1,720,969 research outputs found
Key Genetic and Epigenetic Mechanisms in Chemical Carcinogenesis
No full textDNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved
Pharmacogenetics of tyrosine kinase inhibitors in gastrointestinal stromal tumor and chronic myeloid leukemia
No full textIntroduction: Gastrointestinal stromal tumors (GIST) and chronic myeloid leukemia (CML) are two tumor types deeply different from each other. Despite the differences, these disorders share treatment with tyrosine kinase inhibitor imatinib. Despite the success of imatinib, the response rates vary among different individuals and pharmacogenetics may play an important role in the final clinical outcome. Areas covered: In this review, the authors provide an overview of the pharmacogenetic literature analyzing the role of polymorphisms in both GIST and CML treatment efficacy and toxicity. Expert opinion: So far, several polymorphisms influencing the pharmacokinetic determinants of imatinib have been identified. However, the data are not yet conclusive enough to translate pharmacogenetic tests in clinical practice. In this context, the major obstacles to pharmacogenetic test validation are represented by the small sample size of most studies, ethnicity and population admixture as confounding source, and uncertainty related to genetic variants analyzed. In conclusion, a combination of different theoretical approaches, experimental model systems and statistical methods is clearly needed, in order to appreciate pharmacogenetics applied to clinical practice in the near future
Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis
No full textAutophagy and apoptosis are 2 fundamental biological mechanisms that may cooperate or be antagonistic, although both are involved in deciding the fate of cells in physiological or pathological conditions. These 2 mechanisms coexist simultaneously in cells and share common upstream signals and stimuli. Autophagy and apoptosis play pivotal roles in cancer development. Autophagy plays a key function in maintaining tumor cell survival by providing energy during unfavorable metabolic conditions through its recycling mechanism, and supporting the high energy requirement for metabolism and growth. This review focuses on gastrointestinal stromal tumors and cell death through autophagy and apoptosis, taking into account the involvement of both of these processes in tumor development and growth and as mechanisms of drug resistance. We also focus on the crosstalk between autophagy and apoptosis as an emerging field with major implications for the development of novel therapeutic options
Application of the lymphocyte Cytokinesis-Block Micronucleus Assay to populations exposed to petroleum and its derivatives: Results from a systematic review and meta-analysis
No full textThe lymphocyte cytokinesis-block micronucleus (CBMN) assay is applied in many different in vivo biomonitoring studies of human exposure to genotoxic chemicals. Among extensively chemicals investigated, we identified petroleum and its derivatives, in particular benzene and the most common mixture of benzene, toluene, and xylene. Although conflicting results have been reported on the effects of benzene exposure, the number of positive findings in independent studies suggests that occupational exposure to benzene causes DNA damage in peripheral blood lymphocytes. To assess current evidence on this hypothesis, we conducted a meta-analysis. Our aim was to evaluate the effect of benzene exposure on genetic damage, quantified using the CBMN assay on individuals occupationally exposed to petroleum and its derivatives. Statistical analyses were conducted using the rmeta package from the free Software Environment for Statistical Computing R. Combined study results indicated that benzene exposure is associated with an increased level of genetic damage in peripheral blood lymphocytes, as reflected by an increased MN frequency. The summary mean difference in MN frequency between exposed and unexposed individuals was 1.64 (95% CI: 0.80-2.47). Overall, this finding points to MN frequency as a sensitive biomarker which could be used to evaluate genetic damage induced by occupational - industrial or environmental - exposure to benzene. This review also identified some important knowledge gaps as well as the need of large, well-designed studies. In particular, it is fundamental to accurately characterize the investigated population, including dietary habits and genetic variability which could modulate MN frequency in both exposed individuals and unexposed controls. In conclusion, according to present findings the use of the CBMN assay in biomonitoring studies could provide objective evidence to guide prioritization of preventive interventions in subjects occupationally exposed to petroleum derivatives, and in particular benzene
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Clinical relevance of circulating molecules in cancer: focus on gastrointestinal stromal tumors
Full text linkIn recent years, growing research interest has focused on the so-called liquid biopsy. A simple blood test offers access to a plethora of information, which might be extremely helpful in understanding or characterizing specific diseases. Blood contains different molecules, of which circulating free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and extracellular vesicles (EVs) are the most relevant. Conceivably, these molecules have the potential for tumor diagnosis, monitoring tumor evolution, and evaluating treatment response and pharmacological resistance. This review aims to present a state-of-the-art of recent advances in circulating DNA and circulating RNA in gastrointestinal stromal tumors (GISTs). To date, progress in liquid biopsy has been scarce in GISTs due to several issues correlated with the nature of the pathology. Namely, heterogeneity in primary and secondary mutations in key driver genes has greatly slowed the development and application in GISTs, unlike in other tumor types in which liquid biopsy has already been translated into clinical practice. However, meaningful novel data have shown in recent years a significant clinical potential of ctDNA, CTCs, EVs and circulating RNA in GISTs
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
