| Popis: |
A diet rich in fruits, vegetables and whole grains can help reduce the risk of many cancers (AICR, 2009). Black raspberries (BRB) (Rubus Occidentials) rich in a variety of bioactive compounds may contribute to the preventive effects of BRB in certain cancers with both preclinical and clinical studies. Utilizing BRB in a non-food delivery system has been studied in several cancers with promising results. However, for long term prevention, a dietary approach of utilizing novel BRB food products that are fully characterized, consistent in composition, with high compliance, and excellent bioavailability of phytochemicals may prove more effective. The primary objective of this study is to design, select and fully characterize BRB food products suitable for human cancer prevention studies. In order to better understand cancer preventive effects of BRB on systematic cancers such as prostate cancer, this study also investigates BRB dietary intervention on gene expression changes in early prostate carcinogenesis with transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Three forms of confections containing whole BRB freeze-dried powder were developed with varying release rates of phytochemicals. Successful formulations yielded hard candies (22% BRB) with fast release, pectin based confections (22% BRB) with intermediate release, and starch based confections (40% BRB) with slow release rate as determined by dissolution studies. Pectin confections were selected for scale-up production for clinical trials due to results from sensory, texture, and storage stability studies. Nectars with optimized texture and sensory acceptance were selected. The processing, scale-up and storage effect on the consistency, quality, bioactive stability and sensory acceptability of two BRB delivery systems of varying matrices were studied. Confections and nectars retained high amount of anthocyanins and ellagitannin after processing. Texture of products remained unchanged during storage for two months at 4 ºC. BRB products were well accepted by 32 clinical subjects in a phase II dietary intervention trial. In animal study, 4-week old TRAMP mice and their non-transgenic (WT) littermates were fed with control diet or 10% BRB diet for 6 weeks. As a result, 10-week-old TRAMP mice have developed early prostatic intraepithelial neoplasia (PIN) that leads to distinct changes in prostate lobe weight, histological features, Ki67 protein expression, and prostate mRNA expression regardless of diet. Urolithins were detected and quantified in plasma, liver and prostate of mice fed with BRB by HPLC-MS/MS. Interestingly, BRB diet significantly modulated gene changes in TRAMP mice during 6 weeks of feeding which are related to cell morphology and proliferation. In conclusion, food delivery matrix could modulate the phytochemical release rate from BRB confection and also influence sensory preference. Two different BRB foods can be formulated to meet quality standards with a consistent bioactive pattern and successfully scaled up for a large human clinical trial focusing on cancer risk and other health outcomes. As to BRB intervention on mouse prostate carcinogenesis, diet has effects on pathways and disease related networks through modulating gene expression which may impact prostate carcinogenesis. Further efforts will focus on the connection and comparison of gene expression changes between TRAMP and human prostate. |
