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1.
Eur J Cancer Prev ; 30(6): 448-456, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34292200

RESUMO

OBJECTIVES: Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population. METHODS: Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored. RESULTS: Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects. CONCLUSIONS: Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.


Assuntos
Neoplasias Gástricas , Estudos de Casos e Controles , Dieta/efeitos adversos , Dieta Saudável , Humanos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/prevenção & controle
2.
Hum Gene Ther ; 31(9-10): 565-574, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32220217

RESUMO

A 20-nt long sequence, termed the D-sequence, in the adeno-associated virus (AAV) inverted terminal repeat was observed to share a partial sequence homology with the X-box in the regulatory region of the human leukocyte antigen DRA (HLA-DRA) promoter of the human major histocompatibility complex class II (MHC-II) genes. The D-sequence was also shown to specifically interact with the regulatory factor binding to the X-box (RFX), binding of which to the X-box is a critical step in the MHC-II gene expression, suggesting that D-sequence might compete for RFX transcription factor binding, thereby suppressing expression from the MHC-II promoter. In DNA-mediated transfection experiments, using a reporter gene under the control of the HLA-DRA promoter, D-sequence oligonucleotides were found to inhibit expression of the reporter gene expression in HeLa and 293 cells by ∼93% and 96%, respectively. No inhibition was observed when nonspecific synthetic oligonucleotides were used. D-sequence oligonucleotides had no effect on expression from the cytomegalovirus immediate-early gene promoter. Interferon-γ-mediated activation of MHC-II gene expression was also inhibited by D-sequence oligonucleotides as well as after infection with either the wild-type AAV or transduction with recombinant AAV vectors. These studies suggest that the D-sequence-mediated downregulation of the MHC-II gene expression may be exploited toward the development of novel AAV vectors capable of dampening the host humoral response, which has important implication in the optimal use of these vectors in human gene therapy.


Assuntos
Dependovirus/genética , Antígenos de Histocompatibilidade Classe II/genética , Imunidade Humoral , Sequências Repetidas Terminais , Animais , DNA Viral , Regulação para Baixo , Regulação da Expressão Gênica , Genes MHC da Classe II , Terapia Genética , Vetores Genéticos , Células HEK293 , Antígenos HLA/genética , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Fator Regulador X1/genética , Homologia de Sequência
3.
Nutrients ; 11(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480423

RESUMO

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.


Assuntos
Dieta/efeitos adversos , Alho/efeitos adversos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Alimentos Crus/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , China/epidemiologia , Dieta/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
4.
J Med Chem ; 62(19): 8711-8732, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31532644

RESUMO

Clinical development of catechol-based orthosteric agonists of the dopamine D1 receptor has thus far been unsuccessful due to multiple challenges. To address these issues, we identified LY3154207 (3) as a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity. Conformational studies showed LY3154207 adopts an unusual boat conformation, and a binding pose with the human D1 receptor was proposed based on this observation. In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. This cocrystal form was advanced to clinical development as a potential first-in-class D1 PAM and is now in phase 2 studies for Lewy body dementia.


Assuntos
Isoquinolinas/farmacologia , Receptores de Dopamina D1/agonistas , Acetilcolina/metabolismo , Administração Oral , Regulação Alostérica/efeitos dos fármacos , Animais , Sítios de Ligação , Cristalografia por Raios X , AMP Cíclico/metabolismo , Células HEK293 , Meia-Vida , Humanos , Isoquinolinas/química , Isoquinolinas/farmacocinética , Rim/efeitos dos fármacos , Rim/metabolismo , Locomoção/efeitos dos fármacos , Camundongos , Conformação Molecular , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/metabolismo , Ratos , Receptores de Dopamina D1/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade
5.
Nutrients ; 11(8)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357492

RESUMO

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.


Assuntos
Colesterol na Dieta/efeitos adversos , Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Neoplasias Gástricas/epidemiologia , Idoso , Estudos de Casos e Controles , China/epidemiologia , Colesterol na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle
6.
Liver Int ; 39(8): 1490-1503, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31228882

RESUMO

BACKGROUND & AIMS: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. METHODS: We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. RESULTS: Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). CONCLUSIONS: Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.


Assuntos
Hepatite B/complicações , Neoplasias Hepáticas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
7.
Transl Oncol ; 12(6): 819-827, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959265

RESUMO

Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case-control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at >54 vs. <46 years old) was associated with increased risk of lung cancer (SBOR, semi-Bayes adjusted odds ratio = 1.61, 95% PI, posterior interval = 1.10-2.36). More pregnancies (2 or 3 vs. 0 or 1) was associated with decreased risk (SBOR = 0.71, 95% PI = 0.53, 0.95). Ever being a smoker and having two or fewer pregnancies in one's lifetime could jointly increase the odds of lung cancer (RERI, relative excess risk due to interaction = 1.71, 95% CI = 0.03, 3.38). An increased number of ovulatory cycles was associated with increased risk of lung cancer (SBOR for 13 ovulatory cycles = 1.02, 95% CI = 1.00+, 1.04).

8.
Eur J Cancer Prev ; 28(4): 278-286, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30001285

RESUMO

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Comportamento Alimentar , Alho , Fumar Tabaco/epidemiologia , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , China/epidemiologia , Inquéritos sobre Dietas/estatística & dados numéricos , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar Tabaco/efeitos adversos
9.
J Med Chem ; 61(6): 2303-2328, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29350927

RESUMO

Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking. As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4ß-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses. From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity. Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.


Assuntos
Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/farmacologia , Agonistas de Aminoácidos Excitatórios/síntese química , Agonistas de Aminoácidos Excitatórios/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Animais , Compostos Bicíclicos com Pontes/farmacocinética , Cristalografia por Raios X , AMP Cíclico/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacocinética , Antagonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fenciclidina/antagonistas & inibidores , Fenciclidina/farmacologia , Ligação Proteica , Ratos , Ratos Sprague-Dawley
10.
Int J Cancer ; 142(8): 1560-1567, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29193051

RESUMO

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.


Assuntos
Hepatite B/complicações , Neoplasias Hepáticas/etiologia , Fumar Tabaco/efeitos adversos , Povo Asiático , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos
11.
Eur J Cancer Prev ; 26(4): 357-364, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27275735

RESUMO

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Esofágicas/etiologia , Estilo de Vida , Neoplasias Hepáticas/etiologia , Neoplasias Pulmonares/etiologia , Fumar/efeitos adversos , Neoplasias Gástricas/etiologia , Idoso , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Inquéritos e Questionários
12.
J Med Chem ; 58(18): 7526-48, 2015 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-26313429

RESUMO

Identification of orthosteric mGlu(2/3) receptor agonists capable of discriminating between individual mGlu2 and mGlu3 subtypes has been highly challenging owing to the glutamate-site sequence homology between these proteins. Herein we detail the preparation and characterization of a series of molecules related to (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate 1 (LY354740) bearing C4-thiotriazole substituents. On the basis of second messenger responses in cells expressing other recombinant human mGlu2/3 subtypes, a number of high potency and efficacy mGlu2 receptor agonists exhibiting low potency mGlu3 partial agonist/antagonist activity were identified. From this, (1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 14a (LY2812223) was further characterized. Cocrystallization of 14a with the amino terminal domains of hmGlu2 and hmGlu3 combined with site-directed mutation studies has clarified the underlying molecular basis of this unique pharmacology. Evaluation of 14a in a rat model responsive to mGlu2 receptor activation coupled with a measure of central drug disposition provides evidence that this molecule engages and activates central mGlu2 receptors in vivo.


Assuntos
Compostos Bicíclicos com Pontes/química , Receptores de Glutamato Metabotrópico/agonistas , Triazóis/química , Regulação Alostérica , Animais , Ligação Competitiva , Compostos Bicíclicos com Pontes/farmacocinética , Compostos Bicíclicos com Pontes/farmacologia , Cálcio/metabolismo , AMP Cíclico/metabolismo , Cães , Agonismo Parcial de Drogas , Humanos , Masculino , Camundongos , Modelos Moleculares , Atividade Motora/efeitos dos fármacos , Mutagênese Sítio-Dirigida , Estrutura Terciária de Proteína , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Estereoisomerismo , Triazóis/farmacocinética , Triazóis/farmacologia
13.
Bioorg Med Chem Lett ; 25(16): 3176-8, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26091726

RESUMO

EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2-induced suppression of TNFα production in human whole blood. From this class, a potent and highly bioavailable compound (6) has been selected for potential clinical studies. EP4 binding and functional data, selectivity, and pharmacokinetic properties of this compound are included.


Assuntos
Analgésicos/química , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Analgésicos/metabolismo , Analgésicos/farmacocinética , Animais , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Cães , Meia-Vida , Humanos , Lipopolissacarídeos/toxicidade , Ligação Proteica , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
14.
PLoS One ; 9(7): e102685, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25019554

RESUMO

BACKGROUND: Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk. OBJECTIVES: To explore the association between household ventilation and lung cancer. METHODS: A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj) and their 95% confidence intervals (CI). RESULTS: Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98), bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources. CONCLUSIONS: A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Neoplasias Pulmonares/epidemiologia , Ventilação , Poluição do Ar em Ambientes Fechados/análise , Estudos de Casos e Controles , China , Habitação , Humanos , Modelos Logísticos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Razão de Chances , Fatores de Risco
15.
Zhonghua Liu Xing Bing Xue Za Zhi ; 34(2): 114-9, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23751462

RESUMO

OBJECTIVE: To understand the relationship between green tea drinking and/or garlic consumption and lung cancer. METHODS: A population-based case-control study was conducted in Ganyu county, Jiangsu province. Epidemiological data including demography, lifestyle, environmental exposures and dietary habits were collected by face-to-face interviews using a standardized questionnaire. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CI) in both univariate and multivariate analyses. RESULTS: Both green tea drinking and garlic consumption were inversely associated with lung cancer and the adjusted ORs were: 0.78 (95%CI: 0.65 - 0.95) for green tea, 0.79 (95%CI: 0.66 - 0.95) for garlic intake, and 0.69 (95%CI: 0.53 - 0.89) for both, respectively. They also modified the associations of smoking, fried food intake and cooking oil under high-temperature with lung cancer as risk factors. Potential interactions were found between garlic or green tea and the risk factors of lung cancer. CONCLUSION: Both green tea drinking and garlic consumption might serve as protective factors on lung cancer.


Assuntos
Comportamento Alimentar , Alho , Neoplasias Pulmonares/epidemiologia , Chá , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Cancer Prev Res (Phila) ; 6(7): 711-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23658367

RESUMO

Protective effect of garlic on the development of cancer has been reported in the in vitro and in vivo experimental studies; however, few human epidemiologic studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was used to estimate adjusted ORs and their 95% confidence intervals (CI), and to evaluate ratio of ORs (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44-0.72) with a monotonic dose-response relationship (Ptrend < 0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking [synergy index (SI) = 0.70; 95% CI, 0.57-0.85; and ROR = 0.78; 95% CI, 0.67-0.90], as well as high-temperature cooking oil fume (ROR = 0.77; 95% CI, 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation.


Assuntos
Dieta , Alho/química , Neoplasias Pulmonares/prevenção & controle , Fumar/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Culinária , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Inquéritos e Questionários
17.
Int J Cancer ; 132(8): 1868-77, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22930414

RESUMO

Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population-based case-control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08-1.66] for G-allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A-allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12-2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54-1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high-risk Chinese population.


Assuntos
Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo Único , Idoso , Aldeído-Desidrogenase Mitocondrial , Estudos de Casos e Controles , China , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 33(8): 857-61, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22967345

RESUMO

OBJECTIVE: To examine the association between tea drinking and the risk of lung cancer in Chinese population. METHODS: All relevant published articles in Chinese and English literature database were identified. Meta-analysis was conducted. Combined odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the associations and dose-response relationship between tea drinking and the risk of lung cancer. RESULTS: Twelve studies were included. An inverse association with lung cancer was observed on tea drinkers when compared to non-tea drinkers (OR = 0.66, 95%CI: 0.49 - 0.89). CONCLUSION: Tea drinking might serve as a protective factor on lung cancer in the Chinese population.


Assuntos
Neoplasias Pulmonares/epidemiologia , Chá , Povo Asiático , Estudos de Casos e Controles , Ingestão de Líquidos , Humanos , Fatores de Risco
19.
Cancer Lett ; 308(2): 189-96, 2011 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-21665362

RESUMO

A population-based case-control study was conducted in a high-risk area (Dafeng) and a low-risk area (Ganyu) of Jiangsu province, China. In this analysis, the population attributable fraction (PAF) was calculated to quantify the etiology of risk factors; the relative attributable risk (RAR) was applied to explore how much of the incidence difference could be explained by variations in the distribution of risk factors. Results showed that unhealthy lifestyles accounted for a high fraction of esophageal cancer in China. Dissimilar distribution of several lifestyle factors, together with hereditary variations may be largely responsible for the incidence difference between areas.


Assuntos
Neoplasias Esofágicas/epidemiologia , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Cancer Causes Control ; 22(4): 649-57, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21321789

RESUMO

Although the association for esophageal cancer with tobacco smoking and alcohol drinking has been well established, the risk appears to be less strong in China. To provide more evidence on the effect of smoking and alcohol consumption with esophageal cancer in China, particularly among Chinese women, a population-based case-control study has been conducted in Jiangsu, China, from 2003 to 2007. A total of 1,520 cases and 3,879 controls were recruited. Unconditional multivariate logistic regression analysis was applied. Results showed that the odds ratio (OR) and confidence interval (CI) for ever smoking and alcohol drinking were 1.57 (95% CI: 1.34-1.83) and 1.50 (95% CI: 1.29-1.74). Dose-response relationships were observed with increased intensity and longer duration of smoking/drinking. Risk of smoking and alcohol drinking at the highest joint level was 7.32 (95% CI: 4.58-11.7), when compared to those never smoked and never drank alcohol. Stratifying by genders, smoking and alcohol drinking increased the risk among men with an OR of 1.74 (95% CI: 1.44-2.09) and 1.76 (95% CI: 1.48-2.09); however, neither smoking nor alcohol consumption showed a significant association among women. In conclusion, smoking and alcohol drinking were associated with esophageal cancer risk among Chinese men, but not among Chinese women.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático/estatística & dados numéricos , Carcinoma/etiologia , Neoplasias Esofágicas/etiologia , Caracteres Sexuais , Fumar/efeitos adversos , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma/epidemiologia , Carcinoma/etnologia , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etnologia , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , População , Fatores de Risco , Fumar/epidemiologia
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