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  1. Article ; Online: Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    Méplan, Catherine / Johnson, Ian T / Polley, Abigael C J / Cockell, Simon / Bradburn, David M / Commane, Daniel M / Arasaradnam, Ramesh P / Mulholland, Francis / Zupanic, Anze / Mathers, John C / Hesketh, John

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2016  Volume 30, Issue 8, Page(s) 2812–2825

    Abstract: Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. ... ...

    Abstract Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.
    MeSH term(s) Adult ; Cytoskeleton/drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inflammation/metabolism ; Proteomics ; Rectal Neoplasms/metabolism ; Rectum/cytology ; Selenium/pharmacology ; Transcriptome
    Chemical Substances Selenium (H6241UJ22B)
    Language English
    Publishing date 2016-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.201600251R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2266: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 296: Show issues

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  2. Article ; Online: Quantitative profiling of CpG island methylation in human stool for colorectal cancer detection.

    Elliott, Giles O / Johnson, Ian T / Scarll, Jane / Dainty, Jack / Williams, Elizabeth A / Garg, D / Coupe, Amanda / Bradburn, David M / Mathers, John C / Belshaw, Nigel J

    International journal of colorectal disease

    2012  Volume 28, Issue 1, Page(s) 35–42

    Abstract: Purpose: The aims of this study were to investigate the use of quantitative CGI methylation data from stool DNA to classify colon cancer patients and to relate stool CGI methylation levels to those found in corresponding tissue samples.: Methods: We ... ...

    Abstract Purpose: The aims of this study were to investigate the use of quantitative CGI methylation data from stool DNA to classify colon cancer patients and to relate stool CGI methylation levels to those found in corresponding tissue samples.
    Methods: We applied a quantitative methylation-specific PCR assay to determine CGI methylation levels of six genes, previously shown to be aberrantly methylated during colorectal carcinogenesis. Assays were performed on DNA from biopsies of "normal" mucosa and stool samples from 57 patients classified as disease-free, adenoma, or cancer by endoscopy, and in tumour tissue from cancer patients. Additionally, CGI methylation was analysed in stool DNA from an asymptomatic population of individuals covering a broad age range (mean = 47 ± 24 years)
    Results: CGI methylation levels in stool DNA were significantly higher than in DNA from macroscopically normal mucosa, and a significant correlation between stool and mucosa was observed for ESR1 only. Multivariate statistical analyses using the methylation levels of each CGI in stool DNA as a continuous variable revealed a highly significant (p = 0.003) classification of cancer vs. non-cancer (adenoma + disease-free) patients (sensitivity = 65 %, specificity = 81 %).
    Conclusion: CGI methylation profiling of stool DNA successfully identified patients with cancer despite the methylation status of CGIs in stool DNA not generally reflecting those in DNA from the colonic mucosa.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adenomatous Polyps/diagnosis ; Adenomatous Polyps/genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; CpG Islands/genetics ; DNA Methylation ; Discriminant Analysis ; Epigenesis, Genetic ; Estrogen Receptor alpha/genetics ; Feces ; Female ; Genes, APC ; Genetic Markers ; Humans ; Logistic Models ; Male ; Membrane Proteins/genetics ; Middle Aged ; MutL Protein Homolog 1 ; Neoplasm Proteins/genetics ; Nuclear Proteins/genetics ; Polymerase Chain Reaction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Biomarkers, Tumor ; ESR1 protein, human ; Estrogen Receptor alpha ; Genetic Markers ; MLH1 protein, human ; Membrane Proteins ; Neoplasm Proteins ; Nuclear Proteins ; TMEFF2 protein, human ; MutL Protein Homolog 1 (EC 3.6.1.3)
    Language English
    Publishing date 2012-07-13
    Publishing country Germany
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 84975-3
    ISSN 1432-1262 ; 0179-1958
    ISSN (online) 1432-1262
    ISSN 0179-1958
    DOI 10.1007/s00384-012-1532-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2121: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer.

    Belshaw, Nigel J / Elliott, Giles O / Williams, Elizabeth A / Bradburn, David M / Mills, Sarah J / Mathers, John C / Johnson, Ian T

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

    2004  Volume 13, Issue 9, Page(s) 1495–1501

    Abstract: Hypermethylation of cytosine residues in the CpG islands of tumor suppressor genes is a key mechanism of colorectal carcinogenesis. Detection and quantification of CpG island methylation in human DNA isolated from stools might provide a novel strategy ... ...

    Abstract Hypermethylation of cytosine residues in the CpG islands of tumor suppressor genes is a key mechanism of colorectal carcinogenesis. Detection and quantification of CpG island methylation in human DNA isolated from stools might provide a novel strategy for the detection and investigation of colorectal neoplasia. To explore the feasibility of this approach, colorectal biopsies and fecal samples were obtained from 32 patients attending for colonoscopy or surgery, who were found to have adenomatous polyps, colorectal cancer, or no evidence of neoplasia. A further 18 fecal samples were obtained from healthy volunteers, with no bowel symptoms. Isolated DNA was modified with sodium bisulfite and analyzed by methylation-specific PCR and combined bisulfite restriction analysis for CpG island methylation of ESR1, MGMT, HPP1, p16(INK4a), APC, and MLH1. CpG island methylation was readily detectable in both mucosal and fecal DNA with methylation-specific PCR. Using combined bisulfite restriction analysis, it was established that, in volunteers from whom biopsies were available, the levels of methylation at two CpG sites within ESR1 assayed using fecal DNA were significantly correlated with methylation in DNA from colorectal mucosa. Thus, noninvasive techniques can be used to obtain quantitative information about the level of CpG island methylation in human colorectal mucosa. The methods described here could be applied to a much expanded range of genes and may be valuable both for screening purposes and to provide greater insight into the functional consequences of epigenetic changes in the colorectal mucosa of free-living individuals.
    MeSH term(s) Adenomatous Polyps/diagnosis ; Adenomatous Polyps/genetics ; Adenomatous Polyps/pathology ; Alleles ; Biopsy ; Case-Control Studies ; Colectomy ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; CpG Islands/genetics ; DNA Methylation ; DNA Primers/genetics ; Epigenesis, Genetic ; Feasibility Studies ; Feces/chemistry ; Female ; Genes, Tumor Suppressor ; Humans ; Intestinal Mucosa/pathology ; Male ; Mass Screening ; Middle Aged ; Polymerase Chain Reaction ; Risk Assessment
    Chemical Substances DNA Primers
    Language English
    Publishing date 2004-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1153420-5
    ISSN 1055-9965
    ISSN 1055-9965
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3693: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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