Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
  • 2
    facet.materialart.
    facet.materialart.
    German Medical Science GMS Publishing House; Düsseldorf
    In:  Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi); 20110926-20110929; Mainz; DOC11gmds307 /20110920/
    Publication Date: 2011-09-20
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CELLS ; RISK ; COLORECTAL-CANCER ; TANDEM MASS-SPECTROMETRY ; POSTMENOPAUSAL WOMEN ; DETERMINANTS ; REDUCTASE ; PLASMA HOMOCYSTEINE ; MODERATE FOLATE-DEPLETION ; DECREASES
    Abstract: DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994-1995), peri- (1996-1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%;P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from the inverse (pre-fortification period) to the positive (post-fortification period) relationship. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.
    Type of Publication: Journal article published
    PubMed ID: 24300587
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: PATHWAY ; DIFFERENTIATION ; QUERCETIN ; MUTATIONS ; adenocarcinoma ; GASTRIC-CANCER ; WNT ; BETA-CATENIN EXPRESSION ; TUMOR STEM-CELLS ; DYSREGULATION
    Abstract: BACKGROUND: Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations. METHODS: Two hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5'-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at the baseline. Conditional logistic regression was implemented; effect modification was examined on the basis of known enzyme-nutrient relations. RESULTS: Statistically significant associations were observed between CRC risk and functionally defined candidate SNPs of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1; K134R), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; P450R), and PR domain containing 2 with ZNF domain (PRDM2; S450N) and a literature candidate SNP of thymidylate synthase (TYMS; g.676789A〉T; nominal P 〈 .05). In addition, suggestive associations were noted for tagging SNPs in cystathionine-beta-synthase (CBS), dihydrofolate reductase (DHFR), DNA (cytosine-5-)-methyltransferase 3beta (DNMT3B), methionine adenosyltransferase I alpha (MAT1A), MTHFD1, and MTRR (nominal P 〈 .05; adjusted P, not significant). Significant interactions between nutrient biomarkers and candidate polymorphisms were observed for 1) plasma/RBC folate and folate hydrolase 1 (FOLH1), paraoxonase 1 (PON1), transcobalamin II (TCN2), DNMT1, and DNMT3B; 2) plasma PLP and TYMS TS3; 3) plasma B12 and betaine-homocysteine S-methyltransferase 2 (BHMT2); and 4) homocysteine and methylenetetrahydrofolate reductase (MTHFR) and alanyl-transfer RNA synthetase (AARS). CONCLUSIONS: Genetic variants in FOCM genes are associated with CRC risk among postmenopausal women. FOCM nutrients continue to emerge as effect modifiers of genetic influences on CRC risk. Cancer 2015;121:3684-3691. (c) 2015 American Cancer Society.
    Type of Publication: Journal article published
    PubMed ID: 26108676
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: SURVIVAL ; DISEASE ; C-REACTIVE PROTEIN ; aspirin ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; METAANALYSIS ; INTERLEUKIN-6 ; RANDOMIZED-TRIALS ; ACUTE-PHASE PROTEINS ; SERUM-AMYLOID-A
    Abstract: Initial studies have investigated the association between inflammation and colorectal cancer (CRC) using C-reactive protein (CRP) as a proinflammatory biomarker and have noted inconsistent results among women. We here report the findings from a large prospective study with repeat measurements of CRP, as well as serum amyloid A (SAA), an additional biomarker of inflammation, and risk of CRC. In the Women's Health Initiative Observational Study, we examined associations of CRP and SAA with CRC using repeat assessments (baseline and 3-year follow-up) among 953 matched case-control pairs for CRP and 966 pairs for SAA. Multivariate-adjusted conditional-logistic regression models were used with two-sided tests of significance. Receiver operating characteristic (ROC) curve analysis assessed their utility as early detection markers. Colon cancer risk (odds ratio [OR] and 95% confidence intervals) among women in the highest quintiles of CRP or SAA compared to those in the lowest quintiles was OR(colon/CRP) = 1.37 (0.95-1.97, p-trend = 0.04) and OR(colon/SAA) = 1.26 (0.88-1.80, p-trend = 0.10), respectively. Women with elevated concentrations of both CRP and SAA had an increased risk of OR(colon) = 1.50 (1.12-2.00, p-value = 0.006) compared to those with low concentrations. No positive associations were observed with rectal cancer and weaker associations for CRC overall. Temporal changes in biomarkers more than 3 years did not predict risk. The area under the 6-month ROC curve for CRP+SAA was 0.62 (95% confidence interval = 0.55-0.68). Elevated inflammatory biomarkers are associated with an increased risk of CRC, mainly colon cancer. Nevertheless, changes in the biomarkers over time do not suggest that they merit consideration as early detection markers for CRC.
    Type of Publication: Journal article published
    PubMed ID: 23161620
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Abstract: BACKGROUND: The role of one-carbon metabolism nutrients in colorectal carcinogenesis is not fully understood. Associations might be modified by mandated folic acid (FA) fortification or alcohol intake. OBJECTIVE: We investigated associations between intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and colorectal cancer (CRC) in the Women's Health Initiative Observational Study, stratified by time exposed to FA fortification and alcohol intake. DESIGN: A total of 88,045 postmenopausal women were recruited during 1993-1998; 1003 incident CRC cases were ascertained as of 2009. Quartiles of dietary intakes were compared; HRs and 95% CIs were estimated by Cox proportional hazards models. RESULTS: Dietary and total intakes of vitamin B-6 in quartile 4 compared with quartile 1 (HR: 0.80; 95% CI: 0.66, 0.97 and HR: 0.80; 95% CI: 0.66, 0.99, respectively) and total intakes of riboflavin (HR: 0.81; 95% CI: 0.66, 0.99) were associated with reduced risk of CRC overall and of regionally spread disease. In current drinkers who consumed 〈1 drink (13 g alcohol)/wk, B vitamin intakes were inversely associated with CRC risk (P-interaction 〈 0.05). Dietary folate intake was positively associated with CRC risk among women who had experienced the initiation of FA fortification for 3 to 〈9 y (P-interaction 〈 0.01). CONCLUSIONS: Vitamin B-6 and riboflavin intakes from diet and supplements were associated with a decreased risk of CRC in postmenopausal women. Associations of B vitamin intake were particularly strong for regional disease and among women drinkers who consumed alcohol infrequently. Our study provides new evidence that the increased folate intake during the early postfortification period may have been associated with a transient increase in CRC risk.
    Type of Publication: Journal article published
    PubMed ID: 23255571
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: ENDOTHELIAL-CELLS ; CLINICAL-TRIAL ; OXIDATIVE STRESS ; INFLAMMATORY-BOWEL-DISEASE ; VASCULAR-DISEASE ; PLASMA HOMOCYSTEINE ; FOLATE ; ONE-CARBON METABOLISM ; ADENOMA RECURRENCE ; HYPERHOMOCYSTEINEMIA
    Abstract: BACKGROUND: Inflammation underlies the etiology of colorectal cancer (CRC). Hyperhomocysteinemia is associated with inflammation and may be a risk marker for CRC. Cysteine is a metabolic product of homocysteine and a precursor of the antioxidant glutathione. It is unknown whether cysteine is associated with CRC. OBJECTIVE: The objective was to assess the associations between homocysteine and cysteine and CRC incidence in postmenopausal women. DESIGN: Associations between homocysteine and cysteine and incident CRC in the Women's Health Initiative observational cohort were assessed by using a nested case-control design. Cases and controls (n = 988/group) were matched for age (mean +/- SD age: 67 +/- 7 y), ethnicity (85.2% white, 8.9% black, 2.2% Hispanic/Latina, and 3.6% other), hysterectomy status, and date of blood draw. Homocysteine and cysteine were measured by HPLC with postcolumn fluorimetric detection. RESULTS: Multivariate-adjusted ORs (95% CIs) for CRC were 1.46 (1.05, 2.04) for the highest quartile of homocysteine (〉9.85 mumol/L) compared with the lowest quartile (〈/=6.74 mumol/L) (P = 0.02) and 0.57 (0.40, 0.82) for the highest quartile of cysteine (〉309 mumol/L) compared with the lowest quartile (〈/=260 mumol/L) (P = 0.01). The association with homocysteine was significant for proximal colon tumors (P = 0.008) but not for distal or rectal tumors, whereas the association with cysteine was significant for rectal tumors (P = 0.02), borderline for proximal tumors (P = 0.06), and not significant for distal tumors. The associations with both homocysteine and cysteine were significant for localized tumors (P 〈/= 0.01) but not for metastases. CONCLUSION: High plasma homocysteine is associated with increased risk of CRC, whereas high cysteine is associated with decreased risk. This trial was registered at clinicaltrials.gov as NCT 00000611.
    Type of Publication: Journal article published
    PubMed ID: 23426034
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: DISEASE ; COLORECTAL-CANCER ; DNA methylation ; C-REACTIVE PROTEIN ; OXIDATIVE STRESS ; RHEUMATOID-ARTHRITIS ; PLASMA HOMOCYSTEINE ; ABNORMAL VITAMIN-B-6 STATUS ; FOLIC-ACID SUPPLEMENTATION ; B STATUS
    Abstract: Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's Health Initiative Observational Study, plasma vitamin B-6 [pyridoxal-5'-phosphate (PLP)], plasma vitamin B-12, plasma folate, and RBC folate were measured as nutritional biomarkers; serum C-reactive protein (CRP) and serum amyloid A (SAA) were measured as biomarkers of inflammation; and homocysteine and cysteine were measured as integrated biomarkers of one-carbon metabolism. Student's t, chi-square, and Spearman rank correlations, along with multiple linear regressions, were used to explore relations between biomarkers; additionally, we tested stratification by folic acid fortification period and multivitamin use. With the use of univariate analysis, plasma PLP was the only nutritional biomarker that was modestly significantly correlated with serum CRP and SAA (rho = -0.22 and -0.12, respectively; P 〈 0.0001). Homocysteine (mumol/L) showed significant inverse correlations with all nutritional biomarkers (ranging from rho = -0.30 to rho = -0.46; all P 〈 0.0001). With the use of multiple linear regression, plasma PLP, RBC folate, homocysteine, and cysteine were identified as independent predictors of CRP; and PLP, vitamin B-12, RBC folate, and homocysteine were identified as predictors of SAA. When stratified by folic acid fortification period, nutrition-homocysteine correlations were generally weaker in the postfortification period, whereas associations between plasma PLP and serum CRP increased. Biomarkers of inflammation are associated with PLP, RBC folate, and homocysteine in women. The connection between the pathways needs to be further investigated and causality established. The trial is registered at clinicaltrials.gov as NCT00000611.
    Type of Publication: Journal article published
    PubMed ID: 24647390
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Abstract: Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Because of differential regulation of enzymatic activities, PKM2, but not PKM1, has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC overexpression in murine livers did not affect c-MYC-induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased glucose flux into serine biosynthesis and increased flux into lactate and the Krebs cycle, resulting in reduced total levels of serine. However, these changes also did not affect c-MYC-induced liver tumor development. These results suggest that increased expression of PKM2 is not required to support c-MYC-induced tumorigenesis in the liver and that various PKM1/PKM2 ratios and pyruvate kinase activities can sustain glucose catabolism required for this process. Cancer Res; 77(16); 4355-64. (c)2017 AACR.
    Type of Publication: Journal article published
    PubMed ID: 28630053
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: RECEPTOR ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; tumor ; CELL ; COMBINATION ; human ; IN-VIVO ; KINASE ; neoplasms ; PATHWAY ; PATHWAYS ; VIVO ; COMMON ; GENE ; TUMORS ; MICE ; ACTIVATION ; MECHANISM ; animals ; colon ; PHOSPHORYLATION ; FORM ; gene expression ; HUMANS ; MUTATION ; colorectal cancer ; COLORECTAL-CANCER ; RATES ; metastases ; inactivation ; PATHOGENESIS ; CANCER-CELLS ; COLON-CANCER ; MUTATIONS ; EPITHELIAL-CELLS ; adenocarcinoma ; ADENOCARCINOMAS ; ABNORMALITIES ; BEHAVIOR ; BRAF ; WNT ; CYCLIN D1 ; colon cancer ; TRANSFECTION ; TGF-BETA ; cell proliferation ; LEVEL ; methods ; TRANSCRIPTIONAL ACTIVATION ; EVENTS ; EPITHELIUM ; CANCERS ; colorectal ; Cell Line,Tumor ; COLORECTAL TUMORS ; epigenetic ; neoplasm ; growth factor ; EPIDERMAL-GROWTH ; *Mutation ; *Signal Transduction ; beta Catenin/*metabolism ; Genes,ras/*genetics ; inhibitors/genetics/*metabolism ; Intestinal Mucosa/metabolism ; Intestinal Neoplasms/genetics/metabolism/*physiopathology ; Mice,Transgenic ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism ; raf Kinases/metabolism ; Receptors,Transforming Growth Factor beta/antagonists & ; Wnt Proteins/metabolism
    Abstract: BACKGROUND & AIMS: During colorectal cancer pathogenesis, mutations and epigenetic events cause neoplastic behavior in epithelial cells by deregulating the Wnt, Ras-Raf-extracellular signal-regulated kinase (ERK), and transforming growth factor (TGF)-beta-signaling pathways, among others. The TGF-beta-signaling pathway is often inactivated in colon cancer cells by mutations in the gene encoding the TGF-beta receptor TGFBR2. The RAS-RAF-ERK pathway is frequently up-regulated in colon cancer via mutational activation of KRAS or BRAF. We assessed how these pathways interact in vivo and affect formation of colorectal tumors. METHODS: We analyzed intestinal tumors that arose in mice that express an oncogenic (active) form of Kras and that have Tgfbr2 inactivations-2 common molecular events observed in human colorectal tumors. LSL-KrasG12D mice were crossed with Villin-Cre;Tgfbr2E2flx/E2flx mice, which do not express Tgfbr2 in the intestinal epithelium. RESULTS: Neither inactivation of Tgfbr2 nor expression of oncogenic Kras alone was sufficient to induce formation of intestinal neoplasms. Histologic abnormalities arose in mice that expressed Kras, but only the combination of Tgfbr2 inactivation and Kras activation led to intestinal neoplasms and metastases. The cancers arose via a beta-catenin-independent mechanism; the epidermal growth factor-signaling pathway was also activated. Cells in the resulting tumors proliferated at higher rates, expressed decreased levels of p15, and expressed increased levels of cyclin D1 and cdk4, compared with control cells. CONCLUSIONS: A combination of inactivation of the TGF-beta-signaling pathway and expression of oncogenic Kras leads to formation of invasive intestinal neoplasms through a beta-catenin-independent pathway; these adenocarcinomas have the capacity to metastasize.
    Type of Publication: Journal article published
    PubMed ID: 19208363
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...