63 research outputs found
Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction.
Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered an important risk factor for acute myocardial infarction in aged patients (55-80 years old). On the other hand, in spite of a not different genotypic and allelic distribution for the Leiden FV G1691A mutation, the presence of one or both the two polymorphisms is significantly higher among cases than in controls. In conclusion, our data suggest that FII G20210A and/or Leiden FV might be involved as risk factor for arterial disorders in about 5% of old subjects, justifying the opportunity of a genetic screening and an eventual preventive treatment, in particular in old subjects in which other and major risk factors, as hypertension and atherosclerosis, are detected
Cytokine serum profile in a group of Sicilian Nonagenarians
The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-gamma) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effector's mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile
Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.
The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-α) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-γ) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-α -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-γ, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-γ and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; Pc, 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease
Genetics of longevity. Data from the studies on Sicilian centenarians
The demographic and social changes of the past decades have determined improvements in public health and
longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their
attention on centenarians as optimal model to address the biological mechanisms of âsuccessful and unsuccessful
ageingâ. They are equipped to reach the extreme limits of human life span and, most importantly, to show
relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such
as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background
and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based
on results obtained, we suggest longevity as the result of an optimal performance of immune system and an overexpression
of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known,
genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity.
Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a
global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic
changes in ageing and longevity
Radiobiological Outcomes, Microdosimetric Evaluations and Monte Carlo Predictions in Eye Proton Therapy
CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves
Role of prothrombotic polymorphisms in successful or unsuccessful aging
The study of the genetic profile of
centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy
and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of
selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation
enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these
individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this
study we analyze the frequencies of Leiden Factor V polymorphism (G1691A), and G20210A of prothrombin (FII) in three cohorts of subjects: patients
with Alzheimer\u2019s disease (unsuccessful aging), nonagenarians (successful aging) and young healthy controls, to assess whether allelic variants associated to the modification of haemostatic system function,
may play a role in the protection or susceptibility to Alzheimer disease, as well as to reach a successful aging. No significant differences were observed in the frequencies of the three groups studied. These results indicate that the presence or absence of the gene
variants examined did not influence the achievement of advanced age and are not risk factors for Alzheimer\u2019s disease. The state of hypercoagulability and the
possession of these risk alleles appear to be compatible with the achievement of longevity and are not implied as risk factors in Alzheimer disease
development
Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish
Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryosâ and larvaeâs exposure to radiotherapy treatments
âOmicsâ of HER2-Positive Breast Cancer
HER2/neu amplification/overexpression is the only somatic mutation widely considered to be a marker of
disease outcome and response to treatment in breast cancer. Pathologists have made large efforts to achieve
accuracy in characterizing HER2/neu status. The introduction of transtuzumab contributed to development of
additional measures to identify sensitive and resistant subclasses of HER2/neu-positive tumors. In this article,
we describe the latest advances in HER2/neu status diagnostic assessment and the most relevant research
emerging from ââOmicsââ (genomics, epigenetics, transcriptomics, and proteomics) studies on HER2/neu-positive
breast cancer. A large quantity of biomarkers from different studies highlighted HER2/neu-positive specific
proliferation, cell cycle arrest, and apoptosis mechanisms, as well as immunological and metabolic behavior.
Major driver genes of tumor progression have had a candidate status (GRB7, MYC, CCND1, EGFR, etc.), even
though the main role for HER2/neu is largely recognized. Nonetheless, existing omics data and HER2/neupositive
molecular profiles seem to suggest that few proteogenomic alterations in HER2, EGFR, and PI3K
networks could significantly affect the effectiveness of transtuzumab. The systematic search of molecular alterations
in and across these pathways can help to select the most appropriate drug for a given patient based on
in-depth understanding of complexity in tumor biology
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