Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.
(13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.
Evidence derived from a vast array of laboratory studies and epidemiological investigations have implicated diets rich in fruits and vegetables with a reduced risk of certain cancers. However, these approaches cannot demonstrate causal relationships and there is a paucity of randomized, controlled trials due to the difficulties involved with executing studies of food and behavioral change. Rather than pursuing the definitive intervention trials that are necessary, the thrust of research in recent decades has been driven by a reductionist approach focusing upon the identification of bioactive components in fruits and vegetables with the subsequent development of single agents using a pharmacologic approach. At this point in time, there are no chemopreventive strategies that are standard of care in medical practice that have resulted from this approach. This review describes an alternative approach focusing upon development of tomato-based food products for human clinical trials targeting cancer prevention and as an adjunct to therapy. Tomatoes are a source of bioactive phytochemicals and are widely consumed. The phytochemical pattern of tomato products can be manipulated to optimize anticancer activity through genetics, horticultural techniques, and food processing. The opportunity to develop a highly consistent tomato-based food product rich in anticancer phytochemicals for clinical trials targeting specific cancers, particularly the prostate, necessitates the interactive transdisciplinary research efforts of horticulturalists, food technologists, cancer biologists, and clinical translational investigators.
We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.
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