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  • 1
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 256-256 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A relationship between altered metabolism of estradiol (E2) and personal or familial risk for breast cancer suggests that endocrine changes associated with ovarian function may influence initiation or promotion of carcinogenesis. Evidence for a direct effect of E2 on non-involved mammary tissue (target for carcinogenesis) is equivocal. Explant cultures of human mammary terminal duct lobular units (TDLU) from breast cancer patients are utilized to examine whether (i) E2 metabolism in TDLU is altered in response to the chemical carcinogen benzo(a)pyrene [B(a)P], and (ii) perturbed E2 metabolism is modulated by naturally occurring polyunsaturated fatty acids (PUFA) and indole-3-carbinol (I3C). Treatment of TDLU with 40 nM B(a)P resulted in a 〉 95% decrease in C2/C16α-hydroxylation ratio of E2 relative to that detected in solvent controls. This metabolic alteration was due to a specific increase in E2 C16α-hydroxylation. Exposure of TDLU prior to and during B(a)P treatment with omega-6 PUFA decreased C2/C16α-hydroxylation ratio by 38% (p 〈 0.001). Treatment with omega-3 PUFA and I3C increased the ratio by 318% and 376% respectively (p 〈 0.001), due to a specific increase in E2 C2-hydroxylation. Thus, carcinogen-induced perturbation of E2 metabolism in TDLU and its modulation by dietary modulators of rodent mammary tumorigenesis provide evidence for this endocrine biomarker as a clinically relevant endpoint for chemoprevention of mammary carcinogenesis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 50 (1992), S. 161-169 
    ISSN: 0730-2312
    Keywords: chemoprevention ; in vitro models ; estradiol metabolism ; intermediate biomarker ; mammary preneoplasia ; Ras p21 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro-and micronutrients. In the initiation/promotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistant Ras p21-GTP binding, altered C16α/C2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypic chemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotype is suggestive of their potential clinical application in chemopreventive intervention for breast cancer. © 1992 Wiley-Liss, Inc. © 1992 Wiley-Liss, Inc.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Studies from this laboratory have demonstrated that negative modulation of the C-2/C-16α ratio of estradiol metabolites serves as a marker of the action of oncogenes and carcinogens which increase tumorigenicity, while positive modulation of this ratio measures the preventive effects of chemotherapeutic and chemopreventive agents on tumors and tumor cells. In order to facilitate human studies on chemopreventive agents and facilitate the measurement of this ratio, we have validated an ELISA assay using monoclonal antibodies developed by Immunocare, Inc., coated to 96-well plates.Urine samples (10λ) were diluted in buffer and hydrolyzed with mixed glucuronidase and sulfatase to cleave the conjugates. Aliquots of the hydrolysate were added to ELISA plates coated with the C-2 and C-16α antibodies respectively and the appropriate labeled antigens were added. After incubation the plates were washed, the color reagent added, and the plates read kinetically to determine the amount of compound present. A standard curve is run on each plate along with high and low standards. All samples were run in triplicate and the mean values determined. The ratios were computed automatically by the reader.Blind comparisons of duplicate urine samples showed a mean r value of 97%. Mean intra-assay variability was under 8% and inter-assay variability was under 10%.Studies involving diet modification and the differences between breast cancer patients and controls are underway.
    Type of Medium: Electronic Resource
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