1,721,027 research outputs found
Importance of the mechanical properties of circulating tumor cells during metastatic development
No full textLes métastases apparaissent à la fin de la cascade métastatique, un processus complexe dans lequel plusieurs paramètres biomécaniques jouent un rôle important. La contribution de la déformabilité des cellules tumorales circulantes (CTCs) lors de la dissémination hématogène reste mal comprise. Mes travaux identifient la propriété de viscosité comme composante clé de la mécanique cellulaire impactant le comportement des CTCs dans les étapes intravasculaires de la cascade métastatique. Cette propriété intervient au cours de la déformation permettant aux CTCs de surmonter les contraintes aux sites d’occlusion, leur donnant ainsi accès à des itinéraires de circulation alternatifs dans des vaisseaux à petits diamètres où elles pourront se loger. La propriété de viscosité intervient encore au cours de l’étape d’extravasation en impactant le déclenchement du mécanisme de remodelage endothélial extirpant les cellules tumorales des vaisseaux où elles se trouvent arrêtées.Metastasis occurs at the end of the metastatic cascade, a complex process in which several biomechanical parameters play an important role. The contribution of the deformability of circulating tumor cells (CTCs) during hematogenous dissemination remains poorly understood. My work identifies the property of viscosity as a key component of cell mechanics impacting the behavior of CTCs in the intravascular stages of the metastatic cascade. This property comes into play during deformation, enabling CTCs to overcome constraints at sites of occlusion, giving them access to alternative circulation routes in small-diameter vessels where they can lodge. The property of viscosity also comes into play during the extravasation stage as it impacts the triggering of the endothelial remodeling mechanism that extirpates arrested tumor cells from the circulation
Hemodynamic forces control circulating tumor cells dissemination
No full textLes cellules tumorales circulantes (CTCs) que l’on retrouve dans le sang des patients atteints de cancers sont responsables de la formation de métastases dans des organes vitaux. Pendant ma thèse, nous avons travaillé sur l’étude du rôle de facteurs biomécaniques (tels que le flux sanguin, la force des récepteurs d’adhésion et les contraintes physiques) sur la dissémination des CTCs. En particulier, nous avons pu démontrer le rôle central des forces du flux sanguin dans les étapes d’arrêt, d’adhésion et d’extravasation des CTCs qui précèdent directement la formation des métastases. Nous avons mis en lumière un mécanisme d’adhésion des CTCs en deux étapes in vivo, faisant intervenir plusieurs types de récepteurs d’adhésion et la matrice extracellulaire. Enfin, nous avons mis en évidence la possibilité de bloquer le mécanisme d’extravasation par remodelage de l’endothélium dépendant du flux sanguin autour des cellules tumorales arrêtés dans les vaisseaux. Ceci ouvre la voie à de nouvelles stratégies thérapeutiques pour bloquer la progression tumorale.Blood from patients with cancers contains circulating tumor cells (CTCs) that are responsible for the development of metastases in vital organs. During my PhD, we studied the role of biomechanical factors (such as blood flow, strengths of adhesion receptors and physical constraints) on the dissemination of CTCs. Especially, we demonstrated the central role of blood flow forces during the arrest, the adhesion and the extravasation of CTCs, preceding the metastatic outgrowth. We highlighted a two-step mechanism of CTCs adhesion, based on several adhesion receptors and the extracellular matrix. Finally, we successfully inhibited the extravasation of CTCs, by blocking the flow-dependent endothelial remodeling around arrested tumor cells in the vessels. This paves the way to establish new therapeutic strategies to block cancer progression
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Étude du rôle des gtpases Ral dans la sécrétion des exosomes et la progression métastatique
No full textLes vésicules extracellulaires (VE) cancéreuses font la navette à distance et fertilisent les niches pré-métastatiques facilitant l'ensemencement ultérieur par les cellules tumorales. Cependant, le lien entre les mécanismes de sécrétion d'EV et leur capacité à former des niches pré-métastatiques reste obscur. À l'aide de modèles murins, nous montrons que les GTPases de la famille Ral contrôlent, par l'intermédiaire de la phospholipase D1, l'homéostasie des corps multivésiculaires et règlent la biogenèse et la sécrétion des véhicules électriques pro-métastatiques. Il est important de noter que les véhicules électriques provenant de cellules appauvries en RalA ou RalB ont des capacités organotropes limitées in vivo et sont moins efficaces pour favoriser les métastases. RalA et RalB réduisent les niveaux d'EV de la molécule d'adhésion MCAM/CD146, qui favorise les métastases médiées par EV en permettant aux EV de cibler les poumons. Enfin, RalA, RalB et MCAM/CD146 sont des facteurs de mauvais pronostic chez les patientes atteintes d'un cancer du sein. Dans l'ensemble, notre étude identifie les RalGTPases comme des molécules centrales liant les mécanismes de sécrétion et de chargement des véhicules électriques à leur capacité à disséminer et à induire des niches pré-métastatiques d'une manière dépendante du CD146.Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivo and are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner
Dissecting the metastatic cascade by innovative cell imaging approaches
No full textLa métastase peut être considérée comme le produit final d’un processus à la fois biologique mécanique et chimique où les cellules cancéreuses disséminent dans l’organisme pour envahir un nouvel organe à distance en s’établissant dans un nouvel microenvironnement tissulaire. Bien que les métastases soient la principale cause de décès liée au cancer, les principaux mécanismes impliqués dans ce processus restent à élucider. La communauté scientifique manque de techniques d’imagerie adaptées pour disséquer avec la plus haute résolution possible le comportement des cellules tumorales in vivo. Par conséquent, le but principal de ma thèse a été de développer une approche d’imagerie intravitale non-invasive appliquée à la souris. Cette approche a été inclue dans le développement d’un protocole de microscopie corrélative intravitale permettant l’étude de cellules tumorales à différentes échelles dans leur environnement naturel. Ce protocole a été utilisé dans l’étude de cellules invasives tumorales uniques dans l’oreille et le cerveau de la souris. Le but était de décrire les détails des protrusions cellulaires ainsi que les interactions cellule-matrice lors de l’invasion et l’intravasation de cellules cancéreuses.Metastasis can be considered as the end product of a multistep bio-mechano-chemical process where cancer cells disseminate to anatomically distant organs and home and establish themselves in a new tissue microenvironment. Although metastasis is the leading cause of cancer-related death, the main cellular mechanisms enabling this process remain to be elucidated. Importantly, the scientific community lacks adapted imaging technologies to accurately dissect, at the highest resolution possible, tumor cell behavior in vivo. Therefore, the main goal of my PhD thesis was to develop an intravital and non-invasive imaging approach to track tumor progression in the living mouse. This approach was included in the development of an intravital Correlative Light and Electron Microscopy protocol allowing to track tumor cells at different scales in their natural environment. It was used to study single invasive tumor cells in the mouse ear and brain and to describe the details of cell protrusions and cell-matrix interactions during invasion and intravasation of cancer cells
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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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