El Grano en el Sector Farmacéutico ... A la Cabeza se Sitúa PharmaMar .

J. Muñoz // 5 Julio 2017 .

... El sector farmacéutico cuenta con una de las rentabilidades más altas entre los distintos índices sectoriales con una ganancia anual por encima del 20%. Sin embargo, como en todo, los analistas recuerdan que hay que apartar el grano de la paja.

De las cerca de diez compañías ligadas al sector que cotizan en la bolsa española, los inversores están apostando abiertamente por las grandes, aquellas con mayor capacidad de inversión, mejores productos en cartera y menor apalancamiento.

A la cabeza se sitúa Pharma Mar con una revalorización desde principios de año superior al 45%. Los recientes acuerdos comerciales y los ingresos procedentes de licencia, especialmente del Yondelis, su producto estrella, así como las expectativas de nuevos desarrollos han colocado al grupo no solo a la cabeza de las mayores revalorizaciones del sector sino también la han situado en la elite del conjunto del mercado.

...

Plitidepsin ( Aplidin ) Derails a Series of its Moonlighting Functions that are Essential for the Survival of Tumor Cells, Driving them into Apoptosis.

©2017 American Association for Cancer Research. 
July 2017 // Volume 77, Issue 13 .

Plitidepsin Targets the Moonlighting Functions of eEF1A2 in Cancer Cells .

Alejandro Losada, Maria Jose Muñoz, Juan F. Martínez-Leal, Juan M. Domínguez and Carlos M. Galmarini .




Plitidepsin, a cyclic depsipeptide of marine origin, has shown potent anticancer activity in preclinical assays and recently finished with positive results a pivotal phase III trial (clinicaltrials.gov identifier: NCT01102426) for the treatment of multiple myeloma patients. We have recently found that eukaryotic elongation factor 1A2 (eEF1A2), one of the two isoforms of the alpha subunit of eEF1, is the pharmacological target of plitidepsin.

Although it shares 96% homology with eEF1A1 (the other isoform), they display an exclusive pattern of expression, being eEF1A2 solely expressed in brain and muscle in healthy individuals. However, it has been found that many tumors abnormally overexpress this protein, including multiple myeloma, prostate, pancreatic, ovarian, breast, lung and liver cancers.

Furthermore, although eEF1A2 canonical function consists in the delivery of aminoacyl-tRNAs to the A site in the ribosome, it has been shown to have pro-oncogenic moonlighting activities, including inhibition of apoptosis, protein degradation by the proteasome, heat shock response, cytoskeleton organization and regulation of oxidative stress. 

We now investigated several of the pro-oncogenic activities of eEF1A2 to analyze the impact that plitidepsin could have preventing them. Indeed, we observed that plitidepsin interfered with the interaction between eEF1A2 and Peroxiredoxin 1 (PRDX1), a complex that allosterically enhances the enzymatic activity of PRDX1. 

This way, plitidepsin would diminish PRDX1 antioxidant activity, possibly originating the oxidative stress that has been described in the bibliography as one of the first effects triggered by the drug in cancer cells.

PRDX1 only interacts with the GDP-bound form of eEF1A2, while plitidepsin exclusively binds to the GTP-bound form, most probably sequestering this protein from the pool that could interact with and activate PRDX1.

Furthermore, we have confirmed that eEF1A2 interacts with Sphingosine kinase 1 (SPHK1), a complex that has been described in the bibliography as having enhanced SPHK1 activity. SPHK1 phosphorylates sphingosine producing sphingosine-1-P, second messenger that binds to its receptors in the cell membrane and conveys growth and survival signals to the cell.

We could see that plitidepsin treatment reduced the production of sphingosine-1-P in HeLa cells, destabilizing the equilibrium towards the pro-apoptotic ceramide/sphingosine side and promoting cell death.

Thus, through its binding to eEF1A2, Plitidepsin derails a series of its moonlighting functions that are essential for the survival of tumor cells, driving them into apoptosis.



©2017 American Association for Cancer Research.

Hoteles en España los que quieras ... pero ni se te ocurra buscar una Residencia . Más de 24.000 euros por paciente y año, el coste del Alzheimer en España ... La Medalla para los Familiares que costean el 71 % del Gasto .

Más de 24.000 euros por paciente y año, el coste del Alzheimer en España

MADRID, 4 Jul. (EUROPA PRESS) - 

La atención sociosanitaria del Alzheimer y otras demencias en España tiene un coste medio de 24.184 euros por paciente y año, pero hasta el 71 por ciento de dicho gasto (unos 15.724 euros) es asumido por los familiares, según datos de un informe de The Economist Intelligence Unit presentado en el Ministerio de Sanidad. ARTICULO RELACIONADO Sanidad y tres entidades financian con 100.000 euros 15 proyectos para fomentar la investigación en enfermedades ...