Akiyoshi Nishiyama

Specific inhibitor of MEK-mediated cross-talk between ERK and p38 MAPK during differentiation of human osteosarcoma cells

Osteosarcoma is the most common primary malignant bone tumor, accounting for approximately 20% of all primary sarcomas in bone. Although treatment modalities have been improved over the past decades, it is still a tumor with a high mortality rate in children and young adults. Based on histological considerations, osteosarcoma arises from impaired differentiation of these immature cells into more mature types and that correction of this impairment may reduce malignancy and increase the efficiency of chemotherapy. The purpose of this study was to determine the effect of specific inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK) and p38 on the differentiation of human osteosarcoma cell line SaOS-2 cells. We found that PD98059, a specific inhibitor of MEK, inhibited the serum-stimulated proliferation of SaOS-2 cells; whereas SB203580, a specific inhibitor of p38 MAPK, had little effect on it. SB203580 suppressed ALPase activity, gene expression of type I collagen, and expression of ALP and BMP-2 mRNAs; whereas PD98059 upregulated them dose dependently. In addition, immunoblot and immunostaining analysis revealed that phosphorylation of ERK was increased by treatment with SB203580; whereas PD98059 increased the phosphorylation of p38, which implies a seesaw-like balance between ERK and p38 phosphorylation. We suggest that osteosarcoma cell differentiation is regulated by the balance between the activities of the ERK and p38 pathways and that the MEK/ERK pathway negatively regulates osteosarcoma cell differentiation, whereas the p38 pathway does so positively. MEK inhibitor may thus be a good candidate for altering the expression of the osteosarcoma malignant phenotype.

Class III malocclusion with severe facial asymmetry, unilateral posterior crossbite, and temporomandibular disorders

A 22-year-old woman had a Class III malocclusion with severe facial asymmetry, unilateral posterior crossbite, and temporomandibular disorders. A clicking sound was noted in the temporomandibular joint on the posterior crossbite side during jaw opening, and she complained of pain in the masticatory muscles on both sides. The articular disc on the crossbite side was displaced anteriorly without reduction. The patient was treated orthodontically with edgewise appliances and surgically with LeFort I and intraoral vertical ramus osteotomies. The result of the combined surgical-orthodontic treatment was facial symmetry and optimal occlusion. The displaced articular disc moved into a normal position, and most of the temporomandibular disorder symptoms improved. At the 2.5-year follow-up, the temporomandibular joint conditions had been maintained.

Severe facial asymmetry and unilateral lingual crossbite treated with orthodontics and 2-jaw surgery: 5-year follow-up

A 33-year-old woman with severe facial asymmetry and unilateral lingual crossbite was treated with orthodontics combined with differential maxillary impaction and intraoral vertical ramus osteotomy. After 12 months of preoperative orthodontic treatment, 2-jaw surgery was performed. The total active treatment time was 18 months. Both her occlusion and facial appearance were significantly improved by the surgical-orthodontic treatment. The occlusion was stable after 5 years of retention. Posttreatment records after 5 years showed excellent results with good occlusion and long-term stability.

Effects of bisphosphonate on experimental jaw metastasis model in nude mice

The mechanism of osteolysis associated with metastatic cancer of the jaws is essentially osteoclast-mediated. Therefore, it is likely that potent osteoclastic bone resorption inhibitors such as bisphosphonates would be efficacious for the treatment of jaw metastasis. We examined the effects of a third generation bisphosphonate, YM175, in a nude mice jaw metastasis model with intracardiac injection of a human breast cancer cell line, MDA-MB-231. The metastatic lesions in untreated mice were radiographically observed at the body and angle of the mandible. Histology of the mandible of untreated mice revealed that most of the bone marrow cavities had been occupied by the metastatic tumor with active osteoclasts along the trabecular bone. The experimental group showed that YM175 markedly reduced the size of tumor and the number of osteoclasts. These results suggest that YM175 may suppress metastasis formation and tumor growth in jaw through inhibition of osteoclastic bone resorption.

Functional improvements after orthodontic-surgical reconstruction in a patient with multiple maxillofacial fractures.

Patients with multiple craniofacial fractures often suffer from stomatognathic problems after their primary treatment, because administering emergency care is the clinicians highest priority. Therefore, optimal bone repositioning is sometimes difficult because bone fixation is delayed. Moreover, neither an adequate radiographic examination nor an evaluation of primary occlusion is available during the repair of fractured bones. The lack of these assessments can also lead to occlusal dysfunction after bone fixation. As a result, patients with craniofacial fractures often require occlusal reconstruction. This report describes the successful occlusal reconstruction with orthodontic-surgical treatment of a patient with multiple maxillofacial bone fractures. Combined surgery, including an intraoral vertical ramus osteotomy and a mandibular body osteotomy, was performed to reposition the deviated mandible after 3 months of preoperative orthodontic treatment. The total active treatment period was 25 months. After treatment, both the facial asymmetry and the anterior open bite caused by the skeletal disharmony were significantly improved. Additionally, the range of condylar motion, maximum occlusal force, and occlusal contact area during maximum clenching were also increased. These stomatognathic functions were further enhanced by 2 years of retention. Orthodontic-surgical reconstruction appears to improve both facial esthetics and occlusal function in patients with facial asymmetry caused by severe traumatic maxillofacial fractures.

Diagnostic imaging of Eagle's syndrome: Report of three cases

This article deals with the advantages of axial and three-dimensional computed tomography imaging for the diagnosis, treatment planning and postoperative evaluation of the elongated styloid process and/or ossified stylohyoid ligament. Panoramic radiography is a useful diagnostic method but it does not show the exact relationship of the process to the surrounding soft and hard tissues. However, anatomical relations of the stylohyoid complex are precisely displayed by axial computed tomography and its three-dimensional reconstruction, which were found to be useful for the preoperative and postoperative evaluation of Eagles syndrome. Three illustrative cases are presented and the literature is reviewed.

Orthognathic surgery during breast cancer treatment—A case report

Highlights • In recent years, patients with orthognathic surgery in middle-aged have come to be a more frequent occurrence.• Breast cancer is the most frequently diagnosed cancer in woman worldwide, and its prevalence rate is steadily increasing.• We experienced a case in which breast cancer was found just before the orthognathic surgery we performed a bimaxillary osteotomy, including follow-up tamoxifen administration, during breast cancer treatment.• We performed a bimaxillary osteotomy, including follow-up tamoxifen administration, during breast cancer treatment.

Examination of Diseases Requiring Oral Surgery Treated via Medical- Dental Cooperation in the Department of Oral and Maxillofacial Surgery (Biopathology), Okayama University Hospital

Objective: In recent years, the need for dental treatment and dental hygiene management within the perioperative period and supportive advanced medical treatment has been increasing. However, perioperative intervention in diseases requiring oral surgical treatment is not well understood at present. Here we report our investigation of diseases requiring oral surgical treatment in which Department of Oral and Maxillofacial Surgery (Biopathology) at Okayama University Hospital conducted medicaldental cooperation via Division of Hospital Dentistry. Methods: In the five years from April 2011 to March 2016, we have identified 310 cases that reached the Okayama University Hospital Department of Oral and Maxillofacial Surgery (Biopathology) via the Division of Hospital Dentistry. Results: The patients were treated in 22 clinical departments, the most prevalent treatment was chemotherapy, followed by surgery and then transplantation. The surgical diseases for which our department was consulted were most commonly diseases of the teeth and periodontal disease (269 cases), followed by inflammatory conditions such as implantitis and osteomyelitis, and mucosal diseases such as lichen planus and leukoplakia. The surgical procedure performed was most often tooth extraction (243 cases); there are few cases of cystectomy and sequestrum. In the majority of cases, the surgical treatment was performed on the initial examination day; in about 84% of cases, surgery was performed within 2 weeks. Conclusion: Further investigation is necessary into the practice of preventing adverse events non-dental medical departments by increasing the frequency of oral surgical intervention in appropriate cases during the perioperative period.

Installing an original sleeve for rod unaccessible pain from a distraction device in a hemifacial microsomia patient.

Highlights • Lengthening of the mandible by distraction osteogenesis using an internal device is the preferred method for the treatment of hemifacial microsomia. Despite its advantages, this technique can lead to various complications after the surgery.• We describe a case in which rod unaccessible pain developed after the initial mandibular distraction activation, and the pain was resolved by installing an original sleeve.

Novel pathogenic role of fibrin as revealed by a case study on ligneous gingivitis

Abstract Purpose of the research Ligneous gingivitis is a rare disease characterized by nodular gingival enlargement secondary to fibrin deposits induced by micro-injury in the gingiva, which disorder results from plasminogen (PLG) deficiency. Although none have investigated the association of wound healing factors with ligneous gingivitis. In this study, in addition to a histopathologic examination of ligneous gingivitis in a case of type I PLG deficiency, we further present data showing the effect of wound healing factors in association with fibrin in vitro to clarify the pathobiology of ligneous gingivitis in PLG-deficient patients. Principle results Immunohistochemical analysis revealed that transforming growth factor (TGF)-β1, connective tissue growth factor/CCN2 (CCN2), and endothelin-1 (ET-1) had accumulated in the extracellular matrix around the epithelial and fibroblastic cells near the fibrin deposition. Consistent with these results, fibrin and TGF-β1 synergistically up-regulated CCN2 and ET-1 gene expression in human dermal fibroblasts. Major conclusions Fibrin plays a vicious role in ligneous gingivitis pathobiology by up-regulating CCN2 and ET-1 expression through the TGF-β signaling pathway.