1,720,979 research outputs found
Valutazione del profilo di espressione genica nello studio della leucemia linfatica cronica
Full text linkThe dark side of histones: genomic organization and role of oncohistones in cancer
Full text linkThe oncogenic role of histone mutations is one of the most relevant discovery in cancer epigenetics. Recurrent mutations targeting histone genes have been described in pediatric brain tumors, chondroblastoma, giant cell tumor of bone and other tumor types. The demonstration that mutant histones can be oncogenic and drive the tumorigenesis in pediatric tumors, led to the coining of the term "oncohistones." The first identified histone mutations were localized at or near residues normally targeted by post-translational modifications (PTMs) in the histone N-terminal tails and suggested a possible interference with histone PTMs regulation and reading
Fat and hepatocellular carcinoma
Full text linkObesity and diabetes are associated with the onset of hepatocellular carcinoma (HCC). These two illnesses correlate also with the development of non-alcoholic fatty liver disease (NAFLD). Currently, NAFL is considered the leading form of chronic liver disease in the Western industrialized countries. Insulin resistance is the common pathogenic factor among these three pathologies. NAFL is characterized by fat accumulation in the liver that involves greater than 5% of the liver parenchyma with no evidence of hepatocyte injury. However, NAFL may progress toward non-alcoholic steatohepatitis that in turn may lead to advanced fibrosis, cirrhosis and HCC. It is alarming that NAFLD related HCC has been, at present, considered as a growing burden worldwide, and its prevalence is tending to further increase together with the increasing incidence of obesity and diabetes. Worthy of note is that in the presence of chronic accumulation of fat in the liver it has been reported the emergence of HCC during chronic liver disease in absence of liver cirrhosis, usually the major risk factor for the development of HCC. Thus, in the future NAFLD related HCCs will place a growing strain on health-care systems from the need for their management. Unfortunately, most of the NAFLD related HCC patients are diagnosed at advanced stages and are characterized by a poor prognosis, because they are ineligible to radical treatments. Thus, it is urgent to boost up new screening policies to make early diagnoses, as well as to develop preventive-therapeutic strategies
Myeloid/T-cell acute lymphoblastic leukemia in children and adults
No full textUntil recently, few molecular aberrations were recognized in T-cell acute lymphoblastic leukemia (T-ALL) and they were restricted to aberrations involving the T-cell receptor (TCR). The introduction of powerful technologies has allowed to identify novel rearrangements. In this context, we have performed a gene expression profiling analysis on a relatively large cohort (n=69) of adult patients with a diagnosis of T-ALL. By unsupervised clustering, we identified 5 subgroups. Of these, one branch included 7 patients (10%) whose gene expression profile resembled that of AML. These cases were characterized by the overexpression of a large set of myeloid-related genes, as well as of miR-223. Finally, these patients appear to have an unfavorable clinical course. This newly identified subset of T-ALL cases partly resembles the so-called ETP (early T-precursor) pediatric subgroup: both age groups have in fact a peculiar gene expression profile, an unfavorable outcome and an incidence of about 10%
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
Protein Kinase Gene Expression Profiling and In Vitro Functional Experiments Identify Novel Potential Therapeutic Targets in Adult Acute Lymphoblastic Leukemia
No full textBACKGROUND: Despite recent improvements in the treatment of acute lymphoblastic leukemia (ALL), adult patients still have an overall poor outcome. The future of ALL management relies on the introduction of novel targeted therapies. The authors sought to assess if protein kinases (PKs), frequently deregulated in cancer, show an altered expression pattern and can be considered as suitable therapeutic targets in adult ALL. METHODS: The authors studied the PK gene expression profile by oligonucleotide arrays in 133 adult ALL samples at the onset of the disease and subsequently performed in vitro experiments to evaluate the sensitivity to first- and second-generation PK inhibitors of a set of ALL cell lines, as well as of primary ALL cells. RESULTS: The study documents a distinctive PK signature for different adult ALL subgroups; the PKs identified include several tyrosine kinase (TK) genes, especially in E2A/PBX+ B-lineage ALL (B-ALL), B-ALL without known molecular abnormalities, and T-lineage ALL. Consistently, cell lines and primary samples belonging to these groups proved susceptible to TK inhibitors. CONCLUSIONS: These results indicate that second-generation TK inhibitors may be effective in ALL subsets other than BCR/ABL+ B-ALL and provide the rationale for testing the impact of the newly developed TK inhibitors in the management of adult ALL patients. Cancer 2010;116:3426-37. (C) 2010 American Cancer Society
Characterization of B- and T-Lineage Acute Lymphoblastic Leukemia by Integrated Analysis of MicroRNA and mRNA Expression Profiles
No full textAcute lymphoblastic leukemia (ALL) is an heterogeneous disease comprising several subentities that differ for both immunophenotypic and molecular characteristics. Over the years, the biological understanding of this neoplasm has largely increased. Gene expression profiling has allowed to identify specific signatures for the different ALL subsets and permitted the identification of pathways deregulated by a given lesion. MicroRNAs (miRNAs) are small noncoding RNAs, which play a pivotal role in several cellular functions. In this study, we investigated miRNAs expression profiles in a series of adult ALL cases by microarray analysis. Unsupervised hierarchical clustering largely recapitulated ALL subgroups. Furthermore, we identified miR-148, miR-151, and miR-424 as discriminative of T-lineage versus B-lineage ALL; ANOVA highlighted a set of six miRNAs-namely miR-425-5p, miR-191, miR-146b, miR-128, miR-629, and miR-126-that can discriminate B-lineage ALL subgroups harboring specific molecular lesions. These results were confirmed and extended by quantitative-PCR on a further cohort of cases. Finally, we used Pearson correlation analysis to combine miRNA and gene expression profiles. The distribution of correlation coefficients generated by comparing the expression of every miRNA/gene pair in our data set shows enrichment of both positively and negatively correlated pairs over background distributions obtained using randomized data. Moreover, a clear enrichment for predicted miRNA:target pairs is observed at negative correlation coefficient intervals. Signal-to-noise ratio highlighted several miRNA/gene pairs with a possible role in the disease. In fact, gene set enrichment analysis of genes composing the selected miRNA/gene pairs displays over-representation of functional categories related to cancer and cell-cycle regulation. (C) 2009 Wiley-Liss, Inc
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