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Dean Brenner

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Primary Appointment: Int Med-Hematology/Oncology

  Cancer risk reductive interventions (“chemoprevention”) is the use of natural or synthetic compounds to delay, reverse or prevent the development of invasive cancer. Therapeutic index represents a key barrier in the development and deployment of cancer risk reductive interventions. For example, the cyclooxygenase-2 inhibitors, while potent colorectal cancer risk reductives in rodent models and in humans have an unacceptable therapeutic index due to cardiovascular risk increase. Other non-steroidal agents cause GI bleeding. We have begun development of the polyphenol class of nutritional extracts. Curcumin, an extract of turmeric has multiple cancer risk reductive properties including antioxidant, cyclooxygenase inhibitory, antiangiogenic, and NF-kappa-B activation inhibition. We have found that curcumin at high doses, does not cause unacceptable toxicity. We do not detect curcumin in human plasma, but we detect curcumin conjugates in high concentrations. Curcumin is heavily conjugated in the human colon mucosa and nearly undetected in its parent form. We have found another polyphenol, resveratrol, to have similar properties—poor bioavailability at systemic measuring sites and extensive conjugation with systemic circulation of conjugates. Our current research is focused upon defining the systemic and local effects of curcumin and resveratrol and their conjugates upon eicosanoid homeostasis and normal human breast stem cells in vitro.