27 febrero 2018

PM184 ( PLOCABULIN ) de PharmaMar en la Publicación de Febrero de " BMC Cáncer " . A Novel Tubulin-Binding Agent, Inhibits Angiogenesis by Modulation of Microtubule Dynamics in Endothelial Cells .

P.J. : Resumen de lo que hasta ahora sabíamos sobre este Fármaco ( PM184 ) de Pharmamar :


PM184 ( PLOCABULIN ) es un Compuesto de Origen Marino procedente de una Esponja conocida como Lithoplocamia Lithistoides.



PM184 es un Inhibidor de Microtúbulos que ejerce su efecto mediante un nuevo mecanismo de interacción con Microtúbulos.

PM184 Inhibe el crecimiento de las Células Tumorales Bloqueando su Ciclo Celular al interferir con el Proceso de Mitosis del que se esperan obtener " Resultados muy Novedosos ".

PM184 se encuentra actualmente en Desarrollo Clínico para Tumores Sólidos .

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Este Mes la Prestigiosa Publicación BMC Cáncer le ha dedicado varias páginas en las que Actualiza y Muestra Resultados Obtenidos con PLOCABULIN ( PM184 ) y su Manera Novedosa de Actuar :

Carlos M. Galmarini , Maud Martin ,Benjamin Pierre Bouchet , María José Guillen-Navarro , Marta Martínez-Diez , Juan Fernando Martinez-Leal , Anna Akhmanova and Pablo Aviles

Background: Vascular supply of tumors is one of the main targets for cancer therapy. Here, we investigated if Plocabulin (PM060184), a novel marine-derived microtubule binding agent, presents antiangiogenic and vascular-disrupting activities.

Methods: The effects of Plocabulin on Microtubule network and dynamics were studied on HUVEC endothelial cells. We have also studied its effects on capillary tube structures formation or destabilization in three-dimensional collagen matrices. In vivo experiments were performed on different tumor cell lines.

Results: In vitro studies show that, at picomolar concentrations, Plocabulin inhibits microtubule dynamics in endothelial cells. This subsequently disturbs the microtubule network inducing changes in endothelial cell morphology and causing the collapse of angiogenic vessels, or the suppression of the angiogenic process by inhibiting the migration and invasion abilities of endothelial cells. This rapid collapse of the endothelial tubular network in vitro occurs in a concentration-dependent manner and is observed at concentrations lower than that affecting cell survival. The in vitro findings were confirmed in tumor xenografts where plocabulin treatment induced a large reduction in vascular volume and induction of extensive necrosis in tumors, consistent with antivascular effects.

Conclusions: Altogether, these data suggest that an antivascular mechanism is contributing to the antitumor activities of Plocabulin.


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