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Arenas M.,Rovira i Virgili University | Sabater S.,Complejo Hospitalario Universitario Of Albacete | Hernandez V.,Hospital Universitari Sant Joan Of Reus | Rovirosa A.,University of Barcelona | And 3 more authors.
Strahlentherapie und Onkologie | Year: 2012

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies. © 2012 Urban & Vogel.

Oliveras-Ferraros C.,Catalan Institute of Nanoscience and Nanotechnology | Cufi S.,Catalan Institute of Nanoscience and Nanotechnology | Vazquez-Martin A.,Catalan Institute of Nanoscience and Nanotechnology | Menendez O.J.,Catalan Institute of Nanoscience and Nanotechnology | And 5 more authors.
Cell Cycle | Year: 2012

Active avoidance by tumor cells of attack and elimination by immune cells is an emerging cancer hallmark that is achieved primarily by decreasing the levels of major histocompatibility complex class I (MHC-I) at the cancer cells'surface. Deficiencies in MHC-I antigen-restricted immunosurveillance may be intertwined with an altered, Warburglike cancer cell-intrinsic metabolism, another emerging hallmark of cancer that involves a switch from mitochondrial respiration to glycolysis to efficiently support large-scale biosynthetic programs that are required for active cell proliferation. We recently envisioned that intervention strategies aimed at reversing the bioenergetic signature of cancer cells (e.g., the antidiabetic biguanide metformin) should correct oncogene (e.g., HER2)-driven MHC-I defects, thus preventing immune escape of oncogene transformants. First, we explored how metformin treatment impacted mitochondrial biogenesis in cultured breast cancer cells overexpressing the membrane tyrosine kinase receptor HER2, the best-characterized downregulator of MHC-I. Metformin exposure was found to dose-dependently increase the expression levels of cytochrome c oxidase I and mitochondrial succinate dehydrogenase, which are encoded by mitochondrial and nuclear DNA, respectively. Second, we explored whether metformin-enhanced mitochondrial biogenesis might significantly alter the MHC-I status in breast carcinoma cells. MHC-I expression, as assessed by flow cytometry using an anti- HLA-ABC monoclonal antibody, was fully restored (up to ∼25-fold upregulation) in MHC-I-negative HER2 geneamplified carcinoma cells. These findings may help delineate a previously unrecognized mechanism through which metformin (and metformin-like drugs) may enable a cancer patient's own immune system to mount an efficient anti-metastasis response that can prevent or delay disease recurrence. Restored antigenicity and immunogenicity of tumor cells may represent a previously unrecognized primary mode of action underlying the cancer-preventive effects of metformin. © 2012 Landes Bioscience.

Closa-Monasterolo R.,Rovira i Virgili University | Closa-Monasterolo R.,Hospital Universitari Joan Xxiii Of Tarragona | Gispert-Llaurado M.,Rovira i Virgili University | Luque V.,Rovira i Virgili University | And 6 more authors.
Clinical Nutrition | Year: 2013

Background & aims: The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process. Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation. The aim of this study was to demonstrate the efficacy, safety and tolerance of a 0.8g/dL Orafti®Synergy1 (oligofructose-enriched inulin) supplemented infant formula during the first 4 months of life. Methods: In a double-blind, randomized, placebo-controlled and parallel trial, formula fed healthy term newborns were randomized to receive a control (controls) or SYN1 supplemented infant formula (SYN1). Breastfed newborns (BF) were also followed for comparison. Anthropometry, water balance, blood parameters, adverse events, stool frequency and characteristics and faecal microbiota were assessed. Results: A total of 252 formula fed infants were randomized at birth (n=124 controls, n=128 SYN1) and 131 BF infants were recruited; after 4 months 68 controls, 63 SYN1 and 57 BF completed the study. SYN1 infants showed a microbiota composition closer to that of BF infants, with a trend towards higher Bifidobacterium cell counts, softer stools and a higher deposition frequency compared to controls. There were no differences between formulas in anthropometry and relevant adverse events, water balance or blood parameters. Conclusion: A 0.8g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective, promoting a gut microbiota closer to that of breastfeeding.This clinical trial was registered at Clinicaltrials.gov as Study on Fermentable Carbohydrates in Healthy Infants (number NCT00808756). © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Calvo E.,Rovira i Virgili University | Pastor F.J.,Rovira i Virgili University | Rodriguez M.M.,Rovira i Virgili University | Pujol I.,Hospital Universitari Sant Joan Of Reus | Guarro J.,Rovira i Virgili University
Antimicrobial Agents and Chemotherapy | Year: 2010

We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Hernandez V.,Hospital Universitari Sant Joan Of Reus | Sempau J.,Polytechnic University of Catalonia
Medical Physics | Year: 2011

Purpose: To study the influence of the field setup on the dosimetry at the junction in single-isocenter half-beam techniques. Methods: The dosimetry at the junction for a two-field setup with the gantry at zero was first evaluated with radiochromic films. A three-field setup, with an anterior field and two opposed lateral fields, was also analyzed for two different relative positions of the fields involved. In all cases, the dose increase at the central axis, called the junction dose, was measured. Results: Junction doses varied greatly with the setup. For the three-field setup, the junction dose differed from that obtained with the two-field setup, and it greatly depended on the relative position of the fields. When the anterior field was closer to the gantry than the lateral fields, a field gap occurred and the junction dose was negative. When the anterior field was farther from the gantry than the lateral fields, a field overlap was obtained and the junction dose was positive. The difference in the junction dose between the three-field setups was around 18% for the three accelerators evaluated. Conclusions: Having a uniform dose distribution for two fields at gantry 0° does not guarantee a uniform distribution at other gantry angles. Junction doses are largely affected by the relative position of the radiation fields, which may have an impact in clinical practice. Therefore, any method aiming to assess or to optimize the dose homogeneity at the junction should take this effect into account. © 2011 American Association of Physicists in Medicine.

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