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Erratum: The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic lymphocytic leukemia (Leukemia (2011) 25 (1760-1767) doi: 10.1038/leu.2011.149)
No full textXenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions.
No full text"Xenotransplantation of human tumour cells into immunodeficient mice has been a powerful pre-clinical tool in several hematologic malignancies, with the notable exception of Chronic Lymphocytic Leukemia (CLL). For several decades, this possibility was hampered by the inefficient and\/or short-term engrafment of CLL cells into available animals. The development of new generations of immunocompromised mice has allowed to partially overcome these constraints. Novel humanized animal models have been created that allow to recapitulate the pathogenesis of the disease and the complex in vivo relationships between leukemic cells and the microenvironment. In this review we discuss the development of xenograft models of CLL, how they may help elucidating the mechanisms that account for the natural history of the disease and facilitating the design of novel therapeutic approaches.
Targeting the LYN/HS1 signaling axis in chronic lymphocytic leukemia
No full text"\"\\\"HS1 (Hematopoietic cell-specific Lyn substrate-1) is a cytoskeletal interactor in the B-cell receptor (BCR) signaling pathway whose phosphorylation correlates with prognosis in Chronic Lymphocytic Leukemia (CLL) patients. The differentially phosphorylated sites and the kinases that regulate HS1 activity in CLL remain poorly understood. We demonstrate that HS1 activity is differentially regulated by LYN kinase that, in a sizable subset of patients, phosphorylates HS1 on Tyrosine (Y)397, resulting in its activation. This correlates with increased cytoskeletal functionality in terms of migration, adhesion and F-actin polymerization. In these patients, LYN is also activated on Y396 residue and its inhibition with the Tyrosine Kinase Inhibitor Dasatinib abrogates HS1-Y397 phosphorylation. This results in the reduction of HS1 activation along with that of VAV1 and ERK also in the presence of microenvironmental stimuli including BCR and CXCR4 stimulation. Interestingly, targeting LYN\\\\\\\/HS1 axis in vitro with Dasatinib leads to the concomitant reduction of the cytoskeletal activity, BCR signaling and cell survival in the selected subset of patients with activated LYN\\\\\\\/HS1. Moreover in a transplantable mouse model based on the EμTCL1 transgenic mouse, LYN\\\\\\\/HS1 signaling pharmacological inhibition interferes with CLL progression and lymphoid organ infiltration. These data suggest that the LYN\\\\\\\/HS1 axis marks distinct signaling profiles and cytoskeletal-related features that may represent valuable targets for cytoskeleton-targeted therapeutic intervention in a sizable fraction of CLL 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
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