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Cordoba R.,Fundacion Jimenez Diaz University Hospital | Sanchez-Beato M.,Hospital Universitario Puerta Of Hierro Majadahonda | Sanchez-Beato M.,Lymphoma Group | Herreros B.,Lymphoma Group | And 9 more authors.
Leukemia and Lymphoma | Year: 2016

Biopsy samples of lymph nodes from 38 patients with CLL were analyzed. We found differential expression in 1092 genes in two different subgroups: 418 overexpressed in one subgroup and 674 in another. Molecular pathways identified in one subgroup appear to be characterized by greater dependence of signaling by cytokines and activation of the NFkB pathway, while in the other seem to depend on cell cycle. Despite having found a differential expression between both subgroups, none of these genes reached FDR < 0.25. We have not found significant association with survival or any prognostic factors. Analysis of the differences between normal lymph node and CLL in 253 genes with difference in the intensity of expression revealed upregulated genes different to BCR: CD40, TCL1, IL-7, and PAX5. Using large-scale molecular analysis, we may obtain information about molecular mechanisms of CLL pathogenesis and may contribute to the identification of new therapeutic targets. © 2015 Informa UK, Ltd. Source

Iruzubieta P.,Santander University | Iruzubieta P.,Research Institute Marques Of Valdecilla Idival | Arias-Loste M.T.,Santander University | Arias-Loste M.T.,Research Institute Marques Of Valdecilla Idival | And 4 more authors.
BioMed Research International | Year: 2015

Drug-induced liver injury (DILI) is a potentially fatal adverse event and the leading cause of acute liver failure in the US and in the majority of Europe. The liver can be affected directly, in a dose-dependent manner, or idiosyncratically, independently of the dose, and therefore unpredictably. Currently, DILI is a diagnosis of exclusion that physicians should suspect in patients with unexplained elevated liver enzymes. Therefore, new diagnostic and prognostic biomarkers are necessary to achieve an early and reliable diagnosis of DILI and thus improve the prognosis. Although several DILI biomarkers have been found through analytical and genetic tests and pharmacokinetic approaches, none of them have been able to display enough specificity and sensitivity, so new approaches are needed. In this sense, metabolomics is a strongly and promising emerging field that, from biofluids collected through minimally invasive procedures, can obtain early biomarkers of toxicity, which may constitute specific indicators of liver damage. © 2015 Paula Iruzubieta et al. Source

Arias-Loste M.T.,Santander University | Arias-Loste M.T.,Research Institute Marques Of Valdecilla Idival | Fabrega E.,Santander University | Fabrega E.,Research Institute Marques Of Valdecilla Idival | And 4 more authors.
BioMed Research International | Year: 2015

Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apnea-hypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-related NAFLD has been associated with the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis, may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NFB. Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecular mechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD. © 2015 María Teresa Arias-Loste et al. Source

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