1,720,967 research outputs found

    Pro-apoptotic anti-NG2/CSPG4 monoclonal antibodies for disease therapy

    No full text
    A first aspect of the present invention refers to an antibody, preferably a monoclonal antibody, recognizing the extracellular domain of NG2/CSPG4 and its ability to induce apoptosis and/or autophagy upon antigen-binding in cancer cells expressing NG2/CSPG4. 10 Therefore, the antibody of the invention can be used for cell growth inhibition by exposing a cell expressing NG2/CSPG4 to a therapeutic amount of an antibody capable of binding to NG2/CSPG4. A second aspect of the present invention refers to a pharmacological composition comprising a therapeutic amount of the antibody, in its entirety or single chain variable 15 fragment (scFv) of the invention that is active against NG2/CSPG4, or any other portion of the antibody, preferably, embodied in a bispecific antibody construct (e.g. an antibody binding both NG2/CSPG4 and another cell surface molecule and/or antigen) or a fusion protein comprised of a therapeutic amount of the antibody, in its entirety or single chain variable fragment, or scFv, an another therapeutic molecule, such as a cytochine or an 20 aptoptosis-inducing agent (e.g TRAIL or Fas Ligand), or a CAR T (Chimeric Antigen Receptor T cell) construct in which the scFv derived from the portion of the antibody of the invention is expressed on the surface of a CAR T cell, such as to simultaneously engaging NG2/CSPG4 expressing cells and endogenous T cells and favor the maintenance of the CAR T cell in proximity to the cancer cell to trigger the activation of 25 the engaged T cell. Further provided by the invention is the use of the antibody and the composition of the invention for selective trigger of apoptosis and/or autophagy in cells specifically expressing NG2/CSPG4 recognized by the antibody. A further aspect of present invention refers to the antibody and the composition of the 30 invention for use in the treatment of an apoptosis and/or autophagy-dependent disease, preferably cancer, more preferably solid or hematological cancers, as well as cancerrelated diseases

    Pro-apoptotic anti-NG2/CSPG4 antibodies and their uses in disease therapy

    No full text
    The present invention relates to an antibody capable of binding with highaffinity and high selectivity to the ectodomain of the transmembrane proteoglycan (PG) NG2/CSPG4. The invention specifically refers to said antibody possessing the ability to uniquely induce programmed cell death through canonical caspase-dependent apoptosis or authophagy, 5 in cancer cells specifically expressing such protein, and without the participation of other exogenously added factors. Moreover, the present invention refers to a composition comprising the antibody of the invention as pharmaceutical excipients

    Pro-apoptotic anti-NG2/CSPG4 antibodies and their uses for disease therapy

    No full text
    The present invention relates to an antibody capable of binding with high-affinity and high selectivity to the ectodomain of the transmembrane proteoglycan (PG) NG2/CSPG4, preferably to discrete isoforms of NG2/CSPG4. The invention further relates to said antibody possessing the ability to uniquely induce programmed cell death, exhibited as both canonical caspase-dependent apoptosis and authophagy, in NG2/CSPG4-expressing cancer cells. This action being manifested irrespectively of the coaction of other exogenously added factors. Moreover, the present invention refers to a composition comprising the antibody of the invention, in their naked, encapsulated or genetically engineered form, as pharmaceutical excipients. A further aspect of the present invention refers to the anti-NG2/CSPG4 molecule, or any of its isoforms and fragments, provided as proteolytically generated peptides or produced synthetically and/or recombinantly, for the treatment of apoptosis and/or autophagy-dependent diseases, including but not restricted to cancer

    Interaction between cartilage oligomeric matrix protein and extracellular matrix protein 1 mediates endochondral bone growth

    No full text
    In an effort to define the biological functions of COMP, a functional genetic screen was performed. This led to the identification of extracellular matrix protein 1 (ECM1) as a novel COMP-associated partner. COMP directly binds to ECM1 both in vitro and in vivo. The EGF domain of COMP and the C-terminus of ECM1 mediate the interaction between them. COMP and ECM1 colocalize in the growth plates invivo. ECM1 inhibits chondrocyte hypertrophy, matrix mineralization, and endochondral bone formation, and COMP overcomes the inhibition by ECM1. In addition, COMP-mediated neutralization of ECM1 inhibition depends on their interaction, since COMP largely fails to overcome the ECM1 inhibition in the presence of the EGF domain of COMP, which disturbs the association of COMP and ECM1. These findings provide the first evidence linking the association of COMP and ECM1 and the biological significance underlying the interaction between them in regulating endochondral bone growth

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The 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
    corecore