Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo

Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1-40 microM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (>/=5 microM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w(-1)) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 microM and 0.11 and 63 nmol g(-1), respectively. Cells were exposed to tricin (0.11, 1.1 or 11 microM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 microM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 microM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious

Rejection sampling and agent-based models for data limited fisheries

Many of the world’s fisheries are “data-limited” where the information does not allow precise determination of fish stock status and limits the development of appropriate management responses. Two approaches are proposed for use in data-limited stock management strategy evaluations to guide the evaluations and to understand the sources of uncertainty: rejection sampling methods and the incorporation of more complex socio-economic dynamics into management evaluations using agent-based models. In rejection sampling (or rejection filtering) a model is simulated many times with a wide range of priors on parameters and outcomes are compared multiple filtering criteria. Those simulations that pass all the filters form an ensemble of feasible models. The ensemble can be used to look for robust management strategies, robust to both model uncertainties. Agent-based models of fishery economics can be implemented within the rejection framework, integrating the biological and economic understanding of the fishery. A simple artificial example of a difference equation bio-economic model is given to demonstrate the approach. Then rejection sampling is applied to an agent-based model for the hairtail (Trichiurus japonicas) fishery, where an operating model is constructed with rejection/agent-based methods and compared to known data and analyses of the fishery. The usefulness of information and rejection filters are illuminated and efficacy examined. The methods can be helpful for strategic guidance where multiple states of nature are possible as a part of management strategy evaluatio