1,721,150 research outputs found
Inadequacy of tissue microarrays for the immunohistochemical detection of cancer stem cells in solid tumors: A viewpoint
No full textRpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment
No full text5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU
Multimodal approaches and tailored therapies for pain management: the trolley analgesic model
No full textChronic pain is described as a manifestation of real or potential tissue damage. It is identified as a perception influenced by the complex interactions of biological, psychological, and social factors. Different types of pain and their comorbidities dramatically affect patients' quality of life and their families. Due to diverse etiology and pathogenesis, pain management represents a controversial issue in clinical practice. In 1986, the WHO developed a three-step ladder model based on the use of analgesics for pain management according to pain intensity in a linear up or down movement. Despite its huge value for pain relief, this model has some limitations, and some controversies in the pharmacotherapy of pain management have arisen so far. To bypass these difficulties, the concept of WHO analgesic ladder has been contested and changed into a four bidirectional step model which postulates the use of the invasive procedures (neuromodulatory and neurosurgical procedures). Moreover, with the introduction of the neuromatrix theory for dealing the acute and the chronic pain, the WHO model was newly reinterpreted and changed into a platform analgesic model that includes multimodal pharmacological and alternative treatments applicable to all pain conditions, although excludes the precision therapies. Here, we summarize and revise these concepts in order to propose a new model termed "trolley analgesic model" that will allow adopting tailored therapies with dynamic multimodal approaches for pain management according to 1) the pain intensity, 2) the physiopathology of pain, 3) the complexity of symptoms, 4) the presence of comorbidity, and 5) the physiopathological factors and the social context
Reverse transcriptase inhibition potentiates target therapy in BRAF-mutant melanomas: an in vitro study
No full textBackground: BRAF + MEK inhibitors have become the standard of care for melanoma patients (approximately 50%) harboring BRAF-V600 mutations. However, drug resistance often impairs the efficacy of this combinatorial approach. Hence, the need to identify additional therapeutic approaches capable to control the development of drug resistance and to avoid disease relapse. Towards this goal, our group has been largely involved in the last years in the study of non-mutational mechanisms involved in the acquisition of drug resistance. For example, we reported that monoclonal antibodies targeting ErbB3 receptor are able to delay the emergence of resistance to target therapy in vitro and in vivo. More recently, we have also demonstrated that microRNAs are key players of resistance to target therapy in melanoma and that their targeting is able to restore drug sensitivity. Here, we have started to investigate whether reverse transcriptase inhibitors (RTIs) frequently used in the treatment of AIDS can act in combination with target therapy to fight the development of drug resistance.
Material and methods: Human melanoma cell lines, namely M14 and A375 harboring BRAF-V600E mutation have been treated with different concentration of either BRAFi and/or MEKi in the presence or not of the non-nucleoside RTI, i.e. SPV122. MTT and colony formation assays have been used to determine cell proliferation. Annexin V assay for apoptosis, cell cycle and mitochondrial membrane depolarization have been tested through FACS analyses. DNA double-strand breaks have been determined through Western Blot and Immunofluorescence analyses.
Results: Our present work has reported for the first time the capability of RTIs to mitigate drug resistance to target therapy in BRAF-mutant melanomas in vitro. We show that the novel non-nucleoside RTI, SPV122 synergizes with BRAF and MEK inhibitors to: 1) impair BRAF-mutant melanoma cell growth; 2) induce apoptosis; 3) block cell cycle progression and 4) delay the emergence of resistance in vitro. Mechanistically, we also show that this combination provokes DNA double-strand breaks, mitochondrial membrane depolarization and increased ROS levels.
Conclusions: Our in vitro results pave the way for the combinatorial use of RTi + BRAFi + MEKi as a novel therapeutic option for BRAF-mutant melanoma patients and warrant further investigation in in vivo models
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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