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Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.
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PURPOSE: Worldwide, gastric cancer (GC) is the 5th cancer with the highest incidence and the 4th in mortality. To reduce it, one strategy is to diagnose preneoplastic lesions (PNL): atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS); to form risk groups on which to focus surveillance efforts as are first-degree relatives (FDR). The aim of this study was to determine prevalence of gastric PNL in FDR of patients with GC, and to study association with sex, age, and Helicobacter pylorii (Hp) infection. METHODS: Cross-sectional study. One hundred and ten FDR, aged between 50 and 65 years, 54.5 female, obtained through convenience sampling, were studied. Biodemographic data survey and upper gastrointestinal endoscopy with histological study were applied according to Sidney protocol, and focal lesions found. Diagnosis of these lesions and condition of mucosa was carried out by applying OLGA and OLGIM systems. Descriptive statistics, estimation of prevalence, odds ratio (OR), and 95% confidence intervals (95CI) were calculated. RESULTS: Median age of study group was 56.5 years. Prevalence of PNL, AG, IM, and DYS were 86.4%, 82.7%, 54.5%, and 12.7% respectively. Advanced stages of OLGA and OLGIM were verified in 18.0% and 16.3% respectively. No association with sex, age, and Hp infection were found ([OR 3.10; 95CI 1.0; 9.64]; [OR 0.74; 95CI 0.26; 2.14]; [OR 0.58; 95CI 0.12; 2.77]) respectively. CONCLUSION: FDR of patients with GC have a high prevalence of PNL, which makes them a risk group in which endoscopic surveillance should be applied.
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Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Estudos Transversais , Prevalência , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Fatores de Risco , Hiperplasia/complicações , Metaplasia/epidemiologia , Metaplasia/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Mucosa Gástrica/patologiaRESUMO
Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.
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BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
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Índice de Massa Corporal , Proteína C-Reativa/análise , Neoplasias da Vesícula Biliar/etiologia , Cálculos Biliares/complicações , Adulto , Fatores Etários , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/epidemiologia , Predisposição Genética para Doença/genética , Variação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.
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The photocatalytic activity of TiO2 anodes was enhanced by synthesizing Ru-doped Ti|TiO2 nanotube arrays. Such photoanodes were fabricated via Ti anodization followed by Ru impregnation and annealing. The X-ray diffractograms revealed that anatase was the main TiO2 phase, while rutile was slightly present in all samples. Scanning electron microscopy evidenced a uniform morphology in all samples, with nanotube diameter ranging from 60 to 120 nm. The bias potential for the photoelectrochemical (PEC) treatment was selected from the electrochemical characterization of each electrode, made via linear sweep voltammetry. All the Ru-doped TiO2 nanotube array photoanodes showed a peak photocurrent (PP) and a saturation photocurrent (SP) upon their illumination with UV or visible light. In contrast, the undoped TiO2 nanotubes only showed the SP, which was higher than that reached with the Ru-doped photoanodes using UV light. An exception was the Ru(0.15 wt%)-doped TiO2, whose SP was comparable under visible light. Using that anode, the activity enhancement during the PEC treatment of a Terasil Blue dye solution at Ebias(PP) was much higher than that attained at Ebias(SP). The percentage of color removal at 120 min with the Ru(0.15 wt%)-doped TiO2 was 98% and 55% in PEC with UV and visible light, respectively, being much greater than 82% and 28% achieved in photocatalysis. The moderate visible-light photoactivity of the Ru-doped TiO2 nanotube arrays suggests their convenience to work under solar PEC conditions, aiming at using a large portion of the solar spectrum.
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Dopagem Esportivo , Nanotubos , Rutênio , Catálise , Luz , Titânio , Raios UltravioletaRESUMO
A compelling body of evidence has demonstrated that gastric cancer has a very particular tumor microenvironment, a signature very suitable to promote tumor progression and metastasis. Recent investigations have provided new insights into the multiple molecular mechanisms, defined by genetic and epigenetic mechanisms, supporting a very active cross talk between the components of the tumor microenvironment and thus defining the fate of tumor progression. In this review, we intend to highlight the role of very active contributors at gastric cancer TME, particularly cancer-associated fibroblasts, bone marrow-derived cells, tumor-associated macrophages, and tumor-infiltrating neutrophils, all of them surrounded by an overtime changing extracellular matrix. In addition, the very active cross talk between the components of the tumor microenvironment, defined by genetic and epigenetic mechanisms, thus defining the fate of tumor progression, is also reviewed.
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Neoplasias Gástricas , Microambiente Tumoral , Fibroblastos Associados a Câncer , Matriz Extracelular , Humanos , Macrófagos , Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
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Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Estudos de Associação Genética , Humanos , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , População Branca/genéticaRESUMO
Los tumores neuroendocrinos primarios del testículo son una entidad muy infrecuente, dando cuenta del 1% de las neoplasias testicu-lares. Clínicamente se presentan indolentes, por una masa testicular. En tumores localizados, rara vez presentan síndrome carcinoide. La orquiectomía radical es el tratamiento de elección; el pronóstico es excelente en etapas precoces. Las terapias adyuvantes no han mostrado utilidad.Se presenta un caso de un hombre de 53 años con una masa testicular palpable de larga evolución. Se realiza orquiectomía radical. La biopsia muestra un tumor neuroendocrino bien diferenciado. Sin evidencia de metástasis en etapificación. Se define en comité onco-lógico, realizar seguimiento.
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Testículo , Tumor Carcinoide , Neoplasias , Sistemas NeurossecretoresRESUMO
The environmental bioavailability of zinc (II), i.e., the uptake of the element by an organism, was determined using two microalgae species, Scenedesmus acutus and Pseudokirchneriella subcapitata, and estimated using hollow fiber supported liquid membrane (HF-SLM) device as the chemical surrogate. Several experimental conditions were studied including the presence of organic matter, inorganic anions and concomitant cations and pH. The results show strong positive correlation coefficients between the responses given by the HF-SLM and the microalgae species (r = 0.900 for S. acutus and r = 0.876 for P. subcapitata) in multivariate environments (changes in pH, calcium, humic and citrate concentrations). The maximum amount of zinc (II) retained by the HF-SLM (4.7 × 10-8 mol/cm2) was higher than those for P. subcapitata and S. acutus (9.4 × 10-11 mol/cm2 and 6.2 × 10-11 mol/cm2, respectively). The variation in pH (pH 5.5-9) was the variable with the greatest effect on zinc internalization in all systems, increasing approximately 2.5 times for P. subcapitata and 5.5 times for S. acutus respect to pH = 5.5, while the presence of humic acids did not affect the response. The species' concentration analysis of the experimental design at pH = 5.5 indicated that the amount of internalized zinc (II) by the HF-SLM and both microalgae species is strongly dependent on the free zinc concentration (r = 0.910 for the HF-SLM, r = 0.922 for S. acutus and r = 0.954 for P. subcapitata); however, at pH = 9.0, the amount of internalized zinc (II) is strongly dependent on the sum of free zinc and labile species (r = 0.912 for the HF-SLM, r = 0.947 for S. acutus and r = 0.900 for P. subcapitata). The presence of inorganic ligands (chloride, sulfate, phosphate, carbonate, and nitrate) and metal ions (cobalt (II), copper (II), nickel (II), chromium (VI), lead (II) and cadmium (II)) produced different behaviors both in the chemical surrogate and the biological references. The results showed that the synthetic device can mimic biological uptake in the presence of humic acids, nitrate, sulfate, and phosphate, and pH within the range 5.5-9 when S. acutus was used as the biological reference, considering the simultaneous contribution of the Zn2+ and ZnOH+ labile species depending on the chemical composition of the medium.
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Clorófitas/metabolismo , Microalgas/metabolismo , Zinco/metabolismo , Disponibilidade Biológica , Substâncias Húmicas , Concentração de Íons de Hidrogênio , Nitratos , Fosfatos , SulfatosRESUMO
Gastric cancer (GC) is the fifth most frequent cancer in the world and shows the highest incidence in Latin America and Asia. An increasing amount of evidence demonstrates that lysyl oxidase isoforms, a group of extracellular matrix crosslinking enzymes, should be considered as potential biomarkers and therapeutic targets in GC. In this review, we focus on the expression levels of lysyl oxidase isoforms, its functions and the clinical implications in GC. Finding novel proteins related to the processing of these extracellular matrix enzymes might be helpful in the design of new therapies, which, in combination with classic pharmacology, could be used to delay the progress of this aggressive cancer and offer a wider temporal window for clinical intervention.
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Proteína-Lisina 6-Oxidase/metabolismo , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/metabolismo , Quelantes/uso terapêutico , Colágeno/metabolismo , Elastina/metabolismo , Fibrose , Humanos , Metástase Neoplásica , Isoformas de Proteínas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismoRESUMO
The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype.
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Proteína HMGB1/farmacologia , Macrófagos/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Microambiente Tumoral/genética , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Técnicas de Cocultura , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Macrófagos/classificação , Macrófagos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Interferência de RNA , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The environmental bioavailability of copper was determined using a hollow-fiber supported liquid membrane (HFSLM) device as a chemical surrogate and two microalgae species (Scenedesmus acutus and Pseudokirchneriella subcapitata). Several experimental conditions were studied: pH, the presence of organic matter, inorganic anions, and concomitant cations. The results indicated a strong relationship between the response given by the HFSLM and the microalgae species with free copper concentrations measured by an ion selective electrode (ISE), in accordance with the free-ion activity model (FIAM). A significant positive correlation was evident when comparing the bioavailability results measured by the HFSLM and the S. acutus microalga species, showing that the synthetic device may emulate biological uptake and, consequently, be used as a chemical test for bioavailability measurements using this alga as a biological reference.
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Cobre/análise , Monitoramento Ambiental/métodos , Membranas Artificiais , Microalgas/química , Scenedesmus/química , Poluentes Químicos da Água/análise , Análise de Variância , Disponibilidade Biológica , Cobre/metabolismo , Eletrodos Seletivos de Íons , Microalgas/metabolismo , Modelos Teóricos , Scenedesmus/metabolismo , Poluentes Químicos da Água/metabolismoRESUMO
Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice.
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Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE(-/-) mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE(-/-) mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cells in vivo. These findings support studying the participation of platelets in the formation of atheromatous plate.
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Apolipoproteínas E/metabolismo , Aterosclerose/patologia , Plaquetas/patologia , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/patologia , Endotélio/patologia , Inflamação/patologia , Animais , Adesão Celular , Modelos Animais de Doenças , Progressão da Doença , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Las enfermedades cardiovasculares son la principal causa de muerte a nivel mundial. Entre ellas tienen gran relevancia las de tipo isquémicas, en donde el desarrollo de placas ateroscleróticas es el proceso fisiopatológico central. El estudio de la aterosclerosis es fundamental para comprender como se inicia este proceso patológico y los factores que influyen en su desarrollo. Distintas metodologías de laboratorio, entre otras la inmunohistoquímica, permiten reconocer las células y moléculas que participan en el proceso ateromatoso y que van interactuando según la progresión de la lesión. Un marcador de disfunción endotelial es la mayor expresión de la molécula de adhesión intercelular ICAM-1. En este trabajo se realizó la estandarización de inmunohistoquímica para la molécula de adhesión ICAM-1, y se estudió su expresión en arterias humanas sanas y con placa ateromatosa. En las muestras de arterias humanas con patología aterosclerótica, la expresión de ICAM-1 se observó aumentada, pero fue de difícil reconocimiento. Esto principalmente porque el tejido empleado como control en la estandarización fue una amígdala con hiperplasia y proceso inflamatorio que aumenta notablemente la expresión de ICAM-1. La implementación del método de inmunohistoquímica para ICAM-1 en arterias humanas permitirá conocer estados de disfunción endotelial y el desarrollo futuro del diseño e implementación de métodos de diagnóstico en aquellos procesos ateroclerótico en estado incipiente.
Cardiovascular diseases (CVD) are the leading cause of death in the world. Among them the ischemic type are of great importance, where the development of atherosclerotic plaques is the central pathophysiological process. The study of atherosclerosis is critical to understand how this disease process begins and factors influencing its development. Various laboratory methods, including immunohistochemistry, allow the recognition of cells and molecules involved in the atheromatous process that are interacting according to the progression of the lesion. A marker of endothelial dysfunction is the increased expression of intercellular adhesion molecule ICAM-1. In this paper, an immunohistochemistry method was standardized for the adhesion molecule ICAM-1, and its expression was studied in healthy human arteries with atheromatous plaque. In samples of human arteries with atherosclerotic disease, the expression of ICAM-1 was observed to be increased, but was hardly recognizable. This mainly because the tissue used as a control for standardization was a tonsil with an inflammatory process and hyperplasia, which significantly increases the expression of ICAM-1. The implementation of the immunohistochemistry method for ICAM-1 in human arteries will reveal endothelial dysfunction states that will enable a future design and implementation of methods of diagnosis in atherosclerotic processes in the early stages.
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Humanos , Artérias/metabolismo , Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Imuno-Histoquímica , Fatores de TempoRESUMO
The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years. Although the association is not fully understood, current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms, including hyperinsulinemia, hyperglycemia and chronic inflammation. In this context, the receptor for advanced glycation end-products (RAGE) has emerged as a focal point in its contribution to malignant transformation and tumor growth. We highlight how RAGE, once activated, as it manifests itself in conditions such as diabetes or hyperglycemia, is able to continuously bring about an inflammatory milieu, thus supporting the contribution of chronic inflammation to the development of malignancies.
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The adherence of Helicobacter pylori to gastric epithelial cells is required for prolonged persistence in the stomach and for induction of injury. Here, we first reported a new role of the receptor for advanced glycation end-products (RAGE) on the adherence of H. pylori to gastric epithelial cells, assessed by different methods and binding to immobilized RAGE. RAGE-targeted knock-down in MKN74 cell line markedly reduced not only the adhesion of H. pylori, but also the levels of IL-8 transcripts and protein released in response to infection. These data suggest that RAGE may represent a new factor on the pathogenesis of H. pylori infection.
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Aderência Bacteriana , Células Epiteliais/microbiologia , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno , Receptores Imunológicos/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Interleucina-8/biossíntese , Receptor para Produtos Finais de Glicação AvançadaRESUMO
The prevalence of Helicobacter pylori infection and the gastric cancer mortality rate in Chile are remarkably high. This study identified some virulence-associated genes in 78 H. pylori clinical isolates from dyspeptic patients from the Region del Maule, which is the region with the higher gastric cancer mortality rate in the country. The cagA, vacA and babA2 genes were detected in 94.9%, 100% and 97.4%, respectively. Two or more EPIYA C motifs were presented in 48.6% of cagA-positive strains, and this was associated with more severe histopathological findings in the gastric mucosa.
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Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Adesinas Bacterianas/genética , Motivos de Aminoácidos , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Distribuição de Qui-Quadrado , Chile/epidemiologia , Mucosa Gástrica/microbiologia , Genótipo , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Prevalência , VirulênciaRESUMO
Objetivo: Determinar la efectividad del Gluconato de Clorhexidina al 0.12% y del Bicarbonato de Sodio al 0.12% como desinfectantes de prótesis dentales y antiséptico de la mucosa bucal sobre las diferentes especies del género Cándida presentes en los pacientes con Estomatitis Sub-Protésica. Metodología: La investigación fue desarrollada en el periodo comprendido del 19 de julio al 2 de septiembre de 2011, en las clínicas de la Facultad de Odontología y el Laboratorio Microbiológico del Centro de Investigaciones Científicas y Desarrollo en Salud (CENSALUD) de la Universidad de El Salvador con un total de 30 pacientes portadores de prótesis dentales removibles totales o parciales, con diagnostico de Estomatitis Sub-Protésica tipo I, II, III de Newton. Para la identificación de las diferentes especies de Cándida se utilizo el medio de cultivo selectivo CHROMagar Cándida. Se tomaron muestras de la mucosa bucal de soporte y del aparato protésico antes y después de la aplicación de los fármacos para efectuar los recuentos de Unidades Formadoras de Colonias (U.F.C.) y evaluar la efectividad del tratamiento administrado en un periodo de 14 días. Resultados: Los resultados de este estudio demostraron que los porcentajes de colonización de las especies del genero Cándida en mucosa bucal fueron: C. albicans 52.01% C. krusei 46.93% C. Tropicalis 1.06%; en prótesis dental fueron: C. albicans 47.8% C. krusei 51.56% C. Tropicalis 0.64% utilizando el método estadístico de Dunn se obtuvo que en ambas superficies C. albicans y C. krusei colonizan de forma similar. Conclusión: Ambos fármacos resultaron tener similar efectividad como antiséptico sobre las diferentes especies del género Cándida presentes en mucosa bucal y desinfectante en prótesis dental en el tratamiento de Estomatitis Sub-Protésica.
Objective: To determine the effectiveness of 0.12% Chlorhexidine Gluconate and 0.12% Sodium Bicarbonate as disinfectants for dental prostheses and antiseptic for the oral mucosa on the different species of the genus Candida present in patients with Sub-Prosthetic Stomatitis. Methodology: The research was developed in the period from July 19 to September 2, 2011, in the clinics of the Faculty of Dentistry and the Microbiological Laboratory of the Center for Scientific Research and Development in Health (CENSALUD) of the University of El Salvador with a total of 30 patients with partial or total removable dental prostheses, with a diagnosis of Newton's Sub-Prosthetic Stomatitis type I, II, III. For the identification of the different Candida species, the selective culture medium CHROMagar Candida was used. Samples of the supporting buccal mucosa and the prosthetic apparatus were taken before and after the application of the drugs to carry out the counts of Colony Forming Units (CFU) and evaluate the effectiveness of the treatment administered in a period of 14 days. Results: The results of this study showed that the colonization percentages of the species of the genus Candida in the buccal mucosa were: C. albicans 52.01% C. krusei 46.93% C. Tropicalis 1.06%; in dental prostheses they were: C. albicans 47.8% C. krusei 51.56% C. Tropicalis 0.64% using Dunn's statistical method, it was obtained that C. albicans and C. krusei colonize in a similar way on both surfaces. Conclusion: Both drugs were found to have similar effectiveness as antiseptic on the different species of the genus Candida present in oral mucosa and disinfectant in dental prostheses in the treatment of Sub-Prosthetic Stomatitis.