RESUMO
Circulating tumor cells (CTCs) are cells that have shed into the vasculature or lymphatics from a primary tumor and are carried around the body in the blood circulation. CTCs undergo a series of migration, adhesion and aggregation to form metastases, leading to post-operative recurrence and metastasis in patients with malignant tumors. The detection and analysis of CTCs, as a new non-invasive diagnostic tool, plays an important role in tumor diagnosis, therapeutic efficacy, monitoring recurrence, prognosis assessment and tumor precision medical treatment.
Assuntos
Neoplasias/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Medicina de Precisão , PrognósticoRESUMO
Gout is the most common form of inflammatory arthritis affecting men, and current evidence suggests that genetic factors contribute to its progression. As a previous study identified that WD40 repeat protein 1 (WDR1) is associated with gout in populations of European descent, we sought to investigate its relationship with this disease in the Han Chinese population. We genotyped six WDR1 single nucleotide polymorphisms in 143 gout cases and 310 controls using Sequenom MassARRAY technology. The SPSS 16.0 software was used to perform statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression, with adjustments for age and gender. In an analysis using an allelic model, we identified that the minor alleles of rs3756230 (OR = 0.64, 95%CI = 0.450-0.911, P = 0.013) and rs12498927 (OR = 1.377, 95%CI = 1.037-1.831, P = 0.027) were associated with gout risk. In addition, we found that the "A/A" genotype of rs12498927 was associated with increased risk of gout under codominant (OR = 2.22, 95%CI = 1.12- 4.40, P = 0.042) and recessive models (OR = 2.24, 95%CI = 1.20-4.17, P = 0.012). We also determined the "A/G" genotype of rs12498927 to be significantly associated with higher urea levels in gout patients (P = 0.017). Our data shed new light on the association between genetic variations in the WDR1 gene and gout susceptibility in the Han Chinese population.
Assuntos
Gota/genética , Proteínas dos Microfilamentos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , China , Feminino , Gota/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/sangueRESUMO
Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed. The aim of the present study was to investigate the potential association between variants in these two genes and metabolism-related quantitative phenotypes relevant to gout in a Chinese Tibetan population. In total, 316 Chinese Tibetan gout patients were recruited from rheumatology outpatient clinics and 6 single nucleotide polymorphisms in PDK2 and ABCG2 were genotyped, which were possible etiologic variants as identified in the HapMap Chinese Han Beijing population. A significant difference in blood glucose levels was detected between different genotypes of rs2728109 (P = 0.005) in the PDK2 gene. We also detected a significant difference in the mean serum uric levels between different genotypes of rs3114018 (P = 0.004) in the ABCG2 gene. All P values remained significant after Bonferroni's correction for multiple testing. Our data demonstrate potential roles for PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients, which may provide new insights into the etiology of gout. Further studies are required to confirm these findings.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Glicemia/metabolismo , Predisposição Genética para Doença , Gota/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Ácido Úrico/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Povo Asiático , Feminino , Expressão Gênica , Gota/sangue , Gota/etnologia , Gota/patologia , Projeto HapMap , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Análise de Sequência de DNA , TibetRESUMO
Genetic polymorphisms of very important pharmacogenomic (VIP) variants are important for personalized medicine. However, these have not been extensively studied in the Tibetan population. In this study, 82 VIP variants were detected in the Tibetan and Han (HAN) populations from northwestern China. Subsequently, we compared the differences between the Tibetan population and ten populations, including the HAN, Japanese in Tokyo (JPT), Mexican ancestry in Los Angeles (MEX), Toscans in Italy (TSI), African ancestry in Southwest USA (ASW), Luhya in California Webuye, Kenya (LWK), Gujarati Indians in Houston, Texas (GIH), Maasai in Kinyawa, Kenya (MKK), Yoruba in Ibadan, Nigeria (YRI), and Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). Using the χ(2) test, we identified differences in the frequency distribution of 4, 4, 7, 10, 11, 11, 13, 15, 19, and 20 loci in the Tibetan population, compared to the HAN, JPT, MEX, TSI, ASW, LWK, GIH, MKK, YRI, and CEU populations, respectively [P < 0.05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-endoperoxide synthase 2) genes, respectively, in the Tibetan population were different from those in most of the populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan people, and provide an avenue for personalized treatment in the Tibetan population.
Assuntos
Araquidonato 5-Lipoxigenase/genética , Ciclo-Oxigenase 2/genética , Vitamina K Epóxido Redutases/genética , Adulto , Alelos , Povo Asiático , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Haplótipos , Humanos , Masculino , Farmacogenética , Polimorfismo de Nucleotídeo Único , TibetRESUMO
The association between the rs2230199 C>G single nucleotide polymorphism (SNP) in complement component 3 and age-related macular degeneration (AMD) risk has been examined extensively but the results are not consistent among studies. The aim of this study was to perform a meta-analysis of all available studies on this SNP in relation to AMD. The comprehensive databases of PubMed, Medline, Web of Knowledge, CNKI, and Google Scholar were searched for case-control studies investigating the association between the rs2230199 polymorphism and AMD susceptibility. ORs with 95%CIs were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. A total of 15 published studies including 5593 cases and 5181 controls were used in this meta-analysis. Overall, the rs2230299 SNP was significantly associated with the risk of AMD in the overall population under the additive model (OR = 1.571, 95%CI = 1.414-1.745, P = 0.000), dominant model (OR = 1.681, 95%CI = 1.521-1.858, P = 0.000), and allelic model (OR = 1.597, 95%CI = 1.470-1.734, P = 0.000). In the subgroup analysis by ethnicity, the same results were found in Caucasian populations, while no significant correlations were found in Asian populations for all comparison models. In conclusion, our meta-analysis provides evidence that the rs2230199 polymorphism contributes to the development of AMD. Further large-scale multicenter epidemiological studies are warranted to confirm this finding.
Assuntos
Complemento C3/genética , Degeneração Macular/genética , Alelos , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Current evidence suggests that heredity and metabolic syndrome contribute to gout progression. SLC2A9 and ZNF518B may play a role in gout progression in different populations, but no studies have focused on the Tibetan Chinese population. In this study, we determined whether variations in these 2 genes were correlated with gout-related indices in Chinese-Tibetan gout patients. We detected 6 single nucleotide polymorphisms in SLC2A9 and ZNF518B in 319 Chinese Tibetan gout patients. One-way analysis of variance was used to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators. Polymorphisms in SLC2A9 and ZNF518B affected multiple risk factors related to gout development. Significant differences in serum triglyceride levels and high-density lipoprotein-cholesterol level were detected between different genotypic groups with SLC2A9 polymorphisms rs13129697 (P = 0.022), rs4447863 (P = 0.018), and rs1014290 (P = 0.045). Similarly in ZNF518B, rs3217 (P = 0.016) and rs10016022 (P = 0.046) were associated with high creatinine and glucose levels, respectively. This study is the first to investigate and identify positive correlations between SLC2A9 and ZNF518B gene polymorphisms and metabolic indices in Tibetan gout patients. We found significant evidence indicating that genetic polymorphisms affect gout-related factors in Chinese Tibetan populations.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas Facilitadoras de Transporte de Glucose/genética , Gota/genética , Gota/metabolismo , Metaboloma , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Biomarcadores , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Gota/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tibet/epidemiologia , Dedos de ZincoRESUMO
We aimed to investigate the association of inflammation-related genes such as IL-10, IL-6 and IL-1B with risk of ischemic stroke. We included 426 cases with ischemic stroke and 426 health controls from Xinxiang, China. Genomic DNA was extracted from the buffy coat layer of collected blood with the TIANamp blood DNA kit. Diabetes, hypertension, obesity, and smoking habits were associated with risk of ischemic stroke. We found that individuals carrying the CC genotype of IL-1B rs1864169 had a higher risk of ischemic stroke when compared with the TT genotype (OR = 1.80, 95%CI = 1.16-2.80). The IL-6 rs1800796 TT genotype was associated with increased risk of ischemic stroke. We found that IL-1B rs1864169 and IL-6 rs1800796 polymorphisms may interact with diabetes, hypertension and obesity. Our study suggests that IL-6 rs1800796 and IL-1B rs1864169 polymorphisms are associated with ischemic stroke risk in the Chinese population.
Assuntos
Isquemia Encefálica/genética , Interleucina-10/genética , Interleucina-1beta/genética , Interleucina-6/genética , Trombose Intracraniana/genética , Acidente Vascular Cerebral/genética , Adulto , Povo Asiático , Isquemia Encefálica/sangue , Isquemia Encefálica/etnologia , Isquemia Encefálica/patologia , Estudos de Casos e Controles , Diabetes Mellitus/fisiopatologia , Feminino , Genótipo , Humanos , Hipertensão/fisiopatologia , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Trombose Intracraniana/sangue , Trombose Intracraniana/etnologia , Trombose Intracraniana/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/patologiaRESUMO
We conducted a comprehensive study to investigate the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. Genotyping of seven gene polymorphisms was performed on a 384-well plate format on the Sequenom MassARRAY platform in 162 patients with osteosarcoma. We studied the correlation of the seven gene polymorphisms with response to chemotherapy and clinical outcome of patients. Individuals with the ABCB1 TT genotype had a higher probability of responding poorly to chemotherapy, indicated by an odds ratio (OR) of 2.64 (95%CI=1.04-6.83). Similarly, the genotype of GSTP1 GG was significantly associated with improved responses to chemotherapy, indicated by an OR of 3.33 (95%CI=1.26-8.99). The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter overall survival (OS). Our study found that two gene polymorphisms in two transporter genes and one Phase II metabolism enzymes are associated with response to chemotherapy and OS in osteosarcoma patients, suggesting the potential of the two gene polymorphisms as prognostic biomarkers for osteosarcoma.
Assuntos
Neoplasias Ósseas/genética , Glutationa S-Transferase pi/genética , Osteossarcoma/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Biomarcadores Farmacológicos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Criança , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Desintoxicação Metabólica Fase II/genética , Pessoa de Meia-Idade , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Polimorfismo de Nucleotídeo Único , PrognósticoRESUMO
Hepatic progenitor cells (HPCs) are a potential cell source for liver cell transplantation but do not function like mature liver cells. We sought an effective and reliable method to induce HPC maturation. An immortalized HP14.5 albumin promoter-driven Gaussian luciferase (ALB-GLuc) cell line was established from HPCs isolated from fetal mouse liver of post coitus day 14.5 mice to investigate the effect of induction factors on ALB promoter. HP14.5 parental cells were cultured in DMEM with different combinations of 2% horse serum (HS), 0.1 µM dexamethasone (DEX), 10 ng/mL hepatic growth factor (HGF), and/or 20 ng/mL fibroblast growth factor 4 (FGF4). Trypan blue and crystal violet staining were used to assess cell proliferation with different induction conditions. Expression of hepatic markers was measured by semi-quantitative RT-PCR, Western blot, and immunofluorescence. Glycogen storage and metabolism were detected by periodic acid-Schiff and indocyanine green (ICG) staining. GLuc activity indicated ALB expression. The combination of 2% HS+0.1 µM Dex+10 ng/mL HGF+20 ng/mL FGF4 induced the highest ALB-GLuc activity. Cell proliferation decreased in 2% HS but increased by adding FGF4. Upon induction, and consistent with hepatocyte development, DLK, AFP, and CK19 expression decreased, while ALB, CK18, and UGT1A expression increased. The maturity markers tyrosine aminotransferase and apolipoprotein B were detected at days 3 and 6 post-induction, respectively. ICG uptake and glycogen synthesis were detectable at day 6 and increased over time. Therefore, we demonstrated that HPCs were induced to differentiate into functional mature hepatocytes in vitro, suggesting that factor-treated HPCs may be further explored as a means of liver cell transplantation.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Hepatócitos/citologia , Fígado/citologia , Células-Tronco/efeitos dos fármacos , Animais , Antígenos de Diferenciação/análise , Apolipoproteína B-100 , Apolipoproteínas B/isolamento & purificação , Proliferação de Células , Dexametasona/administração & dosagem , Fatores de Crescimento de Fibroblastos/administração & dosagem , Violeta Genciana , Glicogênio/metabolismo , Fator de Crescimento de Hepatócito/administração & dosagem , Verde de Indocianina/farmacocinética , Camundongos , Cultura Primária de Células/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/citologia , Azul Tripano , Tirosina Transaminase/isolamento & purificaçãoRESUMO
Hepatic progenitor cells (HPCs) are a potential cell source for liver cell transplantation but do not function like mature liver cells. We sought an effective and reliable method to induce HPC maturation. An immortalized HP14.5 albumin promoter-driven Gaussian luciferase (ALB-GLuc) cell line was established from HPCs isolated from fetal mouse liver of post coitus day 14.5 mice to investigate the effect of induction factors on ALB promoter. HP14.5 parental cells were cultured in DMEM with different combinations of 2% horse serum (HS), 0.1 µM dexamethasone (DEX), 10 ng/mL hepatic growth factor (HGF), and/or 20 ng/mL fibroblast growth factor 4 (FGF4). Trypan blue and crystal violet staining were used to assess cell proliferation with different induction conditions. Expression of hepatic markers was measured by semi-quantitative RT-PCR, Western blot, and immunofluorescence. Glycogen storage and metabolism were detected by periodic acid-Schiff and indocyanine green (ICG) staining. GLuc activity indicated ALB expression. The combination of 2% HS+0.1 µM Dex+10 ng/mL HGF+20 ng/mL FGF4 induced the highest ALB-GLuc activity. Cell proliferation decreased in 2% HS but increased by adding FGF4. Upon induction, and consistent with hepatocyte development, DLK, AFP, and CK19 expression decreased, while ALB, CK18, and UGT1A expression increased. The maturity markers tyrosine aminotransferase and apolipoprotein B were detected at days 3 and 6 post-induction, respectively. ICG uptake and glycogen synthesis were detectable at day 6 and increased over time. Therefore, we demonstrated that HPCs were induced to differentiate into functional mature hepatocytes in vitro, suggesting that factor-treated HPCs may be further explored as a means of liver cell transplantation.