title: Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche.
abstract: Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention.
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio. knobloch.1@osu.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Knobloch
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio.
authors.forename: Lana K
authors.initials: LK
authors.lastname: Uhrig
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Statistics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Pearl
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Casto
authors.affiliation: Department of Diagnostic Sciences, Oral and Maxillofacial Pathology, School of Dental Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Blake M
authors.initials: BM
authors.lastname: Warner
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Medical Oncology, Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Sardo-Molmenti
authors.affiliation: The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Ferguson
authors.affiliation: The Ohio State University, Columbus, Ohio.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Daly
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Riedl
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schwartz
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio.
authors.forename: Yael
authors.initials: Y
authors.lastname: Vodovotz
authors.affiliation: Central Ohio Compounding Pharmacy, Columbus, Ohio.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Buchta
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Head and Neck Oncology, Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: David E
authors.initials: DE
authors.lastname: Schuller
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Head and Neck Oncology, Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Enver
authors.initials: E
authors.lastname: Ozer
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Head and Neck Oncology, Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Amit
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Weghorst
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005638:Fruit / Q000737:chemistry; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009367:Neoplasm Staging; D064209:Phytochemicals / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011379:Prognosis; D065856:Rubus / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor; D018836:Inflammation Mediators; D009363:Neoplasm Proteins; D064209:Phytochemicals; D010936:Plant Extracts