0000000000057562

AUTHOR

Giusi Irma Forte

THE METABOLIC SYNDROME: IL-10 POLYMORPHISMS INFLUENCE ON SEROLOGICAL AND HAEMATOLOGICAL PARAMETERS IN TYPE 2 DIABETES.

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Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, develo…

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Radiosensitizing effect of Curcumin loaded lipid nanoparticles in breast cancer cells

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Search for genetic factors associated with susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is a cell-mediated autoimmune disease characterized by type-1 cytokine production. Environmental and individual genetic background might influence this response particularly in cytokine gene polymorphisms. We evaluated whether polymorphisms of interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-alpha genes, which might play a role in MS pathogenesis, are associated with MS susceptibility. Genotype frequencies for all the analyzed polymorphisms were not differently distributed between cases and controls. It is reasonable to suppose that the cytokine single-nucleotide polymorphisms (SNPs) studied must be considered against a larger genetic background involving …

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Valutazione della “gene expression” di Citochine e loro recettori in soggetti dediti ad attività sportiva.

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Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians

Human leukocyte antigen (HLA) alleles, regulating type and intensity of the immune response, might influence life expectancy. In previous case-control studies the authors have demonstrated that both HLA-DR and -DQ alleles are not associated with longevity in the Sardinian population. On the other hand, association studies are subjected (as part of the homogeneity of the population in terms of geographic origin) to a number of possible confounding factors. Therefore, the authors typed the HLA-DQA1 and HLA-DQB1 alleles in 24 sibs (age range 85 to 97) of 17 centenarians by PCR-SSP. Sib pair analysis showed non-significant differences between the observed and expected percentage of DQA* or DQB1…

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Studio delle frequenze alleliche di +1188 A/C di IL12B (p40) in soggetti affetti da Sclerosi Multipla.

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"Omics" 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 ‘‘Omics’’ (genomics, epigenetics, transcriptomics, and proteomics) studies on HER2/neu-positive breast cancer. A large quantity of biomarkers from dif…

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The Genetics of Innate Immunity and Inflammation in Ageing, Age-Related Diseases and Longevity

Inflammation is a key component of age-related diseases such as atherosclerosis and Alzheimer’s disease (AD) and genes coding for inflammatory or anti-inflammatory molecules are, therefore, good candidates for influencing the risk of developing these pathologies. Findings discussed in this chapter suggest that different alleles of genes coding for pro-or anti-inflammatory genes may affect individual life-span expectancy by influencing the type and intensity of immune-inflammatory responses against environmental stressors involved in the development of age-related disease. Our immune system has evolved to control pathogens and so pro-inflammatory responses are likely to be evolutionarily pro…

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The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained…

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Genetic Determined Downregulation of Both Type 1 and Type 2 Cytokine Pathways Might Be Protective against Pancreatic Cancer

Many cytokine polymorphisms have been studied for associations with susceptibility to breast, gastric, liver, lung, prostate, and ovarian cancer without conclusive results. The cytokine network, indeed, is characterized by complex interactions, and the final biological effect of a single genetic variation depends on the balance among different molecular signals. As is well known, Th1/Th2 cytokine unbalanced production might predispose to different pathologies, cancer included. In general, a prolonged type 1 inflammatory response might allow that cells accumulating enough "genetic hits" are promoted to neoplastic transformation. On the other hand, IL-13-producing cells through the IL-13/IL-4…

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Study of the role of particle-particle dipole interaction in dielectrophoretic devices for biomarkers identification

A three dimensional Coupled Monte Carlo-Poisson method has been used to evaluate the impact of particle-particle dipole interactions in the equilibrium distribution of a system of uncharged polarizable particles suspended in a static liquid medium under the action of an oscillating non-uniform electric field generated by polynomial electrodes. We compare the simulated distributions with experimental ones both for micro- (MDA-MB-231 breast tumor cells) and nano-(multiwall carbon nanotubes) particles. In both cases the equilibrium distributions near the electrodes are dominated by dipole interactions which locally enhance the DEP effect and promote long particles chains.

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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 mainte…

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Theoretical and experimental study of the role of cell-cell dipole interaction in dielectrophoretic devices: application to polynomial electrodes

BACKGROUND: We aimed to investigate the effect of cell-cell dipole interactions in the equilibrium distributions in dielectrophoretic devices. METHODS: We used a three dimensional coupled Monte Carlo-Poisson method to theoretically study the final distribution of a system of uncharged polarizable particles suspended in a static liquid medium under the action of an oscillating non-uniform electric field generated by polynomial electrodes. The simulated distributions have been compared with experimental ones observed in the case of MDA-MB-231 cells in the same operating conditions. RESULTS: The real and simulated distributions are consistent. In both cases the cells distribution near the elec…

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Analisi dei Polimorfismi di Citochine Th2 nella Sclerosi Multipla.

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Valutazione delle frequenze alleliche e genotipiche di citochine di tipo Th1 e Th2 in pazienti affetti da malattia di Behçet.

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Polymorphisms of genes of TGF-beta pathway and susceptibility to colorectal cancer

Background: Genetic background implicated in cytokine network may have a key role in the susceptibility to colorectal cancer (CRC). The TGF-β pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Methods: rs1800471 SNP polymorphism of TGF-ß1 rs334348 and rs334349 of TGF-βR1, rs900 of TGF-β2 and rs4522809 of TGF-β2R2 were typed in a group of 82 patients affected by sporadic CRC and in 237 age- and sex-matched healthy controls, using a competitive allele specific PCR assays (KASPar), developed by KBioscience (England). Results: No significant genetic contribution has been observed for 3 of the 5 SNPs tested. Indeed, a sign…

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Evaluation of CD1a polymorphism frequencies in patients with pancreatic cancer

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Analisi del Profilo genetico Th1/Th2 in soggetti allergici.

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Evaluation of cytokine polymorphisms (TNFalpha, IFNgamma and IL-10) in Down patients with coeliac disease.

Abstract Background In Down syndrome there is an increased prevalence of coeliac disease, but the reasons for this association are yet unknown. Aims To evaluate a possible correlation between TNFα, IFNγ and IL-10 genotype polymorphisms with the susceptibility to coeliac disease in Down syndrome patients. Methods Single nucleotide polymorphisms of TNFα (−308G → A promoter region), IFNγ (+874T → A promoter region) and IL-10 (−1082G → A promoter region) have been studied in 10 Down patients with coeliac disease, in 40 Down patients without coeliac disease and in 220 healthy controls. Clinical features were also studied in coeliac disease–Down syndrome patients. Results The 10 coeliac disease–D…

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POLYMORPHISMS IN TYPE 1 AND TYPE 2 CYTOKINE GENES MIGHT PLAY COMPLEMENTARY ROLE IN PANCREATIC CANCER SUSCEPTIBILITY.

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Common polymorphisms in Th1 and Th2 cytokine genes and susceptibility to pancreatic adenocarcinoma

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TNFalfa,IFN gamma, IL-10 gene polymorphisms in a sample of Sicilian patients with coeliac disease

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Frequenze degli aplotipi-1082GA/819CT/592CA della regione promoter del locus IL-10 in campioni di DNA ottenuti da pazienti affetti da Diabete mellito di tipo II.

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Studio delle frequenze alleliche del polimorfismo +1902A/G del gene IL4R in soggetti affetti da sclerosi multipla .

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Role of environmental and genetic factor interaction in the aging related disease development: The gastric cancer paradigm.

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Immunogenetic Markers and Sporadic Alzheimer's Disease Diagnostic Knot.

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TNFalpha, IFNgamma and IL-10 gene polymorphisms in a sample of Sicilian patients with coeliac disease.

Coeliac disease is associated with DQ2 and DQ8 alleles, but other genes also confer an additional genetic risk.Defining whether the genetic profiles of interleukin-10, tumour necrosis factor alpha and interferon gamma are associated with an increased coeliac disease risk.The functionally gene polymorphisms of tumour necrosis factor alpha (-308G/A), interferon gamma (+874T/A) and interleukin-10 (-1082G/A) were typed using sequence specific primer-polymerase chain reaction in 110 Sicilian coeliac disease patients and in 220 Sicilian healthy controls.No differences in genotype frequencies of interleukin-10 polymorphisms were found between coeliac disease patients and healthy controls. A signif…

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FREQUENZA DEGLI ALLELI DEL POLIMORFISMO -330T-->G IL-2 IN UNA POPOLAZIONE DI CENTENARI ITALIANI

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Cytokine Gene Polymorphisms and Breast Cancer Susceptibility

Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-alpha (-308G/A), TGF-beta1 (+869C/T), IL-10 (-1117G/A; -854C/T;…

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Variazioni delle frequenze degli alleli di ApoE in soggetti anziani ed in pazienti affetti da sindrome di Down.

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Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients.

Abstract Infection risk, sepsis and mortality after severe burn are primarily determined by patient age, burn size, and depth. Whether genetic differences contribute to otherwise unexpected variability in outcomes is unknown. We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis. We evaluated 71 patients with burns ≥15% TBSA and 109 healthy subjects. The genotypes of IL-6 (−174C/G), IL-10 (−819C/T and −1082A/G) and IL-17 (7488T/C) polymorphisms were identified applying polymerase chain reaction protocols. The cytokine levels in serum were determined with enzyme-linked immunoabsorbent assays. Our…

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Analisi dei polimorfismi funzionali dei geni IL-10 e TNF e della produzione di citochine in pazienti affetti da Malattia di Alzheimer di tipo sporadico.

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Inflammation genes and Alzheimer’s disease.

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Immune-inflammatory responses in successful and unsuccessful ageing

A dramatic increase in mean life span and life expectancy, coupled with a significant reduction in early mortality, has lead to a large increase in number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases associated with advancing age. Both innate and instructive immunity are implicated in almost all age-related diseases. The modifications of the immune system in the elderly are evaluated as a deterioration of the immune system, the so-called immunosenescence, which is thought to be mostly the result of the declining effectiveness of T cells and it is responsible for the increased susceptibility of elderly to infectious…

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Analysis of functionally Relevant Single nucleotide polymorphisms of TNFα and of IFN-gamma in Celiac Disease

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Frequency of polymorphisms of signal peptide of TGF-β1 and –1082G/A SNP at the promoter region of IL-10 gene in a group of patients with carotid stenosis.

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Analysis of functionally relevant single nucleotide polymorphisms of TNF alfa and of IFN gamma in celiac disease

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Proposta di protocollo per la determinazione dei valori normali di riferimento per i comuni test di routine nella popolazione anziana

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Risk profiles in type 2 diabetes (metabolic syndrome): integration of IL-10 polymorphisms and laboratory parameters to identify vascular damages related complications

Recently it has been reported that low serum IL-10 levels are associated with an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus (T2DM). We investigated whether the -1087G/A (rs1800896), -824C/T (rs1800871), -597C/A (rs1800872) IL-10 polymorphisms were associated with type 2 diabetes in a study on a cohort of Italian Caucasians comprising 490 type 2 diabetic and 349 control subjects. Stratifying the data according to IL-10 genotypes, trends for the progressive increase of glucose and neutrophil levels were observed in -1087GG vs. -1087GA vs. -1087AA positive diabetic patients (-1087GG < -1087GA < -1087AA). In addition, evaluating the laboratory parameters accord…

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Construction of a reference panel for IGF-1 gene expression: strategies for the identification of “genetic doping” practices.

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Valutazione della “gene expression” di IGF-1 ed IGF-1R in soggetti dediti ad attività sportiva: costruzione di un panel di riferimento utile all’identificazione di casi di “doping genico”

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Analisi della frequenza del polimorfismo 1249-1250insACAA del gene TGF-beta2 in un gruppo di pazienti affette da carcinoma della mammella.

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Genetic determined downregulation of both type 1 and type 2 cytokine pathways might be protective against pancreatic cancer

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IL-2 HIGH PRODUCER GENETIC BACKGROUND IS NEGATIVELY ASSOCIATED TO LONGEVITY

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Ruolo del polimorfismo –308 A/G del gene del Tumor Necrosis Factor-a nell’età di insorgenza della malattia di Alzheimer

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ANALYSIS OF HLA-DQA, HLA-DQB FREQUENCIES IN A GROUP OF SARDINIAN CENTENARIANS

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Analisi della frequenza del polimorfismo -330T/G della regione promoter del gene IL-2 in una coorte di centenari italiani

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