1,721,300 research outputs found

    Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: from bench to bedside

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    Many hematological malignancies consist of tumor cells that are spontaneously recognized and killed by Vγ9Vδ2 T cells. These tumor cells generate high amounts of intracellular phosphorylated metabolites mimicking the natural ligands and display a wide range of stress-induced self-ligands that are recognized by Vγ9Vδ2 T cells via TCR-dependent and TCR-independent mechanisms. The intrinsic features of Vγ9Vδ2 T cells and that of tumor cells of hematological origin constitute an ideal combination from which to develop Vγ9Vδ2 T cell-based immune interventions. In this review, we will discuss the rationale, preclinical and clinical data in favor of this therapeutic strategy and the future perspectives of its development

    Effective anti-tumor immunomodulatory properties of zoledronic acid

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    Introduction. Zoledronic acid (Zol) is the most potent aminobisphosphonates clinically available. Preclinical in vivo data suggest that it modulates the development of bone disease, decreases tumor burden with a direct anti-cancer activity, and reduces the migration and the metastatic invasion of cancer cells. Zol efficacy in anti-cancer adjuvant therapy also rests on its anti-angiogenic properties and ability to expand gamma/delta T cells, both in vitro and in vivo. The published data thus far available concern murine models of transplanted tumors. Present work was made to assess Zol immune-mediated activity in impairing spontaneous carcinogenesis in a transgenic mouse model. Materials and Methods. To asses Zol anti-tumor and immunomodulant properties, BALBneuT mice were treated with 16 administrations of 100 μg/Kg of Zol divided into four courses of a single weekly injections for four weeks followed by a three weeks rest. Zol administration was started when mice were 7 weeks old and therefore when all the 10 mammary glands display a widespread atypical hyperplasia. Zol was administered intravenously (i.v.) or into the mammary pad (i.mam.). Mice were evaluated for: 1) tumor onset, 2) tumor multiplicity and 3) overall survival. Results. Data obtained from these first experiments have shown that a similar significant tumor growth impairment was evident in mice receiving Zol administered i.v. or i.mam. Preliminary results have demonstrated Zol capacity to induce a significant increase in the percentage of gammadelta T cells in the spleen and in the lymphonode of Zol-treated mice. Even more importantly, data obtained in IFNg knocked out -NeuT mice have shown that Zol capacity to delay tumor onset and growth and to improve NeuT-mice survival is strictly dependent on the presence of IFNgamma, which is a well known mediator of innate and adaptive immune responses. Zol immune-mediated anti-tumor properties are further and even more convincingly supported by the evidence that NeuT mice knocked-out for the gene encoding for the Fcg receptor (FcgR-KO NeuT) and NeuT mice knocked-out for the gene encoding for the perforin (PF-KO NeuT) did not benefit of Zol anti-tumor action. Conclusions. All together, these data show for the first time that Zol in vivo antitumor functions at least partially relies on broad immunomodulant properties, involving cellular and humoral immunity

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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
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