60 research outputs found

    Biobehavioral research on nicotine use in women

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    More American women are taking up smoking than men and fewer are quitting; if current trends continue, rates for women will surpass those for men by the mid-1990's. But ironically, much of what is known about the biobehavioural aspects of smoking is based on research using male subjects. The present paper reviews evidence suggesting that: (1) women may differ from men with regard to nicotine intake and/or effects; (2) nicotine intake and effects may be influenced by menstrual cycle phase; (3) oral contraceptive use and estrogen replacement therapy may affect intake and effects of nicotine; (4) the effects of chronic nicotine use on female reproductive endocrinology may have implications for the reinforcement of smoking; and (5) pharmacological agents used to treat smoking may have different effects in women than in men. Guidelines and suggestions are presented by future biobehavioural research in women, including standardization of assessment procedures, attention to the use of appropriate controls, and use of pharmacological probes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73978/1/j.1360-0443.1991.tb01802.x.pd

    BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells

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    Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-α) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20 μM) and genistein (0.5–1.0 μM), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER-α activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein

    Microbial carcinogenic toxins and dietary anti-cancer protectants

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    Generalizing Single-View 3D Reconstruction

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    Single-view 3D reconstruction is a task in which an algorithm constructs a 3D model from a single image of an object without seeing the back side of that object or viewing any explicit depth information. We create a standardized approach to the problem, and a new state-of-the-art baseline.Undergraduat

    Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans

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    of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). Purpose: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. Methods: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography–mass spectrometry. Results: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16�hydroxyestrone, were lower after I3C treatment. Conclusions: These findings support the hypothesis that I3Cinduced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. Implications: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation. [J Natl Cancer Inst 1997;89:718-23] A battery of inducible and constitutive enzymes, collectively referred to as cytochrome P450, exists in humans and other animals to metabolize or detoxify endogenous and exogenous substances. Several hundred isoenzymes of cytochrome P450 have been identified, some of which are involved in the formation of various hydroxylated estrogen metabolites. The major metabolites in humans are either catechol estrogens (defined as a 2,3dihydroxyestroge
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