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1.
Chem Res Toxicol ; 34(8): 1866-1878, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34296853

RESUMO

The relationship between human papillomavirus (HPV) and esophageal cancer (EC) has been controversial, which may be caused by the difference in geographic regions of sample origin. Thus, we conducted a case-control study to find that HPV increased the risk of esophageal cancer, and the HPV18 detection rate is the highest (24.2%) among patients with EC, suggesting that HPV18 could be the most risk subtype of HPV infected. We then identified high-risk HPV18 and N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) to establish a model on the viral etiology cooperating with environmental carcinogens. Het-1A cells containing HPV18 were continuously exposed to MNNG or not; then the morphological phenotype and function assays were performed in 25th passage cells. MNNG promoted the proliferation and invasion abilities and inhibited apoptosis both in Het-1A-HPV18 and control group. However, the Het-1A-HPV18 had a stronger change in phenotypic features and formed more transformed foci in soft agar. Further, Western blot found p53 and p21 were down-regulated, and expression of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated. Our results revealed that MNNG was easier to induce malignant transformation of Het-1A cells transfected with HPV18. It is good evidence for the close relationship between HPV and the etiology of EC, providing foundation for further study in molecular mechanism and specific intervention targets.

2.
Acta Diabetol ; 58(11): 1513-1523, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34125293

RESUMO

OBJECTIVE: This study aimed to examine the prevalence of stroke and associated factors of stroke in patients with type 2 diabetes(T2DM) in China. METHODS: Participants were 18,013 T2DM patients recruited with stratified random cluster sampling method from December 2013 to January 2014 in China. Propensity score matching was used to eliminate confounding effects between groups and logistic regression analysis was used to examine factors associated with stroke among T2DM patients. RESULTS: Overall, the prevalence of stroke in the subjects with T2DM was 9.5%. After nearest neighbor matching, smoking (OR = 1.60, 95%CI: 1.26-2.03), hypertension (OR = 2.96, 95%CI: 2.55-3.43), dyslipidemia (OR = 2.00, 95%CI: 1.71-2.33), family history of stroke (OR = 2.02, 95%CI: 1.61-2.54), obesity (OR = 1.21, 95%CI: 1.01-1.45) and sleep duration < 6 h/day (OR = 1.44, 95%CI: 1.20-1.73) or > 8 h/day (OR = 1.22, 95%CI: 1.05-1.42) were positively associated with stroke, whereas drinking 1-3 days/week (OR = 0.64, 95%CI: 0.45-0.90) or daily (OR = 0.45, 95%CI: 0.33-0.60), effective exercise (OR = 0.65, 95%CI: 0.57-0.73) and underweight (OR = 0.30, 95%CI: 0.13-0.71) were negatively related to stroke. Besides, the risk of stroke increased substantially with accumulation of above seven modified risk factors. The odds ratio values of stroke in patients having ≥ 5 of the above seven risk factors was 14.39 (95% CI: 8.87-23.26). CONCLUSIONS: The prevalence of stroke was high among T2DM in China. It is of great significance to strengthen comprehensive management of health-related behaviors including smoking cessation, moderate alcohol consumption, effective exercise, 6-8 h of sleep duration, keeping normal weight and the prevention of hypertension and dyslipidemia to have sustained beneficial effects on improvements of stroke risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , China/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Pontuação de Propensão , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
3.
Transbound Emerg Dis ; 68(2): 773-781, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32725765

RESUMO

We investigated an outbreak of COVID-19 infection, which was traced back to a bathing pool at an entertainment venue, to explore the epidemiology of the outbreak, understand the transmissibility of the virus and analyse the influencing factors. Contact investigation and management were conducted to identify potential cases. Epidemiological investigation was carried out to determine the epidemiological and demographic characteristics of the outbreak. We estimated the secondary attack rate (SAR), incubation time and time-dependent reproductive number (Rt ) and explored the predisposing factors for cluster infection. The incubation time was 5.4 days and the serial interval (SI) was 4.4 days, with the rate of negative-valued SIs at 24.5%. The SAR at the bathing pool (3.3%) was relatively low due to its high temperature and humidity. The SAR was higher in the colleagues' cluster (20.5%) than in the family cluster (11.8%). Super-spreaders had a longer isolation delay time (p = .004). The Rt of the cluster decreased from the highest value of 3.88 on January 27, 2020 to 1.22 on February 6. Our findings suggest that the predisposing factors of the outbreak included close contact with an infected person, airtight and crowded spaces, temperature and humidity in the space and untimely isolation of patients and quarantine of contacts at the early stage of transmission. Measures to reduce the risk of infection at these gatherings and subsequent tracking of close contacts were effective.


Assuntos
COVID-19/diagnóstico , Surtos de Doenças , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/transmissão , Criança , Pré-Escolar , China/epidemiologia , Busca de Comunicante , Transmissão de Doença Infecciosa , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Toxicology ; 447: 152635, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189795

RESUMO

Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis. Our previous research suggested that HPV and MNNG led to malignant transformation of esophageal epithelial cells. To investigate the regulation and function of miR-218(miR-218-5p) during the malignant transformation of esophageal epithelial cells, we found miR-218 was inhibited synergistically by HPV and MNNG, suppressing cell proliferation, migration and invasion by up-regulating 3' untranslated region (3'UTR) GAB2 in Het-1A-HPV-MNNG cells (malignant Het-1A cells induced by HPV and MNNG). A negative correlation was found between miR-218 and GAB2 mRNA expression in esophageal cancer patients and control people. GAB2 was up-regulated in Het-1A-HPV-MNNG cells. Further, down-expression of GAB2 reversed HPV&MNNG-mediated activation of migration and invasion and repressed SHP2/ERK and Akt/mTOR pathway signaling. In conclusion, miR-218 partially accounts for the prevention effect during malignant transformation of normal esophageal epithelial cells, which targets GAB2, which supplies the potential treatment in cancer therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Metilnitronitrosoguanidina/administração & dosagem , Metilnitronitrosoguanidina/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Papillomaviridae/metabolismo , Linhagem Celular , Humanos , Infecções por Papillomavirus/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia
5.
Sci Total Environ ; 738: 139713, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526409

RESUMO

Esophageal cancer (EC) is a deadly malignancy worldwide with a high incidence and exhibits unevenly geographic prevalence, which suggests that environmental factors are deeply involved in the development of EC. Although the carcinogenesis of nitrosamines in the esophagus has been identified by tremendous toxicological data, the role of nitrosamines in the genesis of human EC has so far proved inconclusive largely due to a lack of convincing evidences. In this study, urinary nitrosamines in population controls and cases with esophageal precancerous lesions, including reflux esophagitis (RE) accompanying with basal cell hyperplasia (BCH) and dysplasia (DYS), and esophageal squamous cell carcinoma (ESCC) were detected by a SPE-LC-MS/MS method and the associated risk was evaluated. Higher excretion concentrations of N-nitrosomethylethylamine (NMEA) in the RE/BCH patients, NMEA and N-nitrosodibutylamine (NDBA) in the DYS patients, and NMEA, NDBA, N-nitrosopyrrolidine (NPyr) and N-nitrosomorpholine (NMor) in the ESCC patients were observed compared with the controls (p < .05). And with the progression of esophageal lesion, the exposure complexity increased in terms of the categories of nitrosamines. Furthermore, the observed positive associations between the hazardous exposure of NMEA, NDBA and NPyr and the increased risk of ESCC, and between NMEA and NDBA and RE/BCH were established. These findings provided direct evidence to support the hypothesis that exposure to nitrosamines are involved in the carcinogenesis of esophageal epithelia in this high incidence area from the perspective of endogenous exposure assessment. However, discoveries in this study need to be confirmed by systematic researches in the future. And the dose-response relationships, the reference ranges or cutoff values to predict the risks of nitrosamines exposure also need to be defined.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Nitrosaminas , China , Cromatografia Líquida , Humanos , Incidência , Espectrometria de Massas em Tandem
6.
Front Genet ; 10: 663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396261

RESUMO

Beta-actin (ACTB) loss-of-function mutations result in a pleiotropic developmental disorder of kidney. The present study aims to explore whether the common variants at the ACTB gene contribute to diabetic kidney disease (DKD) susceptibility in patients with type 2 diabetes mellitus (T2DM). From the baseline population of 20,340 diabetic patients, 1,510 DKD cases and 1,510 age-matched T2DM controls were selected. All subjects were Han Chinese. Three tagging single nucleotide polymorphisms (SNPs), rs852423, rs852426, and rs2966449, at the ACTB gene were genotyped. Logistic regression was performed to estimate the association with DKD. SNPs, rs852426 and rs2966449, were significantly associated with DKD [additive model; odds ratio (OR), 1.217 and 1.151; P = 0.001 and 0.018, respectively]. The association of rs852426 with DKD still remained statistically significant after Bonferroni correction and particularly significant in the population older than 70 years rather than the 70 years or younger (P = 0.047 for heterogeneity test). Furthermore, the association of rs852426 with DKD was observed in populations of male and females without smoking, drinking, and with duration for T2DM 10-20 years. The association of rs2966449 with DKD was also found in the populations older than 70 years, male, not smoking, not drinking, and with duration for T2DM over 20 years. The estimated glomerular filtration rate (eGFR) levels of the individuals with TT or CC genotypes of rs2966449 were significantly lower than that of TC genotype in DKD cases (P = 0.021). The present study provides evidence that the ACTB variants, i.e., rs852426 and rs2966449, may confer the genetic susceptibility to DKD in a Han Chinese population.

7.
BMJ Open ; 9(8): e027906, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31444181

RESUMO

OBJECTIVE: Investigating the association between total physical activity, physical activity in different domains and sedentary time with clustered metabolic risk in patients with type 2 diabetes from Jiangsu province, China. DESIGN: Interview-based cross-sectional study conducted between December 2013 and January 2014. SETTING: 44 selected townships across two cities, Changshu and Huai'an, in Jiangsu province. PARTICIPANTS: 20 340 participants selected using stratified cluster-randomised sampling and an interviewer-managed questionnaire. METHODS: We constructed clustered metabolic risk by summing sex-specific standardised values of waist circumference, fasting triacylglycerol, fasting plasma glucose, systolic blood pressure and the inverse of blood high-density lipoprotein cholesterol (HDL-cholesterol). Self-reported total physical activity included occupation, commuting and leisure-time physical activity. The un-standardised regression coefficient [B] and its 95% CI were calculated using multivariate linear regression analyses. RESULTS: This study included 17 750 type 2 diabetes patients (aged 21-94 years, 60.3% female). The total (B=-0.080; 95% CI: -0.114 to -0.046), occupational (B=-0.066; 95% CI: -0.101 to- 0.031) and leisure-time physical activity (B=-0.041; 95% CI: -0.075 to -0.007), and sedentary time (B=0.117; 95% CI: 0.083 to 0.151) were associated with clustered metabolic risk. Total physical activity, occupational physical activity and sedentary time were associated with waist circumference, triacylglycerol and HDL-cholesterol, but not with systolic blood pressure. Commuting physical activity and sedentary time were significantly associated with triacylglycerol (B=-0.012; 95% CI: -0.019 to -0.005) and fasting plasma glucose (B=0.008; 95% CI: 0.003 to 0.01), respectively. Leisure-time physical activity was only significantly associated with systolic blood pressure (B=-0.239; 95% CI: -0.542 to- 0.045). CONCLUSIONS: Total, occupational and leisure-time physical activity were inversely associated with clustered metabolic risk, whereas sedentary time increased metabolic risk. Commuting physical activity was inversely associated with triacylglycerol. These findings suggest that increased physical activity in different domains and decreased sedentary time may have protective effects against metabolic risk in type 2 diabetes patients.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Exercício Físico , Atividades de Lazer , Síndrome Metabólica/epidemiologia , Comportamento Sedentário , Idoso , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
8.
Chemosphere ; 235: 288-296, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31260869

RESUMO

The Huai'an area in Jiangsu Province of East China is an endemic region of esophageal cancer (EC). The regional heterogeneity of EC suggests that the levels of potential carcinogens might vary throughout the environment. It has been suggested that the most likely carcinogens related to EC are a group known as the N-nitrosamines. In this study, we measured the concentrations of nine nitrosamines in drinking water and human urine in two areas in China, one with a high incidence of EC (Huai'an) and one with a low incidence (Nanjing). Among the nine target analytes, N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosodiethylamine (NDEA) and N-nitrosomorpholine (NMor) occurred at higher concentrations in drinking water in the high incidence area. Inhabitants from the high incidence area also had urinary excretions with significantly higher concentrations of NDEA, NDBA, N-nitrosopiperidine (NPip) and N-nitrosodiphenylamine (NDPhA). These findings indicated that people in the high EC incidence area were exposed to higher levels of nitrosamines. However, the association between the incidence of EC and nitrosamines exposure will need to be evaluated in more detail.


Assuntos
Carcinógenos/análise , Água Potável/química , Neoplasias Esofágicas/epidemiologia , Nitrosaminas/análise , China , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/etiologia , Humanos , Incidência , Nitrosaminas/urina
9.
J Diabetes Complications ; 32(7): 623-629, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29884473

RESUMO

OBJECTIVE: To investigate the influence of age at menarche (AM) and age at natural menopause (ANM) on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was undertaken in Jiangsu, China. Logistic regression was used to evaluate the association between AM/ANM and glycemic control. RESULTS: 1195 (14.3%) premenopausal and 7149 (85.7%) postmenopausal women were included in this study. With the increase of AM per 1 year, patients had a low risk of uncontrolled FPG (≥7 mmol/L) and uncontrolled HbA1c (≥7%), as well as poor glycemic control (FPG ≥7 mmol/L and HbA1c ≥7%) after adjusting for age and BMI (model I, P < 0.05) with odds ratio (OR) 0.965, 0.978 and 0.962 respectively. Whereas after adjusting for age, BMI, education, duration of diabetes, smoking, drinking and antidiabetic treatment (model II) as well as further plus diabetic familial history and physical activity (model III), the association between AM and glycemic control was not significant (P > 0.05). Compared with premenopausal women, postmenopausal women had a low risk of uncontrolled FPG and uncontrolled HbA1c after adjusting for confounders in model II (P < 0.05). Furthermore, both patients with early ANM (<45 years) and late ANM (>55 years) had a high risk of uncontrolled HbA1c as well as poor glycemic control even adjusted for full confounders in model III (P < 0.05 for all). CONCLUSION: Early AM, early and late ANM were significantly associated with worse glycemic control. Ascertaining the AM and ANM in women with T2DM may help to identify the risk predisposed to worse glycemic control.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/metabolismo , Menarca/fisiologia , Menopausa/fisiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Glicemia/metabolismo , Criança , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Saúde Reprodutiva/estatística & dados numéricos , Fatores de Risco , Adulto Jovem
10.
Sci Rep ; 7(1): 1432, 2017 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-28469277

RESUMO

To investigate the association of familial history (FH) of diabetes with the glycaemic control status of patients with type 2 diabetes (T2D), a cross-sectional study using stratified cluster sampling was conducted with 20,340 diabetic patients in Jiangsu, China. In total, 21.3% of the subjects reported a FH of diabetes. Patients with a FH of diabetes showed a higher risk of poor glycaemic control (59.7%) than those without a diabetic FH (49.8%), with an odds ratio (OR) of 1.366 (P < 0.001). Glycaemic control status did not significantly differ between the T2D patients with parental FH and those with sibling FH. Compared with patients with paternal FH, patients with maternal FH had a higher risk of poor glycaemic control (OR = 1.611, P = 0.013). Stratified analyses showed that a FH of diabetes was significantly associated with poor glycaemic control among T2D patients with a low education level (P < 0.05). In the <60 years old, overweight, and low level of physical activity groups, patients with a maternal history of diabetes showed a higher risk of poor glycaemic control than those without a FH (P < 0.05). In conclusion, FH of diabetes, especially a maternal history, had an independently adverse effect on the glycaemic control of T2D patients.


Assuntos
Glicemia/genética , Diabetes Mellitus Tipo 2/genética , Hemoglobina A Glicada/genética , Hereditariedade , Hiperglicemia/genética , Padrões de Herança , Idoso , Glicemia/metabolismo , China , Análise por Conglomerados , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Família , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hiperglicemia/sangue , Hiperglicemia/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances
11.
J Neurol Sci ; 376: 176-180, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28431608

RESUMO

OBJECTIVE: To investigate the relationship of serum UA and ischemic stroke in type 2 diabetes patients in China. METHOD: We examined the above relationship using the data of the project "Comprehensive Research on the Prevention and Control of the Diabetes" (CRPCD) study. A total of 19,442 participants were enrolled in the cross-sectional study. The enrolled participants were divided into quintiles of the serum UA levels with cut off values for two age groups (<60 versus ≥60years). Binary logistic regression analyses were used to evaluate whether the levels of serum UA were independently associated with ischemic stroke in type 2 diabetes. RESULTS: The serum UA levels were significantly higher in the participants with age≥60years than those with age<60years (P=0.000). In the age group of <60years, the odds ratio for ischemic stroke with type 2 diabetes in quintile 5 over quintile 1 was 2.420 (95% CI, 1.566-3.470) in the unadjusted model and 1.765 (95% CI, 1.097-2.840) after controlling potential confounders. However, the reverse results were observed in the age group of ≥60years. The odds ratio in quintile 4 over quintile 1 in model 3 and model 4 were 0.767 (95% CI, 0.630-0.934) and 0.782 (95% CI, 0.640-0.957). CONCLUSION: Our results indicated that serum UA levels were independently positively associated with ischemic stroke in patients aged <60years, but the association was U-shaped in patients aged ≥60years.


Assuntos
Isquemia Encefálica/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Acidente Vascular Cerebral/sangue , Ácido Úrico/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Isquemia Encefálica/complicações , China , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Acidente Vascular Cerebral/complicações , Inquéritos e Questionários
12.
Mol Med Rep ; 14(4): 3805-13, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27572636

RESUMO

MicroRNA (miRNA) clusters are expressed universally across different types of organisms, and an accumulating number of studies have demonstrated that miRNA clusters function more efficiently compared with single miRNAs during the development of certain cancer types. miRNA clusters may have increased stability and reliability over individual miRNAs as diagnostic or therapeutic biomarkers. In the present study, the expression levels of mature miRNAs within the miR-144/451 cluster were examined using stem­loop reverse transcription­quantitative polymerase chain reaction in 102 patients pathologically diagnosed with esophageal carcinoma. Bioinformatics tools were used to identify a possible miRNA­mediated network of the miR­144/451 cluster. The expression levels of hsa­miR­451a, hsa­miR­144­3p and hsa­miR­144­5p in tumor tissues were significantly lower compared with those in adjacent non­tumor tissues (P<0.05). Pearson correlation analysis demonstrated that the expression levels of individual miR­144/451 cluster members were correlated with each other, except for the pair of hsa­miR­144­3p and hsa­miR­4732­3p. In particular, hsa­miR­144­5p expression was highly associated with hsa-miR-4732­5p and hsa-miR-451a expression levels, with correlation coefficients of 0.729 and 0.608, respectively. Furthermore, the low expression levels of hsa­miR­144­3p [odds ratio (OR), 0.85; P<0.05] and hsa-miR-144-5p (OR, 0.84; P<0.05) were determined to be risk factors for esophageal carcinoma development. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that miRNAs forming the miR­144/451 cluster may cooperate to regulate the cell cycle. Therefore, the miR­144/451 cluster may serve an important role in the progression of esophageal carcinoma and may be considered as a biomarker for the detection of esophageal carcinoma at an early stage.


Assuntos
Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , Adulto , Idoso , Esôfago/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica , Análise de Componente Principal
13.
Int J Mol Sci ; 16(11): 27781-95, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26610476

RESUMO

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), methylation specific PCR (MSP), and 5-aza-2'-deoxycytidine treatment assay were applied to determine the methyaltion status of miR-218 in cells and clinical samples. In vitro assays were performed to explore the role of miR-218. Results showed that miR-218-1 was significantly CpG hypermethylated in tumor tissues (81%, 34/42) compared with paired non-tumor tissues (33%, 14/42) (p < 0.05). However, no statistical difference was found in miR-218-2. Accordingly, expression of miR-218 was negatively correlated with miR-218-1 methylation status (p < 0.05). After demethylation treatment by 5-aza-2'-deoxycytidine, there was a 2.53- and 2.40-fold increase of miR-218 expression in EC109 and EC9706, respectively. miR-218 suppressed cell proliferation and arrested cells at G1 phase by targeting 3' untranslated region (3'UTR) of roundabout guidance receptor 1 (ROBO1). A negative correlation was found between miR-218 and ROBO1 mRNA expression in clinical samples. In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for miR-218 silencing in ESCC, which impairs its tumor-suppressive function.


Assuntos
Transformação Celular Neoplásica/genética , Repressão Epigenética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Interferência de RNA , Receptores Imunológicos/genética , Regiões 3' não Traduzidas , Azacitidina/farmacologia , Sequência de Bases , Sítios de Ligação , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ilhas de CpG , Metilação de DNA , Carcinoma de Células Escamosas do Esôfago , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ordem dos Genes , Loci Gênicos , Humanos , MicroRNAs/química , RNA Mensageiro/química , RNA Mensageiro/genética
14.
Biomed Res Int ; 2014: 645056, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25530966

RESUMO

BACKGROUND: Cancer is a significant disease burden in the world. Many studies showed that heavy metals or their compounds had connection with cancer. But the data conflicting about the relationship of manganese (Mn) to cancer are not enough. In this paper, the relationship was discussed between Mn concentrations in drinking water for rural residents and incidence and mortality caused by malignant tumors in Huai'an city. METHODS: A total of 158 water samples from 28 villages of 14 towns were, respectively, collected during periods of high flow and low flow in 3 counties of Huai'an city, along Chinese Huai'he River. The samples of deep groundwater, shallow groundwater, and surface water were simultaneously collected in all selected villages. Mn concentrations in all water samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS 7500a). The correlation analysis was used to study the relationship between the Mn concentration and cancer incidence and mortality. RESULTS: Mn concentrations detectable rate was 100% in all water samples. The mean concentration was 452.32 µg/L ± 507.76 µg/L. There was significant difference between the high flow period and low flow period (t = -5.23, P < 0.05) and also among deep groundwater, shallow groundwater, and surface water (F = 5.02, P < 0.05). The ratio of superscale of Mn was 75.32%. There was significant difference of Mn level between samples in the high flow period and low flow period (χ(2) = 45.62, P < 0.05) and also among deep groundwater, shallow groundwater, and surface water (χ(2) = 10.66, P < 0.05). And also we found that, during the low flow period, Mn concentration has positive correlation with cancer incidence and mortality; for a 1 µg/L increase in Mn concentration, there was a corresponding increase of 0.45/100000 new cancer cases and 0.35/100000 cancer deaths (P < 0.05). CONCLUSIONS: In Huai'an city, the mean concentration of Mn in drinking water was very high. Mn concentration correlated with cancer incidence and mortality.


Assuntos
Água Potável/efeitos adversos , Manganês/toxicidade , Neoplasias/mortalidade , China , Cidades , Monitoramento Ambiental , Humanos , Manganês/isolamento & purificação , Neoplasias/induzido quimicamente , Rios , Poluentes Químicos da Água/toxicidade
15.
Mol Cells ; 37(12): 873-80, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25518924

RESUMO

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA microarray was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/genética , Regiões 3' não Traduzidas , Apoptose , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/metabolismo
16.
Med Oncol ; 31(2): 784, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24366688

RESUMO

To determine the relevance of O-6-methylguanine-DNA methyltransferase (MGMT), human mutS homolog 2 (hMSH2), and human mutL homolog 1 (hMLH1) in TP53 mutations in esophageal squamous cell carcinoma, we employed methylation-sensitive high-resolution melting technology and methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of MGMT, hMSH2, and hMLH1, respectively, in 51 paired tumors and their adjacent normal tissues. The protein expression of the three proteins was also evaluated by Western blot analysis, and the PCR products of TP53, from exon 5 to exon 8, were directly sequenced to measure the mutation spectrum. Esophageal tumor tissues embraced statistically higher MGMT and hMSH2 promoter methylation level than normal tissue. The promoter methylation status of MGMT and hMSH2 corresponds positively with the protein expression level of MGMT and hMSH2. However, such relevance was not found for hMLH1. Furthermore, TP53 mutation status was well associated with MGMT and hMSH2 promoter methylation status, indicating that silencing of the two genes could lead to TP53 mutation in ESCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Neoplasias Esofágicas/genética , Proteína 2 Homóloga a MutS/genética , Mutação/genética , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metilases de Modificação do DNA/metabolismo , Reparo do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , DNA de Neoplasias/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Esôfago/patologia , Humanos , Repetições de Microssatélites , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Gradação de Tumores , Proteínas Nucleares/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/metabolismo
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 35(10): 1105-8, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25567013

RESUMO

OBJECTIVE: This study was to understand the status of pollution on drinking water, by volatile organic compounds (VOCs), among rural residents living in the basin of Huaihe River. Relationship between the morbidity, morbidity of cancers and VOCs were also explored. METHODS: 28 villages were chosen from Xuyi,Jinhu, Chuzhou along the Huaihe River, with water samples collected from ditch pond water, shallow wells, deep wells in November-December 2010. VOCs indicators were evaluated according to the Standard Quality GB 5749-2006 for Drinking Water. RESULTS: Methylene chloride, chloroform, benzene and carbon tetrachloride were all detected in 76 water samples. The rates of chloroform, benzene, carbon tetrachloride which exceeding the quality standards were 3.95% , 21.05% and 22.37% , but no significant differences were found among these three water resources in chloroform, benzene or carbon tetrachloride. Results from the correlation analysis showed that benzene had positive correlation with tumor deaths (r = 0.24, P < 0.05). Results from the risk assessment on health showed that some chloroform, benzene, carbon tetrachloride products which were related to the risks of cancers were exceeding the acceptable ranges of risk, with the rates as 28.95%, 22.37% and 64.47% but with no significant differences among the three water resources (P > 0.05). CONCLUSION: Drinking waters for rural residents along the Huaihe River were polluted while VOCs might have related to tumor incidence with potential impact and risk to the health of local residents.


Assuntos
Água Potável/química , Saúde da População Rural/estatística & dados numéricos , Compostos Orgânicos Voláteis/análise , Poluição Química da Água/análise , China , Humanos , Medição de Risco , Compostos Orgânicos Voláteis/efeitos adversos , Poluição Química da Água/efeitos adversos
18.
Int J Mol Sci ; 14(5): 8899-911, 2013 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-23615477

RESUMO

Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Cromatografia Líquida de Alta Pressão/métodos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , Espectrometria de Massas/métodos , Metabolômica/métodos , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Fatores de Risco
19.
Oncol Rep ; 29(1): 169-76, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23124769

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, differentially expressed miRNAs in tumor tissues and adjacent non-tumor tissues were detected by miRNA microarrays. Stem-loop real-time reverse transcription PCR was conducted to verify the candidate miRNAs discovered by microarray analysis. The data showed that hsa-miR-338-3p, hsa-miR­218 and hsa-miR-139-5p were downregulated in tumor tissues compared with adjacent non-tumor tissues, while hsa-miR­183, hsa-miR-574-5p, hsa-miR-21* and hsa-miR­601 were upregulated in tumor tissues. Multiple regression analysis revealed the aberrant expression of hsa-miR-338-3p, hsa­miR-139-5p, hsa-miR­574-5p and hsa-miR-601 increased the risk of esophageal cancer. Furthermore, we found hsa-miR-21* was significantly increased in heavy drinking patients. Therefore, there is a set of differentially expressed miRNAs in esophageal cancer which may be associated with the incidence and development of ESCC. Differential expression profiles of miRNAs in ESCC may be promising biomarkers for the early screening of high-risk populations and early detection.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Perfilação da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Diagnóstico Precoce , Neoplasias Esofágicas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
J Toxicol Environ Health A ; 75(18): 1154-62, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22891887

RESUMO

MicroRNAs (miRNAs) are postulated to play important roles in oncogenesis. Recently, extracellular miRNAs were detected in plasma or serum of diseased subjects. However, the role of circulating miRNAs in plasma/serum remains to be elucidated. In this study, the relative expressions of miR-155, miR-183, and miR-20a in esophageal tissue were found to be significantly associated with increased risk for esophageal cancer. The relative expressions of circulating miR-155 and miR-183 were significantly reduced in cancer patients. Circulating miR-155 showed significantly higher risk for esophageal cancer when adjusted by smoking status and alcohol use. Circulating miR-155 was found to have significant diagnostic value for esophageal cancer as evidenced by a receiver operating characteristic curve area of 66%. However, Pearson analysis showed no statistical correlation in the relative miRNAs expression between plasma and esophageal tissues, which suggested different origins of circulating miRNAs distinct from tumor cell miRNAs. In conclusion, results suggest that circulating miR-155 in plasma may serve as a reliable, novel, noninvasive biomarker for early diagnosis and detection of esophageal cancer.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Detecção Precoce de Câncer , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , MicroRNAs/sangue , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etnologia , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etnologia , Esôfago/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Risco , Sensibilidade e Especificidade , Inquéritos e Questionários
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