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1.
Adv Exp Med Biol ; 1193: 221-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368107

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a member of ALDH family. ALDH1 has been widely recognized for its roles in carcinogenesis and cancer therapy; however, investigation for ALDH2 in cancer is seldom mentioned. The ALDH2 point mutation ALDH2*2 is the most frequent human gene variant, and it is present in approximately 560 million East Asians. ALDH2*2 demonstrates its effect on alcohol consumption limiting and alcoholism developing protection, and this variant is recently found to have an important impact on human health. This chapter focuses on its potential effect on cancer therapy, especially for chemotherapeutics with anthracyclines.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Antraciclinas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Alcoolismo/genética , Humanos
2.
Mol Nutr Food Res ; 63(19): e1900249, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31271251

RESUMO

BACKGROUND: Calorie restriction (CR) is a therapeutically effective method for nonalcoholic fatty liver disease. However, the compliance of the CR method is relatively poor. New CR methods are needed. METHODS AND RESULTS: Each week, mice are given a 5-day high-fat diet (HFD) ad libitum plus 2 days of an intermittent calorie restriction (ICR) diet (50% calorie restriction) consisting of yogurt, fruit, and vegetables, for 16 weeks. The effect of the ICR diet model on the fatty liver of mice is examined. Compared with continuous HFD-fed mice, the mice feeding HFD+ICR have lower body weight and hepatic steatosis, reduced serum lipid and transaminase levels, increased fatty acid oxidation gene of Cpt1a, and decreased hepatic lipid synthesis gene of Pparγ and Srebf-1c, as well as improved insulin resistance and lower level of inflammation. Moreover, ICR reverses the dysbacteriosis in HFD group, including the lower Shannon diversity indexes and lower abundance of Lactobacillus. CONCLUSION: An ICR diet consisting of yogurt, fruit, and vegetables attenuates the development of HFD-induced hepatic steatosis in mice. Furthermore, HFD+ICR diet is associated with a different fecal microbiota that tends to be more similar to normal diet controls.

3.
J Cancer ; 10(16): 3767-3777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333794

RESUMO

Background: Marital status has been reported as an independent prognostic factor for survival in various cancers, but it has been rarely studied in renal clear cell carcinoma (ccRCC). In this study, we aimed to assess the impact of marital status on the survival of ccRCC patients. Methods: We retrospectively investigated the Surveillance, Epidemiology, and End Results (SEER) database and identified 68599 of ccRCC patients between 1973 and 2015. These patients were divided into married, single, divorced and widowed groups. The survival differences among these groups were assessed by Kaplan-Meier method and log-rank test. Multivariate Cox regression analyses were performed to identify the overall survival (OS) and cancer-specific survival (CSS) independent factors. Furthermore, 1:1 propensity score matching (PSM) analysis was performed to minimize the potential confounding factors. Results: Of the 68599 ccRCC patients, 44553 (64.95%) patients were married, 7410 (10.80%) were divorced, 10663 (15.54%) were single, and 5973 (8.71%) were widowed. The 5-year OS was 79.0%, 73.8%, 77.3%, and 66.4 % in the married, divorced, single, and widowed groups, respectively (p = 0.001) and the corresponding 5-year CSS rates were 85.5%, 83.3%, 80.8%, 76.5%, respectively. Multivariate Cox regression analysis marital status was the independent prognostic factor for OS and CSS. Compared with the married patients, the divorced, single, and widowed patients faced increased higher mortality risks for OS and CSS. In stratified analyses by sex, surgery conditions and cancer stages, those unmarried patients still had worse prognosis. The results were further confirmed in the 1: 1 matched group. Conclusion: Unmarried ccRCC patients experienced worse survival than their married counterparts. Among the unmarried patients, the widowed suffered the highest mortality risks for OS and CSS.

4.
Future Oncol ; 15(21): 2503-2515, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31240959

RESUMO

Aim: To evaluate the impact of socioeconomic factors (SEFs) on survival of renal cell carcinoma (RCC) patients. Materials & methods: RCC patients diagnosed between 2007 and 2015 were collected from the SEER database. The crude and multivariate Cox regression analysis was used to identify the independent prognostic factors and quantity the mortality risks for overall survival (OS). Results: Three SEFs including marital status, insurance status and median household income were identified as prognostic factors for OS. SEF-stage was built based on the three SEFs. Moreover, the SEF-stage 1 had superior OS than SEF-stage 2 within the respective American Joint Committee on Cancer stages. Conclusion: The SEF-stage was an independently prognostic factor for OS in RCC. Incorporation of SEF-stage into the American Joint Committee on Cancer staging system might be beneficial for better survival prediction and clinical management. However, further studies were needed to validate these findings in other populations.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Adolescente , Adulto , Carcinoma de Células Renais/diagnóstico , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Vigilância em Saúde Pública , Programa de SEER , Fatores Socioeconômicos , Carga Tumoral , Adulto Jovem
5.
Ann Hepatol ; 18(6): 913-917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31147179

RESUMO

BACKGROUND AND AIMS: Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated. METHODS: Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV+EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed. RESULTS: Hepatic steatosis was significantly more severe in the HBV+EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV+EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV+EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR)=1.43, P<0.01). CONCLUSIONS: Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.

6.
Med Sci Monit ; 25: 2966-2975, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31009445

RESUMO

BACKGROUND This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) of Forkhead box O3 (FOXO3) gene with type 2 diabetes mellitus (T2D). MATERIAL AND METHODS A total of 843 elderly residents from east China were enrolled in this study, which included 426 patients with type 2 diabetes and 417 controls. Four SNPs were analyzed by qPCR. Genotype frequencies of the 4 SNPs in FOXO3 of the patients and controls were analyzed using logistic regression analysis. The association between each SNP and clinical indicators was analyzed by linear regression analysis. RESULTS None of the 4 FOXO3 variants, rs13217795, rs2764264, rs2802292, and rs13220810, were associated with the risk of type 2 diabetes compared to controls. However, rs13217795, rs2764264, and rs2802292 were associated with lower blood glucose levels. Notably, further subgroup analysis indicated that the longevity-associated alleles of FOXO3 SNP (rs13217795, rs2764264, and rs2802292) were associated with lower blood glucose levels in women (TC versus TT, -0.724 mmol/L, P=0.005; CC versus TT, -1.093 mmol/L, P=0.03; TC versus TT, -0.801 mmol/L, P=0.002; CC versus TT, -1.212 mmol/L, P=0.001; TG versus TT, -0.754 mmol/L, P=0.004; and GG versus TT, -1.150 mmol/L, P=0.001) but not in men. CONCLUSIONS The results indicated that longevity-associated FOXO3 variants were correlated with lower blood glucose levels in elderly women with type 2 diabetes in east China.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O3/genética , Longevidade/genética , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Proteína Forkhead Box O3/metabolismo , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
7.
Acta Pharmacol Sin ; 40(2): 231-242, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29921883

RESUMO

Annonaceous acetogenins are a well-established family of natural products with significant bioactivities, especially high cytotoxic and antitumor activities. AA005 is an annonaceous acetogenin mimic that has shown significant cytotoxicity against a variety of cancer cell lines, but its in vivo antitumor effects have not been demonstrated so far, and its anticancer mechanisms remain ambiguous. In this study, we investigated the effects of AA005 on human colon cancer cell lines in vivo. Human colon carcinoma cell line SW620 xenograft nude mice were treated with AA005 (5 mg/kg/day, i.p.) for 21 days. AA005 administration markedly inhibited the tumor growth via promoting nuclear translocation of apoptosis-inducing factor (AIF) and inducing AIF-dependent cell death. Subsequent studies in human colon carcinoma cell lines SW620 and RKO in vitro revealed that after the colon cancer cells exposed to AA005, downregulation of a B-cell lymphoma 2 family protein, myeloid cell leukemia-1 (Mcl-1), was an early event due to the inhibition of Mcl-1 mRNA level and protein synthesis in a time-dependent manner. Intriguingly, knockdown of Mcl-1 using small interfering RNA markedly accelerated the nuclear translocation of AIF and upregulation of receptor interacting protein-1, and enhanced AA005-mediated lethality, whereas ectopic expression of Mcl-1 substantially attenuated AA005-mediated lethality in the colon cancer cells. Finally, silencing Mcl-1 expression markedly enhanced AA005-induced lethality in SW620 xenograft nude mice, demonstrating a pivotal role of Mcl-1 downregulation in mediating the in vivo antitumor effects of AA005. Taken together, this study demonstrates for the first time the anticancer effects of AA005 against human colon cancer cell lines in vivo, which is mediated through the downregulation of Mcl-1.


Assuntos
Acetogeninas/química , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Álcoois Graxos/uso terapêutico , Lactonas/uso terapêutico , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Animais , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Álcoois Graxos/química , Humanos , Lactonas/química , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Oncotarget ; 9(17): 13959-13970, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29568408

RESUMO

Obesity is one of the major risk factors of cancer. However, how body mass index (BMI) influences the prognosis of renal cell cancer (RCC) patient is unclear. In this work, we have performed a meta-analysis to elucidate the role of abnormal weight in RCC mortality and postoperative survival. Articles related to BMI and RCC mortality as well as postoperative survival has been identified by searching PUBMED and ENBASE. Totally, 19 articles have been selected for this meta-analysis, 5 articles for RCC mortality and 14 for postoperative survival. Compared to normal weight, the estimated relative risks of RCC mortality are 0.71 (95% CI: 0.34-1.49), 1.19 (95% CI: 1.05-1.35) and 1.71 (95% CI: 1.27-2.00) respectively for the underweight, overweight and obesity patients. The risk of RCC mortality increase 5% for each 1 kg/m2 increment of BMI. However, the estimated hazard ratios of cancer specific postoperative survival are 2.62 (95% CI: 1.67-4.11), 0.72 (95% CI: 0.63-0.83) and 0.66 (95% CI: 0.49-0.89) respectively for underweight, overweight and obesity RCC patients. The risk of hazard ratio decrease 5% for each 1 kg/m2 increment of BMI. In addition, the hazard ratios of postoperative overall survival show a similar tendency. These results indicate an opposite association of BMI with mortality and postoperative survival in renal cell cancer patients.

9.
Clin Exp Hypertens ; 40(7): 695-701, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29400588

RESUMO

Essential hypertension is a leading global public health issue, billions of people suffered from it every year. Recently, multiple evidence suggests that DNA methylation play an important role in regulating blood pressure. Here, we tested the risk for essential hypertension conferred by single nucleotide polymorphisms (SNPs) within DNA methyltransferase 1 (DNMT1). Three loci (rs2228611, rs2228612, and rs16999593) were selected to be analyzed in 3410 cases and 1307 normal controls in southern Chinese aged 60 or above. No significant association with essential hypertension was observed for rs2228612 and rs16999593. A higher risk of essential hypertension was found in the minor A allele of rs2228611 in the codominant and recessive model (P < 0.05). After stratified by sex, this association was found in male but not female. Furthermore, this difference was abolished after BMI adjustment in the whole population and reduced in male. In addition, the mutation rate of rs2228611 was higher in the obesity group compared with the normal weight group of male. Intriguingly, rs2228611 was also a risk factor of essential hypertension in normal weight male. These findings indicated that rs2228611 might contribute to male hypertension via BMI-dependent mechanisms in obesity male and BMI-independent mechanisms in normal weight male.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/genética , Hipertensão Essencial/genética , Predisposição Genética para Doença/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fatores Sexuais
10.
Oncotarget ; 8(42): 72959-72971, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069840

RESUMO

Excess body weight has a positive association with risk of liver cancer, but the gender difference in the relationship between body mass index and liver cancer risk remains uncertainty. In this work, we performed meta-analysis for excess body weight and risk of liver cancer incidence to identify the gender difference. We searched the English-languages database and the Chinese literature databases to May 12, 2017. Overall, a total of 17 studies were included. Relative risks (RRs) with 95% confidence intervals was used to evaluate the strength of these associations. The RRs of liver cancer incidence for obese men and women were 2.04 (1.70-2.44) and 1.56 (1.37-1.78). The former one was significantly higher than the later one (P for interaction = 0.02). Notably, the RR of liver cancer incidence in non-Asian obese men was even higher than their counter part (2.31(1.85-2.91) vs. 1.56 (1.31-1.86), P for interaction = 0.01). Similar gender difference was observed in the dose-response curve. As example, at the point of BMI = 32 kg/m2, the RRs for men and women were 1.61 (1.45-1.79) and 1.41 (1.02-1.94) respectively. Findings from this meta-analysis indicate that obesity is associated with a higher risk of liver cancer incidence in men, especially in non-Asian men, which might partially contribute to the male dominance of liver cancer incidence.

11.
Nat Commun ; 8: 15337, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28643803

RESUMO

The von Hippel-Lindau (VHL) is deficient in ∼70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in ccRCC cells. Furthermore, VHL regulates ALDH2 expression by directly binding the promoter of -130 bp to -160 bp to activate the transcription of hepatocyte nuclear factor 4 alpha (HNF-4α). In addition, a positive correlation is found among the protein expressions of VHL, HNF-4α and ALDH2 in ccRCC samples. These findings will deepen our understanding of VHL function and shed light on precise treatment for ccRCC patients.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Antraciclinas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Regulação para Baixo/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Antraciclinas/farmacologia , Antraciclinas/toxicidade , Carcinoma de Células Renais/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Proteômica , Transcrição Genética/efeitos dos fármacos
12.
Clin Exp Hypertens ; 39(8): 691-695, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28613083

RESUMO

Essential hypertension (EH) is a worldwide problem. Acetaldehyde dehydrogenase 2 (ALDH2) gene has been suggested to be correlated with EH. However, the results are inconsistent. This study aimed to investigate the associations of ALDH2 rs671 polymorphism with EH in a Chinese Han population in Shanghai. Genotype of ALDH2 rs671 was analyzed in 1923 EH patients and 1115 control subjects. We found no association between ALDH2 rs671 and EH risk or EH-related quantitative blood chemistry values. Furthermore, a meta-analysis was performed and the summary results from 11220 patients and 8339 control subjects were consistent with our findings. These results indicated that rs671 of ALDH2 may not associate with the risk of EH.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Hipertensão Essencial/genética , Predisposição Genética para Doença , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Hipertensão Essencial/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
13.
Mol Cell ; 65(2): 296-309, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28065600

RESUMO

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.


Assuntos
Aminoácido Oxirredutases/metabolismo , Linfócitos T CD4-Positivos/enzimologia , Colite/enzimologia , Processamento de Proteína Pós-Traducional , Fator de Transcrição STAT3/metabolismo , Acetilação , Aminoácido Oxirredutases/deficiência , Aminoácido Oxirredutases/genética , Animais , Linfócitos T CD4-Positivos/imunologia , Catálise , Diferenciação Celular , Núcleo Celular/enzimologia , Proliferação de Células , Colite/genética , Colite/imunologia , Modelos Animais de Doenças , Genótipo , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Domínios Proteicos , Multimerização Proteica , Interferência de RNA , Fator de Transcrição STAT3/genética , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia , Células Th17/enzimologia , Células Th17/imunologia , Transcrição Genética , Transfecção
14.
Oncotarget ; 8(4): 6623-6629, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28036261

RESUMO

Thyroid stimulating hormone receptor messenger RNA (TSHR-mRNA) is over-expressed in thyroid cancer patients, which indicates that TSHR-mRNA is a potential biomarker of thyroid cancer. However, system evaluation for TSHR-mRNA as a diagnostic biomarker of thyroid cancer is deficient. The performance of TSHR-mRNA for thyroid cancer diagnosis was evaluated in this study. Three common international databases as well as a Chinese database were applied for literature researching. Quality assessment of the included literatures was conducted by the QUADAS-2 tool. Totally, 1027 patients from nine studies eligible for the meta-analysis were included in this study. Global sensitivity and specificity for the positivity of TSHR-mRNA in the thyroid cancer diagnosis is 72% and 82%. The value of AUC for this test performance was 0.84. Our meta-analysis suggests that TSHR-mRNA might be a potential biomarker to complete present diagnostic methods for early and precision diagnosis of thyroid cancer. Notably, this findings need validation thorough large-scale clinical studies.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Detecção Precoce de Câncer/métodos , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptores dos Hormônios Tireóideos/genética , Neoplasias da Glândula Tireoide/genética , Área Sob a Curva , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Distribuição de Qui-Quadrado , Humanos , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Curva ROC , Receptores dos Hormônios Tireóideos/sangue , Reprodutibilidade dos Testes , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia
15.
Oncotarget ; 7(28): 43669-43679, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27248320

RESUMO

Obesity is a known cause of gallstone formation and gallstones increases the risk of gallbladder cancer (GBC), but the relation of body mass index (BMI) to GBC remains incompletely understood. To help elucidate the role of obesity in GBC, we performed a meta-analysis of the relationship between BMI and GBC risk. PUBMED and EMBASE databases were searched up to April 17, 2016. Fifteen articles with 5902 cases were identified. Random-effects models and dose-response meta-analyses were used to pool study results. Compared to normal weight, the pooled relative risks (RRs) and the corresponding 95% confidence intervals (CI) of GBC for overweight and obesity is 1.10 (0.98-1.23) and 1.58 (1.43-1.75) respectively. The RRs and 95% CI of overweight and obesity in man are 0.98 (0.90-1.08) and 1.43 (1.19-1.71), while the corresponding RRs in woman are 1.29 (1.08-1.55) and 1.68 (1.41-2.00) when compared to normal weight. A nonlinear dose-response relationship between BMI and risk of GBC was found (P=0.001), and the risk increased by 4% for each 1 kg/m2 increment in BMI. When adjusted for sex, at the point of BMI=25 kg/m2, the RRs (95% CIs) for women and men were 1.13 (1.01-1.25) and 0.98 (0.90-1.07) respectively. The corresponding RRs (95%CIs) at the point of BMI=30 kg/m2 were 1.56(1.39-1.75) vs. 1.24(1.06-1.44). These results suggest that association of obesity and risk of GBC is stronger in woman. Furthermore, overweight is only associated with GBC in woman. A even stricter weight control might be necessary for woman to prevent GBC.


Assuntos
Neoplasias da Vesícula Biliar/epidemiologia , Obesidade/complicações , Sobrepeso/complicações , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
16.
Oncotarget ; 7(30): 47750-47759, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27351286

RESUMO

Thyrotropin (TSH) is thought as a risk factor for thyroid cancer. However, the effect of serum TSH might depend on histological types of thyroid cancer. We searched for related studies including serum TSH as an exposure and thyroid cancer as a result in PUBMED, EMBASE and Chinese National Knowledge Infrastructure up to April 21, 2016. This meta-analysis included 22 articles with 53,538 participants. When comparing all histological thyroid cancer, the pooled odds ratios of thyroid cancer in patients with nodules was found to increase significantly with higher serum TSH concentrations for differentiated thyroid carcinoma (1.88 vs .1.48, P = 0.0000) and papillary thyroid carcinoma (2.08 vs. 1.48, P = 0.0006). Each 1 mU/L increase of serum TSH was associated with 14% greater risk of thyroid cancer for all histological thyroid cancer, 16% for differentiated thyroid carcinoma and 22% for papillary thyroid carcinoma. In addition, high serum TSH was associated with a reduced risk for follicular thyroid carcinoma (OR = 0.73, 95% CI: 0.52, 1.02). This meta-analysis suggested high serum TSH concentration is risky for papillary thyroid carcinoma but not for follicular thyroid carcinoma.


Assuntos
Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Tireotropina/sangue , Humanos , Fatores de Risco
17.
BMC Genet ; 16: 139, 2015 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-26635120

RESUMO

BACKGROUND: Adaption to cold temperatures, especially those below freezing, is essential for animal survival in cold environments. Freezing is also used for many medical, scientific, and industrial purposes. Natural freezing survival in animals has been extensively studied. However, the underlying mechanisms remain unclear. Previous studies demonstrated that animals survive in extremely cold weather by avoiding freezing or controlling the rate of ice-crystal formation in their bodies, which indicates that freezing survival is a passive thermodynamic process. RESULTS: Here, we showed that genetic programming actively promotes freezing survival in Caenorhabditis elegans. We found that daf-2, an insulin/IGF-1 receptor homologue, and loss-of-function enhanced survival during freeze-thaw stress, which required the transcription factor daf-16/FOXO and age-independent target genes. In particular, the freeze-thaw resistance of daf-2(rf) is highly allele-specific and has no correlation with lifespan, dauer formation, or hypoxia stress resistance. CONCLUSIONS: Our results reveal a new function for daf-2 signaling, and, most importantly, demonstrate that genetic programming contributes to freezing survival.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Insulina/metabolismo , Receptor de Insulina/metabolismo , Estresse Fisiológico , Alelos , Animais , Comportamento Animal , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Núcleo Celular/metabolismo , Forma Celular , Congelamento , Genes de Helmintos , Larva/fisiologia , Longevidade/genética , Transporte Proteico , Transdução de Sinais , Análise de Sobrevida
18.
Biochem Biophys Res Commun ; 468(1-2): 312-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26505800

RESUMO

Mammalian CCAAT/enhancer-binding proteins (C/EBPs) are generally known as regulators in adipocyte differentiation. However, more understanding of the role of C/EBPs in lipid and glucose metabolism remains to be discovered. In this study, we verified the effect of CEBP-2, the homolog of CEBPs, on fat storage in Caenorhabditis elegans. Expressions of 85 genes that encode the major enzymes in energy metabolic pathways were then screened in cebp-2-deficient worms using a quantitative real-time polymerase chain reaction (QRT-PCR). Our data implied that loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5. Our findings indicated that cebp-2 controls total body fat content by governing fatty acid mitochondrial ß-oxidation and desaturation in C. elegans. These data provide insights into how C/EBPs may affect lipid metabolism in mammals in addition to regulating adipocyte differentiation.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Ácidos Graxos/metabolismo , Animais , Caenorhabditis elegans/genética , Metabolismo Energético , Deleção de Genes , Regulação da Expressão Gênica , Oxirredução
19.
BMC Cancer ; 15: 139, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25885900

RESUMO

BACKGROUND: Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. METHODS: We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and related proteins were characterized by western blot. Immunofluorescence and subcellular fractionation were used to evaluate AIF nuclear translocation. Reactive oxygen species were assessed by using redox-sensitive dye DCFDA. RESULTS: AA005 induces a unique type of cell death in colorectal adenocarcinoma cells, characterized by lack of caspase-3 activation or apoptotic body formation, sensitivity to poly (ADP-ribose) polymerase inhibitor Olaparib (AZD2281) but not pan-caspase inhibitor Z-VAD.fmk, and dependence on apoptosis-inducing factor (AIF). AA005 treatment also reduced expression of mitochondrial Complex I components, and leads to accumulation of intracellular reactive oxygen species (ROS) at the early stage. Blocking ROS formation significantly suppresses AA005-induced cell death in SW620 cells. Moreover, blocking activation of RIP-1 by necroptosis inhibitor necrotatin-1 inhibits AIF translocation and partially suppresses AA005-induced cell death in SW620 cells demonstrating that RIP-1 protein may be essential for cell death. CONCLUSIONS: AA005 may trigger the cell death via mediated by AIF through caspase-3 independent pathway. Our work provided new mechanisms for AA005-induced cancer cell death and novel clues for cancer treatment via AIF dependent cell death.


Assuntos
Acetogeninas/farmacologia , Fator de Indução de Apoptose/biossíntese , Caspase 3 , Álcoois Graxos/farmacologia , Lactonas/farmacologia , Acetogeninas/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Álcoois Graxos/química , Humanos , Lactonas/química , Espécies Reativas de Oxigênio/metabolismo , Células U937
20.
Mol Med Rep ; 11(4): 2813-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25483709

RESUMO

One member of the highly conserved acidic leucine­rich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, ANP32B, is critical for normal development, as demonstrated by a study in ANP32B­deficient mice. Another study indicated that ANP32B was a direct substrate of caspase­3, and was primarily cleaved at the sequence Ala­Glu­Val­Asp, following Asp­163. To investigate the significance of ANP32B cleavage in apoptosis, leukemic U937T cell lines were generated with inducible expression of ANP32B(wild type; WT), the uncleavable mutant ANP32B(D163A) and the N­terminal fragment ANP32B(1­163). Notably, overexpression of ANP32B(WT) and ANP32B(D163A) moderately increased and significantly enhanced etoposide­induced apoptosis and caspase­3 activation, whereas expression of ANP32B(1­163) produced no effect. Two hypotheses have been generated, which may explain the distinct roles of the various ANP32B forms: i) ANP32B(WT) and ANP32B(D163A) localize in the nucleus while ANP32B(1­163) mainly resides in the cytosol; or ii) ANP32B(WT) and ANP32B(D163A), but not ANP32B(1­163), inhibit the expression of the anti­apoptotic protein Bcl­2. Based on these observations, caspase­3­resistant uncleavable ANP32B(D163A) is hypothesized to be pro­apoptotic in leukemic cells.


Assuntos
Apoptose , Caspase 3/metabolismo , Leucemia/metabolismo , Proteínas Nucleares/metabolismo , Domínios e Motivos de Interação entre Proteínas , Apoptose/genética , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Leucina , Leucemia/genética , Mutação , Proteínas Nucleares/química , Proteínas Nucleares/genética , Domínios e Motivos de Interação entre Proteínas/genética , Proteína Quinase C-delta/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
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