Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • 1
    Publication Date: 2018-02-16
    Description: Purpose: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC. Experimental Design: GWAS scan is performed in a collection of 205 HBV-related HCC trios (each trio includes an affected proband and his/her both parents), and 355 chronic HBV carriers with HCC (cases) and 360 chronic HBV carriers without HCC (controls), followed by two rounds of replication studies totally consisting of 3,796 cases and 2,544 controls. Results: We identified a novel association signal within the CDK14 gene at 7q21.13 (index rs10272859, OR = 1.28, P = 9.46 x 10 –10 ). Furthermore, we observed that the at-risk rs10272859[G] allele was significantly associated with higher mRNA expression levels of CDK14 in liver tissues. Chromosome conformation capture assays in liver cells confirmed that a physical interaction exists between the promoter region of CDK14 and the risk-associated SNPs in strong linkage disequilibrium with the index rs10272859 at 7q21.13. This index rs10272859 also showed significant association with the survival of HCC patients. Conclusions: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. Clin Cancer Res; 24(4); 906–15. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-04-07
    Description: Objective Non-alcoholic fatty liver disease (NAFLD) is a major public health burden in China, and its prevalence is increasing. This study aimed to determine the risk factors and biomarkers of NAFLD. Design An observational cross-sectional primary survey. Setting Central China. Participants The study included 1479 participants aged over 18 and below 80 years, not currently being treated for cancer or infectious disease or no surgery in the previous year, and no history of cancer or an infectious disease. Participants underwent clinical examination, metabolomic assay and anthropometric assessment. Univariate and logistic regression analyses were used to evaluate associations between covariates and NAFLD. Main outcome measures Risk factors and metabolic biomarkers including sex, body mass index, hypertension, body fat ratio, blood triglycerides, blood fasting glucose, liver enzyme elevation, uric acid and oleic acid-hydroxy oleic acid (OAHOA). Results Data from the 447 participants (mean age 44.3±11.9 years) were analysed, and the prevalence of NAFLD was 24.7%. Male sex (OR 3.484, 95% CI 2.028 to 5.988), body mass index ≥24 kg/m 2 (OR 8.494, 95% CI 5.581 to 12.928), body fat ratio (≥25 for women, ≥20 for men) (OR 1.833, 95% CI 1.286 to 2.756), triglycerides ≥1.7 mmol/L (OR 1.340, 95% CI 1.006 to 1.785), fasting glucose ≥6.1 mmol/L (OR 3.324, 95% CI 1.888 to 5.850), blood pressure ≥140/90 mm Hg or antihypertensive drug treatment (OR 1.451, 95% CI 1.069 to 1.970), uric acid (≥357 μmol/L for women, ≥416 μmol/L for men) (OR 2.755, 95% CI 2.009 to 3.778) and OAHOA (〈5 nmol/L) (OR 1.340, 95% CI 1.006 to 1.785) were independent predictors of NAFLD (all P〈0.05). These results were verified by all 1479 participants. Conclusions NAFLD was common among the study participants. In particular, NAFLD was correlated with uric acid. We identified OAHOA as a novel marker of NAFLD prevalence. It provides a reference on the prevention of NAFLD and related metabolic diseases with the rapid urbanisation, technological advancement and population ageing in China over the recent decades.
    Keywords: Open access, Public health, Epidemiology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2018-03-30
    Description: Background/Aim: The family of matrix metalloproteinases (MMPs) controls homeostasis of the extracellular matrix and their genetic polymorphisms may be associated with personal cancer susceptibility. The serum levels of MMP8 was reported to be higher in patients with breast cancer than in healthy individuals. In this study, we aimed to investigate the contribution of a polymorphism in the promoter region of MMP8 (-799C/T) and two nonsynonymous polymorphisms (Val436Ala and Lys460Thr) to breast cancer. Materials and Methods: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes were determined for 1,232 patients with breast cancer and 1,232 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at the MMP8 promoter C-799T were 1.03 (95% CI=0.88-1.23, p=0.7475) and 1.08 (95% CI=0.91-1.53, p=0.3561), respectively, compared to those carrying the wild-type CC genotype. The OR for the combined T-bearing genotypes were of a similar non-significant level (OR=1.05, 95% CI=0.90-1.26, p=0.5176). Supporting this finding, the adjusted OR for those carrying the T allele at MMP8 C-799T was 1.05 (95% CI=0.86-1.21, p=0.3797), compared to those carrying the wild-type C allele. There was also no significant association of MMP8 Lys460Thr with breast cancer. There was no polymorphic genotype at MMP8 Val436Ala found among any of the investigated individuals. Conclusion: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphisms may only play an indirect role in determining personal cancer susceptibility to breast cancer in Taiwan.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-01-05
    Description: Aggression is a complex social behavior that is widespread in nature. To date, only a limited number of genes that affect aggression have been identified, in large part because the complexity of the phenotype makes screening difficult and time-consuming regardless of the species that is studied. We discovered that aggressive group-housed Drosophila melanogaster males inflict damage on each other’s wings, and show that wing damage negatively affects their ability to fly and mate. Using this wing-damage phenotype, we screened males from ~1400 chemically mutagenized strains and found ~40 mutant strains with substantial wing damage. Five of these mutants also had increased aggressive behavior. To identify the causal mutation in one of our top aggressive strains, we used whole-genome sequencing and genomic duplication rescue strategies. We identified a novel mutation in the voltage-gated potassium channel Shaker ( Sh ) and show that a nearby previously identified Sh mutation also results in increased aggression. This simple screen can be used to dissect the molecular mechanisms underlying aggression.
    Print ISSN: 0016-6731
    Topics: Biology
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    facet.materialart.
    facet.materialart.
    German Medical Science; Düsseldorf, Köln
    In:  Evidenzbasierte Medizin - Anspruch und Wirklichkeit; 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft; 20040923-20040926; Berlin; DOC04dogDO.12.04 /20040922/
    Publication Date: 2004-09-21
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    facet.materialart.
    facet.materialart.
    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016); 20161025-20161028; Berlin; DOCPO13-1494 /20161010/
    Publication Date: 2016-10-10
    Keywords: PAO ; Pararectus Zugang ; Navigation ; ddc: 610
    Language: German
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: ANGIOGENESIS ; APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; proliferation ; SURVIVAL ; tumor ; carcinoma ; CELL ; COMBINATION ; Germany ; IN-VIVO ; INHIBITION ; THERAPY ; VIVO ; liver ; PROTEIN ; PROTEINS ; TUMORS ; MICE ; NF-KAPPA-B ; ACTIVATION ; kidney ; INDUCTION ; BINDING ; PROGRESSION ; resistance ; INDUCED APOPTOSIS ; METASTASIS ; IMMUNODEFICIENT MICE ; STEM-CELLS ; STRATEGIES ; side effects ; pancreatic cancer ; ELIMINATION ; ONCOLOGY ; PANCREATIC-CANCER ; development ; SIZE ; COMBINATION THERAPY ; CANCERS ; STEM ; EPITHELIAL-MESENCHYMAL TRANSITION ; MESENCHYMAL TRANSITION ; sorafenib ; TUMOR-INITIATING CELLS ; STRATEGY ; CONTRIBUTE ; Combination treatment ; RAF/MEK/ERK PATHWAY
    Abstract: Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development of a strategy to enhance this effect. Although SO administration diminished clonogenicity, spheroid formation, aldehyde dehydrogenase 1 (ALDH1) activity, growth on immunodeficient mice, proliferation, and angiogenesis and induced apoptosis, we observed SO-induced activation of NF-kappa B associated with survival and regrowth of spheroids. For enhanced elimination of CSC characteristics by SO, we cotreated cells with sulforaphane (SF). This broccoli isothiocyanate was recently described to eliminate pancreatic CSCs by downregulation of NF-kappa B activity without inducing toxic side effects. On combination treatment, SF completely eradicated SO-induced NF-kappa B binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. In vivo, combination therapy reduced the tumor size in a synergistic manner. This was due to induction of apoptosis, inhibition of proliferation and angiogenesis, and downregulation of SO-induced expression of proteins involved in epithelial-mesenchymal transition. Our data suggest that SF may be suited to increase targeting of CSCs by SO. Cancer Res; 70(12); 5004-13. (C)2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20530687
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: LUNG-CANCER ; RISK ; SUSCEPTIBILITY LOCUS ; INITIATION ; DEPENDENCE ; GENOME-WIDE ASSOCIATION ; Adolescent ; NICOTINIC RECEPTOR GENES ; HEAVY SMOKING ; ADULT RATS
    Abstract: Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD 〉20) and light smokers (CPD 〈= 10) with age-at-onset information, re-ducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset 〈= 16 years) and late-onset smokers (age at onset 〉16 years), and a logistic regression of heavy vs light smoking with ther s16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
    Type of Publication: Journal article published
    PubMed ID: 22868939
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: EXPRESSION ; INVASION ; IDENTIFICATION ; PROGRESSION ; METASTASIS ; DRUG-RESISTANCE ; SOLID TUMORS ; EPITHELIAL-MESENCHYMAL TRANSITION ; INITIATING CELLS ; CONTRIBUTES
    Abstract: Tumor hypoxia induces epithelial-mesenchymal transition (EMT), which induces invasion and metastasis, and is linked to cancer stem cells (CSCs). Whether EMT generates CSCs de novo, enhances migration of existing CSCs or both is unclear. We examined patient tissue of pancreatic ductal adenocarcinoma (PDA) along with carcinomas of breast, lung, kidney, prostate and ovary. For in vitro studies, five established PDA cell lines classified as less (CSC(low)) and highly aggressive CSC-like cells (CSC(high)) were examined by single and double immunofluorescence microscopy, wound-, transwell-, and time-lapse microscopy. HIF-1alpha and Slug, as well as HIF-2alpha and CD133 were co-expressed pointing to a putative co-existence of hypoxia, EMT and CSCs in vivo. CSC(high) cells exhibited high basal expression of the mesenchymal Vimentin protein but low or absent expression of the epithelial marker E-cadherin, with the opposite result in CSC(low) cells. Hypoxia triggered altering of cell morphology from an epithelial to a mesenchymal phenotype, which was more pronounced in CSC(high) cells. Concomitantly, E-cadherin expression was reduced and expression of Vimentin, Slug, Twist2 and Zeb1 enhanced. While hypoxia caused migration in all cell lines, velocity along with the percentage of migrating, polarized and pseudopodia-forming cells was significantly higher in CSC(high) cells. These data indicate that hypoxia-induced EMT occurs in PDA and several other tumor entities. However although hypoxia-induced EMT signaling occurs in all tumor cell populations, only the stem-like cells acquire high migratory potential and thus may be responsible for invasion and metastasis.
    Type of Publication: Journal article published
    PubMed ID: 23050024
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: CANCER ; GENE ; DIFFERENTIATION ; IDENTIFICATION ; METHYLATION ; TELOMERASE ACTIVITY ; BONE ; MESENCHYMAL STEM-CELLS ; DNA HYPERMETHYLATION ; FACTOR BINDING-PROTEIN
    Abstract: Giant cell tumor (GCT) of bone is a generally benign tumor with a locally aggressive behavior. Histologically, GCTs consist of multinucleated giant cells, mononuclear histiocytes and the neoplastic fibroblast-like stromal cells (GCTSC). Growing evidence exists that GCTSCs develop from mesenchymal stem cells (MSCs), but little is known about the underlying molecular mechanisms. In previous studies we observed inactivation of the ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene in primary GCTSC due to strong DNA hypermethylation, indicating that epigenetic silencing might be involved in neoplastic transformation of MSCs. Here we investigated further candidate genes and identified strong hypermethylation of the insulin-like growth factor binding protein 4 (IGFBP4) promoter, resulting in IGFBP4 downregulation in GCTs compared to MSCs. Overexpression of UCHL1 and IGFBP4 by stable transfection of GCTSC did not influence cell viability, proliferation, migration and chemosensitivity compared to parental cells. However, colony-formation was significantly decreased suggesting that rescue of UCHL1 and IFGBP4 suppresses clonogenicity of GCT stromal cells. The observation of reduced expression of the stem-cell-specific transcription factors OCT4 and SOX2 in these cell lines further supported our findings. Epigenetic silencing of UCHL1 and IGFBP4 in GCTs might thus be a crucial event during the malignant transformation of MSCs in the context of GCT development and represent promising targets for the development of new diagnostic and therapeutic strategies.
    Type of Publication: Journal article published
    PubMed ID: 23603559
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...