Search results for "Telomerase"

Role of the antioxidant defence system and telomerase in arsenic-induced genomic instability

2016

Arsenic (AS) is a reactive oxygen species (ROS)-inducer carcinogen, whose mode of action is still unclear. To defend against ROS, cells use enzymatic and non-enzymatic antioxidants, such as superoxide dismutase (SOD) and catalase. Failure of antioxidant systems (AXS) can result in dicentric chromosomes formation as well as telomere associations for the reduced activity of telomerase. In order to clarify the long-term effects of a past AS exposure, we evaluated the efficiency of the AXS and the telomerase activity in the progeny of arsenite-treated cells named ASO (arsenic shake-off) cells, previously obtained from arsenite-treated V79 cells and selected by shake-off. Despite SOD1 expression…

GSE4-loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage.

2021

© 2021 The Authors.

Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis

2018

Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium. E6 and E7 viral proteins are involved in the process of carcinogenesis. They interact with suppressors of oncogenesis, including p53 and Rb proteins. Th…

Acute depletion of telomerase components DKC1 and NOP10 induces oxidative stress and disrupts ribosomal biogenesis via NPM1 and activation of the P53…

2020

Mutations in DKC1, NOP10, and TINF2 genes, coding for proteins in telomerase and shelterin complexes, are responsible for diverse diseases known as telomeropathies and ribosomopathies, including dyskeratosis congenita (DC, ORPHA 1775). These genes contribute to the DC phenotype through mechanisms that are not completely understood. We previously demonstrated in models of DC that oxidative stress is an early and independent event that occurs prior to telomere shortening. To clarify the mechanisms that induce oxidative stress, we silenced genes DKC1, NOP10, and TINF2 with siRNA technology. With RNA array hybridisation, we found several altered pathways for each siRNA model. Afterwards, we ide…

Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity

2014

AbstractThe combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which wa…

Lack of TERT promoter mutations in melanomas with extensive regression

2015

Short telomeres in aggressive non-Hodgkin's lymphoma as a risk factor in lymphomagenesis

2007

Objective Telomeres cap chromosomal ends and help to maintain chromosomal integrity. Telomere shortening may result in chromosomal instability and, ultimately, malignant transformation of cells. It has not been systematically studied whether patients with malignancy have shortened telomeres in their normal, nontransformed cells, which might point to a preexisting disposition for chromosomal instability. Methods We designed an (age-) matched pair analysis that compared telomere length in nonmalignant peripheral leukocytes from previously untreated patients who recently developed an aggressive non-Hodgkin's lymphoma, with leukocytes from healthy individuals. Results Telomere lengths in B and …

Alternative lengthening of telomeres--an enhanced chromosomal instability in aggressive non-MYCN amplified and telomere elongated neuroblastomas

2010

Telomere length alterations are known to cause genomic instability and influence clinical course in several tumor types, but have been little investigated in neuroblastoma (NB), one of the most common childhood tumors. In the present study, telomere-dependent chromosomal instability and telomere length were determined in six NB cell lines and fifty tumor biopsies. The alternative lengthening of telomeres (ALT) pathway was assayed by scoring ALT-associated promyelocytic leukemia (PML) bodies (APBs). We found a reduced probability of overall survival for tumors with increased telomere length compared to cases with reduced or unchanged telomere length. In non-MYCN amplified tumors, a reduced o…

Different immunophenotypical apoptotic profiles characterise megakaryocytes of essential thrombocythaemia and primary myelofibrosis.

2009

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as “key-cells”. The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax,…

Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress.

2013

Abstract Background Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems. Negative emotionality has been shown to be associated with telomere shortening. Taken together these observations led us to hypothesize that mast cells activity could be involved in both negative emotionality and telomere shortening in mastocytosis. Objective To demonstrate a possible relationship between negative emotionality in mastocytosis and leukocyt…