Candida albicans Increases Tumor Cell Adhesion to Endothelial Cells In Vitro: Intraspecific Differences and Importance of the Mannose Receptor

The dimorphic fungus Candida albicans is able to trigger a cytokine-mediated pro-inflammatory response that increases tumor cell adhesion to hepatic endothelium and metastasis. To check the intraspecific differences in this effect, we used an in vitro murine model of hepatic response against C. albicans, which made clear that tumor cells adhered more to endothelium incubated with blastoconidia, both live and killed, than germ tubes. This finding was related to the higher carbohydrate/protein ratio found in blastoconidia. In fact, destruction of mannose ligand residues on the cell surface by metaperiodate treatment significantly reduced tumor cell adhesion induced. Moreover, we also noticed that the effect of clinical strains was greater than that of the reference one. This finding could not be explained by the carbohydrate/protein data, but to explain these differences between strains, we analyzed the expression level of ten genes (ADH1, APE3, IDH2, ENO1, FBA1, ILV5, PDI1, PGK1, QCR2 and TUF1) that code for the proteins identified previously in a mannoprotein-enriched pro-metastatic fraction of C. albicans. The results corroborated that their expression was higher in clinical strains than the reference one. To confirm the importance of the mannoprotein fraction, we also demonstrate that blocking the mannose receptor decreases the effect of C. albicans and its mannoproteins, inhibiting IL-18 synthesis and tumor cell adhesion increase by around 60%. These findings could be the first step towards a new treatment for solid organ cancers based on the role of the mannose receptor in C. albicans-induced tumor progression and metastasis.

Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2) Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18) concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18(th) hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1) expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results: Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion-and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions: These results demonstrate multiple sites for therapeutic intervention using resveratrol within the prometastatic microenvironment generated by tumor-induced hepatic IL-18, and suggest a remarkable effect of resveratrol in the prevention of inflammation-dependent melanoma metastasis in the liver.

Certificación energética y proyecto de posibles mejoras de la vivienda carretera Basurto-Castrejana 23 2ºB.

[ES]Se realizará la certificación energética de la vivienda sita en Ctra. Basurto-Castrejana 23 2ºB, mediante la herramienta CE3x, facilitada por el Gobierno de España. Se proyectarán, además, mejoras técnicas a implementar en el edificio para elevar su calificación energética, las cuales se analizarán tanto técnica como económicamente, eligiendo finalmente la solución óptima.

La reforma de las pensiones: Análisis económico de la Ley 23/2013

El siguiente Trabajo Fin de Grado analiza las particularidades de la “Ley 23/2013, de 23 de diciembre, reguladora del Factor de Sostenibilidad y del Índice de Revalorización del Sistema de Pensiones de la Seguridad Social”. El trabajo se centra principalmente en los dos componentes que constituyen la ley anteriormente citada, por un lado en el Factor de Sostenibilidad y por otro lado en el Índice de Revalorización de las Pensiones.

Erretiro pentsio kontributiboak 23/2013 legeak dakartzan aldaketen harira

Ezagun da pentsio sistema espainiarrak arazoak dituela. Arazo horiek, gainera, aspaldidanik datoz; badira 30 urte pentsioen jasangarritasunak kezka sortu zuela Estatu espainiarrean. Kezka horiek Gizarte Segurantzaren oreka ekonomikoan eta epe ertain eta luzera dituen prestazio-konpromezuak betetzeko gaitasunean – edo gaitasun ezean – oinarritu dira, batik bat. Alderdi ekonomikoan, sistema espainiarra moteldu dute krisi ekonomikoak eta lan merkatuaren egoerak. Alderdi demografikoan, sistema espainiarra ahuldu du biztanleria zahartzeak, jaiotza-tasa baxuak eta baby boom belaunaldia erretirora heltzeak. Azkenik, alderdi estrukturalean, banaketa sistemaren beraren izaerak tenkatu du korda.