1,720,977 research outputs found
Clinico-pathological and biological characterization of a cohort of 140 patients affected by relapsed/refractory Diffuse Large B Cell Lymphoma: looking for prognostic factors.
Get PDFDiffuse Large B Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although most patients respond efficaciously to the first line therapy, about 30-40% are primary refractory or present relapse after an initial response, constituting a group with poor prognosis. Many efforts have been made to find prognostic factors, able to identify high-risk patients; however, the currently available scores are often inadequate to this purpose.
In this study we compared the clinical and biological features of a cohort of relapsed/refractory patients (R/R, n = 140), with those a cohort of patients not affected by relapse after at least 5 years of follow-up (controls, n = 45). We divided the R/R patients according to the time of relapse in three subgroups – refractory (characterized by persistence of disease or recurrence within 9 months from diagnosis, n = 72), early relapsed (with recurrence of disease within 10 and 24 months, n = 35) and late relapsed (with recurrence of disease beyond 24 months from diagnosis, n = 33). We also performed gene expression profiling (GEP) analysis on a subgroup of patients, aiming at recognizing differentially expressed genes; through this analysis, we identified the B1 subunit of NADH:Ubiquinone Oxidoreductase (NDUFB1) as a gene with enhanced expression in R/R patients. We further verified NDUFB1 expression and protein levels in DLBCL cell lines and performed ad hoc immunohistochemistry on patients’ samples.
Our results show that the R/R subgroups differentiate in terms of clinical and biological features, but also in terms of outcomes, with an inferior post-relapse overall survival (OS) for refractory patients. In the whole R/R cohort, we confirmed the prognostic value of the International Prognostic Index (IPI) and the Revised-IPI (R-IPI), even when calculated at relapse, and of well-known adverse factors (B-symptoms, advanced stage, lactate dehydrogenase (LDH) increase, bulky disease, extra-nodal involvement), but we also found a novel correlation between male sex and inferior progression-free survival (PFS) and OS, and between inflammatory indexes as neutrophils/lymphocytes (N/L) ratio, Systemic Immune-Inflammation Index (SII) and C-reactive protein value/albumin value (CAR) and outcome. As for immunohistochemistry data, high Ki67 values correlated with reduced OS, while NDUFB1 overexpression caused a PFS disadvantage. We detected a trend of more frequent altered expression of P53 in the R/R cohort, in which all patients with enhanced expression were refractory, while all cases with a “null” phenotype belonged to the late relapsed group. In the second line setting, 23% of patients underwent autologous stem cell transplant (ASCT); transplanted patients had a post-relapse OS significantly superior to patients who did not receive transplant.
Globally, we assessed the importance of the time of relapse for prognosis prediction, and identified some subgroup-specific features and variables impacting on outcome. These results, if validated in larger cohorts could contribute to the formulation of new prognostic scores, improving risk-stratification in DLBCL
Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia
Get PDF: Lymphoplasmacytic lymphoma (LPL) is a rare subtype of B cell-derived non-Hodgkin lymphoma characterized by the abnormal growth of transformed clonal lymphoplasmacytes and plasma cells. This tumor almost always displays the capability of secreting large amounts of monoclonal immunoglobulins (Ig) of the M class (Waldenström Macroglobulinemia, WM). The clinical manifestations of WM/LPL may range from an asymptomatic condition to a lymphoma-type disease or may be dominated by IgM paraprotein-related symptoms. Despite the substantial progresses achieved over the last years in the therapy of LPL/WM, this lymphoma is still almost invariably incurable and exhibits a propensity towards development of refractoriness to therapy. Patients who have progressive disease are often of difficult clinical management and novel effective treatments are eagerly awaited. In this review, we will describe the essential clinical and pathobiological features of LPL/WM. We will also analyze some key aspects about the current knowledge on the mechanisms of drug resistance in this disease, by concisely focusing on conventional drugs, monoclonal antibodies and novel agents, chiefly Bruton's Tyrosine Kinase (BTK) inhibitors. The implications of molecular lesions as predictors of response or as a warning for the development of therapy resistance will be highlighted
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
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
Splenic marginal zone lymphoma with a de novo t(8;14)(q24;q32) and a prolymphocytoid evolution responsive to rituximab-bendamustine
No full textA case of “double hit” mantle cell lymphoma carrying CCND1 and MYC translocations relapsed/refractory to rituximab bendamustine cytarabine (R-BAC) and ibrutinib
No full textDispelling 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
- …
