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1.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299125

RESUMO

Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θpooled = 3.19, 95% CI 1.46-4.93; and θpooled = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.


Assuntos
Biomarcadores/análise , Aberrações Cromossômicas/efeitos da radiação , Dano ao DNA , Pessoal de Saúde/estatística & dados numéricos , Exposição Ocupacional/análise , Radiação Ionizante , Relação Dose-Resposta à Radiação , Humanos , Exposição Ocupacional/efeitos adversos
2.
Mutat Res Rev Mutat Res ; 787: 108348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083055

RESUMO

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Coronary angiography allows an accurate assessment of the extent and severity of atherosclerotic coronary narrowing, but it provides little characterization of early detection of potentially asymptomatic vulnerable plaque. The identification of the coronary "vulnerable patient" or high-risk plaques remains a major challenge in the treatment of CAD. Recently, growing evidence shows that DNA damage plays a role in the initiation and progression of atherosclerotic plaque. Cytokinesis-block micronucleus (CBMN) assay is one of the most frequently used and validated method for assessing chromosomal damage and genetic instability. Accordingly, the purpose of this systematic review was to retrieve and discuss existing literature on the studies assessing the association between MN and angiographically-proven CAD. A total of 8 studies published between 2001 and 2017 were included in the meta-analysis. Despite a large heterogeneity between studies (I2= 99.7 %, p < 0.0001), an overall increase of MN frequencies was found in patients with CAD compared with control group (meta-MR = 1.96; 95 % CI, 1.5-3.2, p = 0.009). A subgroup analysis showed an increase in the frequency of MN formation for both two- vessel (MR = 2.13, 95 % CI: 0.9-6.9, p = 0.08) and three-vessel disease (MR = 2.89, 95 % CI: 1.84-4.55, P = 0.06). Overall, the results of this meta-analysis provide evidence of an association between CBMN and presence, extent and severity of angiographically-assessed CAD. However, the small number of papers analyzed requires further large and more rigorously designed studies, carefully considering a series of clinical confounding factors, such as the quality of the metabolic control, the influence of drugs and radiation imaging treatments.


Assuntos
Doença da Artéria Coronariana/genética , Animais , Citocinese/genética , Citocinese/fisiologia , Dano ao DNA/genética , Dano ao DNA/fisiologia , Humanos , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos
3.
Cardiol Young ; 31(6): 965-968, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33423710

RESUMO

Single-nucleotide polymorphisms in miRNA-machinery genes may alter the biogenesis of miRNAs affecting disease susceptibility. In this case-control study, we aimed to evaluate the impact of three single-nucleotide polymorphisms (DICER rs1057035, DROSHA rs10719, and XPO5 rs11077) and their combined effect in a genetic risk score model on congenital heart disease (CHD) risk. A total of 639 participants was recruited, including 125 patients with CHD (65 males; age 9.2 ± 10 years) and 514 healthy controls (289 males; age 15.8 ± 18 years). Genotyping of polymorphisms in miRNA-machinery genes was performed using a TaqMan®SNP genotyping assay. A genetic risk score was calculated by summing the number of risk alleles of selected single-nucleotide polymorphisms. There was a significantly increased risk of CHD in patients with XPO5 rs11077 CC genotype as compared to AC heterozygote and AA homozygote patients (ORadjusted = 1.7; 95% CI: 1.1-2.8; p = 0.018). A clear tendency to significance was also found for DROSHA rs10719 AA genotype and CHD risk for both codominant and recessive models (ORadjusted = 1.8; 95% CI: 0.91-3.8; p = 0.09 and ORadjusted = 1.9; 95% CI: 0.92-4; p = 0.08, respectively). The resulting genetic risk score predicted a 1.73 risk for CHD per risk allele (95% CI: 1.2-2.5; p = 0.002). Subjects in the top tertile of genetic risk score were estimated to have more than three-fold increased risk of CHD compared with those in the bottom tertile (ORadjusted = 3.52; 95% CI: 1.4-9; p = 0.009). Our findings show that the genetic variants in miRNA-machinery genes might participate in the development of CHD.


Assuntos
Cardiopatias Congênitas , MicroRNAs , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Cardiopatias Congênitas/genética , Humanos , Lactente , Recém-Nascido , Carioferinas/genética , Masculino , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adulto Jovem
4.
Per Med ; 18(1): 21-29, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33124523

RESUMO

Aim: SNPs in miRNA machinery genes may affect miRNA function by impacting their biogenesis. Here, we investigated the association between three SNPs in miRNA machinery genes (DICER rs1057035, DROSHA rs10719 and XPO5 rs11077) and bicuspid aortic valve (BAV). Materials & methods: Three polymorphisms were analyzed in 177 BAV patients and 414 healthy subjects by using a TaqMan®SNP assay. Results: The frequencies of XPO5 rs11077 genotype were significantly different between BAV patients and controls (p = 0.022). On multivariate logistic regression analysis, the XPO5 rs11077 C allele resulted a significant predictor of BAV (odds ratioadjusted = 0.65; CI: 0.42-0.98; p = 0.047). Conclusion: The XPO5 rs11077 SNP was associated with a decreased BAV risk supporting the causative role of miRNAs in aortic valve development.

5.
J Radiol Prot ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32668420

RESUMO

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac component of HARMONIC. A pooled cohort of approximately 100,000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports (RDSRs). Uncertainties in dose estimates will be modelled using 2-dimensional Monte Carlo methods. The cohort will be followed up using national registries and insurance records (Germany) to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.

7.
Mutat Res ; 784: 108309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32430098

RESUMO

Age is the dominant risk factor for the most prevalent atherosclerotic vascular diseases, including coronary artery disease, myocardial infarction, cerebrovascular disease and stroke. In human, telomere erosion and mitochondrial DNA (mtDNA) damage play a central role in the mechanisms leading to cellular aging decline. This review summarizes the most relevant findings on the role of telomere shortening and the common mtDNA4977 deletion in the progression and evolution of atherosclerosis by combining insight from experimental models and human clinical studies. The current evidence shows a link between telomere erosion and compromised mitochondrial function and provides a new perspective regarding their potential role as clinical biomarkers and therapeutic targets.


Assuntos
Envelhecimento/patologia , Aterosclerose/diagnóstico , Biomarcadores/análise , DNA Mitocondrial/genética , Deleção de Genes , Mitocôndrias/patologia , Encurtamento do Telômero/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Humanos , Mitocôndrias/genética , Fatores de Risco
8.
Heart Vessels ; 35(3): 432-440, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31562552

RESUMO

Compelling evidence has shown that microRNAs (miRs) are involved in the pathophysiology of BAV-associated aortopathy. The purpose of this study was to assess the biological role as well as the circulating expression of two miRs (miR-424-3p and miR-3688-3p) that have been previously identified as significantly dysregulated in thoracic aortic aneurysm specimens of BAV patients. Bioinformatic tools were used to predict miR gene targets followed by functional validation transfecting synthetic miR mimics and negative controls into human aortic smooth muscle cells (HASMCs). Levels of miRs and target genes were evaluated by qRT-PCR. The circulating miR expression profile analysis was assessed on plasma samples collected from a cohort of 72 patients with aortopathy including 39 BAV (33 males; 58 ± 13 years) and 33 TAV patients (26 males; 67 ± 9 years). Computational analysis revealed that SMAD7 and YAP1 were potential targets of miR-424-3p and miR-3688-3p, respectively. Transfection with mimics confirmed a significantly decreased gene expression of SMAD7 and YAP1 compared to mimic negative control (p = 0.04 and p = 0.0005, respectively) or blank control (p = 0.01 and p = 0.0007, respectively). Overexpression of miR-3688-3p also significantly upregulated pro-apoptotic caspase-3 gene expression compared to mimic negative control (p = 0.02) or blank control (p = 0.01). Furthermore, a significant down-regulation of the circulating miR-424-3p was observed in BAV compared to TAV patients (p = 0.001). In multiple linear regression analysis, the aortic valve morphology (ß = - 0.29, p = 0.04) and the presence of aortic stenosis (ß = - 0.28, p = 0.03) had a significant effect on the miR-424-3p expression. In conclusion, our study demonstrated that miR-424-3p and miR-3688-3p directly targeted SMAD7 and YAP1 in HASMCs, pivotal genes of the TGF-ß and Hippo-signaling pathways. Circulating miR-424-3p was also found to be significantly decreased in BAV patients when compared to TAV patients, especially in patients with aortic stenosis. Further large studies of well-characterized BAV patient cohorts are needed to define the clinical significance of the miR-424-3p.


Assuntos
Aneurisma Aórtico/sangue , Valva Aórtica/anormalidades , MicroRNA Circulante/sangue , Doenças das Valvas Cardíacas/sangue , MicroRNAs/sangue , Transcriptoma , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/genética , Doença da Válvula Aórtica Bicúspide , Células Cultivadas , MicroRNA Circulante/genética , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteína Smad7/genética , Proteína Smad7/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Environ Mol Mutagen ; 61(3): 361-368, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31605552

RESUMO

Occupational radiation exposure may impact the reproductive outcome of male workers in the cardiac catheterization laboratory (cath Lab) who receive a dose of ~1-10 mSv/year. An increased copy number variation (CNV) in azoospermia factor region c (AZFc) of the Y chromosome is a marker of spermatogenic failure, previously associated with radiation exposure. This study sought to investigate the association between paternal exposure in the Cath Lab and adverse reproductive outcomes as well as to assess the induction of CNV in the AZFc region. In a case-control study, we enrolled 193 catheterization lab workers (Group I) and 164 age-matched unexposed controls (Group II). Reproductive outcomes were assessed through a structured questionnaire. Two sequence-tagged sites (SY1197 and SY579) in AZFc region were evaluated by qRT-PCR in 83 exposed and 47 unexposed subjects. Exposed workers had a higher prevalence of low birth weight in offspring (Group I = 13% vs. II = 5.3%, P = 0.02; ORadjusted = 2.7; 95% CI: 1.1-6.3; P = 0.02). The mean of CNV (microdeletion and microduplication) for SY1197 was significantly higher in the exposed workers (Group I = 1.53 ± 0.85 vs. Group II = 1.02 ± 0.41; P = 0.0005). Despite the study design limitations, our findings show that chronic occupational radiation exposure of male workers is correlated with higher prevalence of low birth weight in offspring and instability in the Y chromosome AZFc region. Environ. Mol. Mutagen. 61:361-368, 2020. © 2019 Wiley Periodicals, Inc.


Assuntos
Instabilidade Cromossômica/efeitos da radiação , Cromossomos Humanos Y/efeitos da radiação , Infertilidade Masculina/etiologia , Exposição Ocupacional/efeitos adversos , Exposição à Radiação/efeitos adversos , Adulto , Cateterismo Cardíaco , Estudos de Casos e Controles , Feminino , Pessoal de Saúde , Humanos , Laboratórios Hospitalares , Masculino , Saúde do Trabalhador , Doses de Radiação
10.
Int J Mol Sci ; 20(21)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694204

RESUMO

Aging is one of the main risk factors for cardiovascular disease, resulting in a progressive organ and cell decline. This study evaluated a possible joint impact of two emerging hallmarks of aging, leucocyte telomere length (LTL) and common mitochondrial DNA deletion (mtDNA4977), on major adverse cardiovascular events (MACEs) and all-cause mortality in patients with coronary artery disease (CAD). We studied 770 patients (673 males, 64.8 ± 8.3 years) with known or suspected stable CAD. LTL and mtDNA4977 deletion were assessed in peripheral blood using qRT-PCR. During a median follow-up of 5.4 ± 1.2 years, MACEs were 140 while 86 deaths were recorded. After adjustments for confounding risk factors, short LTLs and high mtDNA4977 deletion levels acted independently as predictors of MACEs (HR: 2.2, 95% CI: 1.2-3.9, p = 0.01 and HR: 1.7, 95% CI: 1.1-2.9, p = 0.04; respectively) and all-cause mortality events (HR: 2.1, 95% CI: 1.1-4.6, p = 0.04 and HR: 2.3, 95% CI: 1.1-4.9, p = 0.02; respectively). Patients with both short LTLs and high mtDNA4977 deletion levels had an increased risk for MACEs (HR: 4.3; 95% CI: 1.9-9.6; p = 0.0006) and all-cause mortality (HR: 6.0; 95% CI: 2.0-18.4; p = 0.001). The addition of mtDNA4977 deletion to a clinical reference model was associated with a significant net reclassification improvement (NRI = 0.18, p = 0.01). Short LTL and high mtDNA4977 deletion showed independent and joint predictive value on adverse cardiovascular outcomes and all-cause mortality in patients with CAD. These findings strongly support the importance of evaluating biomarkers of physiological/biological age, which can predict disease risk and mortality more accurately than chronological age.


Assuntos
Doença da Artéria Coronariana/genética , DNA Mitocondrial/genética , Encurtamento do Telômero , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Prognóstico , Modelos de Riscos Proporcionais , Deleção de Sequência
11.
G Ital Cardiol (Rome) ; 20(9 Suppl 1): 14S-28S, 2019 09.
Artigo em Italiano | MEDLINE | ID: mdl-31593188

RESUMO

The radiation dose received by interventional cardiologists during their activity in the catheterization laboratory is a matter of concern in terms of possible deterministic and stochastic risk. At the same time, very often, the knowledge of the effect and consequences of radiation exposure in the interventional cardiology community is limited. This document endorsed by the Italian Society of Interventional Cardiology (SICI-GISE) provides recommendations for cardiologists' radiation protection. Radiation safety considerations dedicated to women and other staff personnel working in the catheterization laboratory are also discussed.


Assuntos
Cateterismo Cardíaco/normas , Cardiologia , Exposição Ocupacional/prevenção & controle , Saúde do Trabalhador/normas , Exposição à Radiação/prevenção & controle , Proteção Radiológica/normas , Humanos , Itália , Sociedades Médicas
12.
Thromb Res ; 180: 32-36, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31185329

RESUMO

INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in microRNA (miRNA) machinery genes may affect the regulatory capacity of miRNAs by impacting their biogenesis. The aim of the study was to analyze the association between SNPs in two key genes (DICER rs1057035T>C and XPO5 rs11077A>C) and coronary artery disease (CAD) risk as well as to examine their effects on circulating levels of vascular miRNAs. MATERIALS AND METHODS: Within the Italian GENOCOR cohort, we studied a cohort of 557 patients (502 males, 57 ±â€¯9 years) with angiographically documented CAD. A total of 443 healthy controls (262 males, 56 ±â€¯12 years) was also enrolled. Genotyping was determined by using a TaqMan®SNP genotyping assay. Analysis of miR-132 and miR-140-3p was assessed in a subset of 70 CAD patients by using qRT-PCR. RESULTS: There were statistically significant differences between CAD patients and healthy controls in the distribution of both DICER and XPO5 genotypes (p = 0.03 and p = 0.02, respectively). Multivariate analysis showed a significantly decreased risk of CAD by 50% in patients with DICER rs105703CC genotype as compared to TC heterozygote and TT homozygote patients (ORadjusted = 0.50; CI: 0.30-0.83, p = 0.007). In a recessive model, the XPO5 rs11077CC genotype was associated with a 32% reduced risk of CAD (ORadjusted = 0.68; CI: 0.30-0.99 p = 0.047). XPO5 rs11077CC genotype was significantly associated with higher levels of both miRNA-132 (p = 0.04) and miRNA-140-3p (p = 0.03). CONCLUSIONS: Genetic polymorphisms in DICER and XPO5 genes are associated with a decreased risk of CAD, probably by impacting expression levels of vascular and cardiac-specific miRNAs. Further studies are needed to better elucidate the biological relevance of both variants in CAD development.


Assuntos
Doença da Artéria Coronariana/genética , RNA Helicases DEAD-box/genética , Carioferinas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Ribonuclease III/genética , Adulto , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Feminino , Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade
13.
J Cardiol ; 74(4): 297-303, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31230901

RESUMO

The risk of acute aortic events in patients with bicuspid aortic valve (BAV) constitutes a medical concern in terms of timing and surgical decision. During the past years, there has been a growing interest in the potential of microRNAs (miRNAs) as crucial epigenetic factors in multiple cellular processes associated with BAV aortopathy. Nevertheless, there are still challenges that need to be overcome before miRNAs could enter clinical practice, and further validation studies in larger and well-defined BAV cohorts are now required. This review aims at providing a comprehensive overview of the available data on the expression profiles and function of specific miRNAs in BAV aortopathy, evaluating miRNA signatures as potential molecular markers of disease. We also discuss the role of other novel classes of non-coding RNAs, including long non-coding RNAs and circular RNAs, in BAV-associated aortopathy, mainly regarding their possible implementation as diagnostic and prognostic markers.


Assuntos
Doenças da Aorta/genética , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/genética , MicroRNAs/análise , Aorta/metabolismo , Doença da Válvula Aórtica Bicúspide , Biomarcadores/análise , Humanos
14.
Eur J Prev Cardiol ; 26(9): 976-984, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30782005

RESUMO

AIMS: Ionizing radiation may lead to mitochondrial DNA (mtDNA) mutations and changes in mtDNA content in cells, major driving mechanisms for carcinogenesis, vascular aging and neurodegeneration. The aim of this study was to investigate the possible induction of common mitochondrial deletion (mtDNA4977) and mtDNA copy number (mtDNA-CN) changes in peripheral blood of personnel working in high-volume cardiac catheterization laboratories (Cath Labs). METHODS: A group of 147 Cath Lab workers (median individual effective dose = 16.8 mSv, for the 41 with lifetime dosimetric record) and 74 unexposed individuals were evaluated. The occupational radiological risk score was computed for each subject on the basis of the length of employment, individual caseload and proximity to the radiation source. mtDNA4977 deletion and mtDNA-CN were assessed by using quantitative real-time polymerase chain reaction. RESULTS: Increased levels of mtDNA4977 deletion were observed in high-exposure Cath Lab workers compared with unexposed individuals ( p < 0.0001). Conversely, mtDNA-CN was significantly greater in the low-exposure workers ( p = 0.003). Occupational radiological risk score was positively correlated with mtDNA4977 deletion (Spearman's r = 0.172, p = 0.03) and inversely correlated with mtDNA-CN (Spearman's r = -0.202, p = 0.01). In multiple regression model, occupational radiological risk score emerged as significant predictor of high levels of mtDNA4977 deletion (ß coefficient = 0.236, p = 0.04). CONCLUSION: mtDNA4977 deletion is significantly high in Cath Lab personnel. Beyond the well-recognized nuclear DNA, mtDNA damage might deserve attention as a pathogenetic molecular pathway and a potential therapeutic target of ionizing radiation damage.


Assuntos
Cateterismo Cardíaco/efeitos adversos , DNA Mitocondrial/efeitos da radiação , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Doses de Radiação , Exposição à Radiação/efeitos adversos , Radiografia Intervencionista/efeitos adversos , Deleção de Sequência , Adulto , Cardiologistas , Estudos Transversais , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Feminino , Dosagem de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Medição de Risco , Fatores de Risco
16.
Int J Radiat Biol ; 95(2): 201-206, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30431375

RESUMO

BACKGROUND: Left-sided breast cancer patients treated with radiotherapy (RT) are at risk for late radiation-induced cardiovascular complications. AIM: The aim of this study was to investigate the BNP plasma levels in long-term breast cancer survivors who received only RT as well to assess whether cardiac dose was associated with BNP values. METHODS: Plasma samples for BNP measurement were repeated in 29 patients (63 ± 11 years) who were alive at 5 years after radiotherapy, free of heart disease and available to provide new blood sample. All patients had BNP measurements at baseline. The ΔBNP was measured to analyze the role of marker variations. No patients received chemotherapy. RESULTS: The mean cardiac and ventricle dose were 2.1 ± 1.0 (range 0.02-4.5) Gy and 3.0 ± 1.7 (range 0.02-7.6), respectively. Median value of BNP was 47 pg/mL (interquartile ranges, 26-58.2 pg/mL) at baseline, and 34 pg/mL (interquartile ranges, 17.5-54 pg/mL) at 5 years after radiotherapy. There was no significantly different between two measurements (p = ns). Fifteen (52%) reported an improvement in BNP levels, 1 (3%) no changes and 13 (45%) reported a worsening. There was no correlation between ΔBNP and age (p = ns). When patients were stratified according to the median value of dose-volume data, ΔBNP was significantly higher in patients with increased cardiac Dmean (p = .02) and left ventricle Dmean (p = .009). CONCLUSION: At 5 years after radiotherapy, median plasma BNP levels remained within the normal range, but the delta-BNP levels are directly related to the heart and ventricular dose received.


Assuntos
Neoplasias da Mama/radioterapia , Sobreviventes de Câncer , Peptídeo Natriurético Encefálico/sangue , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade
18.
Ann Ist Super Sanita ; 54(4): 294-299, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30575565

RESUMO

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer after conservative surgery can be life-saving but remains associated with significant late side effects, including lung fibrosis, detected by chest CT. Aim of this study was to assess whether lung ultrasound (LUS) may detect late lung fibrosis through the biomarker of B-lines. MATERIALS AND METHODS: We evaluated 30 women (median age 67 years, range 46-80 years) about 3-8 years after RT (follow up 38-101 months, median 58 months) for left (n = 12) or right (n = 18) breast cancer (stage 1, n = 24; stage 2, n = 6), treated with total dose 40.5 - 50.00 Gy with/without boost dose). In all, both treated and contralateral hemithorax were evaluated. LUS was performed and B-lines evaluated with a 28-region antero-lateral scan, from second to fifth intercostal spaces, along the mid-axillary, anterior axillary, mid-clavicular, and parasternal lines. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. The sum of B-lines in all spaces generated the B-line score of each hemithorax. RESULTS: Median B-line score was higher in the irradiated site than in the contralateral control hemithorax (9, 1st-3rd quartiles: 2-23 vs 3, 1st-3rd quartiles: 1-4; P < 0.05). In the treated hemithorax, higher mean lung doses ( > median value of 2.7 Gy) were associated with more B-lines when compared to lower doses (< 2.7 Gy): 9 vs 5, p <0.001. CONCLUSION: RT in female breast cancer survivors is associated with increase in B-lines in the targeted hemithorax, likely due to lung fibrosis, and related to the lung mean dose. LUS can provide a simple "echo-marker" of lung fibrosis.


Assuntos
Neoplasias da Mama/complicações , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , Radioterapia/efeitos adversos , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Sobreviventes
19.
Atherosclerosis ; 276: 91-97, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30053637

RESUMO

BACKGROUND AND AIMS: Mitochondrial DNA copy number (mtDNA-CN) depletion has been recently associated with an increased cardiovascular risk. However, the integrity of mtDNA is another key aspect of the energy metabolism and mitochondrial function. We investigated the prognostic role of peripheral blood common mitochondrial deletion (mtDNA4977) and mtDNA-CN on long-term major adverse cardiac events (MACEs) and all-cause mortality in a cohort of patients with coronary artery disease (CAD). METHODS: Within the Italian GENOCOR (Genetic Mapping for Assessment of Cardiovascular Risk) cohort, we studied 515 patients (450 males, 65 ±â€¯8 years) with known or suspected stable CAD. mtDNA4977 deletion and mtDNA-CN were assessed in peripheral blood using qRT-PCR. RESULTS: During a mean follow-up of 4.5 ±â€¯1.1 years, 78 (15%) patients had MACEs (15 cardiac deaths, 17 nonfatal myocardial infarction and 46 coronary revascularizations) and 28 patients died for non-cardiac causes. Patients with high levels of mtDNA4977 deletion (>75th) had increased risk of MACEs (log rank = 7.2, p=0.007) and all-cause mortality (log rank = 5.7, p=0.01) compared with patients with low mtDNA4977 deletion (≤75th). Multivariate Cox regression analysis showed that log mtDNA4977 was a significant predictor of MACEs (HR = 2.17; 95% CI, 1.31-3.59; p=0.003) and all-cause mortality (HR = 2.03; 95% CI: 1.13-3.65, p=0.02). Log mtDNA-CN was not significantly associated with MACEs or all-cause mortality. However, patients with high mtDNA4977 deletion (>75th) and low mtDNA-CN (<25th) had significantly increased risk for MACEs (HR: 3.73; 95% CI: 1.79-7.79; p=0.0005). CONCLUSIONS: Mitochondria DNA damage was associated with an increased risk of MACEs and all-cause mortality in patients with stable CAD, confirming the critical role of mitochondrial dysfunction in atherosclerosis.


Assuntos
Doença da Artéria Coronariana/genética , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Deleção de Genes , Dosagem de Genes , Idoso , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , DNA Mitocondrial/sangue , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Revascularização Miocárdica , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco
20.
Cancer Biomark ; 22(2): 179-198, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689703

RESUMO

Cancer is the most important cause of death worldwide, and early cancer detection is the most fundamental factor for efficacy of treatment, prognosis, and increasing survival rate. Over the years great effort has been devoted to discovering and testing new biomarkers that can improve its diagnosis, especially at an early stage. Here we report the potential usefulness of new, easily applicable, non-invasive and relatively low-cost clinical biomarkers, based on abnormalities of oral mucosa spectral reflectance and fractal geometry of the vascular networks in several different tissues, for identification of hereditary non-polyposis colorectal cancer carriers as well for detection of other tumors, even at an early stage. In the near future the methodology/technology of these procedures should be improved, thus making possible their applicability worldwide as screening tools for early recognition and prevention of cancer.


Assuntos
Biomarcadores , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Diagnóstico por Imagem/métodos , Genômica/métodos , Humanos , Metabolômica/métodos , Neoplasias/etiologia , Neoplasias/metabolismo , Proteômica/métodos , Sensibilidade e Especificidade
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