Search results for "DISEASE PROGRESSION"
showing 10 items of 835 documents
The “Janus” Role of C/EBPs Family Members in Cancer Progression
2020
CCAAT/enhancer-binding proteins (C/EBPs) constitute a family of transcription factors composed of six members that are critical for normal cellular differentiation in a variety of tissues. They promote the expression of genes through interaction with their promoters. Moreover, they have a key role in regulating cellular proliferation through interaction with cell cycle proteins. C/EBPs are considered to be tumor suppressor factors due to their ability to arrest cell growth (contributing to the terminal differentiation of several cell types) and for their role in cellular response to DNA damage, nutrient deprivation, hypoxia, and genotoxic agents. However, C/EBPs can elicit completely opposi…
ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated…
2022
Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived mi…
T Cell-Specific Overexpression of TGFß1 Fails to Influence Atherosclerosis in ApoE-Deficient Mice
2013
Clinical data have indicated a negative correlation between plasma TGFß1 concentrations and the extent of atherosclerosis and have thus led to the hypothesis that the pleiotropic cytokine may have anti-atherogenic properties. T-cells are currently discussed to significantly participate in atherogenesis, but the precise role of adaptive immunity in atherogenesis remains to be elucidated. TGFß1 is known to strongly modulate the function of T-cells, however, inhibition of TGFß1 signalling in T-cells of atherosclerosis-prone knock-out mice failed to unequivocally clarify the role of the cytokine for the development of atherosclerosis. In the present study, we thus tried to specify the role of T…
TGF-β Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling
2004
Alterations of TGF-beta signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-depende…
Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection.
2017
Introduction RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active tuberculosis (TB) disease. Conversely, a positive response to heparin-binding haemagglutinin (HBHA)-based IGRAs, among TB-infected subjects, correlates with Mycobacterium tuberculosis (Mtb) containment and low risk of TB progression. The aim of this study was to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). Methods 49 subjects were prospectively enrolled: 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI). Whole blood and peripheral blood mononuclear cells were stimulated with HBHA and RD1 anti…
Genetic and epigenetic alterations as hallmarks of the intricate road to cancer.
2003
Despite the clonal origin of most tumors, their tremendous heterogeneity suggests that cancer progression springs from the combined forces of both genetic and epigenetic events, which produce variant clonal populations, together with the selective pressures of the microenvironment, which promote growth and, perhaps, dissemination of variants with a specific set of characteristics. Although the importance of genetic mutations in cancer has long been recognized, the role of epigenetic events has been suggested more recently. This review focuses on the genetic and epigenetic molecular mechanisms involved in cancer onset and progression, and discusses the possibility of new strategies in the de…
Intermediate Filament Diseases: Desminopathy
2008
Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases are associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial and bulba…
Hypoxia and anemia: effects on tumor biology and treatment resistance
2004
In locally advanced solid tumors, oxygen (O2) delivery is frequently reduced or even abolished. This is due to abnormalities of the tumor microvasculature, adverse diffusion geometries, and tumor-associated and/or therapy-induced anemia. Up to 50-60% of locally advanced solid tumors may exhibit hypoxic and/or anoxic tissue areas that are heterogeneously distributed within the tumor mass. In approximately 30% of pretreatment patients, a decreased O2 transport capacity of the blood as a result of tumor-associated anemia can greatly contribute to the development of tumor hypoxia. While normal tissues can compensate for this O2 deficiency status by a rise in blood flow rate, locally advanced tu…
MHC class II genes influence the susceptibility to chronic active hepatitis C
1997
Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects. Viral factors influence the disease course, but little is known about the importance of host factors.Frequencies of major histocompatibility complex (MHC) class I and class II antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods.DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p0.001). Homozygosity for this allel…
Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review
2018
OBJECTIVE: To summarize the best available evidence regarding the effectiveness of interventions for preventing frailty progression in older adults. INTRODUCTION: Frailty is an age-related state of decreased physiological reserves characterized by an increased risk of poor clinical outcomes. Evidence supporting the malleability of frailty, its prevention and treatment, has been presented. INCLUSION CRITERIA: The review considered studies on older adults aged 65 and over, explicitly identified as pre-frail or frail, who had been undergoing interventions focusing on the prevention of frailty progression. Participants selected on the basis of specific illness or with a terminal diagnosis were …