Korean Association of Anatomists Acta Medica Okayama 2093-3665 2026 Clinical anatomy of the superior labial branch of infraorbital nerve EN Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Airi Tanai Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Norio Kitagawa Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mi-Sun Hur Department of Anatomy, Daegu Catholic University School of Medicine Rizwan Aslam Department of Otolaryngology, Tulane University School of Medicine R. Shane Tubbs Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine The infraorbital nerve (ION), a branch of the maxillary division of the trigeminal nerve, provides sensory innervation to the midface via its terminal divisions. Among these, the superior labial branch (SLb) supplies the upper lip and adjacent mucosa, regions frequently involved in oral, maxillofacial, and cosmetic procedures. Despite its clinical importance, the anatomy of the SLb has received relatively limited attention compared with other ION branches. This review synthesizes current evidence on the SLb’s course, branching patterns, innervation, morphometry, and variations, with emphasis on its relevance to surgical practice. Anatomical studies demonstrate that the SLb is the largest terminal division of the ION, often exhibiting medial and lateral subdivisions that anastomose with neighboring nerves. Its distribution predominantly follows a vertical orientation, supplying both cutaneous and mucosal structures of the upper lip. Variability in origin, branching, and accessory foramina underscores the need for careful surgical planning. Injury to the SLb is a recognized complication of Le Fort I osteotomy, midfacial trauma, and periapical procedures, potentially leading to long-term sensory disturbances. A comprehensive understanding of the SLb enhances intraoperative nerve preservation and may reduce postoperative morbidity, highlighting its significance for clinicians operating in the midfacial region. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 A Case of Psoas Abscess Diagnosed With Oral Bacteria as the Causative Pathogen e97584 EN Koki Umemori Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Kyoichi Obata Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Mayumi Yao Dentistry and Dental Surgery, Tsuyama Central Hospital Koji Fujita General Internal Medicine and Infectious Diseases, Tsuyama Central Hospital Soichiro Ibaragi Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine We report a rare case of a psoas abscess in an 87-year-old woman, in which oral commensal bacteria may have disseminated hematogenously from a chronic oral infection site and served as the causative pathogens. The patient presented with persistent left buttock pain, fever, and swelling, and imaging revealed a fracture of the left iliac bone with an associated psoas abscess. Bacterial cultures identified Streptococcus oralis and Pseudomonas aeruginosa. Her symptoms improved following antibiotic therapy and CT-guided drainage. Although the presence of P. aeruginosa in the oral cavity is generally considered transient, it has been isolated from the oral cavities of elderly and immunocompromised individuals. In the absence of lacerations or other direct portals of entry, and considering the identification of both pathogens, the oral cavity was regarded as the most likely source of infection. This case highlights the importance of correlating culture results with the most probable source of infection to improve the prognosis of systemic infections. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1618-1247 2025 Impact of CT-assessed sarcopenia on the severity of odontogenic deep neck infections: a retrospective cohort study EN Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Eiji Iwata Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yohei Takeshita Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chizuru Kobayashi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroki Kimura Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Kinisada Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Sarcopenia is increasingly recognized as a key predictor of adverse health outcomes. This study aimed to evaluate the impact of computed tomography-assessed sarcopenia (CT–SP) on the clinical severity and hospitalization duration of odontogenic deep neck infections (DNIs). Total of 119 patients admitted for odontogenic DNI treatment were included. Patients were divided into two groups by DNI clinical severity (severe or mild) and the patients' characteristics, including CT–SP based on skeletal muscle index (SMI), were compared between two groups. Multivariable logistic regression analysis was performed to identify independent risk factors for severe DNI. The correlation between SMI and hospitalization duration was assessed using Spearman’s rank correlation coefficient. Of the 119 patients, 60 (50.4%) presented with severe DNIs, including deep neck abscesses and necrotizing soft tissue infections. After adjusting for potential confounders, multivariable analysis identified CT–SP as the sole independent risk factor associated with severe DNI (Odds Ratio = 3.04; 95% Confidence Interval, 1.20–7.71; p = 0.019). Furthermore, SMI demonstrated a significant, weak negative correlation with the hospitalization duration (r = − 0.331, p < 0.001). CT–SP is a powerful, independent risk factor associated with severity in patients with odontogenic DNIs. This finding underscores the critical role of systemic host factors in the clinical course of maxillofacial infections and highlights the potential of opportunistic CT screening as a factor to consider in risk stratification in this vulnerable population. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1618-1247 2025 Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infections EN Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Naoki Kaneko Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Kotaro Sato Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine Norio Kitagawa Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Yohei Takeshita Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Katsuhisa Matsuo Dental and Oral Medical Center, Kurume University School of Medicine Junsei Sameshima Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization. Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearman’s rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration. Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI ≤ 41.2 (odds ratio [OR] = 2.79) and the presence of abscesses in multiple deep neck spaces (OR = 2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P = 0.048). In addition, Spearman’s rank correlation coefficient was r = − 0.471 (P < 0.001), indicating a moderate negative correlation. Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0250-832X 2025 Radiological assessment of dissected cervical lymph nodes in level III affected by the area of supraomohyoid neck dissection EN Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Ohyama Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Matsushita Clinical Anatomy Research Association in Oral and Maxillofacial Surgery R Shane Tubbs Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Norio Kitagawa Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Okayama University Hospital Shunsuke Okada Department of Oral and Maxillofacial Radiology, Okayama University Hospital Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Okayama University Hospital Yoshinobu Yanagi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Objectives: To compare the number of dissected cervical lymph nodes in the anatomical level III with that in supraomohyoid neck dissection (SOHND) level III affected by the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND. Methods: CE-CT images of the patients who suffered from malignant tumours in the oral and maxillofacial regions were reviewed. The number of cervical lymph nodes both in the anatomical level III (area between the centre of the inferior border of the hyoid bone [HB] and the inferior border of the cricoid cartilage [CC]) and SOHND level III (area between HB and the intersection of the omohyoid muscle and internal jugular vein [OM-IJ]) were recorded, respectively. Results: The rate of patients whose number of lymph nodes in level III was affected by the positional relationship between the OM-IJ and CC was almost equal in males and females. As for the patients with OM-IJ below the CC, the number of lymph nodes in SOHND level III increased from that of anatomical level III. Females showed significantly higher values than males (P < .05). Meanwhile, for patients with OM-IJ at or above the CC, the number of lymph nodes in SOHND level III decreased from that of anatomical level III. Conclusions: The number of dissected cervical lymph nodes differed between the SOHND dissection area and levels I, II, and III. In most cases, SOHND dissects more cervical lymph nodes, especially in female patients. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 45 3 2025 Angiogenin-induced Osteoclastogenesis Mediates Bone Destruction in Oral Squamous Carcinoma 1025 1033 EN KASUMI AOKI Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University NANA YOSHITANI Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University NAITO KURIO Department of Oral Surgery, Graduate School of Biomedical Sciences, Tokushima University NORIE YOSHIOKA Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University JUMPEI TERAMACHI Department of Oral Function and Anatomy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University MIKA IKEGAME Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HIROHIKO OKAMURA Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University SOICHIRO IBARAGI Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Aim: Bone destruction caused by oral cancer severely impacts patient quality of life. This study aimed to clarify the role of angiogenin (ANG) in osteoclastogenesis and oral cancer-induced bone destruction. Materials and Methods: Recombinant ANG was used to assess its effects on osteoclast formation and bone resorption activity in bone marrow cultures. ANG-knockdown oral squamous carcinoma HSC-2 cells (ANG-RNAi) were transplanted into intramedullary cavities of femurs. Bone destruction was radiologically analyzed, while angiogenesis and osteoclast induction in the surrounding area of the transplanted lesion were histologically examined. Results: Recombinant ANG promoted osteoclast formation and bone resorption activity. Transplantation of ANG-RNAi cells significantly reduced tumor growth and bone destruction properties compared to transplantation of control cells. Histological analysis revealed lower angiogenesis and fewer osteoclast induction in the ANG-RNAi cells-transplanted group. Conclusion: ANG mediates oral cancer-induced bone destruction by promoting osteoclast formation and resorption. These findings suggest that ANG could be a potential therapeutic target for suppressing tumor growth, angiogenesis, and bone destruction in oral cancer therapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0002-8177 156 2 2025 The greater palatine nerve and artery both supply the maxillary teeth 151 159.e1 EN Joe Iwanaga Division of Gross and Clinical Anatomy, Department of Anatomy, School of Medicine, Kurume University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Muralidharan Anbalagan Department of Structural and Cellular Biology, School of Medicine, Tulane University Binghao Zou Department of Structural and Cellular Biology, School of Medicine, Tulane University Taku Toriumi Department of Anatomy, School of Life Dentistry at Niigata, The Nippon Dental University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University R. Shane Tubbs University of Queensland Background. It is generally accepted that the greater palatine nerve and artery supply the palatal mucosa, gingiva, and glands, but not the bone or tooth adjacent to those tissues. When the bony palate is observed closely, multiple small foramina are seen on the palatal surface of the alveolar process. The authors hypothesized that the greater palatine nerve and artery might supply the maxillary teeth via the foramina on the palatal surface of the alveolar process and the superior alveolar nerve and artery. The authors aimed to investigate the palatal innervation and blood supply of the maxillary teeth. Methods. Eight cadaveric maxillae containing most teeth or alveolar sockets were selected. The mean age at the time of death was 82.4 years. The samples were examined with colored water injection, latex injection, microcomputed tomography with contrast dye, gross anatomic dissection, and histologic observation. Results. Through both injection studies and microcomputed tomographic analysis, the authors found that the small foramina on and around the greater palatine groove connected to the alveolar process and tooth sockets. The small foramina in the greater palatine and incisive canal also continued inside the alveolar process and the tooth sockets. Conclusions. The alveolar branches of the greater palatine nerve and artery as well as the nasopalatine nerve and sphenopalatine artery supply maxillary teeth, alveolar bone, and periodontal tissue via the palatal alveolar foramina with superior alveolar nerves and arteries. Practical Implications. This knowledge is essential for dentists when administering local anesthetic to the maxillary teeth and performing an osteotomy. Anatomic and dental textbooks should be updated with this new knowledge for better patient care. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 7 2025 Tongue Schwannoma at the Median Inferior Surface in the Elderly: A Case Report e70506 EN Kiho Fukushima Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kisho Ono Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Izumi Yamamoto Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Yutori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We report the extremely rare case of an atypical schwannoma that occurred at the median inferior surface of the tongue in an elderly patient. We performed an excisional biopsy to achieve a definitive diagnosis. Based on the histopathological findings, we diagnosed a schwannoma (mixed type, Antoni A/B). No potential conflict of interest relevant to this article was reported.

Korean Association of Anatomists Acta Medica Okayama 2093-3665 58 2 2025 The trochlea for the intermediate tendon of the digastric muscle: a review 145 148 EN Xander du Plooy Tulane University School of Medicine Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Juan J. Cardona Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine Yoko Tabira Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Kathleen Carol Bubb Anatomy Division, Department of Radiology, Weill Cornell Medical College Kazzara Raeburn Department of Anatomical Sciences, St. George’s University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine R. Shane Tubbs Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea. No potential conflict of interest relevant to this article was reported.

Korean Association of Anatomists Acta Medica Okayama 2093-3665 2025 The maxillary vein: an anatomical narrative review with clinical implications for oral and maxillofacial surgeons EN Kazzara Raeburn Department of Anatomical Sciences, St. George’s University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rarinthorn Samrid Marios Loukas Department of Anatomical Sciences, St. George’s University R. Shane Tubbs Department of Anatomical Sciences, St. George’s University Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine The maxillary vein, despite its clinical significance, remains underexplored in anatomical literature. It plays a crucial role in venous drainage of the maxillofacial region and is closely associated with surgical procedures such as sagittal split ramus osteotomy, mandibuloplasty, and condylar or parotid surgeries. Due to its variable anatomy and proximity to critical structures, the maxillary vein poses a risk of significant hemorrhage if injured. Its small size and deep location make preoperative identification challenging, especially without contrast-enhanced imaging. Embryologically, the maxillary vein originates from the primitive maxillary vein and develops through complex anastomoses with other craniofacial veins. Anatomical studies have revealed several variations, including the presence of accessory mandibular foramina and unusual venous connections, which may increase surgical risk. Understanding the detailed anatomy and potential variations of the maxillary vein is essential for minimizing complications and improving surgical outcomes. Despite its importance, more anatomical and clinical research is needed to better define its course, variations, and implications in oral and maxillofacial surgery. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 4 2025 A Case of a Metal Foreign Object Remaining in the Maxillary Bone for an Extended Period: A Case Report e9631 EN Koichi Kadoya Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Ogawa Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences We report a rare case in which a metallic foreign body remained undetected in a patient's maxilla for nearly 40 years after a childhood bicycle accident. Despite the accident, the implant remained in place without causing infection due to the lack of imaging studies at the time. The metal was accidentally discovered during a routine dental imaging examination 40 years later and subsequently surgically removed. This case highlights the importance of comprehensive imaging and the dangers of overlooking foreign bodies, especially in the vulnerable head and neck region. The patient, 53 years old at the time of discovery, presented to the dentist due to discomfort in the palate and nasal cavity. During this visit, radiographs were taken and a foreign body was discovered. Surgical removal of the foreign body revealed significant corrosion and surrounding granulation tissue indicative of foreign body granuloma. Elemental analysis of the foreign body confirmed that it was an iron-based metal, unlike biocompatible materials such as titanium. These findings reinforce the need for close post-trauma evaluation and follow-up, especially in cases of pediatric trauma, to avoid the possibility of long-term complications arising from unnoticed foreign bodies in anatomically significant areas. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2024 2024 A Rare Case of Multiple Myeloma Identified Following the Diagnosis of Amyloidosis of the Tongue 8836103 EN Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Kadoya Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayumi Yao Department of Oral and Maxillofacial Surgery, Tsuyama Chuo Hospital Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amyloidosis is a disease in which amyloid protein is deposited in organs and tissues, resulting in functional impairment. Amyloidosis occurs in 12%-30% of patients with multiple myeloma, but in rare cases, amyloidosis may precede the diagnosis of multiple myeloma. Our patient was a 76-year-old Japanese male on dialysis. Multiple nodules accompanied by ulcers were observed on his tongue. He had no subjective symptoms or clinical findings associated with multiple myeloma. The histopathological findings suggested amyloidosis. We suspected both systemic and localized amyloidosis and performed a comprehensive systemic examination. Since the patient had been on dialysis for only a short period of time (similar to 3 months), dialysis-related amyloidosis was ruled out. After blood and urine tests, a diagnosis of multiple myeloma was made. Chemotherapy treatment was started, but the patient's multiple myeloma could not be suppressed and the tongue amyloidosis worsened, leading to his death 2 years and 2 months after the initial diagnosis. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 24 1 2024 Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome 1099 EN Hitomi Ono-Minagi Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Kiyofumi Takabatake Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital Kohta Miyawaki Division of Precision Medicine, Kyushu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayoshi Sakai Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging. No potential conflict of interest relevant to this article was reported.

Anticancer Research USA Inc. Acta Medica Okayama 1109-6535 21 5 2024 Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells 464 473 EN TAIRA HIROSE Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YUKI KUNISADA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KOICHI KADOYA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences HIROKI MANDAI Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science YUMI SAKAMOTO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KYOICHI OBATA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KISHO ONO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences HIROAKI TAKAKURA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUHIRO OMORI Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University SHOGO TAKASHIBA Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University SEIJI SUGA Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University SOICHIRO IBARAGI Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. Materials and methods: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. Results: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. Conclusion: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate. No potential conflict of interest relevant to this article was reported.

Anticancer Research USA Inc. Acta Medica Okayama 0250-7005 43 11 2023 Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma 4993 5001 EN HIDEKA KANEMOTO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KYOICHI OBATA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOKI UMEMORI Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUAKI HASEGAWA Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital SAWAKO ONO Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KISHO ONO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROKAZU YUTORI Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SOICHIRO IBARAGI Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. Patients and Methods: We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. Results: A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). Conclusion: CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1368-8375 142 2023 EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma 106433 EN Koki Umemori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kisho Ono Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Eguchi Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Ogawa Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kunihiro Yoshida Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Sato Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Ryumon Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Yutori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoki Katase Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University Tatsuo Okui Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance. Materials and methods: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS). Results: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner. Conclusion: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 23 1 2023 Ligneous periodontitis exacerbated by Behçet’s disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report 843 EN Yuki Shinoda-Ito Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anna Hirai Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Ideguchi Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Hideki Yamamoto Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumino Kato Department of Clinical Genomic Medicine, Okayama University Hospital Kyoichi Obata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Ogawa Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takato Nakadoi The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Hirasawa Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. Case presentation This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. Conclusions Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions. No potential conflict of interest relevant to this article was reported.

AME Publishing Company Acta Medica Okayama 2227-684X 11 10 2022 Lip pleomorphic adenomas: case series and literature review 1730 1740 EN Koki Umemori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Nakano Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pleomorphic adenoma (PA) is the most frequent benign salivary gland tumor, but a lip PA is rare. Although this tumor may be definitively diagnosed by imaging or a tissue biopsy if it is reasonably large, PAs on the lip are relatively small, and they present findings that are similar to those of other lip lesions, which can make a preoperative diagnosis difficult. Methods: We analyzed all PAs in the oral region and lesions on the lips treated in our department over the past 20 years, and we discuss them together with the relevant literature. Results: We found that 11.8% (n=6) of the PAs occurred on a lip (upper lip: 9.8%, lower lip: 2.0%), and ~1% of all mass lesions of the lips were PAs. The average size of the lip PAs was 1.5±0.7 cm (range, 0.7–2.2 cm). For preoperative diagnostic assistance, ultrasonography (US) (n=4), magnetic resonance (MR) (n=3), or no imaging (n=2) was used. An excisional biopsy was performed in all cases, and to date, no recurrence or malignant transformation has been observed. Conclusions: Lip PA is relatively rare. Because almost all of these lesions are small, a preoperative diagnosis is more difficult compared to palatal lesions. This tumor is also prone to long-term neglect and has the potential for recurrence and malignant transformation. It is thus necessary to perform an excision that includes the capsule and surrounding tissues, and careful postoperative follow-up should be continued. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2309-608X 9 3 2023 The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model 314 EN Hidefumi Sako Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Nakayama Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Hidetaka Ideguchi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Saki Yoshimura-Nakagawa Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kyosuke Sakaida Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Chiaki Nagata-Kamei Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroya Kobayashi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoki Ishii Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Mitsuaki Ono Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 12 9 2022 Craniomaxillofacial Fibrous Dysplasia Improved Cosmetic and Occlusal Problem by Comprehensive Treatment: A Case Report and Review of Current Treatments 2146 EN Kisho Ono Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norie Yoshioka Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Nakamura Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Minagi Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Sasaki Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fibrous dysplasia (FD) is a fibrous lesion of immature bone, with an incidence of 10-20% in the head and neck region. Most cases are monostotic, but when a lesion occurs on the maxillofacial region and spreads to the surrounding bone, it is classified as polyostotic, despite its localized occurrence. In some cases, surgical intervention is required to improve the cosmetic or functional disturbance of a FD in the maxillofacial region, but it is necessary to confirm symmetry of the maxillofacial region in real time, and a surgical support system is required to compensate. Furthermore, prosthetic intervention is considered when postoperative acquired defects occur or further cosmetic or occlusal function improvement is needed. A comprehensive approach by an oral surgeon and a maxillofacial prosthodontist is necessary for the successful treatment and rehabilitation of such patients. In this article, we describe the case of a craniomaxillofacial FD patient with facial asymmetry and denture incompatibility with improved quality of life measures by integrating surgical treatment using a navigation system and postoperative prosthetic rehabilitation. We also discuss recent diagnostic methods and treatment strategies for craniomaxillofacial FD in the literature. No potential conflict of interest relevant to this article was reported.

Ivyspring International Publisher Acta Medica Okayama 1449-1907 19 8 2022 Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer 1320 1333 EN Kisho Ono Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Sato Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yume Yoshida Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Murata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kunihiro Yoshida Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Ryumon Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuaki Hasegawa Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Okui Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Sasaki Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality. Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared. Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods. No potential conflict of interest relevant to this article was reported.

バイオメディカルサイエンス研究会 Acta Medica Okayama 2185-9361 33 4 SDGsを推進するニコチンと口腔癌の研究 1 2 EN Soichiro Ibaragi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1550 2021 Displacement of lower third molar into floor of mouth: a single institutional experience EN Masanori Masui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Takeshita Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Iwanaga Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine, New Orleans Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose The displacement of the tooth/tooth fragment into the floor of mouth sometimes happens during the lower third molar surgery and the patients are usually referred to oral and maxillofacial surgeons. To date, however, there is no consensus how to manage the displaced tooth due to the lack of available data. Methods In this study, we have retrospectively analyzed the management of the displaced lower third molar into the floor of mouth. Our institute experienced seven cases during 2010 to 2020. Results Incidence rate of the lingual nerve injury caused by displacement of the lower third molar was 1/7. Six patients out of seven underwent surgical removal of the displaced fragment. The direct approach was used when the fragment was palpable superficially and the fragment was horizontally located away from the lingual plate (2 cases). While, when the fragment was not palpable, or was palpable and adjacent to the lingual plate, the lingual mucoperiosteal flap was selected (4 cases). Conclusion We conclude that the palpation and preoperative diagnosis with computed tomographic images are significantly important to decide a better and most effective surgical approach. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 8 2021 Comparative Study on Epstein-Barr Virus-Positive Mucocutaneous Ulcer and Methotrexate-Associated Lymphoproliferative Disorders Developed in the Oral Mucosa: A Case Series of 10 Patients and Literature Review 1375 EN Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Koki Umemori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Ryumon Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayumi Yao Department of Dentistry and Dental Surgery, Tsuyama Chuo Hospital Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is an iatrogenic immunodeficiency-associated lymphoproliferative disorder that occurs mainly with MTX use. This disorder has been associated with Epstein-Barr virus (EBV) infection. In 2017, the WHO newly defined the disease concept of EBV-positive mucocutaneous ulcer (EBV-MCU) as a good-prognosis EBV-related disease. Here, we report 10 cases of MTX-LPD or EBV-MCU in the oral mucosa. This retrospective, observational study was conducted with MTX-LPD or EBV-MCU in the oral mucosa patients who visited us during the nine year period from 2012 to 2021. We gathered the basic information, underlying disease, histopathological evaluation, treatment and prognosis for the subjects. All were being treated with MTX for rheumatoid arthritis. EBV infection was positive in all cases by immunohistochemistry. A complete or partial response was obtained in all cases with the withdrawal of MTX. Our results suggests that the most common risk factor for developing EBV-MCU is the use of immunosuppressive drugs. The most common site of onset is the oral mucosa, which may be attributed to the mode of EBV infection and the high incidence of chronic irritation of the oral mucosa. A small number of patients had been diagnosed with MTX-LPD, but we consider that these cases were EBV-MCU based on our study. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 9 6 2021 A case of langerhans cell histiocytosis of the mandible that spontaneously regressed after biopsy in a child e04321 EN Kisho Ono Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tatsuo Okui Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Kunisada Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kyoichi Obata Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masanori Masui Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shoji Ryumon Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Sasaki Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine In younger patients of LCH, we should consider that the effectiveness of follow-up without aggressive treatment for SS-type LCH in the oral and maxillofacial bone. However, there are very rare case in which an SS-type LCH recurred after showing a healing tendency. Regular follow-up must be performed even after healing. No potential conflict of interest relevant to this article was reported.

Elsevier Sci Ltd Acta Medica Okayama 2210-2612 82 2021 A case of intramandibular neurofibroma resembling a radicular cyst in a neurofibromatosis type 1 patient 105883 EN Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Shimane University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences INTRODUCTION: Neurofibromatosis is a disease that causes various abnormalities such as neurofibroma, mainly in the skin and nerves. The common sites in the oral cavity are the palate, gingiva, tongue, buccal mucosa, and lips but, occurrence in the mandible is rare. PRESENTATION OF CASE: A 26-year-old woman was referred to our clinic because of percussion pain. Radiographic findings showed a radiolucent area. The patient was clinically diagnosed with a radicular cyst by a previous doctor. Multiple cafe-au-lait spots were found disseminated on her body, and she had already been prenatally diagnosed with neurofibromatosis type 1 (NF1). We performed a biopsy and suggested a neurofibroma. Tumor extirpation was performed under general anesthesia. The histopathological diagnosis showed a neurofibroma. CLINICAL DISCUSSION AND CONCLUSION: NF1 is a systemic nevus that causes abnormalities in melanocytes and Schwann cells, and various lesions appear, but intramandibular lesions are extremely rare. Diagnosis of NF1 and radicular cysts in the mandible is difficult due to their image resemblance. However, it should be kept in mind if the underlying disease is NF1. In our case, it was easy to detach and may have originated from small peripheral nerve endings in the mandible. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 6 2021 Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment 1044 EN Shoko Yoshida Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yurika Murase Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Shimane University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 12 2021 The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation 674366 EN Kyosuke Sakaida Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Periodontics and Endodontics, Okayama University Hospital Masaaki Nakayama Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Saki Nakagawa Department of Periodontics and Endodontics, Okayama University Hospital Hidefumi Sako Department of Periodontics and Endodontics, Okayama University Hospital Chiaki Kamei Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Yamamoto Department of Periodontics and Endodontics, Okayama University Hospital Hiroya Kobayashi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoki Ishii Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Mitsuaki Ono Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Yamashiro Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan, 3Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 22121374 26 2021 The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone 100330 EN Tatsuo Okui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masahiro Hiasa Department of Biomaterials and Bioengineerings, University of Tokushima Graduate School of Dentistry Shoji Ryumon Kisho Ono Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yuki Kunisada Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akira Sasaki Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science G. David Roodman Department of Medicine, Hematology Oncology, Indiana University School of Medicine Fletcher A. White Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute Toshiyuki Yoneda Department of Cellular and Molecular Biochemistry, Osaka University Graduate School of Dentistry Bone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0021-8782 238 6 2021 Expression of SARS‐CoV‐2 entry factors in human oral tissue 1341 1354 EN Yoshihiko Sawa Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Junro Yamashita Center for Regenerative Medicine, Fukuoka Dental College Tetsuro Ikebe Department of Oral and Maxillofacial Surgery, Fukuoka Dental College Hiroyuki Harada Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University The distribution of cells expressing SARS‐CoV‐2 entry factor angiotensin‐converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. The investigation was conducted with normal flesh tissue and paraffin‐embedded specimens. The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non‐keratinized stratified squamous epithelia of the lip and cheek. It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. Antibodies’ reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands. The SARS‐CoV‐2 may transiently attach to the oral mucosa and the minor salivary glands which are present under all of the oral mucosa. The oral cavity can be considered an important organ for SARS‐CoV‐2 attachment and may provide a preventive medical avenue to guard against COVID‐19 by preventing saliva from scattering. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Acta Medica Okayama 2001-3078 9 1 2020 Triple knockdown of CDC37, HSP90‐alpha and HSP90‐beta diminishes extracellular vesicles‐driven malignancy events and macrophage M2 polarization in oral cancer 1769373 EN Kisho Ono Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Manh Tien Tran Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eman A. Taha Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yanyin Lu Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University May Wathone Oo Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuka Okusha Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Hospital Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken-Ichi Kozaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Hospital Kuniaki Okamoto Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones – CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial‐mesenchymal transition (EMT), although their contribution to EVs‐mediated cell–cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer‐derived EVs (MEV) were enriched with HSP90α HSP90β and cancer‐initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV‐driven malignancy events. In metastatic oral cancer patient‐derived tumours, HSP90β was significantly accumulated in infiltrating tumour‐associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90‐enriched MEV‐induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA‐mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV‐driven malignancy events in the tumour microenvironment. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1021-335X 44 6 2020 High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer 2547 2558 EN Tomoya Nakamura Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Tatsuo Okui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuaki Hasegawa Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shoji Ryumon Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kisho Ono Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yuki Kunisada Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kyoichi Obata Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masanori Masui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Akira Sasaki Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC‑BP and the pERK1/2 expression in DRG. It was also observed that HNC‑derived HMGB1 increased the expression of the acid‑sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC‑BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC‑BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 9 1 2020 Surgical resection of a giant peripheral ossifying fibroma in mouth floor managed with fiberscopic intubation 180 184 EN Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuaki Hasegawa Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tracheal intubation for general anesthesia can sometimes be difficult in patients with a large mass in the mouth floor. Preoperative evaluation of the patient's airway is most important when treating large oral disease. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0006-291X 531 3 2020 High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4 422 430 EN Yumi Sakamoto Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tatsuo Okui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiyuki Yoneda Department of Cellular and Molecular Biochemistry, Osaka University Graduate School of Dentistry Shoji Ryumon Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tomoya Nakamura Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masanori Masui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kisho Ono Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kyoichi Obata Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Akira Sasaki Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 8 12 2020 A case of oral cancer with delayed occipital lymph node metastasis: Case report 2469 2475 EN Kisho Ono Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Norie Yoshioka Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masanori Masui Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kyoichi Obata Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Kunisada Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tatsuo Okui Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hotaka Kawai Department of Oral Pathology and Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Sasaki Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Consideration of unexpected metastasis in patients who have undergone neck dissection with advanced tumors must be anticipated with careful follow-up. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 1687-9627 2020 2020 Methotrexate-Associated Lymphoproliferative Disorder Developed Ectopically in the Maxillary Gingiva and Bilateral Lungs 4814519 EN Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Koji Kishimoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences A 58-year-old Japanese woman complained of a painful right maxillary premolar gingiva and ulcer. The patient had RA and had been treated with several immunosuppressive drugs such as methotrexate. Head and neck CT indicated no obvious bone destruction with maxillary. However, chest CT indicated the presence of nodular mass of the bilateral lungs. FDG-PET/CT indicated the presence of increased uptake in both lesions. On immunohistochemistry, atypical large-sized lymphocytes were positive for CD20 and EBER-ISH and negative for CD3, CD5, and CD10; the Ki-67 labeling index was high, the histopathological diagnosis was EBV-positive DLBCL, and the clinical diagnosis was MTX-LPD. The patient's treatment with MTX was then discontinued; we removed the alveolar bone which necrosed after 5 weeks. The lesion and the nodular mass at the bilateral lungs had completely disappeared after 7 weeks. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 2042-8812 3 2020 Surgical resection for advanced bisphosphonate-related osteonecrosis of the jaw associated with fibrous dysplasia: a case report rjaa061 EN Yurika Murase Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Koji Kishimoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Shoko Yoshida Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Koichi Kadoya Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1567-5769 83 2020 The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1 106429 EN Saki Nakagawa Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Omori Department of Periodontics and Endodontics, Okayama University Hospital Masaaki Nakayama Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mandai Department of Medical Technology, School of Health Science, Gifu University of Medical Science Satoshi Yamamoto Department of Periodontics and Endodontics, Okayama University Hospital Hiroya Kobayashi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit Hidefumi Sako Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyosuke Sakaida Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Yoshimura ivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Satoki Ishii Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Soichiro Ibaragi Department of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimito Hirai Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Yamashiro Department of Periodontics and Endodontics, Okayama University Hospital Tadashi Yamamoto Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1019-6439 54 1 2018 Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma. 283 294 EN Rieko Shimizu Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Kuwajima Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Kodama Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Nishioka Department of Oral Diagnosis, Tohoku University Graduate School of Dentistry Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kuniaki Okamoto Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance. No potential conflict of interest relevant to this article was reported.

International Society for Contemporary Medical Research Acta Medica Okayama 2454-7379 4 2 2017 Endoscope-Assisted Transoral Reduction and Internal Fixation of a Mandibular Subcondylar Fracture with a 3D - Shaped Plate 574 576 EN Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Kishimoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: Disadvantages of open reduction of subcondylar fractures include visible facial scars and potential facial nerve damage. Endoscope-assisted procedures have solved these problems, however the anatomical adaptation of osteosynthesis plates to the fractured area is difficult in the limited surgical field. Three-dimensional pre-shaped plates specialized for subcondylar fractures recently became available. They are originally not for endoscope-assisted procedures but it may be useful for endoscopic approach because they are very small and pre-shaped. Case report: This paper presents a case of 43-year-old male patient with subcondylar fracture. The treatment provided was open reduction and internal fixation of a subcondylar fracture with three-dimensional pre-shaped plates via transoral approach under endoscopic visualization. Conclusion: The paper highlights contemporary management of subcondylar fracture to avoid complications associated with open reduction and restore the post-operative functions. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1019-6439 51 2 2017 Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma 625 632 EN Hiroyuki Takada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanori Eguchi Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Masui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ayaka Morisawa Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiyofumi Takabatake Departments of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hotaka Kawai Departments of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nur Mohammad Monsur Hassan School of Dentistry and Health Sciences, Charles Sturt University Tsuyoshi Shimo Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Guo-Fu Hu Molecular Oncology Research Institute, Tufts Medical Center Hitoshi Nagatsuka Departments of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 4 2016 Autologous Blood Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation 291 294 EN Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Shimo Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Clinical Study Protocols 10.18926/AMO/54506 Temporomandibular joint (TMJ) dislocation can occur during daily activities and negatively affect a patientʼs quality of life. Although both nonsurgical and surgical techniques have been used to treat recurrent TMJ dislocation, the former is not always successful and the latter, although having a high success rate, is invasive and requires hospitalization. Recently, autologous blood injection has been used to treat recurrent TMJ dislocation. However, this technique is not yet widely used in clinical practice. We designed this study to obtain further information as to efficacy, safety and stability of autologous blood injection for recurrent TMJ dislocation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2007 骨破壊部における癌細胞のMMP-13の発現制御機構に関する研究 EN Soichiro Ibaragi No potential conflict of interest relevant to this article was reported.