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The present findings suggest that changes in H3K9ac occur during the process of oral carcinogenesis along with an increase in cell proliferation and EMT. The results demonstrate that H3K9ac may be a useful novel prognostic marker for OSCC.

Abstract. The aim of the present prospective study was to evaluate the impact of laser phototherapy (LPT) on the healing of oral ulcers. Different power densities were used on oral wounds in Wistar rats (n ¼ 72) randomly divided into three groups: control (0 J∕cm 2 ), 4 J∕cm 2 laser, and 20 J∕cm 2 laser. Ulcers (3 mm in diameter) were made on the dorsum of the tongue with a punch. Irradiation with an indium-gallium-aluminum-phosphide laser (660 nm; output power: 40 mW; spot size: 0.04 cm 2 ) was performed once a day in close contact with the ulcer for 14 consecutive days. A statistically significant acceleration in healing time was found with wounds treated with 4 J∕cm 2 LPT. Moreover, striking differences were found in the ulcer area, healing percentage, degree of reepithelialization, and collagen deposition. The most significant changes occurred after 5 days of irradiation. Based on the conditions employed in the present study, LPT is capable of accelerating the oral mucosa wound-healing process. Moreover, faster and more organized reepithelialization and tissue healing of the oral mucosa were achieved with an energy density of 4 J∕cm 2 in comparison to 20 J∕cm 2 .

Purpose Loco-regional recurrence is a frequent treatment outcome for patients with advanced head and neck squamous cell carcinoma (HNSCC). Emerging evidence suggests that tumor recurrence is mediated by a small subpopulation of uniquely tumorigenic cells, i.e. cancer stem cells (CSC), that are resistant to conventional chemotherapy, endowed with self-renewal and multipotency. Experimental Design Here, we evaluated the efficacy of MEDI0641, a novel antibody-drug conjugate targeted to 5T4 and carrying a DNA-damaging “payload” (pyrrolobenzodiazepine) in preclinical models of HNSCC. Results Analysis of a tissue microarray containing 77 HNSCC with follow-up of up to 12 years revealed that patients with 5T4high tumors displayed lower overall survival than those with 5T4low tumors (p=0.038). 5T4 is more highly expressed in head and neck CSC (ALDHhighCD44high) than in control cells (non-CSC). Treatment with MEDI0641 caused a significant reduction in the CSC fraction in HNSCC cells (UM-SCC-11B, UM-SCC-22B) in vitro. Notably, a single intravenous dose of 1 mg/kg MEDI0641 caused long-lasting tumor regression in 3 patient-derived xenograft (PDX) models of HNSCC. MEDI0641 ablated CSC in the PDX-SCC-M0 model, reduced it by 5-fold in the PDX-SCC-M1, and 2-fold in the PDX-SCC-M11 model. Importantly, mice (n=12) treated with neoadjuvant, single administration of MEDI0641 prior to surgical tumor removal showed no recurrence for over 200 days, while the control group had 7 recurrences (in 12 mice) (p=0.0047). Conclusions Collectively, these findings demonstrate that an anti-5T4 antibody-drug conjugate reduces the fraction of cancer stem cells and prevents local recurrence, and suggest a novel therapeutic approach for patients with HNSCC.