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.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Inflammation Mediators/antagonists & inhibitors , Mouth Neoplasms/drug therapy , Neoplasm Proteins/antagonists & inhibitors , Phytotherapy , Plant Extracts/pharmacology , Rubus/chemistry , Adult , Aged , Biomarkers, Tumor , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Fruit/chemistry , Humans , Male , Middle Aged , Mouth Mucosa/drug effects , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Neoplasm Staging , Phytochemicals/pharmacology , PrognosisABSTRACT
Arthritis is an ancient disorder that defies cure. The management of arthritis may require medication, surgery, and/or nonpharmacologic treatment, and patients whose pain responds to drug therapy often achieve substantial benefit from a compounded preparation. Customized to include analgesics in combinations and concentrations not found in commercially manufactured medications, a pain-relieving compound can be prepared in a transdermal form that minimizes the risk of adverse effects associated with some oral medications. In this article, we present case reports of patients whose arthritic pain was relieved by a pharmaceutical compound. Formulations effective in treating inflammatory pain are also provided.
