21 research outputs found

    The Prometastatic Microenvironment of the Liver

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    The liver is a major metastasis-susceptible site and majority of patients with hepatic metastasis die from the disease in the absence of efficient treatments. The intrahepatic circulation and microvascular arrest of cancer cells trigger a local inflammatory reaction leading to cancer cell apoptosis and cytotoxicity via oxidative stress mediators (mainly nitric oxide and hydrogen peroxide) and hepatic natural killer cells. However, certain cancer cells that resist or even deactivate these anti-tumoral defense mechanisms still can adhere to endothelial cells of the hepatic microvasculature through proinflammatory cytokine-mediated mechanisms. During their temporary residence, some of these cancer cells ignore growth-inhibitory factors while respond to proliferation-stimulating factors released from tumor-activated hepatocytes and sinusoidal cells. This leads to avascular micrometastasis generation in periportal areas of hepatic lobules. Hepatocytes and myofibroblasts derived from portal tracts and activated hepatic stellate cells are next recruited into some of these avascular micrometastases. These create a private microenvironment that supports their development through the specific release of both proangiogenic factors and cancer cell invasion- and proliferation-stimulating factors. Moreover, both soluble factors from tumor-activated hepatocytes and myofibroblasts also contribute to the regulation of metastatic cancer cell genes. Therefore, the liver offers a prometastatic microenvironment to circulating cancer cells that supports metastasis development. The ability to resist anti-tumor hepatic defense and to take advantage of hepatic cell-derived factors are key phenotypic properties of liver-metastasizing cancer cells. Knowledge on hepatic metastasis regulation by microenvironment opens multiple opportunities for metastasis inhibition at both subclinical and advanced stages. In addition, together with metastasis-related gene profiles revealing the existence of liver metastasis potential in primary tumors, new biomarkers on the prometastatic microenvironment of the liver may be helpful for the individual assessment of hepatic metastasis risk in cancer patients

    SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

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    Vitamin D analogues with reduced hypercalcemic activity are under clinical investigation for use against colon cancer and other neoplasias. However, only a subset of patients responds to this therapy, most probably due to loss of vitamin D receptor (VDR) expression during tumour progression. Recent data show that SNAIL transcription factor represses VDR expression, and thus abolishes the antiproliferative and prodifferentiation effects of VDR ligands in cultured cancer cells and their antitumour action in xenografted mice. Accordingly, upregulation of SNAIL in human colon tumours associates with downregulation of VDR. These findings suggest that SNAIL may be associated with loss of responsiveness to vitamin D analogues and may thus be used as an indicator of patients who are unlikely to respond to this therapy

    Study of behaviour on simulated daylight ageing of artists¿ acrylic and poly(vinyl acetate) paint films

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    [EN] This work proposes a multi-method approach that combines advanced microscopy (SEM/EDX, AFM) and spectroscopy (UV-vis and FTIR) techniques. This approach not only characterises the behaviour of the additives of two commercial poly(vinyl acetate) (PVAc) and acrylic emulsion paints but also simultaneously characterises the changes in chemical composition and morphology observed in the paint films as a result of ageing due to the paints being exposed to an intense source of simulated daylight. In parallel, a series of mechanical tests were performed that correlate the chemical changes in composition and the changes observed in the films' mechanical properties. This work was a comparative study between both types of acrylic and PVAc paints. The results obtained are of great interest for the modern paint conservation field as they provide valuable information on the mid- and long-term behaviours of these synthetic paints.Financial support is gratefully acknowledged from the Spanish "I+D+I MICINN" project CTQ2008-06727-C03-01/BQU supported by ERDEF funds and from the "Generalitat Valenciana" I+D project ACOMP/2009/171 and the AP2006-3223 project ascribed to the Predoctoral Stages Programme of Universitary Researchers in Spanish Universities and Research Centres from the Spanish Ministry of Science and Innovation (MICINN). The authors wish to thank Mr. Manuel Planes i Insausti and Dr. Jose Luis Moya Lopez, the technical supervisors responsible for the Electron Microscopy Service at the Polytechnic University of Valencia.Domenech Carbo, MT.; Silva, MF.; Aura Castro, E.; Fuster López, L.; Kröner ., SU.; Martínez Bazán, ML.; Mas Barberà, X.... (2011). Study of behaviour on simulated daylight ageing of artists¿ acrylic and poly(vinyl acetate) paint films. Analytical and Bioanalytical Chemistry. 399:2921-2937. https://doi.org/10.1007/s00216-010-4294-3S2921293739

    The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

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    The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

    Evolution of acute hepatitis C virus infection in a large European city: Trends and new patterns

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    The aims of this study were to describe the evolution of acute hepatitis C virus (HCV) infections since 2004 and to determine its associated factors. Acute HCV infections diagnosed in Barcelona from 2004 to 2015 were included. Incidence ratios (IR) were then estimated for sex and age groups. Cases were grouped between 2004-2005, 2006-2011 and 2012-2015, and their incidence rate ratios (IRR) were calculated. In addition, risk factors for acute HCV infection were identified using multinomial logistic regression for complete, available and multiple imputed data. 204 new HCV cases were identified. Two peaks of higher IR of acute HCV infection in 2005 and 2013 were observed. Men and those aged 35 – 54 had higher IR. IRR for men was 2.9 times greater than in women (95% confidence intervals (CI): 1.8 ‒ 4.7). Factors related to the period 2012 – 2015 (versus 2006 – 2011) were: a) sexual risk factor for transmission versus nosocomial (relative-risk ratio (RRR): 13.0; 95% CI: 2.3 ‒ 72.1), b) higher educated versus lower (RRR: 5.4; 95% CI: 1.6 ‒ 18.7), and c) HIV co-infected versus not HIV-infected (RRR: 53.1; 95% CI: 5.7 ‒ 492.6). Conclusion: This is one of the few studies showing IR and RRRs of acute HCV infections and the first focused on a large city in Spain. Sexual risk for transmission between men, higher educational level and HIV co-infection are important factors for understanding current HCV epidemic. There has been a partial shift in the pattern of the risk factor for transmission from nosocomial to sexual
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