Search results for "epigenetic"
showing 10 items of 632 documents
Nutrigenetics, nutrigenomics and phenotypic outcomes of dietary low-dose alcohol consumption in the suppression and induction of cancer development: …
2020
It is known that the intake of alcoholic beverages may impair genetic and epigenetic regulatory events with consequent crucial effects on cell phenotypes and that its association with selected genotypes can lead to a different risk of cancer in the population. The aim of this review is to pick up selected studies on this topic and recapitulate some of the biochemical and nutrigenetic/nutrigenomic aspects involved in the impact of dietary low-dose alcohol consumption on the switching-on or -off of tumorigenic pathways. These include i) the existence of predisposing or protective human genotypes and the relationship between dietary compounds and alcohol in the promotion or inhibition of carci…
The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to …
2022
Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in melanoma cells bearing BRAF V600E oncogenic mutation. Our results indicate both ITF2357 and SAHA dose-dependently reduce the viability of BRAF-mutated SK-MEL-28 and A375 melanoma cells. The comparison of IC50 values revealed that ITF2357 was much more effective than SAHA. Interestingly, both inhibitors markedly decreased oncogenic BRAF protein expression levels, ITF2357 being the most effective compound. Moreover, the BRAF decrease induced by ITF23…
Circulating Histones and Nucleosomes as Biomarkers in Sepsis and Septic Shock
2016
Sepsis, severe sepsis, and septic shock are among the leading causes of death worldwide and their incidence is constantly increasing. Despite early intervention in intensive care units (ICUs) mortality remains high. There is great interest in understanding the genetics and epigenetics of the host in response to infection because of two reasons: the peculiarities of each patient, and the unclear associations identified between genetic polymorphisms and susceptibility to sepsis. In addition, chromatin remodeling and epigenetic changes occur in crucial genes involved in the inflammatory response and also in the immunosuppression found in sepsis. The early and accurate diagnosis of sepsis is a …
Study of the epi- / genomic dysregulation of breast cancer in women under 35 years and evaluation of cellular models
2019
El cáncer de mama tiene la tasa de incidencia más alta de todos los cánceres en mujeres en todo el mundo. Este cáncer suele tener un excelente pronóstico con un 80% de supervivencia. Aunque las mujeres menores de 35 años representan el 3-4% del total de casos diagnosticados, sus tumores se caracterizan por ser más grandes, más proliferativos y con una mayor representación de subtipos más agresivos y de peor pronóstico. Las transformaciones neoplásicas se asocian con alteraciones en la metilación del ADN, que incluyen tanto la hipometilación global como la hipermetilación específica. Por otro lado, los miRNAs son pequeñas moléculas no codificantes con un papel importante en la regulación de …
Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib
2007
Background. Most chronic myeloid leukemia patients who receive imatinib as first line-terapy will obtain, after 12 months treatment, complete cytogenetic and molecular response . However several cases will not achieve molecular response, but their innate mechanism(s) of resistance remain poorly understood. We tried to explore the molecular events involved in innate resistance in CML. Study design. Five patients who were molecular “non responder” and seven “major” responder were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure (MTP), Significance Analysis of Microarrays (SAM), Empirical Bayes Analysis of Microarrays (EBAM), False Discovery Rate (…
Do epigenetic clocks provide explanations for sex differences in lifespan? A cross-sectional twin study
2021
ABSTRACTBackgroundThe sex gap in life expectancy has been narrowing in Finland over the past four to five decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging that predict lifespan. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.MethodsOur sample included same-sex younger and older twins (21-42-y, n = 1110; 50-76-y, n = 763) and younger opposite-sex twins (21-30-y, n = 302). Blood-based DNA methylation (DNAm) was used to compute epigenetic age acceleration by four epigenetic clocks as a measure of biological aging. Path modelling w…
Targeting epigenetic alterations in cancer stem cells
2022
Oncogenes or tumor suppressor genes are rarely mutated in several pediatric tumors and some early stage adult cancers. This suggests that an aberrant epigenetic reprogramming may crucially affect the tumorigenesis of these tumors. Compelling evidence support the hypothesis that cancer stem cells (CSCs), a cell subpopulation within the tumor bulk characterized by self-renewal capacity, metastatic potential and chemo-resistance, may derive from normal stem cells (NSCs) upon an epigenetic deregulation. Thus, a better understanding of the specific epigenetic alterations driving the transformation from NSCs into CSCs may help to identify efficacious treatments to target this aggressive subpopula…
Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance.
2016
Cancer stem cells (CSCs) have been identified in several solid malignancies and are now emerging as a plausible target for drug discovery. Beside the questionable existence of CSCs specific markers, the expression of CD133 was reported to be responsible for conferring CSC aggressiveness. Here, we identified two G-rich sequences localized within the introns 3 and 7 of the CD133 gene able to form G-quadruplex (G4) structures, bound and stabilized by small molecules. We further showed that treatment of patient-derived colon CSCs with G4-interacting agents triggers alternative splicing that dramatically impairs the expression of CD133. Interestingly, this is strongly associated with a loss of C…
Meeting the Challenge of Targeting Cancer Stem Cells
2019
Notwithstanding cancer patients benefit from a plethora of therapeutic alternatives, drug resistance remains a critical hurdle. Indeed, the high mortality rate is associated with metastatic disease, which is mostly incurable due to the refractoriness of metastatic cells to current treatments. Increasing data demonstrate that tumors contain a small subpopulation of cancer stem cells (CSCs) able to establish primary tumor and metastasis. CSCs are endowed with multiple treatment resistance capabilities comprising a highly efficient DNA damage repair machinery, the activation of survival pathways, enhanced cellular plasticity, immune evasion and the adaptation to a hostile microenvironment. Due…
MLML2R
2019
R package for maximum likelihood estimation of DNA methylation and hydroxymethylation proportions.