1,720,959 research outputs found
Evolutionary Mechanisms of Cancer Suggest Rational Therapeutic Approaches
No full textThe goal in personalized therapeutic approaches for cancer medicine is to identify specific mutations with prognostic and therapeutic value in order to tailor the therapy for the single patient. The most powerful obstacle for personalized medicine arises from intratumor heterogeneity and clonal evolution, which can promote drug resistance. In this scenario, new technologies, such as next-generation sequencing, have emerged as a central diagnostic tool to profile cancer (epi)genomic landscapes. Therefore, a better understanding of the biological mechanisms underlying cancer evolution is mandatory and represents the current challenge to accurately predict whether cancer will recur after chemotherapy with the aim to tailor rational therapeutic approaches
CSB: An Emerging Actionable Target for Cancer Therapy
No full textThe DNA repair protein Cockayne syndrome group B (CSB) is frequently found overexpressed in cancer cells. High CSB levels favor tumor cell proliferation whilst inhibiting apoptosis. Conversely, the suppression of CSB has significant anticancer effects. In this manuscript we describe CSB downregulation as a potential new therapeutic approach in cancer
Interfering with the Ubiquitin-Mediated Regulation of Akt as a Strategy for Cancer Treatment
No full textThe serine/threonine kinase Akt modulates the functions of numerous substrates, many of them being involved in cell proliferation and growth, metabolism, angiogenesis, resistance to hypoxia and migration. Akt is frequently deregulated in many types of human cancers, its overexpression or abnormal activation being associated with the increased proliferation and survival of cancer cells. A promising avenue for turning off the functionality of Akt is to either interfere with the K63-linked ubiquitination that is necessary for Akt membrane recruitment and activation or increase the K48-linked polyubiquitination that aims to target Akt to the proteasome for its degradation. Recent evidence indicates that targeting the ubiquitin proteasome system is effective for certain cancer treatments. In this review, the functions and roles of Akt in human cancer will be discussed, with a main focus on molecules and compounds that target various elements of the ubiquitination processes that regulate the activation and inactivation of Akt. Moreover, their possible and attractive implications for cancer therapy will be discussed
Neuroblastoma cells depend on csb for faithful execution of cytokinesis and survival
No full textNeuroblastoma, the most common extra‐cranial solid tumor of early childhood, is one of the major therapeutic challenges in child oncology: it is highly heterogenic at a genetic, biological, and clinical level. The high‐risk cases have one of the least favorable outcomes amongst pediatric tumors, and the mortality rate is still high, regardless of the use of intensive multimodality therapies. Here, we observed that neuroblastoma cells display an increased expression of Cockayne Syndrome group B (CSB), a pleiotropic protein involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division, and were recently found to confer cell robustness when they are up‐regulated. In this study, we demonstrated that RNAi‐mediated suppression of CSB drastically impairs tumorigenicity of neuroblastoma cells by hampering their proliferative, clonogenic, and invasive capabilities. In particular, we observed that CSB ablation induces cytokinesis failure, leading to caspases 9 and 3 activation and, subsequently, to massive apoptotic cell death. Worthy of note, a new frontier in cancer treatment, already proved to be successful, is cytokinesis‐failure‐induced cell death. In this context, CSB ablation seems to be a new and promising anticancer strategy for neuroblastoma therapy
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
Gene Expression Profiling as a New Real-Time Assay in Human Biomonitoring of Waste-to-Energy Plant Workers
No full textExposure to heavy metals represents one of the most important risk factors for the health of incinerator workers. Indeed, heavy metals can determine increased generation of reactive oxygen species (ROS). In this work, we introduced the use of transcription profiling of detoxifying genes, involved in redox balance and genome integrity, as a highly sensitive assay of heavy metal exposure and subsequent oxidative stress. For this purpose, blood mRNA levels of OGG1, ST13, NQO1 and MT1A genes, as well as urinary concentrations of nine heavy metals and the oxidized base 8-OHdG of 49 subjects (26 controls and 23 employees in the waste-to-energy plant of San Zeno, Arezzo, Italy) were determined. No significant difference between the two populations was observed, thus highlighting, as far as the biomarkers analysed are concerned, the absence of occupational exposure to heavy metals and systemic oxidative stress induction in the workers of the waste-to-energy plant of San Zeno. Correlation analyses underline a close association between heavy metals exposure and changes in expression levels of a number of genes, even at low exposure doses, thus remarking the greater capacity of detection of transcription profiling compared to other biomarkers and the importance of its introduction in future human biomonitoring programs
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
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
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