DNA Methylation of Colon Mucosa in Ulcerative Colitis Patients: Correlation with Inflammatory Status

Background: Although DNA methylation of colonic mucosa in ulcerative colitis (UC) has been suggested, the majority of published reports indicate the correlation between methylation of colon mucosa and occurrence of UC-related dysplasia or cancer without considering the mucosal inflammatory status. The aim of this study was to verify whether mucosal inflammation-specific DNA methylation occurs in the colon of UC. Methods: Of 15 gene loci initially screened, six loci (ABCB1, CDH1. ESR1, GDNF, HPP1, and MYOD1) methylated in colon mucosa of UC were analyzed according to inflammatory status using samples from 28 surgically resected UC patients. Results: Four of six regions (CDH1, GDNF, HPP1, and MYOD1) were more highly methylated in the active inflamed mucosa than in the quiescent mucosa in each UC patient (P = 0.003, 0.0002, 0.02, and 0.048, respectively). In addition, when the methylation status of all samples taken from examined patients was stratified according to inflammatory status, methylation of CDHI and GDNF loci was significantly higher in active inflamed mucosa than in quiescent mucosa (P = 0.045 and 0.002, respectively). Multiple linear regression analysis revealed that active inflammation was an independent factor of methylation for CDHI and GDNF. DNA methyltransferase 1 and 3b were highly expressed in colon epithelial cells with active mucosa] inflammation, suggesting their involvement in inflammation-dependent methylation. Conclusions: Methylation in colonic mucosa of UC was correlated with mucosal inflammatory status, suggesting the involvement of methylation due to chronic active inflammation in UC carcinogenesis

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

<p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods</p> <p>A set of 4 genes, including <it>CDH1 </it>(E-cadherin), <it>SFN </it>(stratifin), <it>RARB </it>(retinoic acid receptor, beta) and <it>RASSF1A </it>(Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters.</p> <p>Results</p> <p><it>CDH1 </it>and <it>SFN </it>genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between <it>RARB </it>and <it>RASSF1A </it>methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for <it>RARB </it>methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for <it>RASSF1A </it>gene, respectively, in relation to the control group.</p> <p>Conclusion</p> <p>Indistinct DNA hypermethylation of <it>CDH1 </it>and <it>SFN </it>genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, <it>RARB </it>and <it>RASSF1A </it>gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection.</p

Role of DNA methylation in head and neck cancer

Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC

Entwicklung umweltgerechter Aufschlussverfahren zur Gewinnung hochwertiger Bastfasern in Deutschland Abschlussbericht

SIGLEAvailable from TIB Hannover: F05B14 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Moeglichkeiten zur Erweiterung der Garnpalette fuer trockengesponnene Flachsgarne

SIGLEAvailable from TIB Hannover: F94B1332+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Aspirin promotes TFF2 gene activation in human gastric cancer cell lines

AbstractTrefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth. In reporter gene assays we show that aspirin (1–12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines. 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C. We mapped an aspirin responding element −546 to −758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis