Browsing by Subject "chemoprevention"

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    The Effects of Tamoxifen on Mammary Organoids from Young and Old MMTV-c-neu Mice
    (2020-12) Troness, Benjamin
    Tamoxifen, an estrogen antagonist, can prevent ER-positive tumor development in women at risk of developing breast cancer. Mouse studies demonstrate that tamoxifen can prevent ER-negative tumors if administered to young mice. This project examined the differences in cell populations and progenitor activity between mammary organoids from young and old MMTV-c-neu mice, treated with or without tamoxifen. Tamoxifen-treatment increased the proportion of luminal, colony-forming cells in 2D but decreased the proportions of basal and CD61-positive, luminal progenitor cells in young and old mouse organoids. Tamoxifen tended to increase the proportions of CD61-negative, luminal cells in old organoids but reduced this population in young mouse organoids. In 3D cultures, tamoxifen increased the number of luminal-like colonies produced by old, but not young, mouse organoid cells. These results suggest that aging renders the CD61-negative, luminal cell population resistant to tamoxifen and that this population should be targeted for the prevention of ER-negative tumors.
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    Glucobrassicin Enhancement Using Low Red To Far-Red Light Ratio In ‘Ruby Ball’ Cabbage And High-Throughput Glucobrassicin Estimation Using Near-Infrared Reflectance Spectroscopy
    (2020-05) Renner, Ilse
    Brassica vegetables produce glucobrassicin (GBS) and gluconasturtiin (GNST), important precursors of chemopreventive compounds. Consuming vegetables with greater GBS and GNST concentrations can lead to enhanced chemoprevention. These vegetables could be produced using GBS- and GNST-enhancing practices, for example, by manipulating light quality. We studied the effect of the red to far-red light (R:FR) ratio on GBS concentration in ‘Ruby Ball’ (red) and ‘Tiara’ (green) cabbage (Brassica oleracea) heads across four seasons. R:FR variation was induced with foliar shading using weed surrogates that competed with cabbage plants for 0, 2, 4, 6 weeks or all season. ‘Ruby Ball’ GBS concentrations were greatest when competition lasted 6 or more weeks; the associated R:FR ratio was lowest in these treatments. ‘Tiara’ was unaffected by competition. Light quality around cabbage plants was recorded using a spectroradiometer (Supplemental Table 1). Confirmation of GBS accumulation in ‘Ruby Ball’ from a low R:FR ratio was observed in controlled experiments. In two replicate studies, a R:FR=0.3 treatment resulted in 2.5- and 1.4-fold greater GBS concentration compared to R:FR=1.1 and R:FR=5.0 treatments combined. In watercress (Nasturtium officinale) subjected to end-of-day (EOD) 10-min R and/or 15-min FR pulses supplied after the main photoperiod, we observed lowest GNST concentrations after an EOD FR pulse, but highest concentrations after a R followed by FR pulse (figure 3.8). Together, these studies demonstrate the role of phytochrome in GBS and GNST accumulation. Fast, inexpensive GBS quantification methods are needed in breeding programs and for growers to verify vegetable quality. Such methods could be developed by pairing near-infrared reflectance spectroscopy (NIRS) with partial least squares regression (PLSR) to create prediction models. We developed a model to estimate GBS concentration in freeze-dried cabbage and Brussels sprout leaf tissue. Our cross-validated models predicted GBS concentration sufficiently for screening purposes (R2=0.75, RPD=2.3 and R2=0.80, RPD=2.4, fresh weight and dry weight basis, respectively). Cultivar selection, R, and FR light manipulation should be considered when developing GBS and GNST-enhancing production systems. GBS quantification is possible using NIRS with PLSR. Such high-throughput phenotyping methods could support breeding programs and provide an inexpensive tool to quantify vegetable chemopreventive value.
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    Harnessing The Power Of Cruciferous Vegetables: Developing A Biomarker For Brassica Vegetable Consumption Using Urinary 3,3´-Diindolylmethane
    (2016-04) Fujioka, Naomi
    Glucobrassicin gives rise to indole-3-carbinol (I3C), a compound with potent anti-cancer effects in preclinical models. We previously showed that urinary 3,3´-diindolylmethane (DIM, the predominate metabolite of I3C), can discriminate between consumption of high and low doses of glucobrassicin-containing vegetables. However, the quantitative relationship between glucobrassicin exposure and urinary DIM level is unclear. We hypothesized that a range of glucobrassicin exposure from Brassica vegetables is reflected in urinary DIM and that this effect plateaus. Forty-five subjects consumed vegetables at 1 of 7 discrete dose levels (25 to 500 umol) of glucobrassicin for 2 days. Urine was collected for 24 hours afterward, and DIM was measured by LC/ESI-MS/MS-SRM. Urinary DIM excretion increased predictably with increasing glucobrassicin dose, plateauing between 200 and 300 umol of glucobrassicin. Glucobrassicin dose and urinary DIM correlated (R=0.82). The positive and strong correlation between glucobrassicin dose and urinary DIM supports its use as a biomarker of glucobrassicin exposure and I3C uptake.