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  • 1
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 252-257 
    ISSN: 0730-2312
    Schlagwort(e): polyamines ; biomarkers ; proliferation ; colorectal cancer risk ; mucosa ; biopsy ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Polyamines are short-chain aliphatic amines required for normal cellular growth that are ubiquitously found in all living tissues. Polyamine content has been shown to correlate with cellular proliferation. Quantitation of polyamines may thus provide a biochemical measure of proliferation in the colorectal mucosa where dysregulated epithelial proliferation is associated with colorectal cancer risk. A case-control study was conducted to validate the hypothesized association between mucosal polyamine measurements and colorectal cancer risk. Polyamines were measured in 4-6 multiple rectal mucosal biopsies from 11 normal control subjects and seven case patients with colon cancer. Compared with the controls, mean polyamine measurements, after adjustment for age and sex, were significantly increased for spermidine (P 〈 0.003) and spermine (P 〈 0.017). Subsequent analyses indicated that in controls 1-4 biopsies appeared adequate to characterize an individual. However, mucosal polyamines in the cases exhibited more sampling variability, requiring 4-8 biopsies to achieve an acceptable level of reliability. After adjustment for age and sex, the odds ratios for spermidine and spermine levels, compared to the controls, were 4.8 (95% confidence interval: 1.6-33.7) and 2.3 (1.2-6.3), respectively. The results of this study indicate that increases of mucosal polyamine measurements, after taking the sampling and methodological variability into account, are significantly associated with colorectal cancer risk, and suggest that polyamine measurements in rectal mucosa may play an important role as biomarkers for identifying high-risk individuals and/or for using as intermediate endpoints in prevention trials. © 1996 Wiley-Liss, Inc.
    Zusätzliches Material: 4 Tab.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 0730-2312
    Schlagwort(e): polyamines ; erythrocyte ; biomarker ; reproducibility ; plasma micronutrients ; antioxidant ; intervention ; cancer prevention ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Erythrocyte polyamine measurements have been previously investigated as candidate biomarkers for hyperproliferation and recently as a potential intermediate endpoint in clinical chemoprevention trials with difluoromethylornithine, an inhibitor of polyamine biosynthesis. This study was performed to determine the reproducibility of erythrocyte polyamine measurements and their possible correlation with plasma micronutrients in seven healthy adults in an antioxidant vitamin intervention study. As part of this cross-over intervention study, three subjects took β-carotene (31.4 mg/day) plus D-α-tocopherol acetate (720 IU/day) supplements during the first 3 months and four subjects took the supplements during the second 3 months. Heparinized blood samples were collected at baseline and every month over total 6 months for simultaneous determination of erythrocyte polyamines and plasma micronutrients by the high-performance liquid chromatographic method. For all the measures of erythrocyte polyamines the intraindividual variation was smaller than that between subjects, and three or four measurements required to accurately characterize long-term erythrocyte polyamines for an individual. The intra-class correlations were moderately high for all erythrocyte polyamine measurements, indicating a good reproducibility for intra-individual erythrocyte polyamine measurements. Based on monthly values, significant inverse correlations were found between erythrocyte spermidine and the plasma levels of retinol (r = -0.50) and lutein (r = -0.52). There were also significant inverse associations between erythrocyte spermine and plasma levels of α-tocopherol (r = -0.29), lutein (r = -0.44), lycopene (r = -0.29), β-cryptoxanthin (r = -0.30), and total carotenoids (r = -0.29). The effects of supplementation upon the associations between erythrocyte polyamines and plasma nutrient levels were additionally addressed. The results indicate an acceptable longitudinal reproducibility of erythrocyte polyamine measurements, support the hypothesis that erythrocyte polyamine measurements may be correlated with plasma levels of certain nutrients, and suggest a further biomarker application in cancer prevention trials involving dietary modifications or specific relevant micronutrients. © 1996 Wiley-Liss, Inc.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 57 (1995), S. 256-261 
    ISSN: 0730-2312
    Schlagwort(e): polyamines ; proliferation ; colorectal cancer ; biomarkers ; mucosa ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Polyamines are low molecular weight aliphatic amines required for normal cellular growth which are ubiquitously found in all living tissues. Polyamine biosynthesis is known to increase with mitogenesis, and elevated polyamine concentrations are found in hyperproliferative tissue. Quantitation of tissue of polyamine content may thus provide a biochemical measure of proliferation, with potential biomarker application to the colonic mucosa where dysregulated epithelial proliferation is associated with cancer risk. This study was performed to validate polyamine analyses as a measure of cellular proliferation, and to preliminarily assess polyamine assay characteristics when applied to clinical samples. Using FHC, a human colonic epithelial cell line, for in vitro experimentation, deoxycholic acid or retinol was added to freshly passaged cultures to either stimulate or inhibit proliferation, respectively. Parallel cultures were then assayed for (1) proliferation by sulforhodamine B staining; and (2) polyamine content by a high-performance liquid chromatographic method. Deoxycholic acid stimulated, and retinol inhibited proliferation in dose-dependent fashion. Polyamine content, specifically the spermidine content and the spermidine/spermine ratio, also increased or decreased in response to culture with deoxycholic acid or retinol, respectively. Significant linear correlations between proliferation and spermidine (r = 0.858, P 〈 0.001), and with the spermidine/spermine ratio (r = 0.574, P 〈 0.05) were observed. When quantitative polyamine analyses were applied to human colonic specimens, replicate mucosal sampling revealed a high degree of intra-individual variability, indicating a heterogeneous distribution of polyamines within anatomically confined colonic segments. The results support a role for quantitative polyamine analyses as a correlative measure of colonic epithelial proliferation; however, intraindividual variability may limit the utility of colorectal biomarker measurements.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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