544 research outputs found

    Serum Apolipoproteins C-I and C-III Are Reduced in Stomach Cancer Patients: Results from MALDI-Based Peptidome and Immuno-Based Clinical Assays

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    Finding new peptide biomarkers for stomach cancer in human sera that can be implemented into a clinically practicable prediction method for monitoring of stomach cancer. We studied the serum peptidome from two different biorepositories. We first employed a C8-reverse phase liquid chromatography approach for sample purification, followed by mass-spectrometry analysis. These were applied onto serum samples from cancer-free controls and stomach cancer patients at various clinical stages. We then created a bioinformatics analysis pipeline and identified peptide signature discriminating stomach adenocarcinoma patients from cancer-free controls. Matrix Assisted Laser Desorption/Ionization–Time of Flight (MALDI-TOF) results from 103 samples revealed 9 signature peptides; with prediction accuracy of 89% in the training set and 88% in the validation set. Three of the discriminating peptides discovered were fragments of Apolipoproteins C-I and C-III (apoC-I and C-III); we further quantified their serum levels, as well as CA19-9 and CRP, employing quantitative commercial-clinical assays in 142 samples. ApoC-I and apoC-III quantitative results correlated with the MS results. We then employed apoB-100-normalized apoC-I and apoC-III, CA19-9 and CRP levels to generate rules set for stomach cancer prediction. For training, we used sera from one repository, and for validation, we used sera from the second repository. Prediction accuracies of 88.4% and 74.4% were obtained in the training and validation sets, respectively. Serum levels of apoC-I and apoC-III combined with other clinical parameters can serve as a basis for the formulation of a diagnostic score for stomach cancer patients

    Formation of Nano-Bio-Complex as Nanomaterials Dispersed in a Biological Solution for Understanding Nanobiological Interactions

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    Information on how cells interface with nanomaterials in biological environments has important implications for the practice of nanomedicine and safety consideration of nanomaterials. However, our current understanding of nanobiological interactions is still very limited. Here, we report the direct observation of nanomaterial bio-complex formation (other than protein corona) from nanomaterials dispersed in biologically relevant solutions. We observed highly selective binding of the components of cell culture medium and phosphate buffered saline to ZnO and CuO nanoparticles, independent of protein molecules. Our discoveries may provide new insights into the understanding of how cells interact with nanomaterials

    TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status

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    <p>Abstract</p> <p>Background</p> <p>Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer.</p> <p>The purpose of this study was to evaluate the impact of TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different K-Ras and B-Raf mutational status.</p> <p>Methods</p> <p>TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2. mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting and cell viability was analyzed by the MTT method.</p> <p>Results</p> <p>We found that mRNA and TAp73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when B-Raf is mutated. This was statistically significant and was also associated with higher cell viability after the treatment.</p> <p>Conclusions</p> <p>Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function.</p> <p>Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab.</p

    Encounters with the moral economy of water: convergent evolution in Valencia

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    [EN] This article presents the results of comparative fieldwork on the huerta of Valencia in Spain, a successful community-managed irrigation system of medium scale, one governed collectively by thousands of small farmers organized into 10 autonomous but highly interdependent irrigator groups. The study tested a model identified previously in research on successful systems of much smaller scale in Peru, a set of principles of operation that, when affirmed by farmers and obeyed as collective-choice rules, interact to create equity among water rights and transparency in water use in an unusual way. The authors show that a nearly identical set are at work in all 10 communities of Valencia, revealing the unique manner in which these work together to promote successful and sustainable cooperation, both within and between the user groups, and arguing that their presence in Spain and the Andes is indicative, not of diffusion from one continent to another, but of independent invention. These principles together laid the foundations for separate Andean and Islamic hydraulic traditions, which were often manifested locally in robust and equitable systems of the same general type, here called the moral economy of water. This kind of communal system appears to have emerged repeatedly, and often independently, in a great many other locales and settings throughout the world; its adaptive dynamics are shown to be of great relevance to small farmers today as they face the growing scarcity of water being induced by population growth and by climate change.Trawick, P.; Ortega Reig, MV.; Palau-Salvador, G. (2014). Encounters with the moral economy of water: convergent evolution in Valencia. Wiley Interdisciplinary Reviews: Water. 1(1):87-110. doi:10.1002/wat2.1008S871101

    Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland

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    <p>Abstract</p> <p>Background</p> <p>New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations.</p> <p>Methods</p> <p>In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims.</p> <p>Results</p> <p>Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07–2.17 and RR 1.50, 95% CI 0.98–2.28) than studies without identified conflict of interest and studies without information on type of funding.</p> <p>Conclusion</p> <p>Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed pharmaceutical claims published in major medical journals are not supported by the cited referenced studies or based on potentially biased study information. In light of the discrepancy between the new legislation and the endorsement of these regulations, physicians should not trust drug advertisement claims even when they seem to refer to scientific studies.</p

    A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses

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    <p>Abstract</p> <p>Background</p> <p>Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment.</p> <p>Methods</p> <p>Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls.</p> <p>Results</p> <p>Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease.</p> <p>Conclusions</p> <p>A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.</p

    Effect of human leukocyte antigen heterozygosity on infectious disease outcome: The need for allele-specific measures

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    BACKGROUND: Doherty and Zinkernagel, who discovered that antigen presentation is restricted by the major histocompatibility complex (MHC, called HLA in humans), hypothesized that individuals heterozygous at particular MHC loci might be more resistant to particular infectious diseases than the corresponding homozygotes because heterozygotes could present a wider repertoire of antigens. The superiority of heterozygotes over either corresponding homozygote, which we term allele-specific overdominance, is of direct biological interest for understanding the mechanisms of immune response; it is also a leading explanation for the observation that MHC loci are extremely polymorphic and that these polymorphisms have been maintained through extremely long evolutionary periods. Recent studies have shown that in particular viral infections, heterozygosity at HLA loci was associated with a favorable disease outcome, and such findings have been interpreted as supporting the allele-specific overdominance hypothesis in humans. METHODS: An algebraic model is used to define the expected population-wide findings of an epidemiologic study of HLA heterozygosity and disease outcome as a function of allele-specific effects and population genetic parameters of the study population. RESULTS: We show that overrepresentation of HLA heterozygotes among individuals with favorable disease outcomes (which we term population heterozygote advantage) need not indicate allele-specific overdominance. On the contrary, partly due to a form of confounding by allele frequencies, population heterozygote advantage can occur under a very wide range of assumptions about the relationship between homozygote risk and heterozygote risk. In certain extreme cases, population heterozygote advantage can occur even when every heterozygote is at greater risk of being a case than either corresponding homozygote. CONCLUSION: To demonstrate allele-specific overdominance for specific infections in human populations, improved analytic tools and/or larger studies (or studies in populations with limited HLA diversity) are necessary
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