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Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed levels of H3K4me3/ H3K27ac and expression of a number of interferon-stimulated genes (ISGs), including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.

Ultrasound-guided inferior alveolar nerve block (UGIANB) is a mandibular analgesic procedure in which local anesthetic is injected into the pterygomandibular space (PMS). Several studies have reported the clinical efficacy of UGIANB for mandibular surgeries; however, its effective range has never been investigated. We performed a cadaveric study to investigate the success rate of UGIANB injections and to determine whether injected dye could stain the mandibular nerve (MN) trunk and its branches. We performed UGIANB on the bilateral faces of 4 Thiel-embalmed cadavers. A needle was advanced to the PMS under ultrasound guidance and 5 mL of dye was injected. The cadaver was dissected and inspected for the presence of dye in the PMS; the range of dye spread to any of the inferior alveolar nerve (IAN), lingual nerve (LN), buccal nerve (BN), mandibular nerve (MN), auriculotemporal nerve (ATN), or facial nerves; and for the presence of intravascular dye. We performed eight UGIANB procedures on four cadavers. Dye was observed in the PMS in 7/8 injections. Staining was observed in all IAN, LN, and BNs that could be identified at dissection. No MN or auriculotemporal nerves (ATNs) were stained in any injections. No intravascular dye was observed in any injections. UGIANB can administer anesthetic into the PMS with high accuracy. UGIANB injections reached the IAN, LN, and BNs, but did not reach the MN or ATNs located outside the PMS. The findings of this cadaveric study indicate that UGIANB can provide sufficient analgesia for mandibular surgeries.

Background/aim The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. Patients and methods We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. Results Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. Conclusion CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.

Intravascular papillary endothelial hyperplasia is an unusual benign lesion of vascular origin. A 56-year-old man presented with a mass in the right side of the lower lip. Before visiting our hospital, he had undergone 3 surgical procedures for recurrence of the mass in a short period of time. Clinical examination revealed a painless, soft, elastic, dark purple obscure mass measuring 17 × 11 mm in the right lower lip. Ultrasonography and magnetic resonance imaging suggested a hemangioma-like lesion. The possibility of malignant transformation could not be ruled out because of the clinical course up to that point, even though it had been histopathologically diagnosed as hemangioma. The lesion was surgically resected and the defect was reconstructed using a vermilion advancement flap combined with a V-Y advancement flap. The histopathological diagnosis was intravascular papillary endothelial hyperplasia. The patient has had no symptoms or any evidence of recurrence in the 4 years since the operation. His postoperative progress has been favorable both functionally and aesthetically.

Background/aim The tumor microenvironment (TME) balances tumor growth and suppression through humoral factors and cell-cell interactions. In oral squamous cell carcinoma (OSCC), TMEs have been associated with prognosis of cancer patients and are evaluated by microscopy; however, these methods of evaluation vary among studies. Materials and methods To evaluate the TME, borderline microenvironment fibrosis (bMF) was evaluated histologically in 236 OSCC cases and used to determine the clinicopathological status. Results bMF was observed in 47% (110 in 236 cases) of OSCC cases and associated with higher T category, N category, stage, histological grade and mode of invasion. bMF-positive was related to overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that bMF-positive was an independent factor for OS in all cases [n=226; HR=1.683 (1.018-2.781); p=0.042], especially in T1+T2 cases [n=186; HR=1.926 (1.079-3.440); p=0.024], and PFS in all cases [n=226; HR=2.254 (1.397-3.637); p=0.001]. Conclusion bMF may act as a novel biomarker for OSCC.

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5‐year overall survival and disease‐specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC., Human leukocyte antigen class Ⅰ expression at the tumor invasive front could be a useful prognostic factor for oral squamous cell carcinoma.

We evaluated the incidence and risk factors for antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate and kidney cancer patients. We retrospectively reviewed the clinical data of 547 patients from 13 hospitals. Prostate and kidney cancer patients with bone metastases who were treated with a bone-modifying agent (BMA) between January 2012 and February 2019 were enrolled. Exclusion criteria were BMA use for hypercalcemia, a lack of clinical data, a follow-up period of less than 28 days and a lack of evaluation by dentists before BMA administration. The diagnosis and staging of ARONJ were done by dentists. Two-hundred eighteen patients were finally enrolled in the study, including 168 prostate cancer patients and 50 kidney cancer patients. Of them, 49 (29%) prostate cancer patients and 18 (36%) kidney cancer patients needed tooth extraction prior to BMA initiation. The mean follow-up period after BMA initiation was 552.9 ± 424.7 days (mean ± SD). In the cohort, 23% of the patients were diagnosed with ARONJ in the follow-up period. The 1-year cumulative incidences of ARONJ were 9.4% and 15.4% in prostate and kidney cancer patients, respectively. Multivariate analysis indicated that kidney cancer, tooth extraction before BMA and a body mass index (BMI) ≥ 25 kg/m2 were significant predictors for ARONJ. ARONJ is not a rare adverse event in urological malignancies. Especially, kidney cancer, high BMI patients and who needed tooth extraction before BMA were high risk for developing ARONJ.

BACKGROUND The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). METHODS We evaluated the associations between tumor-infiltrating CD8+ T-cell density and survival in five distinct compartments in 139 OSCC cases. RESULTS There was a significant association between increased tumor-infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T-cell density at the invading tumor edge was associated with improved overall survival (OS) and disease-specific survival (DSS; P

Methotrexate (MTX) has been reported to be effective for the treatment of rheumatoid arthritis (RA) when a weekly low dose is administered to patients. We carried out microscopic examination of a biopsied specimen suspected of being Wegener’s granulomatosis, IgG4-related disease, or malignant lymphoma. Finally we diagnosed a rheumatoid nodule because his medical history included treatment with MTX. Then we immediately discontinued the MTX and his rheumatoid nodule disappeared after 2 months. Rheumatoid nodules are granulomatous nodules that appear subcutaneously and in tendons in the active phase of RA and commonly occur on the exterior part of the elbow joint and the back of the head where subcutaneous tissue is subject to recurrent pressure against bone. The development of an intraoral rheumatoid nodule in the maxillofacial region of a patient with RA who received MTX has not been few reported. To date, this patient has been followed up for 6 years without recurrence.

// Akihiro Miyazaki 1, * , Hiromi Nakai 1, * , Tomoko Sonoda 2 , Yoshihiko Hirohashi 3 , Mika K. Kaneko 4 , Yukinari Kato 4, 5 , Yoshihiko Sawa 6 and Hiroyoshi Hiratsuka 1 1 Department of Oral Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan 2 Department of Public Health, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan 3 Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan 4 Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan 5 New Industry Creation Hatchery Center, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575, Japan 6 Deparment of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama Kita-ku 700-0914, Japan * These authors have contributed equally to this work Correspondence to: Yoshihiko Sawa, email: ysawa@okayama-u.ac.jp Keywords: LpMab-23; predictor; podoplanin; tongue cancer; antibody Received: October 17, 2017 Accepted: March 12, 2018 Published: April 20, 2018 ABSTRACT Purpose: We report that the reactivity of a novel monoclonal antibody LpMab-23 for human cancer-type podoplanin (PDPN) is a predictor for a poor prognosis of tongue cancer. Patients and Methods: The association between LpMab-23-recognizing cancer-type PDPN expression and clinical/pathological features were analyzed on 60 patients with stage I and II tongue cancer treated with transoral resection of the primary tumor. Results: In the mode of invasion, the LpMab-23-dull/negative cases were significantly larger in cases with low-grade malignancies and without late cervical lymph node metastasis, than in cases with high-grade malignancies and the metastasis. In the high-grade malignant cases, LpMab-23-positive cases were significantly larger than LpMab-23-dull/negative cases. The Kaplan–Meier curves of the five-year metastasis-free survival rate (MFS) were significantly lower in the LpMab-23 positive patients than in LpMab-23 dull/negative patients. The LpMab-23-dull/negative cases showed the highest MFS in all of the clinical/pathological features and particularly, the MFS of the LpMab-23 positive cases decreased to less than 60% in the first year. In the Cox proportional hazard regression models a comparison of the numbers of LpMab-23 dull/negative with positive cases showed the highest hazard ratio with statistical significance in all of the clinical/pathological features. Conclusions: LpMab-23 positive cases may be considered to present a useful predictor of poor prognosis for early stage tongue cancer.

Objective To clarify the relationship between mandibular ramus height and function of masticatory muscles in patients with hemifacial microsomia. Design Retrospective study of imaging and physiological data. Setting Images and physiological data were obtained from the records of Sapporo Medical University Hospital. Patients A total of 29 patients with hemifacial microsomia who showed Pruzansky grades I, II deformity. Main Outcome Measures Mandibular ramus height and masticatory muscle volume were evaluated with multi-detector row computed tomography. The electromyographic value was measured by the K7 Evaluation System. The hemifacial microsomia patients were classified into three groups based on the mandibular ramus height ratio of the affected and unaffected sides: group 0, > 1.00; group 1, 1.00 to 0.85; group 2, < 0.85. The Tukey-Kramer method and Games-Howell method were used to determine correlations between parameters. Results Decreased mandibular ramus height was significantly correlated with both reduced electromyographic values of the masseter muscle (P < .05) and the amount of mandibular lateral deviation at the time of maximum opening (P < .05) on the affected side. These differences were prominent in unilateral hemifacial microsomia patients classified as group 2. Conclusions Decreased mandibular ramus height may cause dysfunction of the masseter muscles but not the temporal muscle on the affected side in patients with hemifacial microsomia.

Objective Epithelial–mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis induced by hypoxia. Here, we examined whether phosphorylation of GSK3-β via phosphoinositide 3-kinase (PI3 K)/Akt signaling is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma (OSCC). Study Design Experiments were performed in OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was assessed by Matrigel invasion assays and wound healing assays. OSCC cell lines (HSC-2 and HSC-4) overexpressing hypoxia-inducible factor (HIF)-1α were established to examine the effects of HIF-1α on EMT-related factors. Immunohistochemical staining was performed to examine phosphorylation of GSK3-β in 33 cases of tongue squamous cell carcinoma. Results Under hypoxic conditions, OSCC cell lines exhibited HIF-1α expression and showed evidence of the EMT. In cells overexpressing HIF-1α, the levels of phospho-Akt and phospho-GSK3-β were increased, resulting in induction of the EMT. Inhibition of GSK3-β phosphorylation suppressed these effects. Moreover, the intensity of pGSK3-β staining was significantly increased with cN stage and cTNM stage in patients with tongue squamous cell carcinoma. Conclusions Our data showed that the hypoxia-induced EMT in OSCC was enhanced by GSK3-β phosphorylation, suggesting that GSK3-β may be important in the invasion and metastasis of OSCC.

Traumatic facial nerve paralysis is often caused by nerve damage in the temporal bone, such as that from temporal bone fractures, and very rarely by direct facial nerve injuries resulting from stings, cuts, bruises or other damage to areas outside of the temporal bone. We report a case of facial nerve paralysis due to pressure from a small bone fragment from a mandibular condylar fracture in which symptomatic improvement was achieved through surgical treatment. The patient was a 30-year-old woman who was injured during a fall. She visited our department after noticing symptoms the following morning that included malocclusion and abnormalities in the muscles of facial expression such as incomplete eye closure. On presentation, a left-side mandibular condylar fracture and severe left-side facial nerve paralysis were identified. As the likely cause of facial nerve paralysis was not a temporal bone fracture, cuts or bruises, but pressure from a small bone fragment, we performed open reduction and internal fixation (ORIF) surgery. In consideration of the surgical risk to nerves, ORIF surgery was performed using a transoral approach. Antecedent steroid therapy was begun just after hospitalization. Improvements were seen in both the malocclusion and facial nerve paralysis. Here we report a case of facial nerve paralysis due to compression from a small bone fragment from a condylar fracture that was treated with ORIF surgery through a transoral approach performed as decompression surgery with a favorable outcome.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. It accounts for 5% of all salivary gland tumors and 20% of salivary malignancies and has various clinical outcomes. Its prognosis is related to the tumor grade in the WHO classification of head and neck tumors. MEC is divided into high, intermediate and low grades. In general, low-grade MEC with cervical lymph node metastasis is rare, and primary MEC that occurs in a minor salivary gland with cervical lymph node metastasis is very rare. Low-grade lesions have quite different behavior from high-grade ones, leading to differences in the treatment course required for disease control. MEC is associated with recurring chromosomal translocation t(11;19)(q21;p13). CRTC1-MAML2 gene fusion was identified from the recurring translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript is detected frequently in MEC and is involved in the transformation of epithelial cells. Detection of the CRTC1-MAML2 fusion transcript is associated with a less advanced clinical stage and low-grade tumor histology. The presence of the transcript is associated with longer disease-free and overall survival periods. Here, we report a rare case of low-grade MEC with cervical lymph node metastasis. The findings for this patient show that the CRTC1-MAML2 fusion transcript may be specific to MEC, and associated with a distinct MEC subset that exhibits favorable clinicopathologic features.

Steroid has recently been reported as a treatment for new coronavirus disease (COVID-19). The incidence of oropharyngeal candidiasis due to the inhaled steroid ciclesonide is lower than that due to other inhaled steroids. We report the first case of oral candidiasis with COVID-19 pneumonia using ciclesonide. A 75-year-old man was hospitalized for COVID-19 pneumonia. After admission, an oral combination of lopinavir/ritonavir was administered, and ciclesonide was inhaled for 7 days. On the 14th day of hospitalization, white plaque was found in his oral mucosa. Candida albicans was identified by oral bacterial tests, and amphotericin B was initiated. On the 35th hospital day, negative result for C. albicans was confirmed. Intraoral monitoring and intervention by dental care workers are considered important for the prevention of infectious complications induced by corticosteroids.

To clarify the morphological characteristics of hemifacial microsomia (HFM) by quantitative analysis of cephalometric radiographs.Retrospective study of imaging data.Imaging data were obtained from the records of Sapporo Medical University Hospital.A total of 183 patients with HFM.We used linear and angular measurements and analyzed the middle face and lower face.The ratios of the affected side to the unaffected (A/U) side of the lateral distance of the mandibular condyle, the mandibular ramus height, and the length of the body of the mandible in the HFM group were significantly lower than in the control group. The inclination of the body of the mandible was significantly larger in the side with HFM than in the unaffected side, and the extent of the mandibular ramus was significantly lower than in the unaffected side. The A/U ratios of the extent of the angle of the mandible and the inclination of the body of the mandible in the HFM group were larger than in the control group. Moreover, the length and the inclination of the body of the mandible had significant correlations with the distance of the shift of the menton.It is suggested that improving the hypoplasia of the length of the body of the mandible and the extent of the angle of the mandible on the affected side will lead to more effective treatment of jaw deformity in patients with HFM.

Desmoplastic fibroblastoma (DF) is a rare benign soft tissue with spindle-to-stellate-shaped fibroblasts and myofibroblasts embedded in a prominent collagenous background. DF, mainly affecting subcutaneous and muscle tissue, very rarely occurs in the oral cavity. Hitherto, only one case of DF on the tongue has been reported. Here, we report another case. A 66-year-old woman was referred to our hospital with a mass formation in the tongue. On examination, a well-circumscribed, elastic, soft tumour with normal surface mucosa, measuring 13×12 mm, was observed on the left dorsal surface of her tongue. MRI and ultrasonography confirmed the mass, and a benign tongue tumour was suspected. The tumour was surgically resected under general anaesthesia 1 month later, leading to the histopathological diagnosis of DF. She experienced an uneventful clinical recovery after surgery, with no recurrence noted for more than 1 year postoperatively.

Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues. We then validated their expression in 18 OSCC cell lines using qRT-PCR and identified 6 lncRNAs frequently overexpressed in OSCC. Among those, we found that knocking down DLEU1 (deleted in lymphocytic leukemia 1) strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion, and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC.

Background Cases of diverticula of the buccal mucosa are extremely rare. Literature searches of databases such as PubMed/MEDLINE for this condition have revealed only 10 case reports. In this case report, we describe our experience in the management of this rare condition and review the previous 10 previously reported cases. Case presentation A 66-year-old man presented with a pouch containing inspissated food debris located posterior to the papilla of the parotid duct in his left buccal mucosa. The diagnosis of a diverticulum arising from the buccal mucosa was confirmed based on clinical and radiographic findings. Gross examination of the locally resected tissue specimen revealed a pouch measuring 14 mm in diameter and 8 mm in depth, that was whitish in color and had an elastic, soft, and smooth surface. Microscopic examination revealed a cyst-like lesion lined by stratified squamous epithelium and granulation tissue, with a chronic inflammatory infiltration in the peripheral stromal tissue of the epithelial layer. After surgical excision of the lesion, there was no recurrence during the follow-up period of 5 years and 10 months. Conclusions We have presented a rare case of a diverticulum of the buccal mucosa. This is the first report of a case confirmed not only by the clinicopathological findings, but also by computed tomography and magnetic resonance imaging findings. From the magnetic resonance imaging and intraoperative findings, we inferred that the diverticulum was caused by an idiopathic developmental anomaly due to a partial defect of the buccinator muscle.

Background Facial asymmetry, which is often due to asymmetry of the mandible, is a naturally occurring phenomenon in patients with hemifacial microsomia (HFM). Only a few attempts have been made to develop specific quantitative diagnostic criteria for the mandibular asymmetry of HFM. This pilot study was designed to determine the soft-tissue and skeletal characteristics of patients perceived to have HFM and the factors affecting objective assessment of mandibular asymmetry. Methods Frontal facial photographs and frontal cephalograms of twelve patients who had HFM with mandibular asymmetry were analyzed. Landmarks and reference lines were determined on the basis of frontal photographs and cephalographic analysis. Linear measurements of the right and left sides were performed to assess the degree of asymmetry of the mandible. The differences between the affected side and the unaffected side were calculated and analyzed statistically. Results Significant differences were found for linear measurements of the gonion distance (GoD), full marginal distance (FMD), external marginal distance (EMD), and gonion-menton distance (Go-MeD) in the hard tissue and sFMD, sEMD, sGo-MeD in the soft tissue but not for the gonion distance in soft tissue (sGoD). The differences in sEMD and EMD were significantly correlated, and represented a valid factor affecting the mandibular asymmetry in soft and hard tissues. Conclusions The results of this study suggest that appropriate measurements affecting the outline of the mandible such as sEMD and EMD taken from frontal facial photographs and frontal cephalograms provide a useful, objective means of assessing mandibular asymmetry for patients with HFM.

Low-dose methotrexate is a standard treatment for rheumatoid arthritis (RA). Immunosuppressive therapies, including methotrexate (MTX), for patients with RA have long been implicated in the development of lymphoproliferative disorders (LPD), as so-called MTX-associated LPD. However, spontaneous remission of MTX-LPD has been observed after discontinuing MTX therapy for RA. The present study summarizes the clinical features from a review of the literature on patients with MTX-associated diffuse large B-cell lymphoma (DLBCL) and reports a case in which MTX-associated DLBCL showed spontaneous complete remission after withdrawal of MTX therapy.

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p

Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and radiotherapies and perpetuate tumor formation in vivo. In this study, we conducted an HLA ligandome analysis to survey HLA-A24 peptides displayed by CSCs and non-CSCs of colorectal cancer. The analysis identified an antigen, ASB4, which was processed and presented by a CSC subset but not by non-CSCs. The ASB4 gene was expressed in CSCs of colorectal cancer, but not in cells that had differentiated into non-CSCs. Because ASB4 was not expressed by normal tissues, its peptide epitope elicited CD8+ cytotoxic T-cell (CTL) responses, which lysed CSCs of colorectal cancer and left non-CSCs intact. Therefore, ASB4 is a tumor-associated antigen that can elicit CTL responses specific to CSCs and can discriminate between two cellular subsets of colorectal cancer. Adoptively transferred CTLs specific for the CSC antigen ASB4 could infiltrate implanted colorectal cancer cell tumors and effectively prevented tumor growth in a mouse model. As the cancer cells implanted in these mice contained very few CSCs, the elimination of a CSC subset could be the condition necessary and sufficient to control tumor formation in vivo. These results suggest that CTL-based immunotherapies against colorectal CSCs might be useful for preventing relapses. Cancer Immunol Res; 6(3); 358–69. ©2018 AACR.

Background It has well known that, compared to normal cells, tumor cells have a different manner of energy metabolism, which influences the sensitivity of radiotherapy (RT). However, whether inhibition of glycolysis enhances the efficacy of radiotherapy is a matter of debate in oral squamous cell carcinoma (OSCC). The aim of this study was to characterize whether the combination of radiotherapy with the glucose inhibitor 2-deoxy-D-glucose (2-DG) affected DNA repair kinetics. Methods To compare the synergistic effect of 2-DG, we examined the cell survival after treatment with radiation, 2-DG and a combination of the two in 5 OSCC cell lines and one lip fibroblast cell line, determined using clonogenic survival assay. Changes in the protein levels of DNA repair kinetics such as PARP, Rad51 and Ku-70 were analyzed by western blotting. Then, using one of the 5 OSCC cell lines, we assessed the inhibition of xenograft tumor growth in vivo. Results We found that 2-DG with radiation induced significant inhibition of cell proliferation in cell line SAS (p

Background It is essential that cytotoxic T-lymphocytes (CTLs) recognize tumor-associated antigens (TAAs) and exhibit antitumor effects in immunological responses for tumor rejection. However, only a few cases with oral squamous cell carcinoma (OSCC) have been studied for these antitumor mechanisms. We established a cancer cell line and autologous CTL pair for identifying TAAs in OSCC, despite difficulties in establishing such a pair. Materials and methods A cell line (OTM) from a primary lesion and a CTL line (TcOTM) were derived from OSCC in a 64-year-old female patient. CTL clones were generated by repetitive limiting dilutions. Accurate characterization was performed by in vitro analysis. Results The TcOTM clone showed specific cytotoxic activity against OTM cells in an human leukocyte antigen (HLA)-A24-restricted manner. Furthermore, it exerted cytotoxicity against the allogenic HLA-A24 cell lines. Conclusion These data indicated that the TcOTM clone recognized a TAA presented by HLA-A24 cells. This unique method will allow for identification of unknown TAAs for OSCC in the future.

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1&ndash, 3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1&ndash, 3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48&ndash, 16.72, p &lt, 0.01, DSS, HR = 6.44, 95% CI: 1.76&ndash, 23.50, p &lt, 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter &le, 3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.

Six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) is a novel cell surface protein overexpressed only in the prostate among normal tissues and various types of cancer including prostate, bladder, lung, and ovarian cancer. Although its function in prostate and tumor cells has been remained unclear, due to its unique and restricted expression, STEAP-1 is expected to be an attractive target for cancer therapy. Here, we show that knockdown of STEAP-1 in human cancer cells caused the retardation of tumor growth compared with wild type in vivo. In contrast, STEAP-1 introduced tumor cells augmented the tumor growth compared with STEAP-1-negative wild type cells. Using dye transfer assay, we demonstrate that the STEAP-1 is involved in intercellular communication between tumor cells and adjacent tumor stromal cells and therefore may play a key role for the tumor growth in vivo. These data indicate the inhibition of the STEAP-1 function or expression can be a new strategy for cancer therapy.

Object: Hypoxia occurs when oxygen tension drops below normal limits, and malignant tumors often experience hypoxia, which activates the expression of genes through oxygen-sensitive transcription factors, including the hypoxiainducible factor (HIF) and the nuclear factor-κB (NF-κB). NF-κB pathway represents an attractive therapeutic target in both cancer cells and ischemic cells, which involves immune response. To investigate the expression of NF-κB target genes in oral squamous cancer carcinoma (OSCC) under hypoxia, we performed cDNA plate array analyses of 23 NF-κB-regulated genes in different cell lines. Our aim was to clarify the functions of NF-κB in OSCC under hypoxia. Results: We conducted an NF-κB reporter assay to examine NF-κB activation under hypoxia. This luciferase-based reporter assay showed that hypoxia induced NF-κB activation after 24 h of hypoxia. We also found that vascular endothelial growth factor-C (VEGF-C) of NF-κB-regulated genes was upregulated in both cell lines under hypoxia. We then tested the influence of NF-κB/p65 knockdown on these cells and NF-κB/p65 knockdown inhibited the proliferation of OSCC cells by colony assay. Conclusion: Based on these findings, we postulate that one mechanism by which hypoxic OSCC cells may involve NF-κB-mediated upregulation. Our results also indicate that the knockdown of NF-κB/p65 subunit lead to growth inhibition during hypoxia in OSCC cells. These results suggest that knockdown of NF-κB/p65 subunit could be a potential therapeutic option for patients with OSCC.

Many studies have attempted to classify the macroscopic shapes of the mandibular condyle in humans; however, no consensus has yet been reached because the shapes vary. One problem is that classification of macroscopic morphological changes of the condylar surface has been largely based on bones from ancient people, with few bones from modern people covering many different age groups. In this study, 144 condyles from 78 cadavers (40 men, 38 women; age at death: >70 years) were investigated. The macroscopic shapes of the condyles were classified from posterior and lateral views into four types: convex, flattened, angled, and irregular. Of the 144 condyles, 25 were investigated microscopically. On macroscopic examination, in both posterior and lateral views, convex-type condyles were most frequently observed. Most posterior convex-type condyles were also categorized as the lateral convex type. On histological examination, we observed an increase in cartilage cells (7 condyles, 28%), a decrease in cartilage cells (3 condyles, 12%). Increases in cartilage cells were seen only in angled and irregular types (P = 0.001), whereas decreases in cartilage cells were only observed in the flattened type (P = 0.01). A convex macroscopic form appears to be standard for human mandibular condyles, even in the elderly. The histological findings suggest that mandibular condyles tend to not only undergo flattening, but also undergo progressive changes toward protrusion with age due to increased numbers of cartilage cells. In other words, this study suggests that there is potential for progressive alterations in mandibular condyles in the elderly. Clin. Anat. 27:399–407, 2014. © 2012 Wiley Periodicals, Inc.

We report herein a case of extensive osteomyelitis of the mandibular region in a 32-year-old woman on hemodialysis. This patient, who showed extensive malnutrition and formation of an abscess in the pterygo-mandibular and lateral pharyngeal space, was referred to our hospital on suspicion of infection. Use of antibiotics allowed reduction of the abscess. However, over the next 12 months, all the teeth of the mandibular region were lost and severe osteomyelitis developed. This patient is being followed up on a regular basis without further treatment. Osteomyelitis of the mandible is still present.

Background. Secondary cancers are severe complications in patients who have had allogeneic bone marrow transplantation for childhood leukemia. We describe here a case of squamous cell carcinoma (SCC) of the buccal mucosa in a young adult patient who had had allogeneic bone marrow transplantation for childhood acute leukemia. Methods and Results. The primary tumor was treated with interstitial brachytherapy, and lymph node metastasis was treated by supraomohyoid neck dissection. The patient had a history of acute lymphoblastic leukemia (ALL) at 11 years of age and had received an allogeneic bone marrow transplant from a female donor. Further investigation of the tissue specimens by fluorescent in situ hybridization (FISH) revealed that an XX chromosome pattern was dominant in the tumor region, and this suggested that donor-derived cells might affect carcinogenesis in the recipient. Conclusions. This case presents an incidence of secondary oral cancer associated with allogeneic bone marrow transplantation. © 2008 Wiley Periodicals, Inc. Head Neck, 2009

Cytotoxic T lymphocytes (CTLs) play an essential role in immunologic responses for tumor rejection. In the past decade, various melanoma tumor-associated antigens (TAAs) have been identified, and several clinical trials of vaccination immunotherapy and adoptive immunotherapy using such antigens with or without adjuvants have had fascinating results. However, this has not been the case with oral squamous cell carcinoma (OSCC) because of the difficulty of establishing oral cancer cell lines and CTLs against autologous oral cancer cells. Therefore, few oral cancer antigens have been identified with such CTLs. We herein present the successful establishment of an oral squamous cell carcinoma cell line, POT-1, and an HLA-A24-restricted CTL line (TcPOT-1) from a patient's autologous peripheral blood lymphocytes. TcPOT-1 recognized autologous POT-1 cells in an HLA-A24-restricted manner, and also allogeneic HLA-A24 (+) OSCC cell lines OSC-70 and HSC-2. We also succeeded in isolating two distinct CTL clones from TcPOT-1, HLA-A24-restricted CTL clone 4F11 and HLA-A33-restricted clone 4A11. Both of these clones recognized autologous POT-1 but not allogeneic OSSC cell lines. These data imply that the TcPOT-1 CTL line may include several CTL subpopulations with distinct antigen specificities, such as an HLA-A24-restricted POT-1-specific clone, HLA-A33-restricted POT-1-specific clone, and HLA-A24-restricted allogeneic OSCC-recognizing clone. Therefore, precise analysis of TcPOT-1-recognizing antigens may provide us with important information on as-yet-unknown tumor rejection antigens in OSCC.

Purpose To predict the relationship between lower third molars and the inferior alveolar canal (IAC) from panoramic radiographs, and to establish criteria for using computed tomography (CT). Materials and Methods A retrospective cohort study was performed involving 443 patients (695 teeth). Predictor variables were the distance between the third molar and the IAC, and findings according to the Rood's criteria. Outcome variables were the absence of cortication between the third molar and the IAC on the CT image, and injury of the inferior alveolar nerve (IAN). Statistical analysis was performed to assess the relationship between predictor and outcome variables. Results All patients had preoperative panoramic radiographs, and 71 patients (119 teeth) also had CT images. On CT examination, 48 teeth (40.3%) showed absence of cortication. Injury of the IAN was reported in 7 cases (1.0%), 5 of which exhibited absence of cortication; the remaining 2 did not have CT scans. Five of the 48 cases showing absence of cortication exhibited IAN injury, and none of the cases with cortication exhibited IAN injury. On the panoramic images, the following signs were strongly correlated with absence of cortication: a superimposed relationship between the third molar and the IAC; darkness of the root; and diversion and narrowing of the IAC. Conclusion Presence of Rood's criteria was a predictor for a contact relationship between the third molar and the IAC, and an indication for CT examination. However, a superimposed relationship and the absence of Rood's criteria did not necessarily signify a separate relationship between third molar and the IAC.