1,721,011 research outputs found
BET inhibitors as potential anticancer agents
No full textIn human cancers, epigenetic alterations such as DNA methylation and histone modifications can play a key role in the dysregulation of gene expression leading to the silencing of tumor suppressor genes or to the overexpression of proto-oncogenes. The bromodomain (BRD) is the sole protein domain capable of recognizing the epsilon-N-acetylation of lysine histone residues, thus mediating epigenetic regulation of DNA transcription. Increasing preclinical evidence shows the BRD might be an interesting potential therapeutic target in human cancer. In particular, selective inhibitors of the bromodomain and extraterminal (BET) family are currently under clinical evaluation in early clinical trials. In this review, we discuss the function of the BRD proteins (and of the BET family proteins in particular) in cellular regulation and in carcinogenesis, and review the preclinical and early clinical evidence suggesting a putative role for BET inhibitors as a new class of anticancer drugs
Reporting of immune checkpoint inhibitor-associated myocarditis
No full textAs reported by the authors, the absence of concomitant cardiovascular or antidiabetic drugs in 75% of all cases could suggest that pre-existing cardiac disorders or cardiovascular risk factors would not predispose patients to develop immune checkpoint inhibitor-associated myocarditis. A more precise analysis of potential predisposing conditions could have been done by capturing comorbidities, such as we have done in a study that we have just finished and submitted for peer-review
Is there a role for dual PI3K/mTOR inhibitors for patients affected with lymphoma?
Full text linkThe activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti-cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical responses, including complete remissions (especially in follicular lymphoma patients), are also observed in the very few clinical studies performed in patients that are affected by relapsed/refractory lymphomas or chronic lymphocytic leukemia. In this review, we summarize the literature on dual PI3K/mTOR inhibitors focusing on the lymphoma setting, presenting both the three compounds still in clinical development and those with a clinical program stopped or put on hold
An overview on anti-tubulin agents for the treatment of lymphoma patients
Full text linkAnti-tubulin agents constitute a large class of compounds with broad activity both in solid tumors and hematologic malignancies, due to the interference with microtubule dynamics. Since microtubules play crucial roles in the regulation of the mitotic spindles, the interference with their function usually leads to a block in cell division with arrest at the metaphase/anaphase junction of mitosis, followed to apoptosis. This explains the reason why tubulin-binding agents (TBAs) proved to be extremely active in patients with cancer. Several anti-tubulin agents are indicated in the treatment of patients with lymphomas both alone and in combination chemotherapy regimens. The article reviews the literature on classic and more recent anti-tubulin agents, providing an insight into their mechanisms of action and their use in the treatment of lymphoma
Adverse event reporting with immune checkpoint inhibitors in older patients: Age subgroup disproportionality analysis in vigibase
Full text linkOlder patients represent a subpopulation of concern for immune checkpoint inhibitor (ICI) toxicity because of changes in the aging immune system and the potentially relevant clinical implications for their quality of life. Current evidence on ICI safety in older patients is conflicting. This study aimed to assess whether older patient age was a risk factor for increased reporting with ICIs as compared to other antineoplastic drugs in VigiBase, the World Health Organization database of suspected adverse drug reactions. Disproportionality analyses computing the reporting odds ratios (RORs) were performed by age subgroups (<18 years, 18–64 years, 65–74 years, 75–84 years and ≥85 years). There were not signals of disproportionate reporting with ICIs specifically detected in older patient age subgroups (≥65 years), which were not present in the disproportionality analysis over the entire dataset. A signal of disproportionate reporting with ICIs emerged for eye disorders only in the age subgroup 18–64 years (ROR 1.13, 95% confidence interval 1.05–1.23). These findings showed that adverse event reporting with ICIs in older patients was comparable to that in the overall patient cohort and prompt for the further investigation of eye disorders with ICIs to elucidating risk factors and defining management strategies
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
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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