Potent Antitumor Effects of a Combination of Three Nutraceutical Compounds.

Head and neck squamous cell carcinoma (HNSCC) is associated with low survival, and the current aggressive therapies result in high morbidity. Nutraceuticals are dietary compounds with few side effects. However, limited antitumor efficacy has restricted their application for cancer therapy. Here, we examine combining nutraceuticals, establishing a combination therapy that is more potent than any singular component, and delineate the mechanism of action. Three formulations were tested: GZ17-S (combined plant extracts from Arum palaestinum, Peganum harmala and Curcuma longa); GZ17-05.00 (16 synthetic components of GZ17-S); and GZ17-6.02 (3 synthetic components of GZ17S; curcumin, harmine and isovanillin). We tested the formulations on HNSCC proliferation, migration, invasion, angiogenesis, macrophage viability and infiltration into the tumor and tumor apoptosis. GZ17-6.02, the most effective formulation, significantly reduced in vitro assessments of HNSCC progression. When combined with cisplatin, GZ17-6.02 enhanced anti-proliferative effects. Molecular signaling cascades inhibited by GZ17-6.02 include EGFR, ERK1/2, and AKT, and molecular docking analyses demonstrate GZ17-6.02 components bind at distinct binding sites. GZ17-6.02 significantly inhibited growth of HNSCC cell line, patient-derived xenografts, and murine syngeneic tumors in vivo (P < 0.001). We demonstrate GZ17-6.02 as a highly effective plant extract combination and pave the way for future clinical application in HNSCC.

Transoral robotic surgery for oropharyngeal cancer: long-term quality of life and functional outcomes.

IMPORTANCE: Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially. OBJECTIVE: To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC. DESIGN, PARTICIPANTS, AND SETTING: This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center. INTERVENTIONS: Primary surgical resection via TORS and neck dissection as indicated. MAIN OUTCOMES AND MEASURES: Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected. RESULTS: Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both). CONCLUSIONS AND RELEVANCE: Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.