1,720,982 research outputs found
Interleukin-10 polymorphisms, cancer susceptibility and prognosis
No full textInterleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic functions and may have both tumour-promoting and -inhibiting properties. A large number of polymorphisms (primarily single nucleotide polymorphisms (SNPs)) have been identified in the IL-10 gene promoter. Convincing evidence that certain of these polymorphisms are associated with differential expression of IL-10 in vitro and in some cases in vivo has been obtained and a number of studies have investigated associations between IL-10 polymorphisms and cancer susceptibility/prognosis. The results from 22 studies in 13 different malignancies are reviewed. In 17 of these studies, positive associations between IL-10 genotype or haplotype and disease susceptibility and/or progression were reported. In some of these cancers genotypes associated with low IL-10 expression were a risk factor for disease or disease progression, while in others genotypes associated with high IL-10 expression were a risk factor. Published findings in breast cancer are as yet conflicting. Most, but not all of the studies reviewed are based on small sample sizes and a limited number of IL-10 polymorphisms. However, the preliminary data obtained thus far indicate that larger studies are required in a number of cancers, in order to confirm initial results, extend studies to include more detailed genotype/haplotype analysis and combine genotype and gene expression studies in the same subjects. Such studies will contribute significantly to our understanding of the biological role of IL-10 in cancer development
VEGF polymorphisms and severity of atherosclerosis
No full textIntroduction: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and neovascularisation has been shown to be important in atherosclerotic plaque development. There is some disagreement as to whether VEGF acts as a pro-atherosclerotic or anti-atherosclerotic factor. In the present study we have sought to clarify this by determining genotypes and haplotypes for three reportedly functional VEGF SNPs in a large series of well documented coronary atherosclerosis patients.Methods: VEGF –2578, –1154, and –634 single nucleotide polymorphisms were genotyped in 984 subjects from the Southampton Atherosclerosis Study, using the 5' nuclease assay for allelic discrimination (TaqMan).Results: VEGF –2578 genotypes showed a significantly different distribution in patients without myocardial infarction when stratified according to number of diseased arteries. VEGF –2578 was also associated with mean number of stenotic segments in the same patient group. The AA genotype was a risk factor and CC was protective. These associations were significant before and after adjustment for classic risk factors, and were reflected in associations between VEGF haplotypes and the number of diseased arteries and stenotic segments. As VEGF –2578 CC has been provisionally shown to be associated with higher VEGF expression than the AA genotype, these results are consistent with a protective effect for VEGF in atherosclerosis development. Some changes in VEGF –1154 genotype frequencies were also detected, but no significant associations were detected for any one particular genotype.Conclusions: This study provides preliminary evidence that VEGF polymorphism is associated with development of atherosclerosis, possibly via regulation of VEGF expression, supporting a protective effect for VEGF in atherosclerosis. These results require replication in an independent study group, combined with study of additional candidate polymorphisms in the VEGF gene
ICAM-1 polymorphisms and development of cutaneous malignant melanoma
No full textTumour growth in cutaneous malignant melanoma (CMM) is mediated by cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression is associated with increasing Breslow thickness of vertical growth-phase tumours and, in patients with stage 1 disease, may be associated with disease free and patient survival. In this study we have investigated whether two single nucleotide polymorphisms (SNPs) in the ICAM-1 gene encoding amino acid substitutions in codons 241 and 469 of the expressed ICAM-1 molecule are associated with susceptibility to and markers of prognosis (including tumour Breslow thickness) in CMM. A total of 164 CMM patients and 264 cancer-free controls were genotyped for these SNPs by the 5' nuclease assay for allelic discrimination (TaqMan). No genotypes showed any significant associations with CMM susceptibility, although there was a non-significant increase in frequency of the ICAM-1 469 AA genotype among CMM patients vs. controls (38.4% vs. 29.9%; P = 0.11). However, the ICAM-1 241 GG genotype was significantly decreased in frequency among patients with primary invasive tumours of greater Breslow thickness (72.5% vs. 91.2%; P = 0.013; OR = 0.25 (0.072-0.85)). These results provide no evidence for a role for the ICAM-1 codon 241 and 469 SNPs in determining susceptibility to CMM, but provide preliminary evidence that the role of ICAM-1 polymorphism in modulating tumour growth in CMM requires further investigation in a larger study group
Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma
No full textVascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR. Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected (association, rho = 0.488-0.965), but not between these SNPs and SNP +936 (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed. However, the VEGF -1154 AA genotype and -2578, -1154, +405 CAC haplotype were both significantly associated with less advanced (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was associated with thinner primary vertical growth phase tumours (P = 0.002), while VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These preliminary results indicate that VEGF genotype may influence tumour growth in CMM, possibly via the effects of differential VEGF expression on tumour angiogenesis
HLA and eye disease: a synopsis
No full textHuman leukocyte antigen (HLA) gene products have been implicated in the pathogenesis of an increasing number of eye diseases, mainly inflammatory in nature. This perspective reviews the current hypotheses for why HLA polymorphisms are associated with specific eye diseases. Statistical problems in studies involving HLA associations are discussed, and possible solutions outlined. The relevance of HLA testing in routine ophthalmic practice, its practical and cost implications is also assessed
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
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