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The circadian production of melatonin by the pineal gland during the night provides an inhibitory signal to tissue-isolated steroid receptor negative (SR-) MCF-7 human breast cancer xenografts in female nude rats.A central mechanism for melatonins anticancer effects in vivo involves a melatonin receptor-mediated inhibition of linoleic acid (LA) uptake and its metabolism to mitogenically active 13-hydroxyoctadecadienoic acid (13-HODE).These human breast cancer xenografts exhibit robust circadian rhythms of glucose uptake and metabolism to lactic acid, LA uptake and metabolism to 13-HODE, cAMP formation, and proliferative activity.