
Año:2012
Volumen:153
Número:8
Página de inicio:3861
Página de fin:3871
DOI: http://dx.doi.org/10.1210/en.2012-1007
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:n acetylsarcosylglycylvalyl dextro alloisoleucylthreonylnorvalylisoleucylarginylproline ethylamide, 251579-55-2, 251579-56-3; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; thrombospondin 1, 343987-56-4; Diethylstilbestrol, 56-53-1; NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt; Oligopeptides; Thrombospondin 1; Transforming Growth Factor beta1; acetyl-glycyl-valyl-allo-isoleucyl-seryl-glutaminyl-isoleucyl-arginyl-prolyl-cysteinamide, 0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v153_n8_p3861_Recouvreux

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Citas:

---------- APA ----------
Recouvreux, M.V., Camilletti, M.A., Rifkin, D.B., Becu-Villalobos, D. & Díaz-Torga, G. (2012) . Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1). Endocrinology, 153(8), 3861-3871.
http://dx.doi.org/10.1210/en.2012-1007
---------- CHICAGO ----------
Recouvreux, M.V., Camilletti, M.A., Rifkin, D.B., Becu-Villalobos, D., Díaz-Torga, G. "Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1)" . Endocrinology 153, no. 8 (2012) : 3861-3871.
http://dx.doi.org/10.1210/en.2012-1007
---------- MLA ----------
Recouvreux, M.V., Camilletti, M.A., Rifkin, D.B., Becu-Villalobos, D., Díaz-Torga, G. "Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1)" . Endocrinology, vol. 153, no. 8, 2012, pp. 3861-3871.
http://dx.doi.org/10.1210/en.2012-1007
---------- VANCOUVER ----------
Recouvreux, M.V., Camilletti, M.A., Rifkin, D.B., Becu-Villalobos, D., Díaz-Torga, G. Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1). Endocrinology. 2012;153(8):3861-3871.
http://dx.doi.org/10.1210/en.2012-1007