RESUMO

Different amounts of graphene quantum dots (CQDs) (0, 1, 2.5, and 5 wt%) were incorporated into an epoxy matrix. The thermal conductivity, density, morphology, and dynamic mechanical thermal (DMTA) properties were reused from the study of Seibert et al.. The Pearson plot showed a high correlation between mass loading, thermal conductivity, and thermal diffusivity. A poorer correlation with density and heat capacity was observed. At lower CQD concentrations (0.1 wt%), the fracture surface showed to be more heterogeneous, while at higher amounts (2.5 and 5 wt%), a more homogeneous surface was observed. The storage modulus values did not change with the CQD amount. But the extension of the glassy plateau increased with higher CQD contents, with an increase of ~40 °C for the 5 wt% compared to the 2.5 wt% and almost twice compared to the neat epoxy. This result is attributed to the intrinsic characteristics of the filler. Additionally, lower energy dissipation and a higher glass transition temperature were observed with the CQD amount. The novelty and importance are related to the fact that for more rigid matrices (corroborated with the literature), the mechanical properties did not change, because the polymer bridging mechanism was not present, in spite of the excellent CQD dispersion as well as the filler amount. On the other hand, thermal conductivity is directly related to particle size and dispersion.

RESUMO

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often present with dyspnea, fatigue, and desaturation. These symptoms can be highly limiting, as they lead to a decrease in performing activities of daily living (ADL). Therefore, it is essential to evaluate the degree of functional limitation of these individuals. OBJECTIVE: The present study aimed to evaluate the validity and reliability of the Glittre-ADL test (TGlittre) and its association with self-reported limitation in ADL and health-related quality of life (HRQoL) in patients with IPF. METHODS: Twenty-seven individuals with IPF (60.5 ± 10.6 years), with forced vital capacity 2.26 ± 1.03 L (51.09 ± 20.62% of predicted) were assessed for the time spent in TGlittre, 6-minute walking distance (6MWD), limitation in ADL and HRQoL. RESULTS: TGlittre was reliable (intraclass correlation coefficient3,1 = 0.96; P < .001); however, a learning effect of 10.6% was observed between the first and second execution of TGlittre. The time spent in TGlittre correlated with 6MWD, limitation in ADL, and disease-specific HRQoL (P < .05). CONCLUSION: TGlittre is valid and reliable for assessing functional capacity in patients with IPF. Still, it presents a learning effect and should be performed twice when assessing functional capacity in clinical practice.

RESUMO

The Glittre ADL-test (TGlittre) is a multiple-task test designed to assess functional limitation in patients with chronic obstructive pulmonary disease (COPD). Although few studies have investigated the TGlittre learning effect, the results are still conflicting. This study aimed to investigate the test-retest reliability and learning effect on TGlittre and to identify predicting factors of the learning effect in patients with COPD. Patients performed the TGlittre twice with a 30-minutes resting period between trials. TGlittre consists in measuring the time to complete five laps of a multiple ADL-like activities circuit: walking stairs, carrying a backpack, lifting objects, bending down and rising from a seated position. 124 patients with COPD were assessed [81 men; 66 ± 8 years, forced expiratory volume in one second (FEV1) 37.1 ± 15.0%pred; TGlittre 120 ± 60%pred; six-minute walking test 75.5 ± 17.4%pred]. The time spent in TGlittre presented excellent reliability (ICC = 0.96; 95%CI 0.92 - 0.98; p < 0.001; SEM 0.46 min; MDC 1.28 min) and decreased in the retest (5.24 ± 2.31 min to 4.85 ± 2.02 min; p < 0.001). Patients presented a learning effect of 6.11 ± 11.1% in TGlittre. A lower FEV1 (r2=0.10; p < 0.001) and a worse performance in the first TGlittre (r2=0.28; p < 0.001) are related to the improvement in performance of the second TGlittre. Although the TGlittre is reliable, patients improve their performance when performing the second test probably because they underestimate their functional capacity. These results should encourage professionals to assess TGlittre twice when using this test as an outcome measure.

Assuntos

Atividades Cotidianas , Doença Pulmonar Obstrutiva Crônica , Teste de Esforço , Humanos , Masculino , Reprodutibilidade dos Testes , Teste de Caminhada

RESUMO

OBJECTIVES: To determine the minimal important difference (MID) for the London Chest Activity of Daily Living scale (LCADL) in patients with chronic obstructive pulmonary disease (COPD), focusing on the percentage of the total score (LCADL%total), using an anchor-based method in addition to distribution-based methods. DESIGN: Non-controlled before-and-after study. SETTING: Two outpatient centres. PARTICIPANTS: Seventy-seven patients with COPD (GOLD II-IV, 47 males, forced expiratory volume in 1second mean 37 (SD 14) % predicted). INTERVENTIONS: Aerobic training and localised training for upper and lower limbs was conducted for 24 sessions, three times per week. MAIN OUTCOME MEASURES: The main outcome was LCADL score pre- and post-exercise training. The MID was established using distribution and anchor-based methods. The modified Saint George Respiratory Questionnaire was the anchor for the analysis of sensitivity and specificity of the MID. RESULTS: The established MIDs ranged from -2.1 to -5.9 points for LCADLtotal and from -2 to -6 points for LCADL%total. The receiver operating characteristic curve indicated a cut-off point of -3 points for LCADLtotal (sensitivity 51%, specificity 82%; P=0.01) and -4 points for LCADL%total (sensitivity 56%, specificity 82%; P=0.04). CONCLUSIONS: The present findings suggest -3 points and -4 points as the MIDs for LCADLtotal and LCADL%total, respectively. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03251781.

Assuntos

Atividades Cotidianas , Terapia por Exercício , Diferença Mínima Clinicamente Importante , Doença Pulmonar Obstrutiva Crônica/reabilitação , Inquéritos e Questionários/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Sensibilidade e Especificidade , Teste de Caminhada

RESUMO

OBJECTIVES: Cardiovascular disease is a major cause of mortality in chronic obstructive pulmonary disease (COPD) and endothelial dysfunction may enhance the mortality risk. Exercise training has shown to be beneficial for improvement of endothelial function in patients with cardiovascular disease, but this remains unclear in COPD. Thus, this study aimed to assess the effect of exercise-based pulmonary rehabilitation (PR) on endothelium function, arterial stiffness and plasma nitrite levels in patients with COPD. METHODS: Patients with COPD engaged a 48-session PR program. Reactive hyperaemia index (RHI), augmentation index (AIx), and heart rate (HR) assed by peripheral arterial tonometry (PAT), plasma nitrite levels, systemic blood pressure, functional capacity (six-minute walk test) and the BODE index were assessed at baseline and after 24 and 48 sessions of PR. Plasma nitrite levels were also assessed before and after the first session of PR. RESULTS: Twenty-one subjects were included and completed 24 PR sessions, and 16 subjects completed 48 sessions. It was observed that a poorer AIx adjusted for HR in frequent COPD exacerbators (4.67 ± 16.5 vs. 20.9 ± 12.9; p = .02). PR improved functional capacity (380 ± 107 m vs. 442 ± 115 m; p < .001) and the BODE index (6 [2.8] vs. 4 [3]; p = .001), but did not change HR, systemic arterial pressure, RHI, AIx, and plasma nitrite levels during the follow-up. Plasma nitrite levels reduced after the first session of PR (0.074 [0.079] µM vs. 0.061 [0.04] µM; p = .027). The acute change in plasma nitrite levels correlated with RHI in patients with preserved endothelial function (r = 0.71; p = .01). CONCLUSIONS: Although exercise-based PR improved functional capacity and the BODE index, it did not change endothelial function and arterial stiffness in patients with COPD.

Assuntos

Endotélio Vascular/fisiopatologia , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Rigidez Vascular/fisiologia , Idoso , Exercício Físico , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teste de Caminhada

RESUMO

We present here the draft genomes of 13 Helicobacter pylori strains isolated from Colombian residents on the Pacific coast (n = 6) and in the Andes mountains (n = 7), locations that differ in gastric cancer risk. These 13 strains were obtained from individuals with diagnosed gastric lesions.

RESUMO

BACKGROUND AND OBJECTIVE: Gastric infection with Helicobacter pylori (H pylori), a strong risk factor for gastric cancer, is highly prevalent in children residing in the Colombian Andes. We aimed to validate the use of the Entero-test to culture and genotype H pylori strains from asymptomatic Colombian children. METHODS: Children (ages 10-15 years, n = 110, 80 of which were H pylori positive by the urea breath test [UBT]) were subjected to the Entero-test, and strings were cultured and/or used for DNA extraction for polymerase chain reaction (PCR). These children had been treated for H pylori in 2007. A second population of children (ages 10-15 years, n = 95),which had not been previously treated, was also subjected to the Entero-test. RESULTS: Of UBT-positive children in the treated group, 29 of 80 (36%) Entero-test samples were H pylori culture positive; 29 additional string extracts were tested by PCR for the H pylori virulence factors cagA and vacA. PCR from cultures and extracts yielded a sensitivity of 74% and specificity of 87%. In the untreated group, 16 of 94 UBT-positive children (17%) produced Entero-tests that were culture positive. Fifty-eight of 94 (62%) string extracts were PCR positive for cagA and/or vacA. In previously treated children, H pylori strains were more often the less virulent vacA s2 (P = 0.001), m2 (P = 0.006), and i2 genotypes (P = 0.039). CONCLUSIONS: The Entero-test may be used as a noninvasive test to detect H pylori in asymptomatic children residing in high-risk areas for gastric cancer. Treatment of H pylori in children was associated with less virulent genotypes.

Assuntos

Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , DNA Bacteriano , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Reação em Cadeia da Polimerase/métodos , Neoplasias Gástricas/microbiologia , Fatores de Virulência/genética , Técnicas de Tipagem Bacteriana , Testes Respiratórios , Criança , Colômbia/epidemiologia , Doenças Endêmicas , Feminino , Genótipo , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade

RESUMO

Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene-environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals.

Assuntos

Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Capsaicina/efeitos adversos , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Interleucina-1beta/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Anticorpos Antibacterianos/análise , DNA/biossíntese , DNA/genética , Dieta , Feminino , Interação Gene-Ambiente , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/análise , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Risco

RESUMO

BACKGROUND: Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer. Many studies of H. pylori virulence markers in children have the bias that symptomatic subjects are selected for endoscopy, and these children may harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA alleles in stool DNA samples of healthy Colombian children residing in an area with high incidence of gastric cancer, to avoid selection bias resulting from endoscopy. METHODS: H. pylori status of 86 asymptomatic children was assessed by (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA genes were amplified from stool DNA samples and sequenced. RESULTS: UBT was positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples, which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1 genotypes (p < 0.0001). CONCLUSIONS: Using stool DNA samples, virulence markers of H. pylori were successfully genotyped in a high percentage of the asymptomatic infected children, revealing a high prevalence of genotypes associated with virulence. Type I hopQ alleles were associated with the presence of cagA and the vacA s1 genotype.

Assuntos

Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Técnicas de Tipagem Bacteriana , Testes Respiratórios , Criança , Pré-Escolar , Colômbia/epidemiologia , Fezes/microbiologia , Genótipo , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/classificação , Humanos , Masculino , População Rural

RESUMO

Helicobacter pylori cagA-positive strains exert population-specific risks for gastric cancer. We determined whether variations in CagA phosphorylation motifs were associated with carcinogenic or proinflammatory epithelial phenotypes induced by strains from regions with divergent cancer risks (Colombia and Nashville, TN). Motif number was significantly related to levels of CagA phosphorylation and cytoskeletal abnormalities. Precancerous isolates possessed a higher number of motifs, and precancerous strains from Nashville induced higher levels of IL-8 than Colombian strains. These results indicate that CagA variants are linked with premalignant lesions in distinct populations and that epithelial responses to these strains are selective based upon locale.

Assuntos

Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Carcinoma/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/classificação , Neoplasias Gástricas/microbiologia , Motivos de Aminoácidos , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Carcinoma/complicações , Carcinoma/epidemiologia , Linhagem Celular , Colômbia/epidemiologia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Masculino , Fenótipo , Fosforilação , Isoformas de Proteínas , Fatores de Risco , Neoplasias Gástricas/complicações , Neoplasias Gástricas/epidemiologia , Tennessee/epidemiologia

RESUMO

Eosinophils and mast cells participate in the immune response against Helicobacter pylori, but their involvement in the gastric precancerous process is unclear. This study aimed to estimate eosinophil and mast cell density in antral mucosa in subjects from 2 Colombian populations with contrasting gastric cancer risks. Gastric mucosa biopsies were collected from 117 adult males (72 from a high-risk area and 45 from a low-risk area). A histopathology score was used to quantify severity of the lesions. Quantitation of eosinophils in hematoxylin-eosin-stained sections and mast cells in immunostained sections for CD117/c-Kit was performed. Helicobacter pylori infection and genotyping were assessed in Steiner stain and polymerase chain reaction, respectively. Logistic regression models and semiparametric cubic smoothing splines were used for analysis of the results. Eosinophil density was significantly higher in subjects from the low-risk area as compared with subjects from the high-risk area. In both populations, eosinophil density increased with the histopathology score in the progression of lesions from normal morphology to multifocal atrophic gastritis. Intestinal metaplasia and dysplasia specimens showed further increase in eosinophil density in the high-risk area but an abrupt decrease in the low-risk area. Mast cell density increased in parallel to the histopathology score in both populations. Our results suggest that eosinophils play a dual role in chronic gastritis. In the low-risk area, elevated eosinophil density represents a T helper 2-biased response that may down-regulate the effects of proinflammatory cytokines preventing cancer development. In contrast, in the high-risk area, eosinophils might promote a T helper 1-type response leading to progression of precancerous lesions.

Assuntos

Eosinófilos/patologia , Gastrite/patologia , Mastócitos/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Colômbia , Mucosa Gástrica/citologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Fatores de Risco , Neoplasias Gástricas/etiologia

RESUMO

BACKGROUND: An inverse association between selenium status and incidence of different neoplasias including gastric cancer has been reported. This pilot study aimed to determine and compare selenium status in two Colombian populations with different gastric cancer risks: a high-risk area in the volcanic region of the Andes Mountains and a low-risk area on the Pacific coast. METHODS: Eighty nine adult males were recruited in the outpatient clinics of two public hospitals (44 and 45 from high- and low-risk areas, respectively) and provided a blood sample. Seventy one (79.8%) participants underwent upper gastrointestinal endoscopy. Plasma selenium was assayed using a fluorometric method, selenoprotein-P by ELISA, and glutathione peroxidase activity by a spectrophometric method. Histological diagnosis and Helicobacter pylori infection were evaluated in gastric biopsy samples. Unpaired samples t-test and linear regression analyses were used for statistical analyses. RESULTS: Although none of the subjects in either of the two geographic areas was selenium deficient, the level of plasma selenium was significantly lower in men from the high-risk area compared with those from the low-risk area. Levels of selenoprotein-P and glutathione peroxidase activity were similar between groups after adjustment for confounders. Selenium measurements were not associated with histopathological diagnosis. CONCLUSIONS: The high incidence of gastric cancer in the Andean region of Colombia is unlikely to be explained by selenium deficiency. We cannot exclude, however, that suboptimal selenium levels may exist in the gastric mucosa of subjects in the high-risk area. Therefore, the benefit of selenium supplementation in gastric cancer prevention cannot be dismissed.

Assuntos

Selênio/sangue , Selenoproteína P/sangue , Neoplasias Gástricas/epidemiologia , Adulto , Colômbia/epidemiologia , Dieta , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Neoplasias Gástricas/sangue

RESUMO

BACKGROUND: cagA-positive and vacA s1 and m1 genotypes of Helicobacter pylori are associated with an elevated risk of gastric cancer (GC). We determined these genotypes using paraffin-embedded gastric biopsy specimens harvested from infected individuals and compared genotype distributions in two Colombian populations residing in geographic regions with a high and low incidence of GC. METHODS: DNA from paraffin-embedded gastric biopsies from 107 adults was amplified using primers specific for cagA, for the cag'empty site', for the s and m alleles of vacA, and for H. pylori 16S rRNA. RESULTS: H. pylori infection was detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in 78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were not significantly associated with a particular geographic area. The vacA m1 allele and s1m1 genotypes were more common in the area of high risk for GC (p = .037 and p = .044, respectively), while the vacA m2 allele and s2m2 genotypes were more prevalent in the low-risk area. The prevalence of the combination of cagA-positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk areas, respectively (p = .011). CONCLUSIONS: H. pylori cagA and vacA genotyping from paraffin-embedded gastric biopsies permitted reliable typability and discrimination. The more virulent cagA-positive s1m1 strains, as well as vacA m1 genotype, were more prevalent in high risk than in low risk areas, which may contribute to the difference in GC risk between those two regions.

Assuntos

Técnicas de Tipagem Bacteriana , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/classificação , Neoplasias Gástricas/microbiologia , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biópsia , DNA Bacteriano/genética , Genótipo , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Inclusão em Parafina , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo

RESUMO

BACKGROUND: Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. METHODS: Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. RESULTS: All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. CONCLUSIONS: The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Assuntos

Adenocarcinoma/genética , Metilação de DNA , Neoplasias da Vesícula Biliar/genética , Regiões Promotoras Genéticas , Hidrolases Anidrido Ácido/genética , Hidrolases Anidrido Ácido/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/metabolismo , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Chile , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/metabolismo , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Análise de Sobrevida

RESUMO

Several polymorphisms of the IL1B and IL10 gene promoters have been reported to be associated with gastric cancer risk in Caucasians. However, studies in other populations have shown differing results. We aimed to test for associations between polymorphisms in IL1B (-31 and +3954), IL10-592 and IL1RN variable number of tandem repeats (VNTR) and risk of gastric cancer in a Mexican population. DNA was extracted from sera of 183 gastric adenocarcinoma patients and 377 controls. The IL1B-31, IL1B+3954 and IL10-592 biallelic polymorphisms were discriminated using 5' Nuclease (TaqMan) assays and Pyrosequencing. The IL1RN penta-allelic VNTR polymorphism was genotyped using PCR followed by GeneScan analysis. A significant interaction was found between IL1B-31 and CagA status for the risk of intestinal-type gastric cancer (p = 0.023). Among CagA positive subjects, those with IL1B-31CC genotype had an increased risk of intestinal-type gastric cancer (OR 3.19, 95%CI = 1.05-9.68), compared to carriers of IL1B-31TT genotype. In contrast, among CagA negative subjects, no significant association of IL1B-31CC genotype with gastric cancer was observed. The IL10-592CC genotype was associated with more than doubling of the risk of the intestinal-type gastric cancer (OR, 2.20, 95%CI = 1.04-4.65). A nonsignificantly increased risk for intestinal-type gastric cancer was found in IL1RN*2 carriers (OR 1.49, 95%CI = 0.89-2.50). None of these polymorphisms was significantly related to the risk of diffuse-type gastric cancer. No significant association was found between risk of gastric cancer and the IL1B+3954 polymorphism. Individuals carrying 2 or more of the risk-associated alleles (IL1B-31C, IL1RN *2 and IL10-592C) were at increased risk for intestinal-type gastric cancer, compared to those with 0 or 1 risk-associated allele. The risk from multiple risk-associated alleles was especially high in subjects infected with CagA positive H. pylori. Our results support the identification of the IL1B-31 promoter polymorphism as a useful marker for risk of intestinal type gastric cancer in persons with CagA positive H. pylori infections.

Assuntos

Adenocarcinoma/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Helicobacter/genética , Interleucina-10/genética , Interleucina-1/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/microbiologia , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Receptores de Interleucina-1/genética , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Sequências de Repetição em Tandem

RESUMO

BACKGROUND: Gallbladder cancer is very common in Chile and is the leading cause of cancer deaths in women aged over 40 years. However, there is limited information about the molecular changes involved in its pathogenesis. Microsatellite analysis was performed using polymerase chain reaction (PCR)-based assays to identify genetic loci that were altered in neoplastic and preneoplastic conditions of early and advanced gallbladder cancer. Our findings were then correlated with clinicopathological variables and survival time. METHODS: We selected 59 surgical specimens of gallbladder adenocarcinomas (29 early cancers and 30 advanced cancers) and 22 surgical specimens from patients with chronic cholecystitis from a high-risk area for gallbladder cancer (Temuco, Chile). Laser capture microdissection (LCM) was used to harvest tumor cells and preneoplastic lesions. Microsatellite analysis was performed using 13 different markers. The tumors and preneoplastic lesions were also examined with immunohistochemistry for hMLH1, hMSH2, and hMSH6. RESULTS: We found that 10% (6/59) of gallbladder cancers showed high-frequency microsatellite instability (MSI-H), with identical proportions in both early and advanced cancers. In premalignant lesions adjacent to the six MSI-H tumors, we detected instability in two of six examples of intestinal metaplasia (33%) and five of six examples of dysplasia (83%). All MSI-H cases showed an altered pattern with the antibodies studied. MSI status was not associated with survival or other clinicopathological features. No MSI or immunohistochemical alterations were found in the chronic cholecystitis group. CONCLUSIONS: Microsatellite instability was observed in equal proportions in early and late cancers, and it was also found in premalignant lesions, indicating that inactivation of mismatch repair genes occurs early in gallbladder carcinogenesis.

Assuntos

Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Instabilidade Genômica/genética , Repetições de Microssatélites/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Adenocarcinoma/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/metabolismo , Biomarcadores Tumorais/metabolismo , Chile/epidemiologia , Colecistite/genética , Colecistite/mortalidade , Colecistite/patologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/metabolismo , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/mortalidade , Estatística como Assunto , Análise de Sobrevida

RESUMO

Background: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Chilean subjects. Aim: To determine the frequency and distribution of exons 5, 6, 7, 8 and 9 mutations and the immunohistochemical expression of p53 gene in biopsy samples of colorectal carcinoma. Material and methods: p53 gene exons 5, 6, 7, 8 and 9 were directly sequenced in 42 biopsy samples of colorectal carcinoma. Immunohistochemical expression of p53 was determined in 35 samples. Results: Thirty one discrete mutations (12 transitions, 11 transversions and 8 insertions) were observed in 21 samples (60 percent). Nine samples had mutations in exon 5, twelve samples had mutations in exon 6, seven samples had mutations in exon 7 and three samples had mutations in exons 8 and 9. Immunohistochemical expression of p53 protein was observed in 18 of 35 cases. There was a high correlation between the genetic alteration and immunohistochemistry, when p53 was expressed in more the 20 percent of cells. The positive and negative predictive values of p53 expression were 87 and 80 percent respectively. There was a non significant lower mortality among patients with mutations in their biopsies. Conclusions: These results confirm the involvement of p53 gene mutations in colonic carcinogenesis. Immunohistochemical methods for the detection of p53 protein have a high predictive value

Assuntos

Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias Colorretais/genética , Adenocarcinoma/genética , Genes p53/genética , Sequência de Bases/genética , Éxons/genética , Intervalo Livre de Doença , Análise Mutacional de DNA , Imuno-Histoquímica , Mutação/genética