1,720,991 research outputs found
Carcinogenesis of Cholangiocarcinoma
No full textDaily clinical practice and recent molecular studies have clearly shown that primitive liver tumours are an extremely heterogeneous group of disease without a steotyped phenotype or molecular signature. Accumulated evidence strongly supports the notion that such heterogeneity stems from the existence within the liver and along the biliary tree of distinct cells of origin susceptible to diffrent risk of factos and liver injuries. Although this new scenario has yet to be fully elucidated, a new physio-pathological classification of primitive liver tumour subtypes based on different cells of origin has been rpoposed. This new classification not only responds to the urgent need to provide homogeneous diagnostic, prognostic and therapeutic categories for these malignancies, but also seems more coherent with the current epidemiological data and risk factors associated with such diseases. The present chapter summarises current knowledge of the putative different cell types that may serve as cells of origin in primitive liver tumours. It also discusses the proposed new physio-pathological classification of different tumour subtypes based on these cells and it association with the current known risk fqactors for these diseases
Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies
Full text linkCholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies.Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy.Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease.A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease
Antitumoral Efficacy of Two Turmeric Extracts According to Different Extraction Methods in Hepatocellular Carcinoma Cell Lines
Full text linkCurcuminoids, bioactive molecules contained in turmeric, have been reported to exert anticancer effects in several human cancers, including hepatocellular carcinoma (HCC). However, the extraction method can significantly affect the structural characteristics of curcuminoids and their biological properties. On this basis, in the present study we investigated the content of curcuminoids and the anticancer activity of two turmeric powders extracted according two different methodologies: solvent extraction with ethyl acetate vs an ancient Indian extraction method of boiling of rhizomes in water followed by dehydration at the sun. Results obtained showed that extraction with ethyl acetate resulted in a significant recovery of curcuminoids and anticancer activity both in terms of cell cytotoxicity and migration/invasiveness inhibition in HCC cell lines, compared to common Indian practice. Overall these findings suggest that turmeric powders could have different efficacy, depending on the extraction method. This aspect should be taken into account when choosing the best product to be employed in the prevention and treatment of human diseases, including cancer
Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link
Full text linkTo date the true global incidence of intrahepatic cholangiocarcinoma (iCCA) and the underlying risk factors remain to be fully defined, in particular, the role of occupational and environmental factors. Currently, the putative role of asbestos exposure as a risk factor for iCCA is gaining increased attention in the international scientific community and agencies. In this commentary we review and integrate available epidemiological and mechanistic evidences that support a potential role of asbestos exposure in iCCA etiology
Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) ranks fifth in frequency worldwide amongst all human cancers causing one million deaths annually. Despite many promising treatment options, long-term prognosis remains dismal for the majority of patients who develop recurrence or present with advanced disease. Notch signaling is an evolutionarily conserved pathway crucial for the development and homeostasis of many organs including liver. Herein we showed that aberrant Notch1 is linked to HCC development, tumor recurrence and invasion, which might be mediated, at least in part, through the Notch1-E-Cadherin pathway. Collectively, these findings suggest that targeting Notch1 has important therapeutic value in hepatocellular carcinoma. In this regard, comparative analysis of the secretome of HepG2 and HepG2 Notch1 depleted cells identified novel secreted proteins related to Notch1 expression. Soluble E-Cadherin (sE-Cad) and Thrombospondin-1 (Thbs1) were further validated in human serum as potential biomarkers to predict response to Notch1 inhibitors for a tailored individualized therapy
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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