1,720,965 research outputs found
Methylenetetrahydrofolate reductase C677T gene polymorphism and homocysteine levels in the Sardinian population
No full textGenome-wide single nucleotide polymorphysm analysis of lung cancer risk detects the KLF6 gen
No full textCancer Lett. 2007 Jun 28;251(2):311-6. Epub 2007 Jan 16.
Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene.
Spinola M, Leoni VP, Galvan A, Korsching E, Conti B, Pastorino U, Ravagnani F, Columbano A, Skaug V, Haugen A, Dragani TA.
SourceDepartment of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy.
Abstract
A genome-wide association analysis using the Affymetrix 100K SNP array was carried out in a case-control study of lung cancer. Allele frequencies were estimated initially in DNA pools. Significant differences in allele frequency detected in the SNP array analysis were first tested in the same DNA pools by pyrosequencing and then by individual genotyping. DNA pooling analysis identified rs10508266 SNP, located approximately 12.5kb from the 5'-end of the KLF6 gene, as a marker showing significant association with lung cancer risk. Since the SNP was in significant linkage disequilibrium with the KLF6 gene region, we analyzed an Italian population of 338 lung adenocarcinoma cases and 335 controls for the possible role of the reported functional rs3750861 SNP, located 15.6kb from the rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of 265 non small cell lung cancer cases, and 356 controls, however, did not confirm the association. In light of the reported functional involvement of the KLF6 gene in lung cancer and in other cancer types and to the functional nature of the rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk, although additional studies in large series are needed to confirm our findings and to elucidate the mechanism by which the KLF6 SNPs influence lung cancer risk.
PMID:17223258[PubMed - indexed for MEDLINE
THYROID HORMONE RECEPTORS DOWNREGULATION IS AN EARLY EVENT AND IS MAINTAINED ALLACROSS THE STEP-BY-STEP PROCESS OF HEPATOCARCINOGENESIS
No full textThyroid hormone receptors (THRs) mediate the pleiotropic activities of the hormone Triiodothyronine (T3) in many biological functions. These receptors are transcription factors expressed as different isoforms encoded by THRα and THRβ genes. Recently, several studies showed altered expression of THRs at mRNA and protein levels and identified somatic mutations of THR genes in several human cancers. Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Despite progress in understanding the molecular mechanism leading to hepatocarcinogenesis, HCC prognosis remains very poor. To investigate the molecular basis of hepatocarcinogenesis we employed a rat model of chemically-induced HCC (R-H model) in which it is possible to generate and analyze discrete lesions at different stages of progression. These lesions can be classified according to their positivity to two markers, glutathione S-transferase (GSTP) and Cytokeratin 19 (CK-19). In contrast with what has been described in human HCC, our studies have shown the complete absence of mutations in the coding regions of THRα and THRβ genes in rat HCCs. In these tumors, instead, we demonstrated a significant downregulation of the expression of the isoforms THRα1 and THRβ1. Moreover, downregulation of THRβ1 was present in very early preneoplastic lesions detected 10 weeks after initiation, suggesting that its downregulation is a very early event in the hepatocarcinogenesis process. Remarkably, THRβ1 downregulation was observed in preneoplastic lesions positive for CK-19, a marker of stem/progenitor cells, characterized by a more aggressive behaviour. Interestingly, we found an inverse relationship between degree of differentiation and THRβ1 expression in 5 human hepatoma cell lines.
In order to analyze the possible mechanism responsible for the decreased expression of THRβ1, we performed epigenetic studies. The results obtained, however, did not show a significant methylation of CpG islands in THRβ promoter. Since miRNAs are important regulators of gene expression, we are currently performing analysis aimed at assessing the role of this miRNAs in the aberrant expression of THRβ1. In particular, 5 identified microRNAs predicted by in silico analysis to bind to THRβ gene will be analyzed
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
Urinary 1H-NMR Metabolic Signature in Subjects Undergoing Colonoscopy for Colon Cancer Diagnosis
Full text linkMetabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests
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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