1,721,019 research outputs found
Modeling and Simulation of VEGF Receptors Recruitment in Angiogenesis
Full text linkAngiogenesis, the process of new blood vessel formation from preexisting ones, plays a pivotal role in tumor growth. Vascular endothelial growth factor receptor-2 (VEGFR2) is the main proangiogenic tyrosine kinase receptor expressed by endothelial cells (ECs). VEGFR2 binds different ligands triggering vascular permeability and growth. VEGFR2-ligands accumulate in the extracellular matrix (ECM) and induce the polarization of ECs as well as the relocation of VEGFR2 in the basal cell membrane in contact with ECM. We propose here a multiphysical model to describe the dynamic of VEGFR2 on the plasma membrane. The governing equations for the relocation of VEGFR2 on the membrane stem from a rigorous thermodynamic setting, whereby strong simplifying assumptions are here taken and discussed. The multiphysics model is validated against experimental investigations
The mechanics of anoikis resistance in cancer
No full textMetastatic cancer cells display a remarkable ability to resist the mechanical and biochemical challenges associated with detaching from the extracellular matrix and metastasize. A key adaptive mechanism in this process is resistance to anoikis. In this review, we explore the molecular and biophysical mechanisms that enable cancer cells to resist anoikis, with a focus on mechanotransduction. We discuss the roles of integrin signaling, the YAP/ TAZ pathway, the mechanosensitive ion channels, and actomyosin contractility in sustaining survival under mechanical stress conditions. Furthermore, we highlight the emerging contribution of soluble mediators, particularly the myokine irisin, which acts as mechanical mimetics by activating survival pathways typically triggered by matrix engagement. We also examined how mechanical heterogeneity across tumor types and metastatic routes shapes context-specific adaptation strategies. By bridging physical forces and cell survival signaling, this review underscores mechanostransduction as fundamental driver of metastatic competence and a promising target for therapeutic intervention
Nitric oxide modulates the angiogenic phenotype of middle T transformed endothelial cells
No full textThe role of nitric oxide (NO) in the induction of angiogenesis was evaluated in a murine heart endothelioma cell line (H.end.FB) carrying the mT oncogene. Two clonal derivatives of H.end.FB, H80 and H73, exhibiting different NO synthase (NOS) activities were selected and used in the study. The relationship among NOS activity and tumor cell behaviour (growth, and angiogenic capacity) and the molecular control of gene expression were investigated. H.end.FB and H80 on one side and H73 on the other side exhibited the highest and lowest NOS activity, respectively. Cell growth was inversely correlated to the amount of NO produced by the cell lines. Conversely, in the avascular rabbit cornea assay, H.end.FB and H80 cells were strongly angiogenic, while H73 were poorly angiogenic, indicating that the ability of the cells to induce neovascularization was associated with the extent of NO produced. Consistently, systemic administration to rabbits of the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the angiogenicity of H.end.FB cells. RT-PCR evidenced that H.end.FB expressed mRNA for TGF-beta1 and all VEGF isoforms, VEGF165 being predominantly expressed. NOS inhibition reduced the basal expression of VEGF isoforms, while it markedly potentiated TGF-beta1 expression. These results indicate that the endogenous production of NO in tumor cells can serve as an autocrine/paracrine signalling mechanism of progression, by controlling angiogenic factor/modulator expressio
Protein domain-based approaches for the identification and prioritization of therapeutically actionable cancer variants
Full text linkThe tremendous number of cancer variants that can be detected by NGS analyses has required the development of computational approaches to prioritize mutations on the basis of their biological and clinical significance. Standard strategies take a gene-centric approach to the problem, allowing exclusively the identification of highly frequent variants. On the contrary, protein domain (PD)-based approaches allow to identify functionally relevant low frequency variants by searching for mutations that recur on analogous residues across homologous proteins (i.e. containing the same PD). Such approaches enable to transfer information about the effects and druggability from one known mutation to unknown ones. Here we describe how PD-based strategies work, and discuss how they could be exploited for mutation prioritization. The principle that mutations clustered on specific residues of PDs have the same functional consequences and are therapeutically actionable in a similar manner could help the choice of patient-specific targeted drugs, eventually improving the management of cancer patients
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
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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