Search

Granular-shaped carbonate apatite (CO3Ap) bone substitute has demonstrated good clinical results, especially in the bone augmentation procedure, because it has high osteoconductivity and can be replaced by a new bone. This study aimed to evaluate the potential usefulness of CO3Ap bone substitute for alveolar ridge preservation of beagle dogs during the 9-week follow-up period after surgery. Reconstruction of extraction sockets with CO3Ap granules (CO3Ap group) allowed approximately 1.0 mm higher alveolar bone height than that with a blood clot (control group) at 4 and 9 weeks after surgery. Additionally, the measured area at the buccal aspect of the alveolar bone in the CO3Ap group was approximately 2 mm2 larger than that in the control group at 4 and 9 weeks after surgery. Continuity from the buccal side to palatal side of the alveolar bone was restored, maintaining its contour at 4 weeks after surgery. The amount of bony tissue, especially the amount of mature bone, in the alveolar part was statistically larger than that of control group at 9 weeks after surgery even though complete replacement of CO3Ap granules with new bone was not observed within 9 weeks. In conclusion, CO3Ap granules have good potential for alveolar ridge preservation.

Calcium hydroxide (Ca (OH)2) paste is widely used as a provisional root canal filling material. This report describes a case of inferior alveolar nerve paresthesia caused by overfilling of Ca (OH)2 paste. A 53-year-old woman had previously undergone root canal filling in the left lower second molar with Ca (OH)2 paste. Immediately after the treatment, she felt sharp pain and paralysis in the left lower lip and chin area and visited our hospital four days later. X-ray examination showed a large radiopacity associated with the left mandibular canal and around the bone marrow from the lower left second premolar to the lower left third molar. We planned a tooth extraction and surgical removal of the Ca (OH)2 paste. However, she declined surgery, and we performed conservative treatment with administration of vitamin B12 and root canal therapy. Approximately one year after her first visit, we filled the root canal with gutta-percha and sealer. The tooth was preserved and paresthesia of the left lower lip and chin largely decreased except for a small remaining numb area. Therefore, it is important to pay scrupulous attention to ensure no extrusion of Ca (OH)2 paste beyond the root apex to avoid complications.

Background: Oral allergy syndrome (OAS) is a type of food allergy that manifests as hypersensitivity symptoms of the oropharyngeal mucosa on ingestion of specific foods with oral findings resembling herpetic gingivostomatitis. Symptoms can also appear in parts other than the oral cavity. There are a few reports of OAS caused by consuming radishes in the literature.Case presentation: A 31-year-old male presented to our department with stomatitis and pharyngeal pain. The patient did not have a history of allergy, and herpetic gingivostomatitis was suspected. He was admitted to the emergency room of our hospital after complaining of oral and epigastric pain a few days later. On admission, symptoms noted were similar to those when he first visited our department. After detailed history taking, he reported consuming raw Japanese radish frequently, which gave rise to his symptoms. Radish was strongly suspected as the causative allergen. The skin prick test result was positive, confirming the diagnosis of OAS.Conclusions: OAS can be diagnosed easily once the food causing symptoms is identified. However, guiding the diagnosis can be challenging if the patient is unaware of food allergies. Upon encountering widespread erosion in the oral cavity, it is essential to consider OAS as the possible cause.

Cancer stem cells (CSCs) exhibit self-replication, self-differentiation, drug resistance and immune evasion activities. In recent years CSCs have become increasingly important for the treatment of malignant tumors. CSCs express specific markers, including cluster of differentiation (CD)44, CD44 variant 9 (CD44v9), ATP-binding cassette sub-family G member 2 (ABCG2), CD24, B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) and aldehyde dehydrogenase 1 (ALDH1). However, the prognostic value of their expression in patients with oral squamous cell carcinoma (OSCC) are not well known. The present study evaluated these markers in stage I and II patients with OSCC and examined the association between T classification, histological differentiation, classification of invasion mode, lymph node metastasis and disease-free survival rate. Tissue specimens were obtained from 70 patients with stage I or II OSCC following either surgery or biopsy. Immunohistochemistry was performed and positive staining was defiend as 10% positive cells. CD44 and CD44v9 expressions were strongly detected in all OSCC tissues compared with normal epithelial cells. A total of 22 (31.4%) cases expressed ABCG2 and there was a significant association between ABCG2 expression and invasion. A total of 41 cases (59.0%) expressed CD24 and there was a significant association between CD24 expression and invasion. A total of 33 cases (47.1%) expressed BMI-1 and there was a significant association between BMI-1 expression and the disease-free survival rate. A total of 18 cases (25.7%) expressed ALDH1. Although there was no association between ALDH1 expression and T classification, there were significant associations between ALDH1 expression and histological differentiation, invasion mode, metastasis and the disease-free survival rate. Multivariate analysis revealed that ALDH1 expression was the only prognostic factor for disease-free survival rate. The results of the present study suggest that the positivity of ALDH1 detected in patients with OSCC correlates with the number of cells undergoing epithelial mesenchymal transition and metastasis. These findings indicated that the expression of ALDH1 may be an effective prognostic marker indicating the survival of patients with stage I and II OSCC.

The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window technique using CO3Ap granules, followed by implant placement after 7 ± 2 months) was employed in 13 patients. Bone-height increase and insertion torque values (ITVs) were assessed along with histological evaluation. The survival and success rates of 3-year functioning implants were also evaluated. Mean of bone-height increase after SFE using CO3Ap granules was 7.2 ± 2.5 mm and this increase allowed implant placement in all cases (17 implants). Mean of ITV was 25.1 ± 13.2 Ncm and primary stability was achieved successfully in all cases. Histological analyses revealed mature new bone formation (36.8 ± 17.3%) and residual CO3Ap granules (16.2 ± 10.1%) in the compartment after SFE. The survival and success rates after 3-year functional loading were 100% and no complications were found. These results clearly indicate the clinical usefulness of CO3Ap granules for SFE.

Objective The aim of this study is to reveal a clinical evaluation of single non-contact Nd: YAG (the neodymium: yttrium-aluminium-garnet laser) photocoagulation irradiation treatment of venous malformation (VM) in the oral region. Patients and methods Seventeen patients with 21 VMs in the oral region who visited our hospital from 2010 to 2015 were subjected. The patients consisted of six males and 11 females, ranging in age from 27 to 71 years old. The VM locations included tongue, buccal mucosa, and lip sites. Their sizes ranged from 4 to 24 mm along the major axis direction, and the thickness ranged from 4 to 13 mm. All patients were treated with single non-contact irradiation using the Nd: YAG laser under local anaesthesia. Results All cases, including the patients with deep-seated lesions, healed after one-time irradiation with the laser beam. Serious complications have not occurred in patients receiving the treatment. There was no recurrence of VMs for at least one year after treatment. Conclusions Using single non-contact irradiation treatment, we obtained good results without clinical complications. The application of the Nd: YAG laser in treatment of lesions has the advantages of no bleeding, minimal scarring, and a short operative time. These results suggest that Nd: YAG laser treatment by a single non-contact irradiation is effective against VMs of thicknesses 13 mm or less in the oral region.

A case of tophaceous pseudogout (i.e., calcium pyrophosphate dihydrate (CPPD) crystal deposition disease) in the temporomandibular joint (TMJ), extending to the base of the skull, is reported. A 38-year-old man was referred to the hospital with mild pain in the right chin and tip of the tongue. Panoramic radiography showed a large calcified mass around the right TMJ. Computed tomography imaging revealed a large, granular, calcified mass surrounding the right condylar head and extending to the base of the skull. The mass was clinically and radiographically suspected to be a pseudogout lesion. A biopsy specimen was collected under general anaesthesia to confirm the diagnosis. On histology, the mass was found to contain deposits of numerous rod-shaped and rhomboid crystals, which suggested tophaceous pseudogout. The deposits were identified as CPPD crystal deposition, based on analysis by X-ray diffraction and Fourier transform infrared spectroscopy. These two crystallography methods were useful in confirming the diagnosis of CPPD crystal deposition disease in the TMJ.

Carbonate apatite (CO3 Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO3 Ap granules through a two-step dissolution-precipitation reaction using CaSO4 as a precursor and 30-, 50-, 120-, and 205-μm diameter microfibers as porogen and to find the optimal pore size of CO3 Ap. Porous CO3 Ap granules were successfully fabricated with pore size 8.2-18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO3 Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO3 Ap (120) [porous CO3 Ap granules made using 120-μm microfiber] followed by CO3 Ap (50) and CO3 Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO3 Ap (120). It is concluded, therefore, that the optimal pore size of the CO3 Ap is that of CO3 Ap (120), which is 85 μm.

Purpose The purpose of this study was to elucidate the efficacy and safety of carbonate apatite (CO3Ap) granules in 2-stage sinus floor augmentation through the radiographic and histomorphometric assessment of bone biopsy specimens. Methods Two-stage sinus floor augmentation was performed on 13 patients with a total of 17 implants. Radiographic assessment using panoramic radiographs was performed immediately after augmentation and was also performed 2 additional times, at 7±2 months and 18±2 months post-augmentation, respectively. Bone biopsy specimens taken from planned implant placement sites underwent micro-computed tomography, after which histological sections were prepared. Results Postoperative healing of the sinus floor augmentation was uneventful in all cases. The mean preoperative residual bone height was 3.5±1.3 mm, and this was increased to 13.3±1.7 mm by augmentation with the CO3Ap granules. The mean height of the augmented site had decreased to 10.7±1.9 mm by 7±2 months after augmentation; however, implants with lengths in the range of 6.5 to 11.5 mm could still be placed. The mean height of the augmented site had decreased to 9.6±1.4 mm by 18±2 months post-augmentation. No implant failure or complications were observed. Few inflammatory cells or foreign body giant cells were observed in the bone biopsy specimens. Although there were individual differences in the amount of new bone detected, new bone was observed to be in direct contact with the CO3Ap granules in all cases, without an intermediate layer of fibrous tissue. The amounts of bone and residual CO3Ap were 33.8%±15.1% and 15.3%±11.9%, respectively. Conclusions In this first demonstration, low-crystalline CO3Ap granules showed excellent biocompatibility, and bone biopsy showed them to be replaced with bone in humans. CO3Ap granules are a useful and safe bone substitute for two-stage sinus floor augmentation. Trial Registration ICTRP Identifier: JPRN-UMIN000019281, Graphical Abstract

Since bone apatite is a carbonate apatite containing carbonate in an apatitic structure, carbonate content may be one of the factors governing the osteoconductivity of apatitic bone substitutes. The aim of this study was to evaluate the effects of carbonate content on the osteoconductivity of apatitic bone substitutes using three commercially available bone substitutes for the reconstruction of alveolar bone defects of a beagle mandible with simultaneous dental implant installation. NEOBONE®, Bio-Oss®, and Cytrans® that contain 0.1 mass%, 5.5 mass%, and 12.0 mass% of carbonate, respectively, were used in this study. The amount of newly formed bone in the upper portion of the alveolar bone defect of the beagle’s mandible was 0.7%, 6.6%, and 39.4% at 4 weeks after surgery and 4.7%, 39.5% and 75.2% at 12 weeks after surgery for NEOBONE®, Bio-Oss®, and Cytrans®, respectively. The results indicate that bone-to-implant contact ratio was the largest for Cytrans®. Additionally, the continuity of the alveolar ridge was restored in the case of Cytrans®, whereas the continuity of the alveolar ridge was not sufficient when using NEOBONE® and Bio-Oss®. Both Cytrans® and Bio-Oss® that has a relatively larger carbonate content in their apatitic structure was resorbed with time. We concluded that carbonate content is one of important factors governing the osteoconductivity of apatitic bone substitutes.

Purpose Carbonate apatite (CO3Ap), an inorganic component of human bone, can be fabricated in chemically pure form from calcium carbonate block via a dissolution-precipitation reaction. A first-in-human clinical trial was conducted in which low-crystalline CO3Ap granules were evaluated for safety and efficacy in sinus floor augmentation and simultaneous implant installation. Materials and Methods Procedures were performed in 8 patients (9 implants) with 2 granule sizes: small (300 to 600 μm) and medium (600 to 1,000 μm). Panoramic radiographic assessment was performed immediately after augmentation, 7 ± 2 months after augmentation, 6 ± 2 months after prosthetic loading, and 12 ± 2 months after prosthetic loading. Results Postoperative healing was uniformly uneventful, with no abnormal bleeding, pain, or swelling, and all implants achieved successful osseointegration. The mean residual maxillary molar bone height was 5.2 ± 0.8 mm preoperatively and increased to 14.0 ± 1.9 mm after augmentation. Implants 9.0 to 11.5 mm in length were placed. The post-augmentation height decreased to 12.4 ± 1.3 mm at 7 ± 2 months; after prosthetic loading, it decreased to 11.9 ± 0.8 mm at 6 ± 2 months and 11.7 ± 0.6 mm at 12 ± 2 months. No abnormal bone resorption of the augmented areas was observed, and bone height supporting the implants was maintained. The overall implant survival rate was 100%, with no implant failures or complications during the first year. Conclusions Low-crystalline CO3Ap granules were useful and safe for sinus floor augmentation and simultaneous implant installation, providing a promising bone substitute for dental implant surgery.

We have previously demonstrated that the stromal cell‑derived factor (SDF‑1)/CXCR4 system is involved in the metastasis of head and neck cancer. Additionally, it has been revealed that the blockade of CXCR4 by subcutaneous daily injection with AMD3100, a CXCR4 antagonist, may be effective in preventing metastasis in CXCR4‑related head and neck cancer. Recent investigations have suggested that AMD070, a novel orally bioavailable inhibitor of CXCR4, may be minimally invasive compared with AMD3100. In the present study, we examined the effect of AMD070 on metastasis induced by the SDF‑1/CXCR4 axis in B88‑SDF‑1 oral cancer cells, which express high levels of SDF‑1 and CXCR4. Although treatment with AMD070 did not affect the anchorage‑dependent growth of B88‑SDF‑1 cells, it significantly suppressed the anchorage‑independent growth. Moreover, the SDF‑1/CXCR4‑dependent migration and invasion of B88‑SDF‑1 cells was significantly inhibited following treatment with AMD070. Subsequently, we performed an experimental therapy using AMD070 to prevent the distant metastasis of B88‑SDF‑1 cells in vivo. Daily oral administration of AMD070 significantly inhibited the lung metastasis of B88‑SDF‑1 cells in nude mice. These results indicated that AMD070 could be useful as a novel orally bioavailable inhibitor of oral cancer metastasis.

Objectives: Palatine tonsilloliths incidentally detected on diagnostic imaging should be differentiated from pathologic calcifications to enable correct diagnosis and treatment. The aim of this study is to clarify the prevalence and imaging characteristics of palatine tonsilloliths on panoramic radiographs. Materials and Methods: We retrospectively reviewed 2,244 individuals who underwent pairs of consecutive panoramic radiography and computed tomography (CT) of the head and neck region. The imaging characteristics of palatine tonsilloliths on panoramic radiography were compared with the findings from CT, which was considered the gold standard. Results: Tonsilloliths were detected in 300 (13.4%) and 914 (40.7%) of the 2,244 individuals on panoramic radiographs and CT, respectively. On panoramic radiographs, tonsilloliths were superimposed over the ramus of the mandible at the level coincident with and inferior to the soft palate in 176 (7.8%) and 90 (4.0%) individuals, respectively. Tonsilloliths were also superimposed over the surrounding soft tissue inferior to the body of the mandible, postero-inferior to the angle of the mandible, and posterior to the ramus of the mandible in 33 (1.5%), 26 (1.2%), and 28 (1.3%) individuals, respectively. A significant correlation was observed between the detectability on panoramic radiographs and the size (Spearman r=1.000) and number (Spearman r=0.991) of tonsilloliths, as revealed by CT images. Conclusions: The present results suggest that tonsilloliths are commonly detected on panoramic radiographs. Furthermore, they can be superimposed on both the mandible and the surrounding soft tissue. Clinical Relevance: Clinicians should include tonsilloliths among the differential diagnoses when calcified bodies are detected on panoramic radiographs.

The zygomaticus implant (Brånemark system, Nobel Biocare, Gotebörg, Sweden) was developed for patients with severe bone resorption of the posterior maxilla, which may eliminate or minimize the need for bone grafting. Although the zygomaticus implant has had a remarkable success rate in a difficult patient population, the method requires an advanced surgical technique and carries increased risk of complications, such as the perforation of the orbital floor or infratemporal fossa. Although it is important to have a detailed understanding of the anatomy of the zygomatic bone when performing the installation, there have been few anatomic studies on the zygomatic bone for installation of zygomaticus implants. In this study, we measured the height and thickness of the zygomatic bone for the installation. The thickness at a 90-degree angle point, where the upper margin of the zygomatic arch and the temporal margin of the frontal process of the zygomatic bone intersect and where the apex of the implant penetrates, according to the original method, was 1.8 ± 0.4 mm, which gradually increased inferiorly and anteriorly. In conclusion, the penetration point of the apex of the zygomaticus implant should be located more inferoanterior to the 90-degree angle point, as the thickness of the 90-degree angle point is thinner than the diameter of the implant. Based on these results, we have proposed a newer and safer installation method for the zygomaticus implant using a drill guide, which can be easily made.

Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are mostly observed in the gastrointestinal tract, pancreas, and lungs. NETs in the oral and maxillofacial region are extremely rare. We report a case of a 59-year-old woman with an NET in the mandible. The patient did not show any symptoms except for remarkable swelling and bleeding. The lesion appeared as a radiolucent honeycomb abnormality with bone destruction on panoramic radiography. The histopathologic diagnosis following a biopsy was NET. Contrast-enhanced computed tomography (CT), 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT), and adrenal scintigraphy-labeled meta-iodobenylguanidine were the modalities added to identify the primary site. Multiple lesions were confirmed in the gastrointestinal tract. Endoscopy was performed to identify the lesions, and several lesions were observed protruding from the mucous membranes. However, the endoscopy specimens did not yield an accurate diagnosis because adequate samples were not acquired. Blood and urine tests revealed no functional activity caused by the tumors. Although the origin was not histopathologically confirmed with endoscopy, this patient was situationally diagnosed with nonfunctional NET originating from the duodenum, as demonstrated by the metastases in the mandible.

Background The purpose of this retrospective study was to compare fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and ultrasonography (US) in the staging of patients with squamous cell carcinoma of the oral cavity. Methods We compared preoperative evaluations regarding lymph nodes using PET/CT, US, and both methods. The cutoff for the maximum standardized uptake value (SUVmax) in PET/CT was set at 2.7 by a receiver operating characteristic analysis that was based on the histopathological diagnosis. US was used to examine internal structural changes on B-mode and hilar vascularity on power Doppler. Results The performance of PET/CT and US in combination was better than that of each modality separately. However, there were histopathological changes that could not be detected on PET/CT or US. PET/CT could not detect nodes with necrotic or cystic changes. US could not detect lymph nodes that did not have abnormal structures. Conclusions PET/CT and US are complementary tools to evaluate preoperative patients.

Despite the clinical adoption of distraction osteogenesis (DO), studies examining the bone healing process at the distraction gap in osteoporotic bone are limited. We examined the effect of osteoporosis in the ovariectomized rat on DO.Mid-diaphyseal osteotomies were performed on the femurs of ovariectomized (OVX) rats. External distractors were placed on these rats and also on sham-ovariectomized rats. After a 7-day latency period, distraction was carried out at a rate of 0.5mm/day for 10 days. The bone volume (BV) of the distraction gap was measured by Micro-focused X-ray computed tomography (micro-CT) at 0, 2, and 4 weeks after completion of the distraction, and the distraction gap was examined histologically.The BV of the distraction gap in the OVX group was significantly lower than that in the sham group at 2 and 4 weeks after completion of distraction (p0.01). On histological examination, the distraction gap in the OVX group was filled with scattered smaller bone trabeculae than those seen in the sham group at 4 weeks after completion of distraction. Osteoclast numbers at the distraction gap in the OVX group were significantly increased when compared to the sham group (p0.01).Bone turnover with osteoclast predominance in ovariectomized rats is likely to be the cause of a reduction in new bone formation at the distraction gap.

[Background] Cancer stem cells (CSCs) exhibit self-replication, self-differentiation, drug resistance, and immune evasion activities. Recently, CSC has become increasingly important in the treatment of malignant tumors. Cancer stem cells express specific molecules termed CSC marker, including sex determining region Y-box2 (SOX2), and octamer-binding transcription factor 4 (Oct4), and their expression has been reported to be the potential prognostic values. However, the prognostic values of SOX2 and Oct4 expression in patients with stage I and II oral cancer are less understood. [Purpose] The aims of present study were to evaluate the expression of SOX2 and Oct4 in stage I and II oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the CSC marker expression, clinical stages, histological differentiation, classification of invasion mode, cerebral lymph node metastasis, distant metastasis, and disease-free survival rate. [Materials and Methods] Tissue specimens were obtains from 83 patients with OSCC after surgery or biopsy. Immunohistochemistry was used to assess SOX2 and Oct4 protein using at least 10% staining-positive cells as the definition of positive staining. [Results] Immunohistochemical analysis of 83 cases showed that 31 cases (37%) expressed SOX2. There was no significant association between SOX2 expression and tumor size, invasion mode or histological differentiation. However, there was significant association between SOX2 expression and distant metastasis or disease-free survival rate at stage 1 and 2 patients. Otherwise, fifty three cases (64%) of 83 OSCC patients expressed Oct4. There was significant association between Oct4 expression and histological differentiation. There was no significant association between Oct4 expression and tumor size, invasion mode, metastasis, or disease-free survival rate. [Conclusions] These findings suggested that the expression of SOX2 may be good marker indicating survival in patients with stage 1 and 2 OSCC. Citation Format: Tetsuya Tamatani, Natsumi Takamaru, Go Ohe, Takayuki Nakagawa, Naito Kurio, Keiko Kudou, Yoshiko Yamamura, Takamitsu Mano, Youji Miyamoto. The clinicopathologic roles of SOX2 and Oct4 expressions in stage 1 and 2 oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3061.

OBJECTIVES: Nasopharyngeal tonsilloliths (NT) and eustachian tube tonsilloliths (ET) are not as well-known to radiologists as palatine and lingual tonsilloliths. The aim of this investigation was to determine the prevalence and imaging characteristics of NT and ET using CT and panoramic radiographs. METHODS: We retrospectively assessed the scans of 2244 patients who underwent consecutive CT and panoramic radiographs of the maxillofacial region. The prevalence, size, number, and position of NT and ET were analysed. RESULTS: NT and ET were detected in 14 (0.6%) and 6 (0.3%) of 2244 patients on CT, respectively, but they were undetectable on panoramic radiographs. No significant difference was found in the prevalence with respect to sex. Although there was also no significant difference in the prevalence among age groups, tonsilloliths were most commonly noted in patients over 40 years old; they appeared as small and round calcified bodies, ranging from 1 to 3 mm in diameter. All NT were found 0 to 3 mm beneath the nasopharyngeal mucosal surface. CONCLUSIONS: The prevalence of NT and ET on CT was lower than that of palatine and lingual tonsilloliths. However, since they are encountered more frequently than clinically significant calcifying diseases such as retropharyngeal calcific tendinitis, clinicians should be able to correctly diagnose NT and ET based on their anatomical features.

Patients Titanium has been considered to be a non-allergenic material. However, several studies have reported cases of metal allergy caused by titanium-containing materials. We describe a 69-year-old male for whom significant pathologic findings around dental implants had never been observed. He exhibited allergic symptoms (eczema) after orthopedic surgery. The titanium screws used in the orthopedic surgery that he underwent were removed 1 year later, but the eczema remained. After removal of dental implants, the eczema disappeared completely. Discussion Titanium is used not only for medical applications such as plastic surgery and/or dental implants, but also for paints, white pigments, photocatalysts, and various types of everyday goods. Most of the usage of titanium is in the form of titanium dioxide. This rapid expansion of titanium-containing products has increased percutaneous and permucosal exposure of titanium to the population. Conclusions In general, allergic risk of titanium material is smaller than that of other metal materials. However, we suggest that pre-implant patients should be asked about a history of hypersensitivity reactions to metals, and patch testing should be recommended to patients who have experienced such reactions.

Although apatite cement (AC) and sintered hydroxyapatite (s-HAP) are known to show good osteoconductivity, it is not clear whether or not the degree of their osteoconductivity is the same. In addition, it has not been clarified whether or not it is dependent on the type of AC; conventional AC (c-AC), fast-setting AC (fs-AC) or anti-washout AC (aw-AC). The aim of this study was to investigate the effects of ACs on cultured human osteoblasts, as they may provide a useful index of osteoconductivity. Human osteoblasts were cultured on the surfaces of ACs and s-HAP, and were evaluated with respect to cell attachment, proliferation, and differentiation. We found that ACs and s-HAP showed similar cell attachment. No significant difference between ACs and s-HAP was found with respect to the proliferation of osteoblasts. In contrast, we found that the differentiation of osteoblasts was enhanced on the surface of ACs compared with that of s-HAP. However, there was no difference among the types of AC. We therefore concluded that AC may show better osteoconductivity than s-HAP, and that osteoconductivity of AC may be similar, regardless of the type of AC.

The aim of this study was to elucidate the effect of the additional installation of implants in the posterior region on the prognosis of treatment in the edentulous mandibular jaw. Fifteen patients who had received implants (Branemark system, Nobel Biocare, Goteborg, Sweden) in the edentulous mandible and completed a 1-year follow-up after the fitting of implant-anchored fixed prostheses were selected. In seven patients (Group A), four or five implants were installed between the mental foramina, and in eight patients (Group P), one or two implants, one on each side, were installed in the posterior regions in addition to the implants between the foramina. All implants of both groups achieved osseointegration. In Group A, there was no implant loss after loading. Six implants were lost in five patients of Group P within 1 year after loading. All of them were located in the posterior region. To elucidate whether or not the failure rate of the implants in the posterior region of Group P after loading was especially high, the failures were also compared with 89 implants, which were installed in the posterior region of the mandibles to support implant-anchored fixed partial prosthesis, during the same period (Group C). The cumulative survival rate of the implants of Group P was 60%, while that of the implants of Group C was 100% (P

Background: The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva. Methods: Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models. Results: EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF. Conclusion: Basic FGF may be effective for refractory oral mucosal lesions.

Lingual tonsilloliths are not as well-known to radiologists than palatine tonsilloliths, although they might be common in clinical practice. The aim of this investigation was to clarify the prevalence and imaging characteristics of lingual tonsilloliths using panoramic radiographs and CT images.This study included 2244 patients without pathology at the base of tongue who had undergone panoramic radiography and CT of the maxillofacial region. The size, number and position of lingual tonsilloliths relative to the mandible and tongue were evaluated.Lingual tonsilloliths were observed in 33 (1.5%) and 108 (4.8%) of all patients on panoramic radiographs and CT images, respectively. The prevalence was higher in patients aged ≥40 years than in those aged40 years (χLingual tonsilloliths commonly appear on CT. They also appear on panoramic radiography and may superimpose the surrounding soft tissue of the mandible. Although lingual tonsilloliths may resemble other pathological calcifications including submandibular sialoliths and lingual osseous cholistoma, they can be differentiated by carefully observing panoramic radiographs. When clinicians detect calcified bodies near the base of tongue, lingual tonsilloliths should be included in the differential diagnoses.

Background: A cancer stem cell (cancer initiating cell, CSC) is considered capable of self -replication, self-differentiation, drug resistance, and immune evasion. Recently, CSC has become increasingly important in the treatment of malignant tumors. Cancer stem cells express specific molecules termed CSC marker, including sex determining region Y-box2 (SOX2), and octamer-binding transcription factor 4 (Oct4), and their expression has been reported to be the potential prognostic values. However, the prognostic values of SOX2 and Oct4 expression in patients with oral cancer are less understood. [Purpose]The aims of present study were to evaluate the expression of SOX2 and Oct4 in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the CSC marker expression, clinical stages, histological differentiation, the classification of invasion mode, cerebral lymph node metastasis, distant metastasis, and disease-free survival rate. Materials and Methods: Tissue specimens were obtains from 108 patients with OSCC after surgery or biopsy. Immunohistochemistry was used to assess SOX2 and Oct4 protein using at least 10% staining-positive cells as the definition of positive staining. Results: Immunohistochemical analysis of 108 cases showed that 42 cases (39%) expressed SOX2. There was no significant association between SOX2 expression and tumor size, invasion mode or histological differentiation. However, there was significant association between SOX2 expression and distant metastasis or disease-free survival rate at stage 1 and 2 patients (73 cases). Otherwise, seventy cases (65%) cases of 108 OSCC patients expressed Oct4. There was significant association between Oct4 expression and histological differentiation. There was no significant association between Oct4 expression and tumor size, invasion mode, metastasis, or disease-free survival rate. Conclusions: These findings suggested that the expression of SOX2 may be good marker indicating survival in patients with OSCC. Citation Format: Tetsuya Tamatani, Natsumi Takamaru, Go Ohe, Keiko Kudo, Takaharu Kudo, Akira Takahashi, Yoshiko Yamamura, Kenji Fujisawa, Hirokazu Nagai, Youji Miyamoto. Expression of sox2 and oct4 in human oral squamous cell carcinoma and its relationship with clinical factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3879. doi:10.1158/1538-7445.AM2017-3879

Anti-washout-type fast-setting calcium phosphate cement using chitosan (aw-FSCPC(chi)), conventional CPC (c-CPC), CPC mixed with citric acid (CPC(citric)) and CPC mixed with polyacrylic acid (CPC(acrylic)) were implanted subcutaneously in rats immediately after mixing to shed some light on the understanding of the appearance of excellent tissue response to CPC. CPC(citric) and CPC(acrylic) set quickly, similar to aw-FSCPC(chi), but the former two stopped their transformation to apatitic minerals. The c-CPC, which required a long setting time, was found to be crumbled, but the other CPCs maintained the shape at implantation. The aw-FSCPC(chi) and CPC(citric) showed no inflammatory response whereas c-CPC and CPC(acrylic) showed an inflammatory response one week after implantation. A component of the aw-FSCPC(chi) and c-CPC was an apatitic mineral whereas CPC(citric) and CPC(acrylic) showed no transformation to apatite. We concluded that the non-crumbling property plays a more dominant role in the appearance of excellent tissue response to CPC than the transformation to apatite. Also, a non-crumbling property is not a sufficient condition, but a necessary condition for the appearance of the excellent tissue response to CPC.

Fast-setting calcium phosphate cement (FSCPC) is a promising new bioactive cement with a significantly short setting time (approximately 5-6 min) compared to conventional calcium phosphate cement (c-CPC) (30-60 min) at physiologic temperatures. As a result of its ability to set quickly, it is applicable in surgical procedures where fast setting is required. In this study, FSCPC was implanted in rat tibiae to evaluate tissue response and biocompatibility. FSCPC was converted to hydroxyapatite (HAP) in bone faster than c-CPC in the first 6 h. By 24 h, significant amounts of both FSCPC and c-CPC had been converted to HAP. The conversion of FSCPC into HAP further proceeded gradually, reaching 100% within 8 weeks. Infrared spectroscopic analysis disclosed the deposition of B-type carbonate apatite, which is a biological apatite contained in human dentin or bone, on the surface of the FSCPC. Histologically, FSCPC showed a tissue response similar to that of c-CPC. A slight inflammatory reaction was observed in the soft tissue apposed to both cements in the early period, and new bone was formed along the surface of the FSCPC at the adjacent bone. However, no resorption of either cement by osteoclasts or macrophages was observed within 8 weeks. We conclude that FSCPC is superior to c-CPC in clinical applications in oral and maxillofacial, orthopedic, plastic, and reconstructive surgery, since it shows a faster setting time and higher mechanical strength in the early period that are required in these surgical procedures, as well as osteoconductivity and excellent biocompatibility similar to that of c-CPC.

A carcinoma in pleomorphic adenoma occurring in the tongue of a 47-year-old Japanese woman is reported. The present report is the first to describe a carcinoma in pleomorphic adenoma derived from the posterior lingual glands.

Objectives: To demonstrate the usefulness of intraoral ultrasonography (IOUS) for tongue mass lesions, we analyzed surgery cases excluding squamous-cell carcinoma and leukoplakia and compared IOUS and pathological findings. Methods: We used the hospital information system and Radiology Information System to evaluate the IOUS and pathological findings of patients who underwent surgeries for tongue masses in the past 11 years. Results: Surgeries for the tongues were performed in 268 cases. Imaging examinations were carried out in 52 (19.4%) cases including 42 (15.7%) cases by IOUS. The pathological results of the surgeries were as follows: 36 cases were inflammatory lesions, 74 cases were tumours, 131 cases were hyperplasia, 8 cases were cystic lesions and 19 cases were other miscellaneous lesions. On the other hand, the number of patients who received IOUS in the same period was 87, and 42 of them had surgeries. In 32 out of the 42 (76.2%) cases, pre-operative IOUS features matched with pathological results. Most of the haemangiomas and lipomas could be diagnosed by IOUS alone. Conclusions: IOUS of the tongue revealed the nature of the lesions including the border, size, location, depth, the presence or absence of a capsule and the internal structure including vascularity of the mass. The ultrasonographic findings well reflected the histological findings. IOUS is a simple and useful technique that provides additional information beyond inspection, clarifying the internal structure, blood flow and relationships with the adjacent tissues. In this article, we indicated 11 representative cases (fibrous polyp, haemangioma, pyogenic granuloma, lipoma, liposarcoma, chondroma, lymphangioma, schwannoma, neurofibroma, pleomorphic adenoma and amyloidosis) to show the usefulness of IOUS.

A number of regimens composed of concurrent chemoradiotherapy (CCRT) have been attempted as radical or adjuvant therapies for locally advanced oral cancer. CCRT with S-1 is considered promising due to its efficacy and simplicity of application. Patients (n=16) with locally advanced squamous cell carcinoma of the oral cavity were enrolled. Chemotherapy consisted of oral administration of S-1 (65 mg/m(2)) for 14 consecutive days followed by a 1-week rest. Radiation treatment at a dose of 30 Gy in 15 fractions was administered concomitantly with S-1. A course schedule of 3 weeks of treatment was applied twice. The overall response rate was 87.5%. Median progression-free survival and median overall survival were 6.3 and 42.5 months, respectively. Although no grade 4 adverse events were observed, grade 3 adverse events, such as anemia (12.5%), stomatitis (25%) and anorexia (18.8%) were present. Thus, CCRT with S-1 is an effective modality that can be safely conducted with minimal burden on patients.

Cementifying fibroma is a relatively rare odontogenic tumor with a predilection for the jaw bone. We reported here 4 cases of cementifying fibroma we had recently encountered.The tumors of all 4 cases were surgically removed. Histopathological examination revealed that the tumorous lesions consisted of various amounts of fibrous tissues with extensive proliferation of cementum-like tissues.Therefore, the tumors were histopathologically diagnosed as cementifying fibromas. The prognosis of these cases are favorable with no sign of recurrence.

重複癌は悪性腫瘍の増加にともない増加する傾向にあり, 転移性腫瘍との鑑別が困難な症例も多い。われわれは左顎下腺および肺の重複癌の1例を経験した。患者は77歳男性で, 1990年8月22日, 左顎下部の無痛性の腫脹を主訴に当科受診した。初診時, 胸部X線写真にて右肺に腫瘍を思わせる陰影を認めた。顎下部生検で粘表皮癌との病理組織診断を得た。また, 肺の腫瘍様病変の穿刺細胞診では粘表皮癌を示唆する所見がみられ, 左顎下腺癌の肺転移と診断した。同年10月2日, 左全頸部郭清術, 下顎骨区域切除術, 腫瘍切除術, チタンプレートおよびD-P皮弁による即時再建術を行い, D-P皮弁切離術と同時に右肺中葉切除術を施行した。肺腫瘍の病理組織検査の結果, 組織型は腺癌で, 本症例は左顎下腺と右肺の同時性重複癌であることが判明した。術後1年3か月を経過した現在, 再発, 転移等を認めず経過良好である。

We have demonstrated that CXCR4 system is involved in the metastatic process of oral cancer. Recently, we identified the miR-518c-5p as a downstream target of the CXCR4 system, which was involved in the metastasis of B88, a CXCR4-expressing oral cancer cell line (2014 AACR annual meeting). In this study, we examined the function of miR-518c-5p in an oral cancer cell line, CAL27, which did not express CXCR4 and did not exhibit metastatic potential in vivo. We transfected a miR-518c expression vector into parental CAL27 cells and isolated a stable transfectant, CAL27-518c. We could detect the upregulation of miR-518c-5p in the miR-518c transfectants compared with mock cells, which was completely inhibited by treatment with the miR-518c-5p LNA inhibitor. The growth and migration of CAL27-518c cells were significantly enhanced compared with those of mock cells. The miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of CAL27-518c cells, indicating that these phenomena were mainly dependent on the expression of miR-518c-5p. Next, we examined the function of miR-518c-5p in vivo. miR-518c or mock transfectants were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with miR-518c transfectants. These results indicate miR-518c-5p promotes the metastasis of oral cancer in a CXCR4-dependent and -independent manner. Citation Format: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Hitoshi Kawamata, Youji Miyamoto. miR-518c-5p promotes the metastasis of oral cancer cells in a CXCR4-dependent and -independent manner. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3059. doi:10.1158/1538-7445.AM2015-3059

The aim of this study was to examine the influence of smoking on osseointegrated implant failure by performing a meta-analysis. A computerized literature search using PubMed database (in English) and Japana Centra Revuo Medicina (in Japanese) was carried out to identify all relevant studies. Among 175 studies identified and chosen for detailed review, 19 were appropriate for inclusion in our meta-analysis. When smokers were compared with non-smokers, odds ratio (OR) for osseointegrated implant failure was significantly elevated (OR 2.17, 95% confidence intervals (CI), 1.67-2.83). Seven studies were appropriate to examine the influence of intra-oral location (maxillary arch vs. mandibular arch) of implant failure on smoking. The OR for implant failure occurring in the maxillary arch was significantly elevated (OR 2.06, 95% CI, 1.61-2.65), whereas the OR in the mandibular arch did not demonstrate a significant increased risk associated with smoking (OR 1.32, 95% CI, 0.72-2.4). Our meta-analysis revealed a significant relationship between smoking and the risk of osseointegrated implant failure, more particularly those implants located in the maxillary arch.

The purpose of this study was to evaluate changes in disc position, mobility, and morphology in patients with temporomandibular joint disorders (TMD) in response to four different treatments, splint therapy, pumping manipulation, arthrocentesis, and arthroscopic surgery, using magnetic resonance imaging (MRI).Eighty-five joints (85 patients) with unilateral internal derangement or osteoarthritis that were successfully treated were included in this study. The patients were divided into four groups as follows: splint therapy group, pumping manipulation group, arthrocentesis group, and arthroscopic surgery group. Changes in the disc position, mobility, and morphology before and after treatment were compared among the four groups using MRI.All discs showed anterior disc displacement (ADD) without reduction before treatment. Only 10% of the joints became ADD with reduction after treatment, and the other joints remained ADD without reduction in spite of treatment. Discs treated by arthroscopic surgery were located more anteriorly compared with pre-treatment. In pre-treatment MRI, the rate of stuck disc increased as the stage of the treatment advanced. In post-treatment MRI, all temporomandibular joints (TMJs) had mobile discs. The disc deformity advanced after arthrocentesis and arthroscopic surgery.Even though clinical signs and symptoms were alleviated by treatment, most discs remained ADD without reduction on MRI in spite of treatment. This suggests that the four treatments do not necessarily improve the position and deformity of the disc, and that arthroscopic surgery advances the deformity and anterior displacement of the disc. Disc mobility is important for improving clinical signs and symptoms.

Background: The synovial tissues with temporomandibular disorders (TMDs) often show chronic inflammatory changes and the synovial cells participate in the pathogenic processes of TMDs. The synovial membrane is composed of a synovial lining layer and a connective sublining layer. The synovial lining layer is made up of two kinds of cells: macrophage-like type A and fibroblastic type B cells. The aim of this study was to isolate and characterize synovial cells from the human temporomandibular joint (TMJ). Methods: Synovial cells were isolated using an explant culture method. Then, we characterized the cultured synovial cells (SGA2 cells) using immunocytochemistry. Results: SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. However, some cells expressed the macrophage marker CD68. These CD68-positive cells simultaneously expressed laminin. Conclusions: We isolated and cultured synovial type B cells from the human TMJ, and identified the presence of intermediate type synovial lining cells, having the phenotypic properties of both type A and type B cells, among the synovial lining cells.

Recently, the results of treatment in patients with chronic renal failure have improved owing to progress in hemodialysis. Consequently, there is expected to be an increase in patients with head and neck cancer complicated by chronic renal failure. We performed radiation therapy, surgery and chemotherapy using cis-diamminedichloroplutinum (CDDP) and 5-fluorouracil ( 5-FU) to treat tongue cancer in a 60-yearold man with chronic renal failure who was undergoing hemodialysis. Here we present our results and discuss some problems in treatment. Close attention should be paid to unusual tumor growth when performing anticancer therapy for malignancy in patients undergoing hemodialysis for chronic renal failure.

Although bone wax is known to cause an inflammatory reaction in soft tissue and a delay of bone healing, it is usually the first choice to arrest bleeding from bone. Hydroxyapatite (HAP) putty is proposed here. This study evaluated the feasibility of HAP putty with respect to whether or not it has potential value as a hemostatic agent for bone. First, the adhesive strength of HAP putty to bone was evaluated. The adhesive strength of HAP putty to wet bone was much higher when compared with that of bone wax, even though the adhesive strengths of HAP putty and bone wax to dry bone were equivalent. Next, to evaluate the hemostatic ability of HAP putty, bony defects were made in rabbits. HAP putty could arrest bleeding from bone within 3 min. However, when the hemostasis was performed with bone wax, bleeding was arrested within 8 min. Thus, HAP putty showed better hemostatic ability than bone wax. Finally, the tissue response to HAP putty in rabbit subcutaneous tissue was evaluated. Histological observation revealed a slight inflammatory response around HAP putty, whereas bone wax was surrounded by moderate inflammatory tissue. In conclusion, HAP putty has good potential value to be a hemostatic agent for bone because it has strong adhesion, good hemostatic ability, and biocompatibility.

We identified a metastasis-related gene, metabotropic glutamate receptor (mGluR)-5, as a target gene of stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. In this study, we examined the role of mGluR5 on the lymph node metastasis of oral cancer. mGluR5-specific antagonists, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) did not affect the growth of oral cancer cells, but did inhibit the SDF-1/CXCR4 dependent-migration of the cells. When the CXCR4 expressing-oral cancer cells were orthotopically transplanted into masseter muscle of nude mice, these antagonists significantly inhibited lymph node metastases of the cells. Immunohistochemical analysis revealed that there was a significant association between CXCR4 and mGluR5 protein expression. Furthermore, the mGluR5 protein expression in clinical specimen was significantly associated with the lymph node metastases and the modes of invasion. Moreover conditioned media derived from the oral cancer cells acquiring SDF-1/CXCR4 system enhanced the migration of lymphatic endothelial cells, which was significantly suppressed by the treatment with MPEP or MTEP. Although SDF-1/CXCR4 dependent-production of angiogenic factors, including interleukin-6, interleukin-8, and vascular endothelial growth factor (VEGF)-A were observed, mGluR5 antagonists did not affect the production of these factors. However, induction of a lymphangiogenic factor, VEGF-C was specifically impaired by the treatment with these mGluR5 antagonists. These results suggested that mGluR5 promotes the lymph node metastases of oral cancer cells by the SDF-1/CXCR4 system via enhancement of cancer cell migration and induction of lymphangiogenesis by VEGF-C. Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. The role of metabotropic glutamate receptor 5 on the lymph node metastases in oral cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1993. doi:10.1158/1538-7445.AM2014-1993

We have demonstrated that stromal-cell derived factor (SDF)-1/CXCR4 system is involved in the metastatic process of oral cancer. Recently, small non coding RNAs, microRNAs (miRNAs) are involved in the metastatic process of several types of cancers. However, the miRNAs contributed to metastases induced by the SDF-1/CXCR4 system in oral cancer are largely unknown. Thus, we examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system, using oral cancer cells, B88-SDF-1 which exhibits functional CXCR4 and distant metastatic potential, in vivo. We examined metastasis-related miRNAs induced by the SDF-1/CXCR4 system using miRNA microarray analysis. Among these miRNAs, we confirmed the upregulation of miR-518c-5p in B88-SDF-1 cells by the real-time PCR analysis. Although LNA-based miR518c-5p inhibitor did not affect the cell growth, but did significantly inhibit the migration of B88-SDF-1 cells. Next, we transfected miR-518c expression vector into parental B88 cells, and isolated stable transfectant, B88-518c. The anchorage dependent and independent growth of B88-518c cells were significantly enhanced in compared with those of mock cells. Moreover, we could detect the enhanced migration of B88-518c cells. LNA-based miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of B88-518c cells, indicating that these phenomenon were dependent on the expression of miR-518c-5p, not on that of miR-518c-3p. Next, we examined the function of miR-518c-5p in vivo. B88-518c cells or mock cells were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with B88-518c cells. These results indicate that SDF-1/CXCR4 system regulates the metastases of oral cancer via induction of miR-518c-5p. Citation Format: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. Isolation of a novel metastasis-related microRNA, miR-518c-5p, induced by the stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1446. doi:10.1158/1538-7445.AM2014-1446

Statement of the Problem: Effective bone regeneration system requires artificial bone substitutes to replace bone. We developed carbonate apatite (CAp) blocks, which is a component of in vivo bone, by using a new procedure. We have already reported that CAp blocks receive absorption by osteoclasts just like in vivo bone and induce effective bone replacement[1]. Here, we further investigated modified CAp granules, which could be controlled with its absorption. Materials and Methods: CAp granules were prepared by using dissolution-precipitation reaction from carbonate calcium (CaCO3) as a precursor[2]. During that reaction, we were able to get the intermediate block, ‘‘carbonate apatite coated carbonate calcium’. The degree of coating with CAp was measured by X-ray diffraction (XRD), then 10% and 30% CAp-coated CaCO3 were prepared. Sixteen rabbits were subjected to bone regeneration assay. We examined 5 groups, 1) Sham group, 2) CaCO3 group, 2) 10% CAp-coated CaCO3 (10% CAp) group, 3) 30% CAp-coated CaCO3 (30% CAp) group, 4) CAp group. Cylindrical bone defects (F5.0 mm 8.0 mm) of rabbit femurwere formedbyusing dental trephinebar. Those rabbits were sacrificed at 4 and 8 weeks after material implantation surgery and analyzed by means of microcomputed tomography (microCT; Latheta LCT-200, ALOKA). Histological observation (MMA embedded; Villanueva-Goldner staining, Toluidine blue staining) was used to quantify new bone volume at the defect site. Methods of Data Analysis: For quantification of the degree of absorption of those granules in rabbit bone defect study (n=3/group), the sacrificed samples at 4 and 8 weeks after operation were scanned by microCT. After standardizing the images, the area of granules was evaluated with Photoshop CS5.1 (Adobe). For quantification of new bone volume, we calculated the area of new bone in five random images/group (40X-magnification) using ImageJ in toluidine blue stained sections. For

To evaluate the replacement of apatite cement (AC) with bone, osteoclasts were incubated for 48 h on the surface of three AC types: conventional AC (c-AC), fast-setting AC (fs-AC), and anti-washout AC (aw-AC), using sintered apatite (AP) and cortical bone as control materials. We found osteoclasts attached to the surface of AC and osteoclastic resorption pits after 48 h of incubation for all experimental AC types. In contrast, no resorption pit was observed on the surface of sintered AP although osteoclasts were attached to the surface of sintered AP. There was no significant difference among the types of AC with respect to the resorption area, but the resorption areas were only approximately 1% of that on the surface of cortical bone. We concluded, therefore, that ACs could be replaced with bone regardless of the type but that it takes extensive time for the ACs to be completely replaced with bone.

We have previously demonstrated that stromal cell-derived factor (SDF)-1/CXCR4 system is involved in the metastatic process of oral cancer. Recently, small non coding RNAs, microRNAs (miRNAs) are involved in the metastatic process of several types of cancers. However, the miRNAs contributed to metastases induced by the SDF-1/CXCR4 system in oral cancer are largely unknown. Thus, we examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system, using oral cancer cells, B88-SDF-1, which exhibits functional CXCR4 and distant metastatic potential, in vivo. We examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system by use of a miRNA microarray representing approximately 1700 miRNA. Consequnetly, we identified 4 kinds of upregulated-miRNAs in B88-SDF-1 cells whose functions are unknown. Among these miRNAs, we confirmed the upregulation of miR-5XX in B88-SDF-1 cells by the real-time PCR analysis. Although LNA-based miR-5XX inhibitor did not affect the growth of the cells, it did significantly inhibit the migration of B88-SDF-1 cells. Thus, we examined the target gene(s) of miR-5XX in the SDF-1/CXCR4 system. cDNA microarray analysis revealed that 6 kinds of mRNA containing the predictive binding site of miR-5XX were upregulated by the treatment with miR-5XX inhibitor. Furthermore, gene A mRNA and protein was downregulated in B88-SDF-1 cells, and upregulated by the treatment with miR-5XX inhibitor. These results indicating that SDF-1/CXCR4 system might regulate the metastases of oral cancer by the downregulation of gene A via upregulation of miR-5XX. Citation Format: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. Functional analysis of metastasis-related microRNA induced by the stromal-cell derived factor (SDF)-1/CXCR4 system in oral cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2697. doi:10.1158/1538-7445.AM2013-2697

A verruciform xanthoma occurring within lichen planus on the lateral aspect of the tongue in a 68-year-old Japanese woman is reported. The features suggest that the condition of altered epithelial turnover, as in repeated epithelial desquamation, may cause the verruciform xanthoma.