1,720,972 research outputs found
Cellule immunocompetenti associate alla mucosa nella patologia della cervice uterina dei soggetti HIV-infetti
No full textMKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer
Full text link: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients
Beneficial effects of SR140333, a novel substance P antagonist, in a rat model of experimental colitis
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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
Tumor Regression Grade After Neoadjuvant Chemoradiation and Surgery for Low Rectal Cancer Evaluated by Multiple Correspondence Analysis: Ten Years as Minimum Follow-up
No full textThe tumor regression grade (TRG) role was investigated by multiple correspondence analysis (MCA) in 174 low rectal cancer patients undergone neoadjuvant chemoradiation and radical surgery, with a minimum follow-up of 10 years. The TRG 1 and 2 showed better survival than TRG 4 and 5 subgroups. MCA allocated TRG 3 together with other prognostic variables better than multivariate analysis. Background: The role of Mandard's tumor regression grade (TRG) classification is still controversial in defining the prognostic role of patients who have undergone neoadjuvant chemoradiation (CRT) and total mesorectal excision. The present study evaluated multiple correspondence analysis (MCA) as a tool to better cluster variables, including TRG, for a homogeneous prognosis. Patients and Methods: A total of 174 patients with a minimum follow-up period of 10 years were stratified into 2 groups: group A (TRG 1-3) and group B (TRG 4-5) using Mandard's classification. Overall survival and disease-free survival were analyzed using univariate and multivariate analysis. Subsequently, MCA was used to analyze TRG plus the other prognostic variables. Results: The overall response to CRT was 55.7%, including 13.2% with a pathologic complete response. TRG group A correlated strictly with pN status (P =.0001) and had better overall and disease-free survival than group B (85.1% and 75.6% vs. 71.1% and 67.3%; P =.06 and P =.04, respectively). The TRG 3 subset (about one third of our series) showed prognostically heterogeneous behavior. In addition to multivariate analysis, MCA separated TRG 1 and TRG 2 versus TRG 4 and TRG 5 well and also allocated TRG 3 patients close to the unfavorable prognostic variables. Conclusion: TRG classification should be used in all pathologic reports after neoadjuvant CRT and radical surgery to enrich the prognostic profile of patients with an intermediate risk of relapse and to identify patients eligible for more conservative treatment. Thus, MCA could provide added value
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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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