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Garrido F.,University of Granada | Garrido F.,Hospital Universitario Virgen Of Las Nieves | Garrido F.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Aptsiauri N.,Hospital Universitario Virgen Of Las Nieves | And 5 more authors.
Current Opinion in Immunology | Year: 2016

Immune escape strategies aimed to avoid T-cell recognition, including the loss of tumor MHC class I expression, are commonly found in malignant cells. Tumor immune escape has proven to have a negative effect on the clinical outcome of cancer immunotherapy, including treatment with antibodies blocking immune checkpoint molecules. Hence, there is an urgent need to develop novel approaches to overcome tumor immune evasion. MHC class I antigen presentation is often affected in human cancers and the capacity to induce upregulation of MHC class I cell surface expression is a critical step in the induction of tumor rejection. This review focuses on characterization of rejection, escape, and dormant profiles of tumors and its microenvironment with a special emphasis on the tumor MHC class I expression. We also discuss possible approaches to recover MHC class I expression on tumor cells harboring reversible/'soft' or irreversible/'hard' genetic lesions. Such MHC class I recovery approaches might well synergize with complementary forms of immunotherapy. © 2016 Elsevier Ltd. Source


Romero M.,University of Granada | Romero M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Toral M.,University of Granada | Gomez-Guzman M.,University of Granada | And 9 more authors.
Food and Function | Year: 2016

The effects of chronic consumption of oleuropein-enriched (15% w/w) olive leaf extract (OLE) on blood pressure, endothelial function, and vascular oxidative and inflammatory status in spontaneously hypertensive rats (SHR) were evaluated. Ten Wistar Kyoto rats (WKY) and twenty SHR were randomly assigned to three groups: a control WKY group, a control SHR group and a SHR group treated with OLE (30 mg kg-1) for 5 weeks. Long-term administration of OLE reduced systolic blood pressure, heart rate, and cardiac and renal hypertrophy. OLE treatment reversed the impaired aortic endothelium-dependent relaxation to acetylcholine observed in SHR. OLE restored aortic eNOS phosphorylation at Ser-1177 and Thr-495 and increased eNOS activity. OLE eliminated the increased aortic superoxide levels, and reduced the elevated NADPH oxidase activity, as a result of reduced NOX-1 and NOX-2 mRNA levels in SHR. OLE reduced the enhanced vascular TLR4 expression by inhibition of mitogen-activated protein kinase (MAPK) signaling with the subsequent reduction of proinflammatory cytokines. In conclusion, OLE exerts antihypertensive effects on genetic hypertension related to the improvement of vascular function as a result of reduced pro-oxidative and pro-inflammatory status. © The Royal Society of Chemistry 2016. Source


Rodriguez-Barranco M.,University of Granada | Rodriguez-Barranco M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Lacasana M.,University of Granada | Lacasana M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | And 12 more authors.
Environmental Research | Year: 2014

This study assessed the association between cadmium exposure and neuropsychological development in children from a region with high industrial and mining activities in southwestern Spain. We conducted a cross-sectional study with 261 children aged 6-9 years between January and March 2012. Cadmium exposure was measured in urine and hair of children, and neuropsychological development was assessed with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and with three computerized tests from the Behavioral Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariate linear regression models, adjusted for potential confounders, were used to estimate the association between neuropsychological development and cadmium exposure measured in urine and hair samples. Geometric means of urine and hair cadmium levels were 0.75. μg/g creatinine and 0.01. μg/g, respectively. We observed that doubling of levels of cadmium in urine was associated with a reduction of two points (95% CI: -3.8 to -0.4) in the Full-Scale intelligence quotient (IQ) in boys. By domains, association was statistically significant for Verbal Comprehension ( β=-2.0; p=0.04) and close to the significance level for Perceptual Reasoning ( β=-1.8; p=0.06). Among girls, only Verbal Comprehension showed suggestive associations with cadmium exposure ( β=-1.7; p=0.06). Cadmium exposure is associated with cognitive delays in boys in our region. Our results provide additional evidence of the neurotoxic effect of low-level postnatal cadmium exposure among children, and support the hypothesis of differences between sexes in the neurotoxic effect of metals on children. © 2014 Elsevier Inc. Source


Real M.,University of Granada | Real M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Molina-Molina J.-M.,University of Granada | Molina-Molina J.-M.,CIBER ISCIII | And 9 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2015

Medicinal plants are widely used for the treatment of diseases and for the development of new drugs. This study was designed to determine the presence of hormone-like activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in methanol extracts prepared from three medicinal plants historically and currently used for therapeutic purposes: Ginkgo biloba leaves (GBL), Elettaria cardamomum seeds (ECS) and Plantago ovata seeds (POS). After a solid–liquid extraction (SLE) step, their effects on hERa function were assessed in MCF-7 breast cancer cells using the E-Screen bioassay, and their ability to induce hAR-mediated reporter gene expression was evaluated using the androgen-sensitive stable prostatic PALM cell line. Unlike POS extracts, GBL and ECS extracts showed estrogenic (0.07 and 0.20 nM E2Eq mg–1, respectively) and anti-estrogenic (0.01 and 0.02 μM ICI182780Eq mg–1, respectively) activities. ECS extracts evidenced androgenic activity (0.30 nM R1881Eq mg–1) and POS extracts anti-androgenic activity (22.30 μM ProcEq mg–1). According to these findings, these plant extracts may interfere with the endocrine system via one or more hormonal receptors, and further investigation is warranted into their role as endocrine disrupters in humans. © 2015 Taylor & Francis. Source


Molina-Molina J.-M.,University of Granada | Molina-Molina J.-M.,CIBER ISCIII | Molina-Molina J.-M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Real M.,University of Granada | And 10 more authors.
Food and Chemical Toxicology | Year: 2014

Zearalenone (ZEN) is a well-known mycotoxin present in numerous agricultural products. Humans and animals are therefore at a risk of exposure to zearalenone through consumption of contaminated food. After intake, ZEN is reduced to α- and β-zearalenol (α-ZEL and β-ZEL), zearalanone (ZAN), and α- and β-zearalanol (α-ZAL and β-ZAL). Although their estrogenicity has been well characterized, much less is known about their interaction with other nuclear receptors. This study was undertaken to investigate interactions of ZEN and its five metabolites, with the human androgen receptor (hAR) and estrogen receptor alpha (hERα). Their ability to induce hAR-mediated reporter gene expression was examined in androgen-sensitive PALM cells, whereas the effects on hERα function were assessed in MCF-7 cells using the E-Screen bioassay. We confirm that ZEN and its metabolites are full agonists for hERα and demonstrate that all six compounds tested possess hAR-mediated antagonistic activity in PALM cells, in which ZAN, α-ZAL, and β-ZAL were the most effective hAR antagonists. Overall, the observed estrogenic and anti-androgenic potencies of ZEN and its metabolites suggest that these compounds may interfere with the endocrine system by various modes of action and that further investigation is warranted into their role as endocrine disrupters in animals and humans. © 2014 Elsevier Ltd. Source

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