We analyzed the mutational and methylation status of the spleen tyrosine kinase (Syk) gene and both mRNA and protein levels in primary oral squamous cell carcinoma (OSCC) and OSCCderived cell lines and examined the function of the Syk gene in OSCC-derived cell lines in vitro. Using quantitative real-time reverse transcription polymerase chain reaction, Western blotting and immunofluorescence on 7 OSCC-derived cell lines and normal oral keratinocytes (NOKs), Syk mRNA and protein expression were commonly downregulated in all cell lines compared to the NOKs. Although no sequence variation in the coding region of the Syk gene was identified in these cell lines, we found frequent hypermethylation in the CpG island region. Syk expression was restored by experimental demethylation. In addition, using a wound healing assay and in vitro invasion assay, we performed functional analysis using Syk transfected into the OSCC-derived cell lines, and they showed significant inhibition of motility and invasiveness. In clinical samples, high frequencies of Syk downregulation were detected by immunohistochemistry (33 of 53 [62%]). Furthermore, the Syk expression status was correlated significantly (p 5 0.047) with tumor metastasis to cervical lymph nodes. These results suggest that the Syk gene is frequently inactivated during oral carcinogenesis and that an epigenetic mechanism may regulate loss of expression possibly leading to metastasis.

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Bisphosphonate-related osteonecrosis of the jaw (BRONJ) affects quality of life and is an important problem for dentists. A Japanese position paper on BRONJ was published in 2010. The purpose of this study was to review clinical data on the treatment of BRONJ obtained at the Clinic of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba Hospital to further our understanding of this disease. A total of 13 patients (6 men and 7 women) were included. All the patients included in this study had received Bisphosphonate (BP) therapy and had BRONJ. Five of them (38.5%) had received oral BP therapy for osteoporosis, while the remaining 8 (61.5%) had received parenteral BP therapy for bone metastases from breast or prostate cancer. Osteoporosis patients were treated with risedronate or alendronate. Breast or prostate cancer patients were treated with zoledronate. Two patients with rheumatoid arthritis were treated with corticosteroid. Three patients had diabetes mellitus. Eleven patients were treated with antibiotics, while 5 underwent surgical treatment. Discontinuation of BP was recorded in 7 patients during dental treatment. Sequestration was observed in 6 patients during an 11-month follow-up. Eventually, healing and improvement of the oral mucosa were observed in 3 patients. The current standard treatment for BRONJ does not always provide good results. It is necessary to accumulate further clinical data to establish more effective treatment strategies for BRONJ.

Background In the most cases of oral squamous cell carcinoma (OSCC), oral epithelial dysplasia (OED) is found adjacent to the primary tumor. The delineation of surgical margins for OSCC is critical to minimize the risk for local recurrence. The aim of this study is to demonstrate that the fluorescence visualization (FV)- device can delineated the lesion visualizes OED of adjacent primary tumors by histopathologically comparison to conventional iodine vital staining. Material and methods The study involved 40 patients with superficial tongue squamous cell carcinoma treated from July 2016 to July 2018 at the Oral Cancer Center, Tokyo Dental College. Results Cytokeratin 13 (CK13) expression rate in the area of fluorescence visualization loss (FVL) was significantly lower than that in the area of fluorescence visualization retention (FVR). In addition, CK17, Ki-67, and p53 expression rates were significantly higher in FVL than FVR. There was no significant difference in the delineation rate or area between FVL and iodine-unstained area. High-grade dysplasia was observed most frequently at the FV and iodine-unstained boundary, but no significant pathological differences were found. Conclusion We strongly suggest the FV-guided surgery is a useful method for accurate resection in early-stage tongue squamous cell carcinoma.

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Objectives: We aimed to investigate the relationship between MR imaging detectability and its pathological depth of invasion (DOI) of oral tongue cancer, as well as its usefulness to assess the necessity of elective neck dissection. Methods: We retrospectively reviewed early stage oral tongue cancer patients treated with radical surgery with clinically N0, between May 2009 and February 2016. Collected data include age, sex, pathological DOI, DOI on MRI, locoregional control rate, disease-free survival rate, and overall survival rate. These data were statistically compared between the detectable lesion (DL) group and undetectable lesion (UL) group on MRI. Interobserver agreement in evaluation of detectability of the oral tongue cancer was assessed by k statistics. Results: Total of 53 patients were studied, and 28 were DLs and 25 ULs. Pathological DOI in UL was significantly smaller than that of DL (average 1.7 vs 4.6 mm, p < 0.001). Cutoff value between UL group and DL group was 3.5 mm (sensitivity 96 %, specificity 75 %). 96 % of ULs had pathological DOI smaller than 4 mm, the recommended cutoff value for neck dissection. There was no significant difference in locoregional control rate (p = 0.24), disease-free survival rate (p = 0.24) or overall survival rate (p = 0.92). Interobserver agreement in evaluation of detectability on MRI was very good (k-value = 0.89, p < 0.001). conclusions: When oral tongue cancer is not detected on MRI, it indicates pathological DOI being smaller than 4 mm, which may imply that elective neck dissection is unnecessary.

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