IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover pituitary active transforming growth factor beta 1 (TGF-1).
Autor/es:
MV RECOUVREUX; MA CAMILLETTI; RIFKIN DB; D. BECU-VILLALOBOS; DIAZ DE TORGA, GRACIELA S
Lugar:
Houston
Reunión:
Congreso; ENDO 2012; 2012
Institución organizadora:
Endocrine Soc
Resumen:
Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover pituitary active transforming growth factor beta 1 (TGF-1). M. Victoria Recouvreux, M. Andrea Camilletti, Daniel B. Rifkin, Damasia Becu-Villalobos, Graciela Díaz-Torga 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. TSP-1 is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF-1. Since tumors that over-express TSP-1 grow slower, have fewer metastases and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 (Abbott Laboratories) are TSP-1 synthetic analogues that mimic its antiangiogenic action. The aim of the present study was to explore the potential therapeutic effect of ABT-510 and ABT-898, on experimental prolactinomas developed after 4 weeks of diethylstilbestrol (DES) treatment in female rats. Two weeks after DES pellet (20mg) implant, rats were injected three times a week during two weeks with vehicle, ABT-510 or ABT-898 (100mg/kg ip). Both TSP1 analogues were effective in decreasing pituitary tumor size (p=0.03) and PRL serum levels (P=0.0002), induced by DES. PCNA protein expression evaluated by western blot, was also reduced after treatment, indicating a decrease in tumor proliferation rate (P