1,721,002 research outputs found
Letter: Does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks?
No full textCancer stem cells and therapeutic perspectives
No full textThe cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for increasing evolution toward malignancy.
Herein, we discuss the evidences reported in literature on existence of cancer stem cells in several tumors and mechanisms of the extrinsic and intrinsic circuitry controlling stem cell fate as well as their possible connections to cancer. In particular, the review will focus on recent results on conserved Polycomb Group (PcG) gene family, an epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. There are two distinct multiprotein PcG complexes identified, Polycomb repressive complex (PRC) 1 and 2. The fact that either PRC1 Bmil than PRC2 SU(Z)12 components are implicated in self-renewal stem cells and up-regulated in several kind of human cancer, confirm the importance of (dc)regulation of the PcG genes in cancer and stem cell biology. Moreover, Bmil and SU(Z)12 are downstream target of Sonic hedgehog (Shh) and Writ signaling respectively, providing for a connection between epigenetic change regulators (PcG) and developmental-signaling pathways.
Finally, potential therapies using inhibitors acting on cancer stem cell population such as cyclopamine, an inhibitor of hedgehog signalling, 6-bromoindirubin-3'-oxime (BIO) which acts on GSK3 and inhibitors of beta-catenin signaling such as exisulind and the tyrosine-kinase inhibitor ST1571/Gleevac/imatinib will also discuss
Letter: Do interferon lambda 3 polymorphisms predict the outcome of interferon therapy in hepatitis B infection? Authors' reply
No full textSystematic review with meta-analysis : do interferon lambda 3 polymorphisms predict the outcome of interferon-therapy in hepatitis B infection?
No full textSummary Background Interferon lambda 3 (IFN-λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon (PegIFN)-based therapy. Whether this holds true for hepatitis B virus (HBV) infection is matter of controversy. Aim To review the association between host genomics and spontaneous or interferon-induced clearance of HBV with specific reference to the recently identified interleukin 28B gene now renamed IFN-λ3. Methods A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts using free text words and combinations of the following terms 'IL28B', 'IFN lambda', 'genomics', 'hepatitis B virus', 'interferon' 'GWAS', 'treatment', 'SNPs', 'HLA', 'polymorphisms'. Results Genome-wide association studies convincingly demonstrated an association between SNPs in the HLA locus and spontaneous resolution of HBV infection in subgroups of Asian patients, yet no information is available for Caucasians. The preliminary observations of an association between IFN-λ3 SNP and virological and serological responses to IFN in both HBeAg-positive and -negative patients could not be replicated by subsequent studies. Yet, majority of studies performed so far suffer several limitations in terms of sample size, selection of the patients, endpoints of therapy, treatment strategies and duration of follow-up. Conclusions While host genetics is associated with an increased likelihood of spontaneous clearance of HBV among genotype B/C patients, the relationship between IFN-λ3 polymorphisms and response to IFN has not been confirmed. Further studies in large cohorts of homogeneous patients are required, before this genetic test can be recommended in clinical practice
Studies of IL28B genotype and response to peginterferon in chronic hepatitis B should be stratified by HBV genotype
No full textGenetic testing for hepatocellular carcinoma: An ambitious goal still to achieve
No full textBackground & Aims: A single nucleotide polymorphism
61⁄G (rs4444903) in the epidermal growth factor (EGF) gene has
been associated, in two case–control studies, with hepatocellular
carcinoma (HCC). We tested associations between demographic, clinical,
and genetic data and development of HCC, and developed a simple
predictive model in a cohort of patients with chronic hepatitis C
and advanced fibrosis.
Methods: Black and white subjects from the Hepatitis C Antiviral
Long-term Treatment against Cirrhosis (HALT-C) trial (n = 816) were
followed up prospectively for development of a definite or presumed
case of HCC for a median time period of 6.1 years. We used the Cox
proportional hazards regression model to determine the hazard ratio
for risk of HCC and to develop prediction models.
Results: Subjects with EGF genotype G/G had a higher adjusted risk
for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence
interval, 1.05–4.23; P = .03). After adjusting for EGF genotype,
blacks had no increased risk of HCC risk compared with
whites. Higher serum levels of EGF were observed among subjects
with at least one G allele (P = .08); the subset of subjects with EGF
G/G genotype and above-median serum levels of EGF had the highest
risk of HCC. We developed a simple prediction model that included
the EGF genotype to identify patients at low, intermediate, and high
risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%,
and 26%, respectively.
Conclusions: We associated the EGF genotype G/G with increased
risk for HCC; differences in its frequency among black and white subjects
might account for differences in HCC incidence between these
groups. We developed a model that incorporates EGF genotype and
demographic and clinical variables to identify patients at low, intermediate,
and high risk for HCC
Allelic inhibition of displacement activity : a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms
No full textRecently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan® SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs
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
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