1,720,962 research outputs found
Theranostic impact of NG2/CSPG4 proteoglycan in cancer
No full textNG2/CSPG4 is an unusual cell-membrane integral proteoglycan widely recognized to be a prognostic factor, a valuable tool for ex vivo and non-invasive molecular diagnostics and, by virtue of its tight association with malignancy, a tantalizing therapeutic target in several tumour types. Although the biology behind its involvement in cancer progression needs to be better understood, implementation of NG2/CSPG4 in the routine clinical practice is attainable and has the potential to contribute to an improved individualized management of cancer patients. In this context, its polymorphic nature seems to be particularly valuable in the effort to standardize informative diagnostic procedures and consolidate forcible immunotherapeutic treatment strategies. We discuss here the underpinnings for this potential and highlight the benefits of taking advantage of the intra- tumour and inter-patient variability in the regulation of NG2/CSPG4 expression. We envision that NG2/CSPG4 may effectively be exploited in therapeutic interventions aimed at averting resistance to target therapy agents and at interfering with secondary lesion formation and/or tumour recurrence
Proteoglycans in the control of tumor growth and metastasis formation
No full textProteoglycans (PGs) as a whole, or when considering their GAG chains as single entities, are emerging as key regulators of tumor progression. Expectations on using them as putative prognostic markers and potential therapeutic targets are increasing coincidentally. Due to the multitude of biological roles that they may invest and the ample spectrum of cellular processes that they may control, we still need to learn better how they regulate phenomena such as intracellular signaling, proliferation, apoptosis, motility, and drug resistance. Depending on the type, their expression pattern, and the accessibility of their molecular ligands, PGs can either promote or inhibit tumorigenesis. The structural and functional diversity of PGs coupled with their ubiquitous abundance place them at the crossroads of many critical steps within the metastatic cascade. As this phenomenon is the pivotal factor for patient survivals, particular attention should be given to the understanding of how PGs govern metastasis formation
Fluorescence-based assays for in vitro analysis of cell adhesion and migration
No full textCell adhesion and cell migration are two primary cellular phenomena for which in vitro approaches may be exploited to effectively dissect the individual events and underlying molecular mechanisms. The use of assays dedicated to the analysis of cell adhesion and migration in vitro also afford an efficient way of conducting larger basic and applied research screenings on the factors affecting these processes and are potentially exploitable in the context of routine diagnostic, prognostic, and predictive tests in the biological and medical fields. Therefore, there is a longstanding continuum in the interest in devising more rationale such assays and major contributions in this direction have been provided by the advent of procedures based on fluorescence cell tagging, the design of instruments capable of detecting fluorescent signals with high sensitivity, and informatic tools allowing sophisticated elaboration of data generated through these instruments. In this report, we describe three representative fluorescence-based model assays for the qualitative and quantitative assessment of cell adhesion and cell locomotion in static and dynamic conditions. The assays are easily performed, accurate and reproducible, and can be automated for high-to-medium throughput screenings of cell behavior in vitro. Performance of the assays involves the use of certain dedicated disposable accessories, which are commercially available, and a few instruments that, due to their versatility, can be regarded as constituents of a more generic laboratory setup
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
Basi cellulari e molecolare per il ruolo pro-tumorigenico del proteoglicano NG2/CSPG4
No full textCSPG4/NG2 is a unique, variably glycanated transmembrane proteoglycan that has been thoroughly documented to exhibit aberrant expression patterns in solid and haematological tumours. Hence, it has been strongly associated with the pathological traits and progression of several tumours, but the precise molecular mechanisms through which it controls tumour development are not fully unveiled. The aim of my thesis work was therefore to approach the cellular and molecular mechanisms underlying the capability of NG2 to confer to cancer cells a more malignant phenotype. This direct correlation, between ectopic/overexpression of surface NG2 and a higher degree of malignancy, was demonstrated by the diverse tumorigenic behaviour displayed in vitro and in vivo of: immunoselected NG2-expressing and NG2-deficient cell subsets; cells in which their endogenous NG2 was knocked down with siRNAs; or cells engineered to overexpress the full-length or truncated variants of the proteoglycan. In vivo tumorigenesis experiments were supported by comparative in situ analyses of the tumour masses formed by NG2-expressing and NG2 deficient cells, DNA microarray global gene profiling and wide spectrum antibody array-based phospho-proteomic screens. Accentuated malignant behaviour of NG2 expressing cells was corroborated in vitro by: the diverse capacity to grow anchorage independently; the increased survival capabilities; the higher migration rates; and a diverse capability to form cellular aggregates. A substantial part of my studies also addressed the role of the NG2-collagen type VI interaction in the control of malignant behaviour in sarcoma cells. Diversified cellular interactions and migratory abilities were observed between NG2-positive and NG2-negative sarcoma cells with purified Col VI, basement membrane matrices supplemented with Col VI, and cell-free matrices isolated from wild type and Col VI null fibroblasts. The NG2-mediated binding to Col VI triggered activation of convergent cell survival- and cell adhesion/migration-promoting signal transduction pathways, implicating PI-3K as a common denominator and supporting the idea that an NG2-Col VI interplay may govern cancer cell-host microenvironment interactions sustaining sarcoma progression.
Further, analysis of biopsies from soft-tissue sarcoma patients demonstrated that enhanced expression of NG2 in pre-surgical primary lesions predicts post-surgical metastasis formation. Thereby it could stratified patients into disease-free survivors and patients destined to succumb from the disease.
Cumulatively, the study provides insights into the complex and multivalent role of NG2 in the control of cancer cell behaviour and reinforces its putative effectiveness as a therapeutic target for ablation of malignant cancer cell subsets
Basi cellulari e molecolare per il ruolo pro-tumorigenico del proteoglicano NG2/CSPG4
No full textCSPG4/NG2 is a unique, variably glycanated transmembrane proteoglycan that has been thoroughly documented to exhibit aberrant expression patterns in solid and haematological tumours. Hence, it has been strongly associated with the pathological traits and progression of several tumours, but the precise molecular mechanisms through which it controls tumour development are not fully unveiled. The aim of my thesis work was therefore to approach the cellular and molecular mechanisms underlying the capability of NG2 to confer to cancer cells a more malignant phenotype. This direct correlation, between ectopic/overexpression of surface NG2 and a higher degree of malignancy, was demonstrated by the diverse tumorigenic behaviour displayed in vitro and in vivo of: immunoselected NG2-expressing and NG2-deficient cell subsets; cells in which their endogenous NG2 was knocked down with siRNAs; or cells engineered to overexpress the full-length or truncated variants of the proteoglycan. In vivo tumorigenesis experiments were supported by comparative in situ analyses of the tumour masses formed by NG2-expressing and NG2 deficient cells, DNA microarray global gene profiling and wide spectrum antibody array-based phospho-proteomic screens. Accentuated malignant behaviour of NG2 expressing cells was corroborated in vitro by: the diverse capacity to grow anchorage independently; the increased survival capabilities; the higher migration rates; and a diverse capability to form cellular aggregates. A substantial part of my studies also addressed the role of the NG2-collagen type VI interaction in the control of malignant behaviour in sarcoma cells. Diversified cellular interactions and migratory abilities were observed between NG2-positive and NG2-negative sarcoma cells with purified Col VI, basement membrane matrices supplemented with Col VI, and cell-free matrices isolated from wild type and Col VI null fibroblasts. The NG2-mediated binding to Col VI triggered activation of convergent cell survival- and cell adhesion/migration-promoting signal transduction pathways, implicating PI-3K as a common denominator and supporting the idea that an NG2-Col VI interplay may govern cancer cell-host microenvironment interactions sustaining sarcoma progression.
Further, analysis of biopsies from soft-tissue sarcoma patients demonstrated that enhanced expression of NG2 in pre-surgical primary lesions predicts post-surgical metastasis formation. Thereby it could stratified patients into disease-free survivors and patients destined to succumb from the disease.
Cumulatively, the study provides insights into the complex and multivalent role of NG2 in the control of cancer cell behaviour and reinforces its putative effectiveness as a therapeutic target for ablation of malignant cancer cell subsets
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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