Cooney, Robert V.

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    Inhibition of colonic aberrant crypt formation by the dietary flavonoids (+)-catechin and hesperidin.
    (2002) Franke, Adrian A.; Custer, Laurie J.; Cooney, Robert V.; Tanaka, Yuichiro; Xu, Meirong; Dashwood, Roderick H.
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    The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain.
    (2002-03) Williamson, Kelly S.; Gabbita, S Prasad; Mou, Shenyun; West, Melinda; Pye, Quentin N.; Markesbery, William R.; Cooney, Robert V.; Grammas, Paula; Reimann-Philipp, Ulrich; Floyd, Robert A.; Hensley, Kenneth
    Oxidative stress and quasi-inflammatory processes recently have been recognized as contributing factors in the pathogenesis of Alzheimer's disease (AD). Reactive nitrating species have specifically been implicated in AD based on immunochemical and instrumental detection of nitrotyrosine in AD brain protein. The significance of lipid-phase nitration has not been investigated in AD. This study documents a significant two- to threefold increase in the lipid nitration product 5-nitro-gamma-tocopherol in affected regions of the AD brain as determined by high-performance liquid chromatography with electrochemical detection. In a bioassay to compare the relative potency of alpha-tocopherol and gamma-tocopherol against nitrative stress, rat brain mitochondria were exposed to the peroxynitrite-generating compound SIN-1. The oxidation-sensitive Kreb's cycle enzyme alpha-ketoglutarate dehydrogenase was inactivated by SIN-1, in a manner that could be significantly attenuated by gamma-tocopherol (at <10 microM) but not by alpha-tocopherol. These data indicate that nitric oxide-derived species are significant contributors to lipid oxidation in the AD brain. The findings are discussed in reference to the neuroinflammatory hypothesis of AD and the possible role of gamma-tocopherol as a major lipid-phase scavenger of reactive nitrogen species.
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    Bioavailability and antioxidant effects of orange juice components in humans.
    (2005-06) Franke, Adrian A.; Cooney, Robert V.; Henning, Susanne M.; Custer, Laurie J.
    Seven healthy females and six males consumed daily 256 mg of vitamin C, 271 mg of flavanones (mainly as glycosides), 6 mg of carotenoids (mainly xanthophylls and cryptoxanthins), and 0.16 mg of folate by incorporation of daily three times 236 mL of not from concentrate orange juice (OJ) into their habitual diet. At the end of 3 weeks, mean vitamin C, folate, carotenoid, and flavanone plasma concentrations increased significantly relative to baseline by 59% (p < 0.001), 46% (p = 0.018), and 22% (p < 0.001), and 8-fold (p = 0.045), respectively. Flavanones were excreted in urine 9-fold more at the end of the intervention (p = 0.01) but returned to baseline 2 days after study completion. After the 3 week intervention, plasma concentrations of vitamins A and E did not change. 8-Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11), and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7), respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric acid reactive substance plasma concentrations did not change significantly. We conclude from this pilot study that OJ is an excellent food source to enhance circulating concentrations of valuable hydrophilic as well as lipophilic phytochemicals.
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    Tocopherols and prostate cancer.
    (2006-09) Cooney, Robert V.
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    Enhancement of intracellular gamma-tocopherol levels in cytokine-stimulated C3H 10T1/2 fibroblasts: relation to NO synthesis, isoprostane formation, and tocopherol oxidation.
    (2007) Tanaka, Yuichiro; Wood, Leslie A Lesoon; Cooney, Robert V.
    Stimulation of C3H 10T1/2 murine fibroblasts with interferon-gamma(IFN) and bacterial lipopolysaccharide (LPS) generates reactive oxygen and nitrogen species leading to DNA damage, lipid oxidation, and tocopherol oxidation. The tocopherols possess unique chemical and biological properties that suggest they have important roles related to intracellular defense against radical-mediated damage.
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    Association of leptin, 25-hydroxyvitamin D, and parathyroid hormone in women.
    (2009) Maetani, Micah; Maskarinec, Gertraud; Franke, Adrian A.; Cooney, Robert V.
    Vitamin D deficiency and adipocytokines have been implicated in the etiology of aging-related diseases such as cancer, osteoporosis, and diseases of the cardiovascular system. The association between elevated parathyroid hormone (PTH) and low 25-hydroxyvitamin D (25-OH-VitD) in plasma is used to define vitamin D deficiency, yet their associated mechanistic pathways are unclear. Utilizing plasma samples from women in a previous intervention study, we measured plasma 25-OH-VitD, leptin, adiponectin, PTH, and lipid levels. We observed strong positive associations for leptin with PTH, gamma -tocopherol, and body mass index (BMI) and inverse associations with 25-OH-VitD and adiponectin. Although commonly accepted that vitamin D deficiency causes hyperparathyroidism, we observed this association primarily in individuals with elevated leptin levels, suggesting that leptin may be an important modifier of this effect consistent with 25-OH-VitD-mediated inhibition of leptin. Leptin was highly correlated with the BMI/25-OH-VitD ratio (r = 0.80; P < 0.0001), consistent with a model in which BMI (adiposity) and 25-OH-VitD are the primary determinants of circulating leptin and PTH levels. This model may explain the failure of some studies to observe elevated PTH in vitamin D deficient adolescents and provides important insight into epidemiological studies exploring the associations of these individual biomarkers with chronic disease risk and mortality.
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    Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study.
    (2009) Epplein, Meira; Shvetsov, Yurii B.; Wilkens, Lynne R.; Franke, Adrian A.; Cooney, Robert V.; Le Marchand, Loïc; Henderson, Brian E.; Kolonel, Laurence N.; Goodman, Marc T.
    Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk.
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    Inflammatory markers in a 2-year soy intervention among premenopausal women.
    (2009) Maskarinec, Gertraud; Steude, Jana S.; Franke, Adrian A.; Cooney, Robert V.
    Epidemiologic evidence supports a role of soy foods in breast cancer etiology. Because chronic inflammation appears to be a critical component in carcinogenesis, we examined the potential anti-inflammatory effects of soy foods.
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    Association of plasma micronutrient levels and urinary isoprostane with risk of lung cancer: the multiethnic cohort study.
    (2009-07) Epplein, Meira; Franke, Adrian A.; Cooney, Robert V.; Morris, J. Steven; Wilkens, Lynne R.; Goodman, Marc T.; Murphy, Suzanne P.; Henderson, Brian E.; Kolonel, Laurence N.; Le Marchand, Loïc
    Although smoking is the primary risk factor for lung cancer, there is evidence to suggest that fruit and vegetable intake are important cofactors. The present case-control study, nested within the Multiethnic Cohort Study, examined the associations of biomarkers of fruit and vegetable intake (individual plasma micronutrient levels), serum selenium, and a urinary biomarker for total lipid peroxidation with lung cancer risk. Two hundred seven incident cases were matched to 414 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection, and hours of fasting. We measured prediagnositic circulating levels of individual tocopherols and carotenoids, retinol, and serum selenium, and urinary 15-isoprostane F(2t). Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI). For men, strong reductions in risk were seen with increasing tertiles of each plasma carotenoid, with the ORs for the third tertile, compared with the first tertile, ranging from 0.24 to 0.45 (P(trends), 0.002-0.04). No associations were found among women for carotenoids or among either sex for tocopherols, selenium, and retinol. A doubling in risk was seen for men in the second and third tertiles, compared with the first tertile of urinary 15-isoprostane F(2t) (OR, 2.31; 95% CI, 1.02-5.25; and OR, 2.16; 95% CI, 0.98-4.78). This study supports the previously observed association between circulating carotenoids and lung cancer risk in men, and adds to the limited literature regarding urinary 15-isoprostane F(2t) as a marker of cancer risk. Future research examining the possible relationship between isoprostanes and lung cancer is warranted.
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    Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F(2t) in serum or urine with prostate cancer risk: the multiethnic cohort.
    (2009-09) Gill, Jasmeet K.; Franke, Adrian A.; Morris, J. Steven; Cooney, Robert V.; Wilkens, Lynne R.; Le Marchand, Loic; Goodman, Marc T.; Henderson, Brian E.; Kolonel, Laurence N.
    We examine the association of antioxidants and 15-isoprostane F(2t) with risk of prostate cancer.