Nutritional intervention of freeze-dried black raspberries (BRBs) in a group of human colorectal cancer patients has demonstrated beneficial effects, including pro-apoptosis, anti-proliferation and anti-angiogenesis. 3-hydroxyphenylacetate has been reported from rutin (33); 5-hydroxymethyl-2-furoic acid was detected in urine from subjects that consumed dried plum juice (34). GSS All of the tumor samples buy Azelnidipine from these patients were used to validate the effects of BRB on inhibition of cell proliferation by Ki67 immunohistochemistry, on apoptosis by TUNEL assays and to determine the levels of gene methylation on tumor suppressor genes (19). In the current study, the urinary and plasma specimens of the colorectal patients before BRB buy Azelnidipine intervention served as their own control in comparison with the specimens gathered after BRB treatment; consequently noticed differences could be associated with the BRB intervention, dietary changes during the BRB intervention, or other time-associated differences. We used published information from many groups that have conducted comprehensive metabolomic studies to determine the tumor-specific metabolic profiles in colorectal cancer patients (8, 11C15). Thus, large scale studies which include metabolic analysis of tumors, of the microenvironment and of the microbiome are needed to accurately buy Azelnidipine measure the effects of BRBs on colorectal cancer patients in comparison with healthy controls. Together, our results suggest that BRBs significantly induce metabolic changes in colorectal cancer patients. These BRB-derived metabolites may contribute to an overall beneficial regulation against colorectal tumors. Acknowledgments We thank Dr. Mark Arnold, Dr. Edward Martin and Dr. Christine Sardo, as well as Comprehensive Cancer Center Tissue Procurement Shared Resource at Ohio State University for managing the trial and handling the specimens in this trial at the Ohio State University. We also thank Dr. John Winston III and Sara Olivarri for their help in the trial at the University of Texas, San Antonio. Finally, we thank all patients for their participation in this trial. Funding: This work was supported by NIH grant 5 R01 CA148818 04 and American Cancer Society, RSG-13-138-01CNE to L.-S. Wang. Footnotes Conflict of interest: No potential conflicts of buy Azelnidipine interest were disclosed..