Calvo E.,Centro Integral Oncologico Clara Campal and START Madrid |
Ravaud A.,Bordeaux University Hospital Center |
Bellmunt J.,University of the Sea
Cancer Treatment Reviews | Year: 2013
Sequential treatment with targeted therapies is the current standard of care for patients with metastatic renal cell carcinoma (mRCC). Most patients are initially treated with a first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI), but will eventually develop resistance and subsequent disease progression. Patients with mRCC whose disease progresses during initial VEGFr-TKI therapy may continue treatment with a different VEGFr-TKI or they may switch to treatment with a mammalian target of rapamycin (mTOR) inhibitor which has a different mechanism of action. Based on positive results of the phase III RECORD-1 trial, clinical guidelines in the United States and Europe recommend use of everolimus, an mTOR inhibitor, in patients with VEGFr-TKI-refractory mRCC. Positive results of the phase III AXIS trial led to recent approval in the United States of the VEGFr-TKI axitinib for use in patients with mRCC who failed one previous therapy. VEGFr-TKIs and mTOR inhibitors have distinct clinical effects with differing safety profiles, but to date, no head-to-head comparisons in the post-VEGFr-TKI second-line setting are available. This review discusses multiple factors that should be considered when selecting a second-line therapy for patients with VEGFr-TKI-refractory mRCC, including evidence-based guidelines, efficacy, safety, patient profile, and clinician familiarity with available agents. © 2012 Elsevier Ltd.
Bellmunt J.,University of the Sea |
Dutcher J.,St Lukes Roosevelt Hospital Center
Annals of Oncology | Year: 2013
Background: Targeted therapies have shown profound effects on the outcome of patients with advanced renal cell carcinoma (RCC). However, the optimal treatment for RCC of non-clear cell histology (nccRCC)-typically excluded from trials of targeted agents-remains uncertain. Materials and methods: By carrying out extensive searches of PubMed and ASCO databases, we identified and summarised research into the biological characteristics, clinical behaviour and treatment of different histological subtypes of nccRCC, focusing on targeted therapy. Results: The available data suggest that treatments currently approved for RCC are active in ncc subtypes, although the overall clinical benefit may be less than for clear cell RCC. Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with nccRCC, based on phase III data, while everolimus, sunitinib and sorafenib have all demonstrated some degree of activity in nccRCC in expanded-access trials. No clear picture has emerged of whether individual histological subtypes are particularly responsive to any individual treatment. Conclusions: Further molecular studies into the pathogenesis of RCC histological subtypes will help direct the development of novel, appropriate targeted agents. Clinical trials specifically designed to evaluate the role of targeted agents in nccRCC are ongoing, and data from trials with sunitinib and everolimus will be reported soon. © The Author 2013. All rights reserved.
Mosiewicki M.A.,CONICET |
Aranguren M.I.,University of the Sea
European Polymer Journal | Year: 2013
The last two decades have witnessed an exponential growth in the interest for using bio-derived products, which has been driven by the need for replacing petroleum based materials reducing the fuel consumption and, equally important, for producing materials with lower environmental impact. Vegetable oils constitute a rich source for many different polymers and polymer precursors and they are being considered for the production of "greener" composites. The wide range of possible combinations of vegetable oils, chemical modifications, polymerization routes, nature of the fillers and fibers used as reinforcement materials allows tailoring the composite properties to fit the requirements of structural or functional materials. Thus, a wide range of macro, micro and nanosized particles and fibers have been proposed as reinforcements/fillers, including organic and inorganic ones, natural or synthetic, in order to give adequate answers to specific requirements. Although, the role of oil-based products may seem modest in some cases (partial replacement of synthetic materials), there is a clear trend to increase the percentage of "green"-based raw materials in the formulations of commodities as well as specialty polymers/composites for high added value applications. Examples of different types of reinforced thermoset and elastomeric bio-composites are presented in this short review. © 2013 Elsevier B.V. All rights reserved.
Zaman M.J.,University of the Sea |
Bhopal R.S.,University of Edinburgh
Heart | Year: 2013
Studying ethnic differences in health not only benefits minority groups but is a powerful tool for scientific analysis and for social action in the wider field of health inequalities. Coronary mortality in developed countries is well-known to be higher for men and women born in south Asia compared to other ethnic groups. The aim of this review is to examine how the knowledge of ethnic differences in coronary health in south Asians has advanced in the last decade. We set out to answer the following: Is the high rate of coronary mortality in south Asians a result of high incidence or high case fatality? Why are there ethnic differences, and are they the result of biology, healthcare or social circumstances? Is the cardiovascular health future for south Asians (and especially the UK-born second generation) any brighter than in their parents?
Alegado R.A.,University of the Sea |
King N.,Howard Hughes Medical Institute
Cold Spring Harbor Perspectives in Biology | Year: 2014
Animals evolved in seas teeming with bacteria, yet the influences of bacteria on animal origins are poorly understood. Comparisons among modern animals and their closest living relatives, the choanoflagellates, suggest that the first animals used flagellated collar cells to capture bacterial prey. The cell biology of prey capture, such as cell adhesion between predator and prey, involves mechanisms that may have been co-opted to mediate intercellular interactions during the evolution of animal multicellularity. Moreover, a history of bacterivory may have influenced the evolution of animal genomes by driving the evolution of genetic pathways for immunity and facilitating lateral gene transfer. Understanding the interactions between bacteria and the progenitors of animals may help to explain themyriad ways in which bacteria shape the biology of modern animals, including ourselves. © 2014 Cold Spring Harbor Laboratory Press. All rights reserved.
Yu M.,University of Edinburgh |
Lamattina L.,University of the Sea |
Spoel S.H.,University of Edinburgh |
Loake G.J.,University of Edinburgh
New Phytologist | Year: 2014
A major route for the transfer of NO bioactivity is S-nitrosylation, the covalent attachment of an NO moiety to a protein cysteine thiol to form an S-nitrosothiol (SNO). This chemical transformation is rapidly emerging as a prototypic, redox-based post-translational modification integral to the life of plants. Here we review the myriad roles of NO and SNOs in plant biology and, where known, the molecular mechanisms underpining their activity. © 2014 New Phytologist Trust.
Di Mauro M.F.,University of the Sea
Plant signaling & behavior | Year: 2012
Transcriptional co-activators of the multiprotein bridging factor 1 (MBF1) controls gene expression by connecting transcription factors and the basal transcription machinery. In Arabidopsis thaliana functions of MBF1 genes have been related to stress tolerance and developmental alterations. Endogenous ABA plays a major role in the regulation of Arabidopsis seed dormancy and germination. Seed dormancy and ABA sensitivity are enhanced in ethylene insensitive mutants suggesting that ethylene signal transduction pathway is necessary to fully develop ABA-dependent germination. In this report we showed that a triple knock-down mutant for Arabidopsis MBF1 genes (abc-) has enhanced seed dormancy and displays hypersensitivity to exogenous ABA. In addition, higher ABA contents were detected in abc- seeds after imbibition. These evidences suggest a negative role of MBF1s genes in ABA-dependent inhibition of germination. The participation of MBF1s in ethylene signal transduction pathway is also discussed.
Chapetti M.D.,University of the Sea
Procedia Engineering | Year: 2010
This work deals with the very high cycle fatigue behavior of high strength steels in which the fracture origins are mostly at nonmetallic inclusions. The estimation of the total fatigue life for these materials could only success if the fatigue crack initiation life could be properly quantified. This is a very hard task because the phenomenous involved in the fatigue crack nucleation and initiation processes are not well understood yet. This stage is not uniquely governed by fatigue, but also by other processes that are usually active helping the pure fatigue process. From an analysis of several features involved in the crack initiation and propagation processes and taking into account that the fatigue limit usually observed for metals is mainly given for a microstructural threshold for fatigue crack propagation, an expression was deduced to estimate the internal fatigue resistance for a given fatigue life for fracture produced by cracks initiated from an internal inclusion. Such estimation becomes very important when it is necessary to assess fatigue resistance of components subjected to very high cycle fatigue, for which the experimental measure of the fatigue limit could require very long time by using traditional fatigue testing machines. © 2010 Published by Elsevier Ltd.
Barreiro E.,University of the Sea |
Barreiro E.,Institute Salud Carlos III ISCIII
Mass Spectrometry Reviews | Year: 2014
Skeletal muscle, the most abundant tissue in mammals, is essential for any activity in life. Muscle dysfunction is a common systemic manifestation in highly prevalent conditions such as chronic obstructive pulmonary disease (COPD), cancer cachexia, and sepsis. It has a significant impact on exercise tolerance, thus worsening the patients' quality of life and survival. Among several factors, oxidative stress is a major player in the etiology of skeletal muscle dysfunction associated with those conditions. Whereas low levels of oxidants are absolutely required for normal cell adaptation, high levels of reactive oxygen species (ROS) alter the function and structure of molecules such as proteins, DNA, and lipids. Specifically, protein carbonylation, a common variety of protein oxidation, was shown to alter the function of key enzymes and structural proteins involved in muscle contractile performance. Moreover, increased levels of ROS may also activate proteolytic systems, thus leading to enhanced protein breakdown in several models. In the current review, the specific modifications induced by carbonylation in protein structure and function in muscles have been described. Furthermore, the potential role of ROS in the activation of proteolytic systems in skeletal muscles is also discussed. The review summarizes the effects of protein carbonylation on muscles in several models and conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and aging. Future research should focus on the elucidation of the specific protein sites modified by ROS in these muscles using redox proteomics analyses and on the assessment of the consequent alterations in protein function and stability. © 2013 Wiley Periodicals, Inc.
Chapetti M.D.,University of the Sea
International Journal of Fatigue | Year: 2011
This work deals with the very high cycle fatigue behavior of high strength steels where fracture origins are mostly at non-metallic inclusions. From the analysis of several features involved in the crack initiation and propagation processes, and since the fatigue resistance usually observed for metals is mainly due to a microstructural threshold for pure fatigue crack propagation, the following expression is proposed to estimate the internal fatigue resistance for a given fatigue life for fractures produced by cracks initiated from an internal inclusion: σ e Int=444ΔK thnRi where σ e Int is given in MPa, the inclusion radio R i is in μm, n is a dimensionless factor and the pure fatigue crack propagation threshold ΔK th is equal to the lower value given by the following expressions:Δ K th=4.10 -3( HV+120)a1 /3ΔKth- 1=-0. 0038 σu+15.5where the pure fatigue crack propagation thresholds ΔK th (function of crack length) and ΔK th -1 (a constant value for a given tensile strength or hardness) are in MPa m 1/2, the crack length a in μm, the Vicker harness H V in kgf/mm 2 and the ultimate tensile strength σ u in MPa. Such estimation becomes very important in the assessment of the fatigue resistance of components subjected to very high cycle fatigue, as this might become a very expensive and time consuming task. © 2010 Elsevier Ltd. All rights reserved.