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The EP4 prostanoid receptors are one of four receptor subtypes for prostaglandin E2 (PGE2). Therefore, EP4 may play an important role in cancer progression. However, little information is available regarding their function per se, including migration and the cellular signaling pathway of EP4 in oral cancer. First, we found that mRNA and protein expression of EP4 was abundantly expressed in human‐derived tongue squamous cell carcinoma cell lines HSC‐3 and OSC‐19. The EP4 agonist (ONO‐AE1‐437) significantly promoted cell migration in HSC‐3 cells. In contrast, knockdown of EP4 reduced cell migration. Furthermore, we confirmed that knockdown of EP4 suppressed metastasis of oral cancer cells in the lungs of mice in vivo. Therefore, we focused on the mechanism of migration/metastasis in EP4 signaling. Interestingly, EP4 agonist significantly induced intracellular Ca2+ elevation not in only oral cancer cells but also in other cells, including normal cells. Furthermore, we found that EP4 activated PI3K and induced Ca2+ influx through Orai1 without activation of store depletion and stromal interaction molecule 1 (STIM1). Immunoprecipitation showed that EP4 formed complexes with Orai1 and TRPC1, but not with STIM. Moreover, the EP4 agonist ONO‐AE1‐437 phosphorylated ERK and activated MMP‐2 and MMP‐9. Knockdown of Orai1 negated EP4 agonist‐induced ERK phosphorylation. Taken together, our data suggested that EP4 activated PI3K and then induced Ca2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration. Migration is regulated by EP4/PI3K/Orai1 signaling in oral cancer., EP4 activated PI3K and then induced Ca2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration.

Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P P Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Objective We previously reported that daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for locally advanced oral cancer provided good local control and overall survival rates. This study was performed to evaluate the therapeutic results of daily concurrent intra-arterial chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the mandibular gingiva. Methods Sixteen patients with T3, 4 mandibular gingiva cancer who refused surgery underwent definitive intra-arterial chemoradiotherapy between August 2006 and July 2014. Treatment consisted of concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion (60 Gy, total dose; 60 mg/m2 for docetaxel and 150 mg/m2 for cisplatin). Results Complete response of the primary site was obtained in 14 patients (87.5%). Five-year local control and survival rates were 73.4%and 81.3%, respectively. Grade 3 or 4 toxicities including mucositis and neutropenia were seen in 13 patients (81.3%) and 6 patients (37.5%), respectively. Grade 3 osteoradionecrosis occurred as a late adverse event in 1 patient (6.3%). Conclusions Retrograde daily concurrent intra-arterial chemoradiotherapy for locally advanced carcinoma of the mandibular gingiva provided good local control and overall survival rates. This method can become one of the therapeutic options for patients with locally advanced carcinoma of the mandibular gingiva.

Ultraviolet treatment of titanium implants makes their surfaces hydrophilic and enhances osseointegration. However, the mechanism is not fully understood. This study hypothesizes that the recruitment of fibrinogen, a critical molecule for blood clot formation and wound healing, is influenced by the degrees of hydrophilicity/hydrophobicity of the implant surfaces. Computational fluid dynamics (CFD) implant models were created for fluid flow simulation. The hydrophilicity level was expressed by the contact angle between the implant surface and blood plasma, ranging from 5&deg, (superhydrophilic), 30&deg, (hydrophilic) to 50&deg, and 70&deg, (hydrophobic), and 100&deg, (hydrorepellent). The mass of fibrinogen flowing into the implant interfacial zone (fibrinogen infiltration) increased in a time dependent manner, with a steeper slope for surfaces with greater hydrophilicity. The mass of blood plasma absorbed into the interfacial zone (blood plasma infiltration) was also promoted by the hydrophilic surfaces but it was rapid and non-time-dependent. There was no linear correlation between the fibrinogen infiltration rate and the blood plasma infiltration rate. These results suggest that hydrophilic implant surfaces promote both fibrinogen and blood plasma infiltration to their interface. However, the infiltration of the two components were not proportional, implying a selectively enhanced recruitment of fibrinogen by hydrophilic implant surfaces.

This study aimed to evaluate swallowing function in advanced tongue cancer patients before and after bilateral neck dissection following superselective intra-arterial chemoradiotherapy (CRT). A videofluoroscopic swallowing study (VFSS) was used to evaluate swallowing function in 10 patients with advanced tongue cancer before and after bilateral neck dissection. Laryngeal penetration increased in the postoperative VFSS. Temporal analysis comparing two time points revealed that, after surgery, oral transit time increased significantly, but there was no difference in pharyngeal delay time or pharyngeal transit time. Spatial analysis revealed significant decreases after surgery in the maximum distance of upper esophageal sphincter (UES) opening, the maximum distance of hyoid bone movement in both the anterior and superior direction, and the maximum velocity of hyoid bone movement. Laryngeal penetration and aspiration increased as a result of limited hyoid movement and diminished UES opening after bilateral neck dissection following superselective intra-arterial CRT for advanced tongue cancer.

// Rina Nakakaji 1, 2, * , Masanari Umemura 1, * , Kenji Mitsudo 2 , Jeong-Hwan Kim 1 , Yujiro Hoshino 3 , Itaru Sato 1, 2 , Takatsugu Masuda 4 , Masahiro Yamamoto 5 , Mitomu Kioi 2 , Toshiyuki Koizumi 2 , Takayuki Fujita 1 , Utako Yokoyama 1 , Masaki Iida 2 , Motohiko Sato 6 , Hiroshi Sato 7 , Shoko Murofushi 7 , Sayaka Shibata 8 , Ichio Aoki 8 , Haruki Eguchi 7 , Iwai Tohnai 2 and Yoshihiro Ishikawa 1 1 Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan 2 Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan 3 Department of Environment and Natural Sciences, Yokohama National University Graduate School of Environment and Information Sciences, Yokohama, Japan 4 Tokyo Neutron Science Laboratory, Tokyo University Institute for Solid State Physics, Kashiwa, Japan 5 Department of Chemistry of Functional Molecules, Konan University Faculty of Science and Engineering, Kobe, Japan 6 Department of Physiology, Aichi Medical University, Nagakute, Japan 7 Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, Japan 8 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan * These authors contributed equally to this work Correspondence to: Masanari Umemura, email: umemurma@yokohama-cu.ac.jp Yoshihiro Ishikawa, email: yishikaw@med.yokohama-cu.ac.jp Keywords: iron-salen; taxol; oral cancer; paclitaxel; magnetism Received: July 14, 2017 Accepted: February 20, 2018 Epub: February 26, 2018 Published: March 20, 2018 ABSTRACT N,N’-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.

Introduction Although chemoradiotherapy (CRT) for oral squamous cell carcinoma (SCC) has been shown to preserve organ function and improve cosmetic results, site-specific data, especially mandible, are limited. The aim of this study was to evaluate the predictability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on response to super-selective intra-arterial CRT for advanced SCC of the mandible. Methods Fifteen patients with advanced SCC of the mandible underwent super-selective intra-arterial CRT followed by radical resection. Maximum standardized uptake value (SUVmax) of the mandibular lesion was evaluated with FDG-PET/CT before and after CRT. The SUVmax before and after CRT was defined as pre-SUVmax and post-SUVmax, respectively. The difference between pre- and post-SUVmax was calculated as SUVmax reduction rate to evaluate treatment response of the mandibular lesion. Each SUVmax reduction rate and surgical specimen of the corresponding lesion was analyzed to evaluate an accuracy of the modality for predicting pathological response. Results The median of pre-SUVmax was significantly lower than that of post-SUVmax (p = 0.001). Of the 15 patients, 6 had a pathological complete response (pCR) and 9 had a non-pCR. Neither pCR patients nor non-pCR patients showed significant difference of the median of SUVmax between pre- and post-CRT (pre-CRT p = 0.099 post-CRT p =0.074). The SUVmax reduction rate in patients with pCR was significantly higher than that with non-pCR (p = 0.002). Receiver operating characteristic analysis revealed that the optimal cut-off point of the reduction rate was 64.7%, with 83% sensitivity and 100% specificity. Conclusions These results concluded that SUVmax reduction rate can predict pathological complete response of preoperative super-selective intra-arterial CRT for advanced SCC of the mandible.

Purpose Dexamethasone seems to suppress postoperative swelling. However, the standard administration dose of dexamethasone for bilateral sagittal split osteotomy (BSSO) has not been reported. This study focused on clarifying the most effective dose of dexamethasone for BSSO. Materials and Methods This research was planned as a prospective, randomized controlled, double-blind study. Patients undergoing BSSO were randomly assigned to receive intravenous preoperative dexamethasone under 3 different dose conditions: 16 mg, 8 mg, and 0 mg (control). The endpoints of this study were 1) postoperative changes in masseter muscle thickness and buccal soft tissue thickness; 2) postoperative changes in maximum incisal opening; 3) postoperative changes in sensation of the chin and lower lip region; 4) postoperative changes in blood examination findings (white blood cell count, neutrophil count, C-reactive protein level, and lymphocyte count); and 5) types of complications. Data were recorded at 2 to 4 time intervals: before surgery, postoperative day 1, postoperative day 2, and postoperative day 3. Average age, gender, average body mass index, average surgery time, and average blood loss also were examined. Data were analyzed by 1-way analysis of variance (Bonferroni multiple-comparisons test) after the Bartlett test. Results We enrolled 24 patients, including 5 men and 19 women, in this study. The rate of increase in the thickness of the masseter muscle 24 hours after BSSO was 38.4% in the 16-mg group (n = 8), 57.7% in the 8-mg group (n = 8), and 56.1% in the 0-mg group (n = 8). The rate of increase in masseter muscle thickness in the 16-mg group was significantly lower than that in the 0-mg group (P < .05). Regarding the number of lymphocytes after surgery, the 16-mg and 8-mg groups maintained preoperative levels whereas there was a reduced number of lymphocytes in the control group. No statistically significant results were obtained for the following study endpoints: postoperative changes in maximum incisal opening and postoperative changes in sensation of the chin and lower lip region. Conclusions This investigation showed that the most effective dose of dexamethasone for BSSO is 16 mg.

Aim We aimed to retrospectively investigate the outcomes and pathological effects of retrograde superselective intra-arterial chemoradiotherapy (IACRT) combined with hyperthermia on metastatic lymph nodes of patients with oral squamous cell carcinoma. Patients and methods Patients with lymph node metastasis from oral cancer were treated with IACRT using cisplatin plus docetaxel combined with hyperthermia prior to surgical removal 8 weeks after completion of IACRT and hyperthermia. The locoregional control and overall survival rates were calculated using the Kaplan-Meier method. Results A total of 35 patients received the combination therapy of whom 26 received it as definitive treatment and in the rest, it was administered as preoperative treatment. The 5-year locoregional control and overall survivaI rates were 95.6% and 80.2% in the definitive-treatment group, and 100% and 66.6% in the preoperative-treatment group, respectively. Conclusion The combination therapy provided good outcomes in patients with lymph node metastases from advanced oral cancer.

Aneurysms of the external carotid artery and its branches are rare, and usually occur in the more superficial branches. Lingual artery (LA) aneurysms are particularly rare, and pseudoaneurysms are associated with trauma, infection, and surgical intervention. Only a few cases of idiopathic LA aneurysms have been reported in the English literature. LA aneurysms can be fatal if they are not recognized and treated. Here, we report a case of bilateral idiopathic aneurysms of the LA identified by three-dimensional (3D) computed tomography angiography (CTA). An 80-year-old man with right tongue cancer (T2N0M0) and left tongue leukoplakia was referred to our department for treatment. He had no previous history of trauma, infection, surgery, or aneurysm in the oral and maxillofacial region. CTA with 3D reconstruction showed right and left aneurysms of the LA, with sizes of 2.4 × 2.3 × 2.1 mm and 3.4 × 3.2 × 2.5 mm, respectively. The patient underwent bilateral partial glossectomy under general anesthesia without intervention for the aneurysms, and the post-operative course was uneventful. A radiological follow-up has been performed regularly for the small unruptured aneurysms.

BACKGROUND The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. METHODS A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. RESULTS The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P

Superselective intra-arterial chemoradiation therapy for locally advanced oral cancer induces complications such as mucositis, which impedes oral intake. Thus, at our hospital, a gastrostomy is performed in almost all patients during the treatment period to ensure the presence of an alternative administration route for nutrition and drugs. The purpose of this study was to calculate the mean number of days from completion of superselective intra-arterial chemoradiation therapy to the decannulation of gastrostomy, and extract patient factors for the decannulation. A retrospective follow-up study was conducted from April 2016 to March 2017 on patients who underwent superselective intra-arterial chemoradiation therapy at our department of oral surgery. The patients were divided into 2 groups:one who was decannulated and the other who did not. Clinical backgrounds and data were compared between the 2 groups. In the group with the decannulation, the mean period from treatment completion to the decannulation was 132±51.6 days. Heavy alcohol consumption, absence of haphalgesia before treatment, and possible securement of the opening with the breadth of 3 fingers, were determined as factors contributing to the decannulation of gastrostomy tube.

Superselective intra-arterial chemoradiation therapy for oral cancer induces the complication of mucositis. Although the associated pain is controlled using opioids, major questions from patients in clinical practice are as follows:(1)the mean number of days from the completion of superselective intra-arterial chemoradiation therapy to the discontinuation of opioid administration, and(2)patient factors enabling the discontinuation of opioids. The purpose of this study was to clarify these points. A retrospective follow-up study was conducted from April 2016 to March 2017 on patients who underwent superselective intra-arterial chemoradiation therapy at our department of oral surgery. The patients were divided into 2 groups:one who discontinued opioids, and the other who did not. Clinical backgrounds and data were compared between the 2 groups. The mean number of days from the completion of superselective intra-arterial chemoradiation therapy to the discontinuation of opioid administration was 51±34.4 days. The absence of diabetes and deliria during treatment were determined as factors contributing to the discontinuation of opioids.

Objectives To evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy. Materials and methods Between June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50–70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50–70 mg/m2; cisplatin, total 125–175 mg/m2) for 5–7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox’s proportional hazards model was used for both univariate and multivariate analyses. Results The median follow-up for all patients was 38.5 months (range, 3–129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification. Conclusion Retrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.

We herein report a case of squamous cell carcinoma of the buccal mucosa with N3 cervical lymph node metastasis in a 63-year-old man. The patient was treated with combination therapy comprising radiotherapy (2 Gy/day, total of 70 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery (docetaxel, total of 70 mg/m2 and cisplatin, total of 175 mg/m2), cetuximab (initial dose of 400 mg/m2 with subsequent weekly doses of 250 mg/m2 intravenously), and four sessions of hyperthermia for cervical lymph node metastases. The patient responded well to the therapy, with a complete response of the primary tumor. Radical neck dissection was performed with reconstructive surgery, including resection of the overlying skin. A pathologic complete response was achieved for the N3 and all other cervical lymph node metastases. The patient showed no evidence of recurrence in the 3 years following treatment. Based on the findings in the present case, the use of retrograde superselective intra-arterial chemoradiotherapy combined with hyperthermia and cetuximab seems to be a promising modality for patients with N3 cervical lymph node metastasis of oral cancer.

Background The aim of this retrospective observational study was to evaluate toxicities, overall survival, and locoregional control in elderly oral squamous cell carcinoma patients who had undergone retrograde intra-arterial chemotherapy combined with radiotherapy. Methods Thirty-one elderly patients over 80 years old with oral squamous cell carcinoma were enrolled in present study. The treatment schedule consisted of intra- arterial chemotherapy (docetaxel, total 60 mg/m2; cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. Results The median patient age was 82.5 years old (range, 80–88 years). Of the 31 patients, six (19%) had stage II, 6 (19%) had stage III, 17 (55%) had stage IVA, and 2 (6%) had stage IVB. The median follow-up period for all patients was 37 months (range, 7–86 months). The 3-year overall survival and locoregional control rates were 78% and 81%, respectively. The major acute grade 3 adverse events were oral mucositis in 22 (71%) patients, neutropenia in 16 (52%), and dermatitis in 11 (35%). With respect to late toxicities, 1 patient (3%) developed grade 3 osteoradionecrosis of the jaw. No grade 4 or higher toxicities were observed during the treatment and follow-up periods. Conclusions Retrograde intra-arterial chemotherapy combined with radiotherapy was effective in improving overall survival and locoregional control even for elderly patients.

Purpose To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Materials and methods One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60mg/m 2 , cisplatin, total 150mg/m 2 ) and daily concurrent radiotherapy (total of 60Gy) for 6weeks. Results The median follow-up for all patients was 46.2months (range, 10–76months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients. Conclusion Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.

Objective To evaluate the therapeutic results and control of occult neck metastasis in patients with T2-4N0 oral tongue squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Study Design Forty-two patients with T2-4N0 tongue cancer (17 with late T2; 13 with T3; and 12 with T4a disease, M0) were treated with intra-arterial chemoradiotherapy. Treatment consisted of retrograde superselective intra-arterial chemotherapy (docetaxel 50-70 mg/m2, cisplatin 125-175 mg/m2) and daily concurrent radiotherapy (50-70 Gy) for 5-7 weeks. Results The median follow-up for all patients was 46.5 months (range, 8-105 months). Primary-site complete response was achieved in 42 of 42 cases (100%). Three-year overall survival, progression-free survival, and local control rates were 85.0%, 77.8%, and 91.7%, respectively. Delayed neck metastasis was detected in 5 of 42 cases (11.9%). Grade 3 or 4 toxic changes included oral mucositis in 92.9%, neutropenia in 21.4%, and thrombocytopenia in 4.8%. Grade 3 toxicities included anemia in 16.7%, radiation dermatitis in 9.5%, nausea in 4.8%, and fever in 2.4%. Conclusions Retrograde superselective intra-arterial chemotherapy for T2-4N0 tongue cancer provided good overall survival and local control rates and was effective for occult neck metastasis.

A solitary myofibroma (MF) is an unusual spindle cell neoplasm that usually arises in the soft tissue, skin, or bone of the head and neck region in infancy. We report an extremely rare case of MF of the mandible in an 18-year-old Japanese woman together with the conventional histologic, immunohistochemical, and electron microscopic findings. The tumor was well circumscribed and composed of fibroblast-like or myofibroblast-like spindle cells. On immunohistochemical evaluation the tumor cells were positive for vimentin, α-smooth muscle actin, HHF-35, and calponin, but negative for neurogenic antigens and markers for vascular endothelial cells. The Ki-67 labeling index was 10 % and the p53 labeling index was 10 %. Ultrastructural examination revealed smooth muscle cell differentiation. The patient was treated by surgical resection and underwent follow-up without any signs of recurrence. MF presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessarily aggressive therapy.

Facial nerve paralysis (FNP) after super-selective intra-arterial chemotherapy (SSIAC) is a relatively rare local side effect of SSIAC to the maxillary artery (MA) or the middle meningeal artery (MMA). The incidence and prognosis of FNP after SSIAC in 381 patients with oral cancer (133 with catheterization of the MA, 248 without) was investigated retrospectively. Only three patients (two male and one female) had FNP, for an incidence of 0.8%. All patients with FNP had undergone catheterization of the MA, and the incidence of FNP in this group was 2.3% (3/133). One of the three patients with FNP had paralysis of the third branch of the trigeminal nerve. FNP occurred a mean of 8.7 days (range 5-11 days) after initial SSIAC, and the mean total dose of cisplatin was 55.8mg (range 42.5-67.2mg) and of docetaxel was 25.4mg (range 17.0-33.6mg). FNP resolved completely a mean of 12.7 months (range 6-19 months) after onset. Because the administration of anticancer agents via the MA or MMA carries a risk of FNP, this information will be useful when obtaining informed consent from patients before treatment.

Squamous cell carcinoma (SCC) of the tongue is the most common oral cancer. Most cases occur on the lateral border of the tongue and only very rarely on the dorsum. We retrospectively investigated the incidence of SCC of the tongue dorsum in our department between April 2006 and March 2015. Of the 368 patients with tongue cancer, only 3 had SCC of the tongue dorsum (incidence, 0.8 %). All patients with advanced cancer of the tongue dorsum underwent superselective intra-arterial chemoradiotherapy for organ preservation. We discuss the present findings in relation to past case reports and series in the English language literature as well as discuss treatments for SCC of the tongue dorsum.

進行口腔癌に対する逆行性超選択的動注化学療法は放射線療法との連日同時併用が可能となることから高い抗腫瘍効果が得られる。今回われわれは進行口腔癌に対して根治的逆行性超選択的動注化学放射線療法を施行し，治療効果，累積生存率，局所制御率について検討したので報告する。2003年1月から2009年12月に受診した口腔・顎顔面悪性腫瘍688例中，根治的逆行性超選択的動注化学放射線療法を施行した175症例を対象とした。治療は逆行性超選択的動注化学放射線療法（docetaxel, total 60mg/m2, cisplatin, total 125-150mg/mm2, total 50-60Gy）を5～6週間行った。治療4週後に画像検索および原発の生検にて腫瘍残存の有無の確認を行ったところ，175例中160例（91.4%）がCR，腫瘍残存は15例（8.6%）に認めた。CRであった160例についてはその後の経過観察中に14例（8.0%）の再発を認めた。5年累積生存率および局所制御率はそれぞれ71.6%と82.2%であった。

The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone response after the placement of implants in the femurs of mice. titanium implants 1.0mm in diameter were placed into the middle of the femurs of 9-week-old male COX-2 wild-type ( COX-2 +/+ ) and knockout ( COX-2 −/− ) mice. For RNA analysis, the mice were killed 0, 1, 2, 4, 7 and 56 days after implantation. RNA was extracted from the bone surrounding the implants. For histological analysis, the mice were killed 4 and 8 weeks after treatment, and undecalcified sections were prepared. Contact microradiography was performed, and the sections were stained with 1% toluidine blue for histological examination. Histomorphometric measurements were obtained with a computer-based image analyser to quantify bone newly formed around the implant and the rate of implant–bone contact. Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in COX-2 +/+ mice, but not in COX-2 −/− mice. In cortical bone, the implant surface was in direct contact with newly formed bone lamellae in COX-2 +/+ mice; new bone formation was minimal in COX-2 −/− mice. These results suggest that COX-2 plays an essential role in osseointegration and provide evidence that COX-2-selective non-steroidal anti-inflammatory drugs may interfere with osseointegration clinically.

Objective To investigate whether 2-[18 F]fluoro-2-deoxy-D-glucose (FDG) uptake of primary tumor in oral squamous cell carcinoma (OSCC) could predict prognosis. Study Design Sixty-nine patients with OSCC who underwent retrograde superselective intra-arterial chemoradiotherapy were recruited and underwent dual-time-point FDG positron emission tomography twice, before treatment and 4 weeks after treatment. FDG uptake was defined as the standardized uptake value (SUVmax). The retention index (RI) and the percent change in SUV (% change SUV), derived from the dual-time-point scan, were calculated. Results On univariate analysis, patients with high pre-SUV, RI, and percent change SUV values had significantly worse overall survival and disease-free survival compared with patients with low values. On multivariate analysis, high pre-RI (≥20.6%) and high percent change SUV (≥60.0%) (delayed-image) were associated with significantly worse overall survival. High pre-SUV (≥9.6) (delayed-image) and high pre-RI (≥20.6%) were associated with significantly shorter disease-free survival. Conclusions Dual-time-point FDG positron emission tomography in OSCC provided prognostic information and predicted patient outcome.

Objective: To assess the transcriptional regulation of cyclooxygenase-2 by bone morphogenetic protein2 in isolated bone marrow stromal cells obtained from cyclooxygenase-2 wild-type and cyclooxygenase-2defrcient mice. Materials and Methods: Bone marrow stromal cells were cultured for 14 days in the presence of osteogenic medium with or without bone morphogenetic protein-2. Real-time polymerase chain reaction analysis of the relative expression of cyclooxygenase-2 and osteocalcin, a late osteogenic differentiation marker mRNA, were examined. Prostaglandin EZ accumulation in the culture media were measured by radioimmunoassay. Activity and staining of alkaline phosphatase, an early osteogenic differentiation marker, were examined. Results: Bone morphogenetic protein-2 induced cyclooxygenase-2 mRNA and prostaglandin production in cultured bone marrow stromal cells derived from cyclooxygenase-2 wild-type mice. Alkaline phosphatase activity was lower in cyclooxygenase-2-deficient control cultures than in cyclooxygenase-2 wild-type cultures, and treatment with bone morphogenetic protein-2 stimulated alkaline phosphatase activity only in cyclooxygenase-2 wild-type cultures. A similar reduction was seen in cyclooxygenase-2 wild-type cells treated with NS-398, a selective inhibitor of cyclooxygenase-2. Alkaline phosphatase staining revealed a 30% decrease in the cyclooxygenase-2-deficient control cultures, and the addition of bone morphogenetic protein-2 increased alkaline phosphatase staining only in cyclooxygenase-2 wild-type cultures. Bone morphogenetic protein-2 stimulated osteocalcin mRNA expression in bone marrow stromal cells derivedfrom cyclooxygenase2 wild-type mice but not in cyclooxygenase-2-deficient cells. Conclusions: Bone morphogenetic protein-2 induces cyclooxygenase-2 in bone marrow stromal cells transcriptionally and the induction of cyclooxygenase-2 may play a role in the effects of bone morphogenetic protein-2 on bone metabolism in vitro.

Objective : To report a simplified technique for nasoalveolar moulding for treatment of infants with unilateral and bilateral cleft lip and palate. Patients and Methods : One or 2 stents made of plastic cobalt-chrome orthodontic wires 0.8-mm thick were used with a conventional palatal plate (Hotz plate) to treat 7 patients with unilateral cleft lip and palate and 3 with bilateral cleft lip and palate. Results : This modified technique for nasoalveolar moulding permitted the nose of patients with unilateral and bilateral cleft lip and palate to be easily and precisely moulded. This technique also reduced stress for the patients and their parents because it did not require extraoral appliances, except for surgical tape over the cleft lip. Time-consuming adjustments of the nasal stent were also unnecessary. Conclusion : The wire nasal stent facilitated nasoalveolar moulding before cheiloplasty for unilateral and bilateral cleft lip and palate.

A two-dimensional intracellular Ca(2+) ([Ca(2+)](i)) imaging system was used to examine the relationship between [Ca(2+)](i) handling and the proliferation of MC3T3-E1 osteoblast-like cells. The resting [Ca(2+)](i) level in densely cultured cells was 1.5 times higher than the [Ca(2+)](i) level in sparsely cultured cells or in other cell types (mouse fibroblasts, rat vascular smooth muscle cells, and bovine endothelial cells). A high resting [Ca(2+)](i) level may be specific for MC3T3-E1 cells. MC3T3-E1 cells were stimulated with ATP (10 microM), caffeine (10 mM), thapsigargin (1 microM), or ionomycin (10 microM), and the effect on the [Ca(2+)](i) level of MC3T3-E1 cells was studied. The percentage of responding cells and the degree of [Ca(2+)](i) elevation were high in the sparsely cultured cells and low in densely cultured cells. The rank order for the percentage of responding cells and magnitude of the Ca(2+) response to the stimuli was ionomycin > thapsigargin = ATP > caffeine and suggests the existence of differences among the various [Ca(2+)](i) channels. All Ca(2+) responses in the sparsely cultured MC3T3-E1 cells, unlike in other cell types, disappeared after the cells reached confluence. Heptanol treatment of densely cultured cells restored the Ca(2+) response, suggesting that cell-cell contact is involved with the confluence-dependent disappearance of the Ca(2+) response. Immunohistological analysis of type 1 inositol trisphosphate receptors and electron microscopy showed distinct expression of inositol trisphosphate receptor proteins and smooth-surfaced endoplasmic reticulum in sparsely cultured cells but reduced levels in densely cultured cells. These results indicate that the underlying basis of confluence-dependent [Ca(2+)](i) regulation is down-regulation of smooth-surfaced endoplasmic reticulum by cell-cell contacts.

To determine the roles of nitric oxide (NO) and its metabolite, peroxynitrite (ONOO−), on osteoblastic activation, we investigated the effects of a NO donor [ethanamine, 2,2′-(hydroxynitrosohydrazono)bis- (dNO)], an [Formula: see text] donor (pyrogallol), and an ONOO− scavenger (urate) on alkaline phosphatase (ALPase) activity and osteocalcin gene expression, which are indexes of osteoblastic differentiation. dNO elevated ALPase activity in the osteogenic MC3T3-E1 cell line. The combination of dNO and pyrogallol reduced both ALPase activity and osteocalcin gene expression. Because both indexes were recovered by urate, ONOO−, unlike NO itself, inhibited the osteoblastic differentiation. Furthermore, treatment with a combination of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was found to yield ONOO−as well as NO and [Formula: see text]. The reductions in ALPase activity and osteocalcin gene expression were also restored by urate. We conclude that ONOO− produced by TNF-α and IL-1β, but not NO per se, would overcome the stimulatory effect of NO on osteoblastic activity and inhibit osteoblastic differentiation.

The effect of nitric oxide (NO) on osteoblastic differentiation was examined in cultured mouse osteoblasts. Interleukin-1β and tumor necrosis factor-α expressed inducible NO synthase gene with little effect on constitutive NO synthase gene. These cytokines increased NO production, which was inhibited by l-NMMA pretreatment, and decreased alkaline phosphatase (AIPase) activity, which was not restored by l-NMMA. Furthermore, NO donors, sodium nitroprusside and NONOate dose-dependently elevated AIPase activity and expression of osteocalcin gene. These results suggest that NO directly facilitates osteoblastic differentiation and the cytokine-induced inhibition of AIPase activity is mediated via mechanism other than NO.

Objectives The aim of this study was to establish a simple method for the early detection of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using computed tomography (CT). Materials and methods CT images of the mandible were obtained from a total of 20 patients with BRONJ and 20 control subjects. BRONJ was classified into 2 groups, with bone exposure (Stage 1–3 BRONJ) or without (Stage 0 BRONJ). In each patient, 15 transaxial CT images were selected and 30 configured regions of interest (ROI) were identified. The ANOVA test was applied to test the relationship between the severity of systemic risk factors. Results Regarding the local status of the mandible, significant differences were observed among the Stage 0 BRONJ, Stage 1–3 BRONJ, non-BRONJ and control groups in the cancellous bone CT radiodensity values, but there were no significant differences between the Stage 0 and Stage 1–3 BRONJ groups. In the cortical bone widths, significant differences were observed only between BRONJ and the controls. Conclusions Measuring cancellous bone CT radiodensity value has the potential to be a simple and quantitative method to detect the early stages of BRONJ.

The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma.In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors.Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment.Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma.