研究者詳細 - 伊原木　聰一郎

論文 - 伊原木　聰一郎

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Angiogenin-induced Osteoclastogenesis Mediates Bone Destruction in Oral Squamous Carcinoma

KASUMI AOKI, NANA YOSHITANI, NAITO KURIO, NORIE YOSHIOKA, JUMPEI TERAMACHI, MIKA IKEGAME, HIROHIKO OKAMURA, SOICHIRO IBARAGI

Anticancer Research 45 ( 3 ) 1025 - 1033 2025年3月

The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts

Izumi Yamamoto, Kazuyo Igawa, Natsuko Kondo, Yoshinori Sakurai, Atsushi Fujimura, Kiyofumi Takabatake, Peng Huang, Hiroyuki Michiue, Soichiro IBARAGI, DDS, PhD, FIBCSOMS-ONC, Kenji Izumi

International Journal of Translational Medicine 2025年3月

Evidence-Based Anatomical Terminology in Dentistry Developed by a Consortium of Experts. 国際誌

Joe Iwanaga, Sergey L Kabak, Puhan He, Yusuke Hamada, Shogo Kikuta, Yohei Takeshita, Rarinthorn Samrid, Thewarid Berkban, Norio Kitagawa, Junichiro Wada, Taku Toriumi, Yuki Matsushita, Soichiro Ibaragi, Mi-Sun Hur, Hee-Jin Kim

Clinical anatomy (New York, N.Y.) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

This article aimed to develop evidence-based anatomical terminology in dentistry agreed upon by experts in multiple fields and ultimately to bridge anatomy and clinical dentistry. A comprehensive list of dental anatomical terminology was detailed in table format, and specific terms of interest were highlighted with their respective literature review. The presence of teeth is a unique feature of the oral cavity where dental professionals work. Dentistry is a highly specialized field focusing on preserving the health of dentition and its supporting and surrounding structures. Thus, "teeth" and "mouth" related anatomical terms must be very specialized for dentistry. Many of the terms highlighted were clinical dental or alveolar-related terms that were not clearly established in the general anatomical terminology. The authors hope the evidence-based anatomical terminology in dentistry developed by a consortium of experts will be generally accepted worldwide and ultimately bridge the fields of anatomy and clinical dentistry.

DOI： 10.1002/ca.24260

The trochlea for the intermediate tendon of the digastric muscle: a review. 国際誌

Xander du Plooy, Yuki Kunisada, Juan J Cardona, Yoko Tabira, Kathleen Carol Bubb, Kazzara Raeburn, Soichiro Ibaragi, Joe Iwanaga, R Shane Tubbs

Anatomy & cell biology 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.5115/acb.24.178

Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome. 国際誌

Hitomi Ono-Minagi, Tsutomu Nohno, Kiyofumi Takabatake, Takehiro Tanaka, Takayuki Katsuyama, Kohta Miyawaki, Jun Wada, Soichiro Ibaragi, Seiji Iida, Tadashi Yoshino, Hitoshi Nagatsuka, Takayoshi Sakai, Hideyo Ohuchi

BMC oral health 24 ( 1 ) 1099 - 1099 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1186/s12903-024-04869-4

Does the anatomy around the pterygomaxillary suture contribute to the risk of bad fractures in Le Fort I osteotomy? 査読国際誌

Kyoichi Obata, Hideka Kanemoto, Koki Umemori, Kisho Ono, Norie Yoshioka, Akiyoshi Nishiyama, Joe Iwanaga, Soichiro Ibaragi

Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery 52 ( 11 ) 1193 - 1198 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Le Fort I (LF1) osteotomy, a common orthognathic procedure for the maxilla aimed at achieving maxillary mobility by separating the pterygomaxillary suture, poses a risk of bad fracture that may lead to complications and inadequate mobility. Our study analyzed two- and three-dimensional computed tomography images to identify the anatomical factors associated with bad fractures due to an LF1 osteotomy. Point 'a' is where the lateral pterygomaxillary suture on the axial image aligns with the zygomatic alveolar line near the line used for an LF1 osteotomy, with the base line connecting the bilateral 'a' points.Two risk factors were identified on the pterygoid side: (i) when the distance from point 'a' to the intersection of the base line and the medial pterygoid plate was <6.0 mm; and (ii) when the distance from the piriform aperture margin to the base line was <44.78 mm. Six risk factors were identified on the maxillary side, including the distance between the most anterior and most lateral points of the internal surface of the maxillary sinus being <31.9 mm. Our analyses revealed that fractures that occur during pterygomaxillary suture separation in an LF1 osteotomy are influenced by anatomical factors of the maxilla and pterygoid process, which form the pterygomaxillary suture.

DOI： 10.1016/j.jcms.2024.02.018

Lingual nerve revisited-A comprehensive review Part II: Surgery and radiology. 査読国際誌

Kisho Ono, Takashi Nishioka, Kyoichi Obata, Yohei Takeshita, Chista Irani, Yuki Kunisada, Norie Yoshioka, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Clinical anatomy (New York, N.Y.) 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal nerve, arising in the infratemporal fossa. It provides sensory fibers to the mucous membranes of the floor of the mouth, the lingual gingiva, and the anterior two-thirds of the tongue. Although the LN should rarely be encountered during routine and basic oral surgical procedures in daily dental practice, its anatomical location occasionally poses the risk of iatrogenic injury. The purpose of this section is to consider this potential LN injury risk and to educate readers about the anatomy of this nerve and how to treat it.

DOI： 10.1002/ca.24211

Lingual nerve revisited-A comprehensive review Part I: Anatomy and variations. 査読国際誌

Norio Kitagawa, Keiko Fukino, Chista Irani, Yushi Abe, Yuki Kunisada, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Clinical anatomy (New York, N.Y.) 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal. It primarily carries sensory fibers from the lingual gingiva, mucous membranes of the floor of the mouth, sublingual gland, and the anterior two-thirds of the tongue. Recent studies have explored and reclassified the five branches of the LN as branches to the isthmus of the fauces, lingual branches, sublingual nerves, posterior branch to the submandibular ganglion, and branches to the sublingual ganglion. The knowledge of the LN anatomy and its variants is clinically relevant to avoid its injury during oral procedures. The objective of this paper is to review the literature on the LN and to describe the anatomy, its course, and its functions.

DOI： 10.1002/ca.24210

Spontaneous Eruption of Permanent Teeth That Had Eruption Disturbances After Extirpation of Odontomas: A Report of Two Cases 査読国際誌

Yuki Kunisada, Norie Yoshioka, Kyoichi Obata, Koki Umemori, Soichiro Ibaragi

Cureus 16 ( 5 ) e61460 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Odontomas, often found adjacent to impacted teeth, are tumors of abnormal tissue morphology arising from the tooth germ and are usually asymptomatic. They are often found by accident on X-ray images, and the eruption of permanent teeth is often caused by odontomas. In most cases, the tooth is extracted with the permanent tooth or orthodontic treatment is performed after extraction. However, the criteria are not clear. We encountered two cases of dental eruption in which permanent teeth, which originally seemed to be suitable for orthodontic treatment, spontaneously erupted after odontoma removal. It is necessary to examine the indications and timing of tooth extraction.

DOI： 10.7759/cureus.61460

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system. 査読国際誌

Tatsuo Ogawa, Kisho Ono, Shoji Ryumon, Hotaka Kawai, Tomoya Nakamura, Koki Umemori, Kunihiro Yoshida, Hideka Kanemoto, Kyoichi Obata, Norie Yoshioka, Tatsuo Okui, Kuniaki Okamoto, Hitoshi Nagatsuka, Soichiro Ibaragi

Head & neck 46 ( 3 ) 636 - 650 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC. METHODS: We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression. RESULTS: The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect. CONCLUSIONS: EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.

DOI： 10.1002/hed.27620

Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells. 査読国際誌

Taira Hirose, Yuki Kunisada, Koichi Kadoya, Hiroki Mandai, Yumi Sakamoto, Kyoichi Obata, Kisho Ono, Hiroaki Takakura, Kazuhiro Omori, Shogo Takashiba, Seiji Suga, Soichiro Ibaragi

Cancer genomics & proteomics 21 ( 5 ) 464 - 473 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.21873/cgp.20464

Radiological assessment of the dissection area in supraomohyoid neck dissection 査読国際誌

Yohei Takeshita, Joe Iwanaga, Yoshio Ohyama, Soichiro Ibaragi, Yuki Matsushita, R. Shane Tubbs, Norio Kitagawa, Toshiyuki Kawazu, Miki Hisatomi, Shunsuke Okada, Mamiko Fujikura, Junichi Asaumi

Surgical and Radiologic Anatomy 46 ( 10 ) 1643 - 1652 2024年

A Rare Case of Multiple Myeloma Identified Following the Diagnosis of Amyloidosis of the Tongue. 国際誌

Hideka Kanemoto, Kyoichi Obata, Koichi Kadoya, Kisho Ono, Hotaka Kawai, Yuki Kunisada, Mayumi Yao, Soichiro Ibaragi

Case reports in dentistry 2024 8836103 - 8836103 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

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 (~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.

DOI： 10.1155/2024/8836103

Rab11 suppresses head and neck carcinoma by regulating EGFR and EpCAM exosome secretion. 査読国際誌

Kunihiro Yoshida, Kaung Htike, Takanori Eguchi, Hotaka Kawai, Htoo Shwe Eain, Manh Tien Tran, Chiharu Sogawa, Koki Umemori, Tatsuo Ogawa, Hideka Kanemoto, Kisho Ono, Hitoshi Nagatsuka, Akira Sasaki, Soichiro Ibaragi, Kuniaki Okamoto

Journal of oral biosciences 66 ( 1 ) 205 - 216 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Rab11(Rab11a and Rab11b) localizes primarily along recycling endosomes in cells and is involved in various intracellular trafficking processes, including membrane receptor recycling and secretion of exosomes or small extracellular vesicles (EVs). Although Rab11 is closely associated with the progression and metastasis of various cancer types, little is known about Rab11' role in head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the roles of Rab11a and Rab11b in HNSCC. METHODS: The clinical significance of Rab11 expression in HNSCC was investigated using a public database and tissue microarray analysis. Stable cell lines with loss and gain of Rab11a or Rab11b were originally established to investigate their roles in the proliferative, migratory, and invasive capabilities of HNSCC cells. RESULTS: Database analysis revealed a significant association between Rab11b mRNA expression and a favorable patient survival rate in HNSCC. Tissue microarray analysis revealed that Rab11b expression was the highest in normal tissues and gradually decreased across the stages of HNSCC progression. Overexpression of Rab11a or Rab11b resulted in a decrease in epidermal growth factor receptor (EGFR), Epithelial cell adhesion molecule (EpCAM) exosome secretion, and the migratory and invasive potential of HNSCC cells. The knockdown of Rab11a or Rab11b increased EpCAM/CD9 exosome secretion in addition to the migratory and invasive potential of HNSCC cells. CONCLUSIONS: Rab11 suppresses HNSCC by regulating EGFR recycling and EpCAM exosome secretion in HNSCC cells. Our results indicate that Rab11b is a superior prognostic indicator of HNSCC and holds promise for developing novel therapeutic strategies.

DOI： 10.1016/j.job.2023.11.007

Mylohyoid Muscle: Current Understanding for Clinical Management Part II: Clinical Anatomy, Radiology, and Surgical/Clinical Relevance. 査読国際誌

Kyoichi Obata, Norio Kitagawa, Kisho Ono, Hideka Kanemoto, Keiko Fukino, Yohei Takeshita, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

The Journal of craniofacial surgery 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The mylohyoid is one of the suprahyoid muscles along with the geniohyoid, digastric, and stylohyoid muscles that lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part II, the radiology and clinical/surgical importance of the mylohyoid muscle will be discussed.

DOI： 10.1097/SCS.0000000000009797

Mylohyoid Muscle: Current Understanding for Clinical Management-Part I: Anatomy and Embryology. 査読国際誌

Kyoichi Obata, Norio Kitagawa, Kisho Ono, Hideka Kanemoto, Keiko Fukino, Yohei Takeshita, Soichiro Ibaragi, Richard S Tubbs, Joe Iwanaga

The Journal of craniofacial surgery 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The mylohyoid is one of the suprahyoid muscles, along with the geniohyoid, digastric, and stylohyoid muscles. It lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part I, the anatomy and embryology of the mylohyoid muscle will be reviewed in preparation for the clinical discussion in Part II.

DOI： 10.1097/SCS.0000000000009812

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. 査読国際誌

Yuki Shinoda-Ito, Anna Hirai, Kazuhiro Omori, Hidetaka Ideguchi, Hideki Yamamoto, Fumino Kato, Kyoichi Obata, Tatsuo Ogawa, Keisuke Nakano, Takato Nakadoi, Eri Katsuyama, Soichiro Ibaragi, Tadashi Yamamoto, Hitoshi Nagatsuka, Akira Hirasawa, Shogo Takashiba

BMC oral health 23 ( 1 ) 843 - 843 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1186/s12903-023-03586-8

Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma. 査読国際誌

Hideka Kanemoto, Kyoichi Obata, Koki Umemori, Kazuaki Hasegawa, Sawako Ono, Kisho Ono, Hirokazu Yutori, Soichiro Ibaragi

Anticancer research 43 ( 11 ) 4993 - 5001 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.21873/anticanres.16698

Preservation of the Nerve to the Mylohyoid Muscle During Submental Island Flaps: An Anatomic Feasibility Study for Facial Nerve Reanimation Procedures. 査読国際誌

Kisho Ono, Soichiro Ibaragi, Kyoichi Obata, Tatsuo Okui, Norio Kitagawa, R Shane Tubbs, Joe Iwanaga

The Journal of craniofacial surgery 34 ( 7 ) 2201 - 2205 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The submental island flap is an axial pattern pedicle flap widely used in head and neck surgery because of its ease and success. Indications of the submental island flap range from reconstruction for the malignant tumor resection to loss of temporal bone and facial skin due to trauma. Whereas, intraoperative facial nerve injury is not uncommon. We verified whether it was possible to localize the nerve to the mylohyoid muscle and reanimate the facial nerve during submental island flap procedures by preserving the mylohyoid muscle using human fresh cadaveric specimens. Six cadaveric heads were dissected and the position of the nerve to the mylohyoid muscle identified to the mylohyoid triangle documented. We identified the nerve to the mylohyoid muscle on all sides within the mylohyoid triangle and were able to separate the nerve from the submental island flap completely. Our results suggest that facial nerve reanimation using the nerve to the mylohyoid muscle can be used while reconstructing with a submental island flap in cases of intraoperative facial nerve injury.

DOI： 10.1097/SCS.0000000000009589

顔面軟部組織に発生したランゲルハンス細胞組織球症の1例査読

増井正典, 吉岡徳枝, 伊原木聰一郎, 小野喜章, 長塚仁, 佐々木朗

日本口腔外科学会雑誌 69 ( 6 ) 298 - 303 2023年6月

EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma. 査読国際誌

Koki Umemori, Kisho Ono, Takanori Eguchi, Hotaka Kawai, Tomoya Nakamura, Tatsuo Ogawa, Kunihiro Yoshida, Hideka Kanemoto, Kohei Sato, Kyoichi Obata, Shoji Ryumon, Hirokazu Yutori, Naoki Katase, Tatsuo Okui, Hitoshi Nagatsuka, Soichiro Ibaragi

Oral oncology 142 106433 - 106433 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1016/j.oraloncology.2023.106433

The notch of the mandible: what do different fields call it? 査読国際誌

Norio Kitagawa, Keiko Fukino, Yuki Matsushita, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Anatomy & cell biology 56 ( 3 ) 308 - 312 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The bony notch on the inferior border of the mandible, anterior to the attachment of the masseter muscle, where the facial vessels commonly pass, has been called different names in the literature, e.g., premasseteric notch, antegonial notch, and notch for the facial vessels. Interestingly, various disciplines have leaned toward different names for this notch. Therefore, to aid in consistent communication among professionals, the present study aimed to analyze usage of these varied terms and make recommendations for the best terminology. Based on the adjacent anatomical structures used to name this notch, three groups were analyzed in this study, a group using masseter in the term, a group using gonion in the term, and a group using facial vessels in the term. A literature search found that the group using gonion in the term was found most in the literature. The orthodontics field used gonion in the term the most (29.0%: 31/107) followed by the oral and maxillofacial surgery field (14.0%: 15/107), the plastic surgery field (4.7%: 5/107), and the anatomy field (3.7%: 4/107). The dental field used gonion in this term the most (43.9%: 47/107) and the medical field used facial vessels in the term the most (33.3%: 6/18). Based on these results, the use of gonial terms for this notch seems to be preferred.

DOI： 10.5115/acb.23.022

The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model 査読国際誌

Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Journal of Fungi 9 ( 3 ) 314 - 314 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

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.

DOI： 10.3390/jof9030314

Lactate secreted via MCT4 from bone‑colonizing breast cancer excites sensory neurons via GPR81. 査読国際誌

Tatsuo Okui, Masahiro Hiasa, Kazuaki Hasegawa, Tomoya Nakamura, Kisho Ono, Soichiro Ibaragi, Takahiro Kanno, Akira Sasaki, Toshiyuki Yoneda

International journal of oncology 62 ( 3 ) 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Breast cancer (BC) bone metastasis causes bone pain (BP), which detrimentally damages the quality of life and outcome of patients with BC. However, the mechanism of BC‑BP is poorly understood, and effective treatments are limited. The present study demonstrated a novel mechanism of BC‑BP using a mouse model of bone pain, in which mouse (EO771) and human (MDA‑MB‑231) BC cells were injected in the bone marrow cavity of tibiae. Western blot analysis using sensory nerves, in vivo assessment of cancer pain and in vitro calcium flux analysis were performed. These mice developed progressive BC‑BP in tibiae in conjunction with an upregulation of phosphorylated pERK1/2 and cAMP‑response element‑binding protein (pCREB), which are molecular indicators of neuron excitation, in the dorsal root ganglia (DRG) of sensory nerves. Importantly, mice injected with BC cells, in which the expression of the lactic acid transporter monocarboxylate transporter 4 (MCT4) was silenced, exhibited decreased BC‑BP with downregulated expression of pERK1/2 and pCREB in the DRG and reduced circulating levels of lactate compared with mice injected with parental BC cells. Further, silencing of the cell‑surface orphan receptor for lactate, G protein‑coupled receptor 81 (GPR81), in the F11 sensory neuron cells decreased lactate‑promoted upregulation of pERK1/2 and Ca2+ influx, suggesting that the sensory neuron excitation was inhibited. These results suggested that lactate released from BC cells via MCT4 induced BC‑BP through the activation of GPR81 of sensory neurons. In conclusion, the activation of GPR81 of sensory neurons by lactate released via MCT4 from BC was demonstrated to contribute to the induction of BC‑BP, and disruption of the interactions among lactate, MCT4 and GPR81 may be a novel approach to control BC‑BP.

DOI： 10.3892/ijo.2023.5487

Lingual nerve impairment/injury after retrieval of the displaced mandibular third molar into the floor of the mouth. 査読国際誌

Joe Iwanaga, Tomotaka Kato, Kisho Ono, R Shane Tubbs, Soichiro Ibaragi

The British journal of oral & maxillofacial surgery 61 ( 3 ) 193 - 197 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Retrieval of the displaced mandibular third molar in the floor of the mouth is challenging as the lingual nerve is always at risk of injury. However, there are no available data to show the incidence of the injury caused by the retrieval. The goal of this review article is to provide the incidence of the iatrogenic lingual nerve impairment/injury caused by the retrieval based on the review of the existing literature. The retrieval cases were collected with the search words below using PubMed, Google Scholar, and CENTRAL Cochrane Library database on October 6, 2021. A total of 38 cases of lingual nerve impairment/injury in 25 studies were eligible and reviewed. Temporary lingual nerve impairment/injury due to retrieval was found in six cases (15.8%) and all recovered between three to six months after retrieval. General anaesthesia and local anaesthesia were used for retrieval in three cases each. The tooth was retrieved using a lingual mucoperiosteal flap in all six cases. The permanent iatrogenic lingual nerve impairment/injury due to retrieval of the displaced mandibular third molar is considered extremely rare as long as the appropriate surgical approach is chosen based on surgeons' clinical experience and anatomical knowledge.

DOI： 10.1016/j.bjoms.2023.01.002

Anatomical Study of the Communication Between the Mental Nerve and Marginal Mandibular Branch of the Facial Nerve 査読国際誌

Joe Iwanaga, Naotaka Kishimoto, Soichiro Ibaragi, Juan J Cardona, Arada Chaiyamoon, Mi-Sun Hur, Yoshiaki Nakamura, Jingo Kusukawa, R. Shane Tubbs

Cureus 15 ( 1 ) e33733 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cureus, Inc.

Background Trigeminal-facial nerve communications have been recognized for over 100 years. More specifically, the mental nerve (MN) and marginal mandibular branch of the facial nerve (MMb) communication have been studied but the termination of these branches remains unclear. Therefore, we aim to classify the anatomical communication between the MN and MMb by its course. Methods Sixty sides from thirty adult cadaveric heads were dissected. The communicating branches were dissected and observed anatomically and histologically. Results Communication between the MN and MMb was found on all sides. Based on the course, the communication was classified into two types, superior and anterior. For the superior type, a small branch of the MN and MMb join and travel superiorly to reach the lower lip area. The communication was observed at the level of the mental foramen or above it. For the anterior type, a small branch of the MN and MMb join and travel anteriorly to reach the chin area. The termination was either in the subcutaneous tissue of the chin or in the mentalis. This communication was observed below the mental foramen. Histological observation revealed that these communications contained two or more perineuria. Conclusions Although the function of such neural communications is still unclear, this study helps better understand the anatomical variants of these unions and provides a novel classification system.

DOI： 10.7759/cureus.33733

舌扁平上皮癌と悪性リンパ腫の同時性重複がんに対し集学的な治療を行った1例

金本栄華, 小畑協一, 竜門省二, 岸本晃治, 伊原木聰一郎, 佐々木朗

日本口腔外科学会雑誌 69 ( 1 ) 15 - 21 2023年1月

含歯性嚢胞摘出後の顎骨欠損に起因する歯列不正に対し骨移植とともに矯正治療を行った1症例

橋本真奈, 田中敦子, 吉田祥子, 伊原木聰一郎, 上岡寛

岡山歯学会雑誌 41 ( 2 ) 35 - 42 2022年12月

What is a superior labial frenulum? An anatomical and histological study. 査読国際誌

Joe Iwanaga, Puhan He, Keiko Fukino, Mi-Sun Hur, Hee-Jin Kim, Aya Han, Koichi Watanabe, Soichiro Ibaragi, Norio Kitagawa, R Shane Tubbs

Clinical anatomy (New York, N.Y.) 36 ( 1 ) 161 - 169 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Anatomy of the superior labial frenulum (SLF), at first glance, seems to be well established. However, existing studies on the SLF lack description of the incisivus labii superioris (ILS), which cannot be ignored when discussing the SLF. We believe that thorough understanding of the SLF necessitates the anatomical knowledge of the ILS. This study aimed to elucidate the anatomical relationship between the orbicularis oris (OO), ILS, and SLF. A total of twenty formalin fixed human cadaveric specimens were used for gross anatomical and/or histological observation. For histological observation, all specimens were stained with Masson-trichrome. The SLF was a mucosal fold between the gingival mucosa and alveolar mucosa with connective tissue deep to it. The connective tissue attached to the alveolar bone in the junction between the right and left ILS. Skeletal muscle fibers other than orbicularis oris was found in one specimen, which were considered the ILS. During a frenulectomy, removal of the connective tissue bundle is required to prevent recurrence of the high SLF insertion. This article is protected by copyright. All rights reserved.

DOI： 10.1002/ca.23973

Lip pleomorphic adenomas: case series and literature review 査読国際誌

Koki Umemori, Kisho Ono, Hideka Kanemoto, Kyoichi Obata, Hotaka Kawai, Tomoya Nakamura, Keisuke Nakano, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

Gland Surgery 11 ( 10 ) 1730 - 1740 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AME Publishing Company

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.

DOI： 10.21037/gs-22-308

Craniomaxillofacial Fibrous Dysplasia Improved Cosmetic and Occlusal Problem by Comprehensive Treatment: A Case Report and Review of Current Treatments. 査読国際誌

Kisho Ono, Norie Yoshioka, Yuki Kunisada, Tomoya Nakamura, Yuko Nakamura, Kyoichi Obata, Soichiro Ibaragi, Shogo Minagi, Akira Sasaki

Diagnostics (Basel, Switzerland) 12 ( 9 ) 2022年9月

記述言語：英語

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.

DOI： 10.3390/diagnostics12092146

Relationships between squamous cell carcinoma antigen and cytokeratin 19 fragment values and renal function in oral cancer patients 査読

K. Obata, H. Yutori, K. Yoshida, Y. Sakamoto, K. Ono, S. Ibaragi

International Journal of Oral and Maxillofacial Surgery 2022年9月

The Transoral Endoscope-Assisted Approach for Removal of a Dental Implant Displaced into the Maxillary Sinus: A Case Report and Review of the Literature. 査読国際誌

Yurika Murase, Shoko Yoshida, Koji Kishimoto, Rieko Shimizu, Soichiro Ibaragi, Akira Sasaki

Journal of maxillofacial and oral surgery 21 ( 2 ) 639 - 647 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: A dental implant displaced into the maxillary sinus can be removed transorally or transnasally. There is no report investigating any potential positional limitations by the transoral endoscope-assisted approach. The implant's location within the maxillary sinus was reviewed to clarify indications for this approach. Case report: A 36-year-old man was referred to us for removal of a dental implant displaced into the right maxillary sinus. The implant changed position preoperatively, but the transoral endoscope-assisted approach proved successful. Methods: A literature search through October 2020 was performed in PubMed for cases of implant removal from the maxillary sinus via transoral endoscope-assisted and transnasal endoscopic approaches. Results: Sixty-two prior cases were identified, 20 cases by the transoral endoscope-assisted approach and 43 cases by one or two transnasal endoscopic approaches, including one duplicate case. There were no cases in which the implant was not identified by the transoral endoscope-assisted approach, but two cases in which the implant had moved to an unfavorable location and was not identified by only the initial transnasal endoscopic approach. Conclusion: Clinicians can preferentially choose the transoral endoscope-assisted approach, considering the possibility of unfavorable repositioning of the displaced implant within the maxillary sinus.

DOI： 10.1007/s12663-022-01703-8

Clinical Anatomy Research Association in Oral and Maxillofacial Surgery. 査読国際誌

Joe Iwanaga, Yuki Matsushita, Koichi Watanabe, Ikuo Kageyama, R Shane Tubbs, Soichiro Ibaragi

The Journal of craniofacial surgery 33 ( 3 ) 942 - 944 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

ABSTRACT: Sufficient knowledge of anatomy is critical for oral and maxillofacial surgeons to provide the best treatment to their patients. The authors have recently established the "Clinical Anatomy Research Association in Oral and Maxillofacial Surgery." There is no doubt as to the benefits of collaboration between oral and maxillofacial surgeons/radiologists and anatomists. In this article, we share what was accomplished at the first annual online conference and discuss our mission for the future.

DOI： 10.1097/SCS.0000000000008053

Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival. 査読国際誌

Hailing Yang, Liang Yuan, Soichiro Ibaragi, Shuping Li, Robert Shapiro, Nil Vanli, Kevin A Goncalves, Wenhao Yu, Hiroko Kishikawa, Yuxiang Jiang, Alexander J Hu, Daniel Jay, Brent Cochran, Eric C Holland, Guo-Fu Hu

British journal of cancer 127 ( 3 ) 422 - 435 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Angiogenin is a multifunctional secreted ribonuclease that is upregulated in human cancers and downregulated or mutationally inactivated in neurodegenerative diseases. A role for angiogenin in glioblastoma was inferred from the inverse correlation of angiogenin expression with patient survival but had not been experimentally investigated. METHODS: Angiogenin knockout mice were generated and the effect of angiogenin deficiency on glioblastoma progression was examined. Angiogenin and plexin-B2 genes were knocked down in glioblastoma cells and the changes in cell proliferation, invasion and vascular association were examined. Monoclonal antibodies of angiogenin and small molecules were used to assess the therapeutic activity of the angiogenin-plexin-B2 pathway in both genetic and xenograft animal models. RESULTS: Deletion of Ang1 gene prolonged survival of PDGF-induced glioblastoma in mice in the Ink4a/Arf-/-:Pten-/- background, accompanied by decreased invasion, vascular association and proliferation. Angiogenin upregulated MMP9 and CD24 leading to enhanced invasion and vascular association. Inhibition of angiogenin or plexin-B2, either by shRNA, monoclonal antibody or small molecule inhibitor, decreases sphere formation of patient-derived glioma stem cells, reduces glioblastoma proliferation and invasion and inhibits glioblastoma growth in both genetic and xenograft animal models. CONCLUSIONS: Angiogenin and its receptor, plexin-B2, are a pair of novel regulators that mediate invasion, vascular association and proliferation of glioblastoma cells. Inhibitors of the angiogenin-plexin-B2 axis have therapeutic potential against glioblastoma.

DOI： 10.1038/s41416-022-01814-6

Cutaneous branch of the nerve to the mylohyoid muscle: Potential cause of postoperative sensory alteration in the submental area. 査読国際誌

Joe Iwanaga, Soichiro Ibaragi, Tatsuo Okui, Vasu Divi, Yoshio Ohyama, Koichi Watanabe, Jingo Kusukawa, R Shane Tubbs

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 243 151934 - 151934 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Previous studies suggest that the nerve to the mylohyoid muscle could have a cutaneous branch. However, its clinical relevance has rarely been discussed because there is insufficient evidence for it. Our aim in this study was to investigate the anatomy of the cutaneous branch of the nerve to the mylohyoid muscle and extend the discussion to surgical management. METHODS: Twenty sides from ten embalmed cadaveric heads were dissected to identify the cutaneous branch of the nerve to the mylohyoid muscle. The cutaneous branch was traced up to its termination. RESULTS: The cutaneous branch was observed in 90% and classified into types I and II. In type I, the terminal trunk reached the anterior belly of the digastric muscle. In type II there were two types of terminal trunks, superior and inferior branches, which were identified on all sides. The number of the terminal trunk was one in 23.1% (type I; 6/26) and two in 76.9% (type II; 20/26). The terminal points of the cutaneous branch were all located within a 3 cm × 2 cm rectangular segment in the center of the submental area. CONCLUSIONS: We propose a new dermatome including the nerve to the mylohyoid muscle in the center. Understanding the cutaneous branch of the nerve could help surgeons to prevent iatrogenic sensory loss of the submental area.

DOI： 10.1016/j.aanat.2022.151934

3D anatomy of the ostiomeatal complex: A challenging concept in dentistry. 査読国際誌

Joe Iwanaga, Yuki Matsushita, Soichiro Ibaragi, R Shane Tubbs

Journal of dental education 2022年3月

Subcutaneous Emphysema Related to Dental Treatment: A Case Series. 査読国際誌

Rieko Shimizu, Shintaro Sukegawa, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Ai Fujimura, Izumi Yamamoto, Soichiro Ibaragi, Akira Sasaki, Yoshihiko Furuki

Healthcare (Basel, Switzerland) 10 ( 2 ) 2022年2月

記述言語：英語

Cervicofacial subcutaneous emphysema (SE) is primarily caused by dental treatment introducing gas into the subcutaneous tissue. Air rapidly dissects into the subcutaneous tissue with face and neck swelling, leading to respiratory distress, patient discomfort, and chest pain. Computed tomography (CT) can detect spreading SE patterns. However, the true volume of SE and the degree of air changes in the body over time remain unknown. We evaluated the healing process of SE and the temporal changes in the volume of emphysema in three cases detected using our hospital's electronic health record systems based on inclusion and exclusion criteria over the past 10 years, with CT and three-dimensional (3D) images. The first case was a 46-year-old woman who presented with complaints of swelling from her right eyelid to the neck and clavicles, pain on swallowing, respiratory distress, and hoarseness. The second case was a 35-year-old man who presented with complaints of swelling over the face. The third case was a 36-year-old man who presented with complaints of swelling from the left cheek to the neck. CT revealed SE and pneumomediastinum in all cases. All the patients were administered an antibacterial drug. The CT and 3D images showed an improvement in emphysema 3 days after the onset, with more than half of the volume reduction in emphysema. This made it possible to evaluate the changes in the air content of SE. Observation with CT until the healing process of SE is completed is crucial, and 3D images also help evaluate changes over time.

DOI： 10.3390/healthcare10020290

An anatomical study of the blood supply to the mylohyoid muscle: the so-called "mylohyoid branch" of the inferior alveolar artery is an arterial anastomosis. 査読国際誌

Joe Iwanaga, Soichiro Ibaragi, Tatsuo Okui, Mi-Sun Hur, Ikuo Kageyama, R Shane Tubbs

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 240 151852 - 151852 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The aim of this study was to clarify the morphology of the mylohyoid branch of the inferior alveolar artery and the main blood supply to the mylohyoid muscle. METHODS: The maxillary artery (MA) and inferior alveolar artery (IAA) within the infratemporal fossa, the facial and submental arteries within the submandibular triangle, and the nerve to the mylohyoid muscle and related artery were dissected in twelve sides from embalmed cadaveric heads. The main blood supply to the extraoral (inferior) surface of the mylohyoid muscle was recorded. RESULTS: The mylohyoid branch of the inferior alveolar artery was an anastomosis of the descending branch of either the inferior alveolar or maxillary artery and the ascending branch of either the submental or facial artery. The anastomosis was classified into four types according to the origins of the arteries. The main blood supply to the extraoral surface of the mylohyoid muscle was the submental artery. CONCLUSIONS: The results of this study indicate that the mylohyoid branch of the IAA in human adults is an anastomosis of branches of the maxillary and facial arteries.

DOI： 10.1016/j.aanat.2021.151852

A narrative review and clinical anatomy of herpes zoster infection following COVID-19 vaccination. 査読国際誌

Joe Iwanaga, Hiroshi Fukuoka, Nobuko Fukuoka, Hirokazu Yutori, Soichiro Ibaragi, R Shane Tubbs

Clinical anatomy (New York, N.Y.) 35 ( 1 ) 45 - 51 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: In this review, cases of herpes zoster (HZ) infection following receipt of COVID-19 vaccines will be analyzed. We also present two cases of oral HZ following the COVID-19 vaccine and discuss this clinical anatomy. MATERIALS AND METHODS: A database search using PubMed was conducted in August 2021 and 20 articles were found to be eligible for review. Patient data and vaccine information were analyzed. In addition, two cases of oral HZ infection following the receipt of COVID-19 vaccines are presented. RESULTS: A total of 399 cases were identified. The affected dermatomes mimicked the regular distribution of HZ. For the dermatomes of the face, the various reports used different ways to describe the areas involved; CNV, CNV1, CNV2, CNV3, lower jaw, forehead, and under the eyebrow (CNV, 2 cases; CNV1, 4 cases; CNV2, 3 cases; and CNV3, 3 cases). Some patients who had a history of varicella zoster virus vaccination had HZ following the COVID-19 vaccination. Two patients with oral HZ following vaccination were found to have involvement of the greater palatine nerve. CONCLUSIONS: Vaccine-related HZ cases have been reported worldwide. Although many studies with a larger number of cases are ongoing, detailed information can be obtained from case reviews as reported herein.

DOI： 10.1002/ca.23790

What are the retromolar and bifid/trifid mandibular canals as seen on cone-beam computed tomography? Revisiting classic gross anatomy of the inferior alveolar nerve and correcting terminology. 国際誌

Joe Iwanaga, Yohei Takeshita, Yuki Matsushita, Mi-Sun Hur, Soichiro Ibaragi, R Shane Tubbs

Surgical and radiologic anatomy : SRA 44 ( 1 ) 147 - 156 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Since cone-beam computed tomography was developed, a number of radiological studies on the bifid mandibular canals (BMCs) and trifid mandibular canals (TMCs) have been reported. However, many of the suggested subtypes of the BMC described in the literature seem to be normal branches of the inferior alveolar nerve. This might be due to a lack of revisiting classic anatomical studies in the field of radiology. Therefore, such studies are revisited here. METHODS: A database search using PubMed and Google Scholar was conducted on BMC and TMC. Eighty-nine articles underwent full-text assessment. The reported three classifications of BMC and the six modified classifications were reviewed and compared to the intramandibular inferior alveolar nerve branches. RESULTS: Some subtypes of BMC and TMC simply represent normal inferior alveolar nerve branches, i.e., retromolar branch, molar branch (alveolar branch/dental branch), large mental branch, or communicating branch. Others such as Naitoh's type III BMC and forward canal might be a true BMC. CONCLUSION: We found that the bifid mandibular canal is an additional intramandibular canal running parallel to the mandibular canal with/without confluence with the main canal through comparison of classifications of BMC/TMC between the radiology and anatomy fields.

DOI： 10.1007/s00276-021-02862-y

Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer. 査読国際誌

Kisho Ono, Kohei Sato, Tomoya Nakamura, Yume Yoshida, Shogo Murata, Kunihiro Yoshida, Hideka Kanemoto, Koki Umemori, Hotaka Kawai, Kyoichi Obata, Shoji Ryumon, Kazuaki Hasegawa, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

International journal of medical sciences 19 ( 8 ) 1320 - 1333 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.7150/ijms.74109

Anatomical contribution of the orbicularis oculi to the zygomaticus major: An improved understanding of the smile with consideration for facial cosmetic procedures. 査読国際誌

Joe Iwanaga, Mi-Sun Hur, Shogo Kikuta, Soichiro Ibaragi, Koichi Watanabe, R Shane Tubbs

PloS one 17 ( 7 ) e0272060 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

The aim of the present study was to determine the contribution of the orbicularis oculi (OOc) to the zygomaticus major (Zmj) in connecting the orbital region to the corner of the mouth. The OOc and Zmj of 22 embalmed adult Korean cadavers were dissected in 44 hemifaces. The OOc fibers were traced to determine their contribution to the Zmj. Parts of the superficial bundle in the orbital region of the OOc extended directly or indirectly to the Zmj in 22.7% of the specimens. The anatomical contribution of the OOc to the Zmj was divided into three categories depending on whether the connection between them was direct or indirect: (1) superficial orbital OOc fibers extended directly to the Zmj in 6.8% of the specimens, (2) superficial orbital OOc fibers extended to the zygomaticus minor and their small portion joined to the upper fibers of the Zmj in 15.9% of the specimens, and (3) no connection was identified between the OOc and Zmj in 77.3% of the specimens. The results of this study provide further anatomical insight into the relationship between the OOc and zygomaticus muscle complex. This information could be helpful for elucidating the anatomy of smiling and treatment and surgery designs for balanced or ideal smiles.

DOI： 10.1371/journal.pone.0272060

Displacement of lower third molar into floor of mouth: a single institutional experience. 国際誌

Masanori Masui, Soichiro Ibaragi, Yohei Takeshita, Joe Iwanaga, Yuki Kunisada, Akira Sasaki

Oral and maxillofacial surgery 26 ( 3 ) 447 - 453 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1007/s10006-021-01012-3

A rare anatomical variation of the submental artery. 国際誌

Masanori Masui, Soichiro Ibaragi, Tatsuo Okui, R Shane Tubbs, Joe Iwanaga

Surgical and radiologic anatomy : SRA 43 ( 11 ) 1805 - 1808 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The submental artery usually runs anteriorly on the inferior surface of the mylohyoid muscle, giving branches to that muscle and to the anterior belly of the digastric muscle, finally supplying the submental skin. Branches of it often perforate the mylohyoid muscle and enter the sublingual space. During a routine anatomy dissection, we encountered a case in which the main trunk of the submental artery perforated the mylohyoid muscle, where the sublingual artery usually runs. No branches coursed anteriorly to supply the submental skin. To our knowledge, this submental artery variation has not been reported in the English literature. Any surgical procedure in the submandibular area, such as the axial pattern submental local flap, requires knowledge of such arterial variations.

DOI： 10.1007/s00276-021-02830-6

Extended crossing fibers of the mentalis muscle attaching to the contralateral mandible. 国際誌

Joe Iwanaga, Mi-Sun Hur, Shogo Kikuta, Soichiro Ibaragi, R Shane Tubbs

Anatomy & cell biology 54 ( 4 ) 522 - 524 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Fibers of the facial muscles occasionally extend, cross the midline, and connect to surrounding structures on the contralateral side, perhaps enabling the mouth to make more delicate movements and generate more facial expressions. This case report describes a variant in which the extended fibers of the mentalis crossed the midline and indicates the relationship of these fibers to the surrounding structures. Some of the deepest fibers of the mentalis descended inferomedially and crossed transversely just below the chin prominence to attach to the periosteum of the mandible on the contralateral side. The variation presented in this study shed light on the interactions of the mentalis with the surrounding muscles.

DOI： 10.5115/acb.21.127

Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma. 国際誌

Qiusheng Shan, Kiyofumi Takabatake, Haruka Omori, Hotaka Kawai, May Wathone Oo, Keisuke Nakano, Soichiro Ibaragi, Akira Sasaki, Hitoshi Nagatsuka

International journal of oncology 59 ( 3 ) 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The stromal cells in the tumor microenvironment (TME) can influence the progression of multiple types of cancer; however, data on oral squamous cell carcinoma (OSCC) are limited. In the present study, the effects of verrucous squamous cell carcinoma‑associated stromal cells (VSCC‑SCs), squamous cell carcinoma‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the tumor nest formation, proliferation, invasion and migration of HSC‑3 cells were examined in vitro using Giemsa staining, MTS, and Transwell (invasion and migration) assays, respectively. The results revealed that both the VSCC‑SCs and SCC‑SCs inhibited the tumor nest formation, and promoted the proliferation, invasion and migration of OSCC cells in vitro. Furthermore, the effects of VSCC‑SCs, SCC‑SCs and HDFs on the differentiation, proliferation, invasion and migration of OSCC cells in vivo were evaluated by hematoxylin and eosin staining, tartrate‑resistant acid phosphatase staining, immunohistochemistry and double‑fluorescent immunohistochemical staining, respectively. The results demonstrated that the VSCC‑SCs promoted the differentiation, proliferation, invasion and migration of OSCC cells, while the SCC‑SCs inhibited the differentiation, and promoted the proliferation, invasion and migration of OSCC cells in vivo. Finally, microarray data were used to predict genes in VSCC‑SCs and SCC‑SCs that may influence the progression of OSCC, and those with potential to influence the differential effects of VSCC‑SCs and SCC‑SCs on the differentiation of OSCC. It was found that C‑X‑C motif chemokine ligand (CXCL)8, mitogen‑activated protein kinase 3 (MAPK3), phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA), C-X-C motif chemokine ligand 1 (CXCL1) and C‑C motif chemokine ligand 2 (CCL2) may be involved in the crosstalk between VSCC‑SCs, SCC‑SCs and OSCC cells, which regulates the progression of OSCC. Intercellular adhesion molecule 1 (ICAM1), interleukin (IL)1B, Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), bone morphogenetic protein 4 (BMP4), insulin (INS) and nerve growth factor (NGF) may be responsible for the differential effects of VSCC‑SCs and SCC‑SCs on the differentiation of OSCC. On the whole, the present study demonstrates that both VSCC‑SCs and SCC‑SCs may promote the progression of OSCC, and SCC‑SCs were found to exert a more prominent promoting effect; this may represent a potential regulatory mechanism for the progression of OSCC.

DOI： 10.3892/ijo.2021.5252

The potential for facial artery injury during mandibular third molar extraction. An anatomical study using contrast-enhanced computed tomography. 国際誌

Yohei Takeshita, Soichiro Ibaragi, Hirokazu Yutori, Jingo Kusukawa, R Shane Tubbs, Toshiyuki Kawazu, Junichi Asaumi, Joe Iwanaga

Clinical anatomy (New York, N.Y.) 34 ( 8 ) 1215 - 1223 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The purpose of this study was to evaluate the risk of injury to the facial (FA) and related arteries during mandibular third molar (MTM) extraction using contrast-enhanced computed tomography (CE-CT). CE-CT images of the MTM region were retrospectively reviewed. The area of the MTM was equally divided into three zones in the coronal images from mesial to distal, that is, zone 1, zone 2, and zone 3. The FA, submental artery (SMA), and sublingual artery (SLA) were identified. The distance from the mandible to FA, SMA, and SLA and the diameter of the FA, SMA, and SLA was measured in three zones, respectively. The thickness of the facial soft tissues and width of the mandible were measured at their maximum. The mean distance from the FA to the buccal cortical bone in zone 1, zone 2 and zone 3 was 2.24 mm, 2.39 mm and 1.67 mm, respectively. The SMA and SLA were found to be distal to the mandible. The mean diameter of the FA was 1.26 mm in males and 1.04 mm in females, respectively (p < 0.0001). The distance between the FA and buccal cortical bone of the mandible, and the patients' weight showed moderate correlation in zones 1 and 2. Based on our findings, the FA can be damaged if the surgical invasion reaches the facial soft tissues during MTM surgery. The patients' weight might be a good predictor for FA injury when CE-CT is not available.

DOI： 10.1002/ca.23779

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. 国際誌

Kyoichi Obata, Tatsuo Okui, Sawako Ono, Koki Umemori, Shoji Ryumon, Kisho Ono, Mayumi Yao, Norie Yoshioka, Soichiro Ibaragi, Akira Sasaki

Diagnostics (Basel, Switzerland) 11 ( 8 ) 2021年7月

記述言語：英語

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.

DOI： 10.3390/diagnostics11081375

Clinical anatomy of the inferior labial gland: a narrative review. 国際誌

Daniel Shen, Kisho Ono, Quang Do, Hiroe Ohyama, Ken Nakamura, Kyoichi Obata, Soichiro Ibaragi, Koichi Watanabe, R Shane Tubbs, Joe Iwanaga

Gland surgery 10 ( 7 ) 2284 - 2292 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective: In this article we review the literature on the inferior labial gland from a clinical and anatomical perspective. Background: Regardless of its importance in clinical practice, there are no medical literature that comprehensively reviewed the inferior labial gland. Methods: A database search using PubMed and Google Scholar was conducted. The following keywords were used in the search: "lower labial salivary gland", "lower labial gland", "inferior labial salivary gland", AND "inferior labial gland". Conclusions: The human labial glands are types of minor salivary gland that continuously secrete small amounts of mucous and serous substances to maintain oral health. The inferior labial glands are innervated by the inferior labial branch of the mental nerve, and the inferior labial branch of the facial artery is the main arterial supply to the lower lip. Although they only have an auxiliary role in saliva production compared to the major salivary glands, minor salivary glands provide a certain amount of lubrication in the oral cavity by the continuous outflow of saliva. The inferior labial gland not only promotes moisturization in the oral cavity but also secretes substances with antibacterial effects, which is important for the function of the oral cavity. A recent study showed that the rate of salivary secretion from the inferior labial glands does not change with age, and in some cases the inferior labial glands are used for diagnosing intractable diseases such as Sjogren's syndrome and cystic fibrosis. In addition, since the inferior labial glands themselves can be the site of cyst and/or neoplasia development, we should be careful to distinguish them from other diseases. Elucidation of the anatomy, physiology, and pathology of the inferior labial glands, is important for understanding human health and diseases.

DOI： 10.21037/gs-21-143

Expression of SARS-CoV-2 entry factors in human oral tissue. 国際誌

Yoshihiko Sawa, Soichiro Ibaragi, Tatsuo Okui, Junro Yamashita, Tetsuro Ikebe, Hiroyuki Harada

Journal of anatomy 238 ( 6 ) 1341 - 1354 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1111/joa.13391

A case of langerhans cell histiocytosis of the mandible that spontaneously regressed after biopsy in a child. 国際誌

Kisho Ono, Tatsuo Okui, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Shoji Ryumon, Soichiro Ibaragi, Tomoya Nakamura, Akira Sasaki

Clinical case reports 9 ( 6 ) e04321 2021年6月

Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment 国際誌

Shoko Yoshida, Tsuyoshi Shimo, Kiyofumi Takabatake, Yurika Murase, Kyoichi Obata, Tatsuo Okui, Yuki Kunisada, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

DIAGNOSTICS 11 ( 6 ) 2021年6月

Localizing the nerve to the mylohyoid using the mylohyoid triangle. 国際誌

Joe Iwanaga, Hee-Jin Kim, Grzegorz Wysiadecki, Kyoichi Obata, Yosuke Harazono, Soichiro Ibaragi, R Shane Tubbs

Anatomy & cell biology 54 ( 3 ) 304 - 307 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The nerve to the mylohyoid muscle has been well studied but there are no specific anatomical landmarks for identifying it. Therefore, we aimed to identify anatomical landmarks for localizing the nerve to the mylohyoid muscle in the submandibular region. Sixteen sides from eight embalmed Caucasian cadaveric heads were used in this study. The mean age at the time of death of the specimens was 80.3 years. The anterior and posterior bellies of the digastric muscle, submental artery, and mylohyoid muscle were dissected to verify their relationships with the nerve to the mylohyoid muscle. The nerve to the mylohyoid muscle was found medial to the submental artery, lateral to the anterior belly of the digastric muscle, and anterior to the posterior border of the mylohyoid muscle on all sides. Herein, we identified what we term the mylohyoid triangle. This anatomical region can help localize the nerve to the mylohyoid muscle.

DOI： 10.5115/acb.21.019

A case of intramandibular neurofibroma resembling a radicular cyst in a neurofibromatosis type 1 patient. 国際誌

Yuki Kunisada, Norie Yoshioka, Soichiro Ibaragi, Tatsuo Okui, Hitoshi Nagatsuka, Akira Sasaki

International journal of surgery case reports 82 105883 - 105883 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

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 café-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.

DOI： 10.1016/j.ijscr.2021.105883

Mandibular canal versus inferior alveolar canal: A Delphi study. 国際誌

Joe Iwanaga, Soichiro Ibaragi, Yohei Takeshita, Junichi Asaumi, Keith Horner, Thomas R Gest, R Shane Tubbs

Clinical anatomy (New York, N.Y.) 34 ( 7 ) 1095 - 1100 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The general principles of anatomical terminology indicate that the "mandibular canal" should be named the "inferior alveolar canal" as it accommodates the inferior alveolar neurovascular bundles. Therefore, we performed a Delphi study to evaluate the current understanding and use of the terminology in different geographical regions and areas of expertise and to determine the appropriate terminology for this bony canal. A Delphi panel was formed and questions sent and answered via email about: field of expertise (anatomy, oral surgery/oral and maxillofacial (OMF) surgery, oral radiology/OMF radiology, plastic surgery, ENT surgery, or dentistry with the exception of oral/OMF surgery and oral/OMF radiology), years of experience in the field of expertise, country currently working in, "what is the name of the bony canal that contains the inferior alveolar neurovascular bundle," and "what should the structure above be called, in general?" A total of 52 participants responded to the questionnaire. Half or more of the experts in anatomy, oral/OMF surgery, and ENT/plastic surgery considered "mandibular canal" to be the most appropriate name for this bony canal. In contrast, more than half of all experts in oral/OMF radiology and dentistry, that is, most fields of dentistry, considered "either mandibular canal or inferior alveolar canal" to be the appropriate name. The results of the Delphi study and general principles suggest that an alternative term for the "mandibular canal" should be "inferior alveolar canal."

DOI： 10.1002/ca.23740

Correction to: Duplication of the external jugular vein: a language barrier of database search in classic anatomical studies. 国際誌

Kisho Ono, Norie Yoshioka, Dany Hage, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Surgical and radiologic anatomy : SRA 43 ( 10 ) 1729 - 1730 2021年4月

切除後に再発を認めた舌のhobnail hemangiomaの1例

國定勇希, 槇野隆秀, 伊原木聰一郎, 熊谷智代, 小野喜章, 佐々木朗

日本口腔外科学会雑誌 67 ( 4 ) 239 - 242 2021年4月

Mandibular canal vs. inferior alveolar canal: Evidence-based terminology analysis. 査読国際誌

Joe Iwanaga, Yuki Matsushita, Tess Decater, Soichiro Ibaragi, R Shane Tubbs

Clinical anatomy (New York, N.Y.) 34 ( 2 ) 209 - 217 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The mandibular canal, as it was formerly named in Terminologia Anatomica (TA), has also been called the inferior alveolar (nerve) canal in many scientific publications. This study was conducted to investigate how these terms have been understood in different regions and different areas of expertise and to discuss the appropriate future application of the term "mandibular canal." METHODS: A literature search was conducted using PubMed, and articles using different terms for this structure were classified into two groups, inferior alveolar canal/inferior alveolar nerve canal (IAC/IANC) and the mandibular canal (MC). The 50 most recent articles in each group were included. Publication year, journal title, country of the first author, and affiliation of all authors were recorded in both groups for all 100 articles. RESULTS: There was a significant difference between the IAC/IANC and MC groups in the numbers of anatomy journals, other journals, and anatomy affiliations. Turkey published most frequently with a total of 15 articles, followed by Iran with 10 articles, and China/India/United States with seven each. When the six countries of the first author that had three or more publications in each group were compared, only Turkey appeared in both groups; otherwise, different countries were in the two groups. CONCLUSIONS: Based on the results of this analysis, and considering that the tentative new term "inferior alveolar foramen" is used in the latest TA, we suggest that the mandibular canal should be renamed the "inferior alveolar canal."

DOI： 10.1002/ca.23648

Comprehensive review of lower third molar management: A guide for improved informed consent. 国際誌

Joe Iwanaga, Yuki Kunisada, Masanori Masui, Kyoichi Obata, Yohei Takeshita, Kotaro Sato, Shogo Kikuta, Yushi Abe, Yuki Matsushita, Jingo Kusukawa, R Shane Tubbs, Soichiro Ibaragi

Clinical anatomy (New York, N.Y.) 34 ( 2 ) 224 - 243 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

DOI： 10.1002/ca.23693

Duplication of the external jugular vein: a language barrier of database search in classic anatomical studies. 国際誌

Kisho Ono, Norie Yoshioka, Dany Hage, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Surgical and radiologic anatomy : SRA 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Many anatomical variations of the superficial veins of the head and neck have been reported throughout the literature. Accordingly, anatomists and surgeons must have a comprehensive understanding of these variations to avoid confusion. Duplication of the external jugular vein (EJV) is occasionally observed during routine cadaveric dissections; however, this variation seems to be reported less often than actual experience suggests. Therefore, to gain a better understanding of its anatomical and clinical implications, an analysis of the available data should be available. Thus, in this article, we reviewed the current available literature for studies reporting duplication of the EJV. METHODS: We conducted a search using PubMed and Google Scholar with the following keywords: "duplication of the external jugular vein," "division of the external jugular vein," and "fenestration of the external jugular vein," "double external jugular vein," and "doubled external jugular vein." As a case illustration, we also describe a case of a duplicated EJV found during a right neck dissection of a female cadaver. RESULTS: Twenty sides across sixteen different studies were analyzed including the present case. All studies were published between 2009 and 2020. EJV division patterns were classified as either duplication, fenestration, fenestration followed by duplication, or double fenestrations. CONCLUSIONS: We have reviewed the literature regarding cases documenting duplication/fenestration of the EJV. As it is often difficult to find recent studies that report on classic anatomical variations, therefore, revisiting older articles and textbooks is necessary for achieving a "comprehensive" review, especially across different languages.

DOI： 10.1007/s00276-021-02717-6

The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone. 国際誌

Tatsuo Okui, Masahiro Hiasa, Shoji Ryumon, Kisho Ono, Yuki Kunisada, Soichiro Ibaragi, Akira Sasaki, G David Roodman, Fletcher A White, Toshiyuki Yoneda

Journal of bone oncology 26 100330 - 100330 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1016/j.jbo.2020.100330

No convincing evidence for the presence of tubarial salivary glands: A letter to the editor regarding "The tubarial salivary glands: A potential new organ at risk for radiotherapy". 国際誌

Joe Iwanaga, Soichiro Ibaragi, Keisuke Nakano, Yohei Takeshita, R Shane Tubbs

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 154 321 - 322 2021年1月

Surgical resection of a giant peripheral ossifying fibroma in mouth floor managed with fiberscopic intubation. 国際誌

Tatsuo Okui, Soichiro Ibaragi, Kisho Ono, Kazuaki Hasegawa, Akira Sasaki

Clinical case reports 9 ( 1 ) 180 - 184 2021年1月

The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation. 国際誌

Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Frontiers in pharmacology 12 674366 - 674366 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

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-κB 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 PKCα/βII, 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.

DOI： 10.3389/fphar.2021.674366

Endoscopic-assisted resection of pleomorphic adenoma in the accessory parotid gland.

Kazuaki Hasegawa, Shintaro Sukegawa, Sawako Ono, Midori Ando, Akane Shibata, Yuka Sukegawa-Takahashi, Ai Fujimura, Tamamo Matsuyama, Soichiro Ibaragi, Hitoshi Nagatsuka, Koichi Mizobuchi, Akira Sasaki, Yoshihiko Furuki

The journal of medical investigation : JMI 68 ( 3.4 ) 376 - 380 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background : An accessory parotid gland (APG) is a common anatomical structure that occurs in 10%-56% of individuals. Pleomorphic adenomas are the most common benign tumors of the APG, and their ideal treatment is surgical excision, although there is a risk for aesthetic disorders and facial nerve damage due to the site of origin. Moreover, despite being benign, these tumors are known to recur. Therefore, it is necessary to achieve both reliable excision and avoidance of facial nerve damage. Case presentation : We report a case of a 49-year-old Japanese man with a mass in his left cheek. The lesion was diagnosed as a benign salivary gland tumor derived from the APG by computed tomography imaging, magnetic resonance imaging and fine needle aspiration cytology. We resected the tumor using modified high submandibular incision under the endoscopic-assisted field of view. Discussion and Conclusions : The tumor was less invasive and reliably resected using an endoscope. In surgical treatment, the endoscopic-assisted technique is very useful to achieve complete tumor resection and prevent relapse while avoiding serious complications due to surgical procedures. J. Med. Invest. 68 : 376-380, August, 2021.

DOI： 10.2152/jmi.68.376

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer. 国際誌

Tomoya Nakamura, Tatsuo Okui, Kazuaki Hasegawa, Shoji Ryumon, Soichiro Ibaragi, Kisho Ono, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Tsuyoshi Shimo, Akira Sasaki

Oncology reports 44 ( 6 ) 2547 - 2558 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.3892/or.2020.7788

A case of oral cancer with delayed occipital lymph node metastasis: Case report. 国際誌

Kisho Ono, Norie Yoshioka, Masanori Masui, Kyoichi Obata, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Hitoshi Nagatsuka, Akira Sasaki

Clinical case reports 8 ( 12 ) 2469 - 2475 2020年12月

Evaluation of overall and disease-free survival in patients with free flaps for oral cancer resection. 国際誌

Takaya Makiguchi, Takahiro Yamaguchi, Hideharu Nakamura, Yukie Yamatsu, Yuki Hirai, Koki Shoda, Sasagu Kurozumi, Soichiro Ibaragi, Norifumi Harimoto, Sei-Ichiro Motegi, Ken Shirabe, Satoshi Yokoo

Microsurgery 40 ( 8 ) 859 - 867 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap. METHODS: SMM was evaluated using the skeletal muscle index (SMI cm2 /m2 ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival. RESULTS: A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm2 /m2 . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival. CONCLUSIONS: Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.

DOI： 10.1002/micr.30668

The accelerator-based boron neutron capture reaction evaluation system for head and neck cancer 査読国際誌

Shou Wang, Kazuyo Igawa, Ryo Ogawara, Mitsuru Suda, Tsuyoshi Hamano, Soichiro Ibaragi, Tadashi Hanafusa, Yasuaki Ichikawa, Akira Sasaki

APPLIED RADIATION AND ISOTOPES 165 109271 - 109271 2020年11月

Anatomy of the mandibular canal and surrounding structures. Part II: Cancellous pattern of the mandible. 査読国際誌

Joe Iwanaga, Koshi Shiromoto, Tomotaka Kato, Tsuyoshi Tanaka, Soichiro Ibaragi, R Shane Tubbs

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 232 151583 - 151583 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: It is necessary to correlate cancellous bone patterns with cone beam computed tomography (CBCT) images, but this has not been done to date. The goal of this study was to establish how the superior wall of the mandibular canal (MC) on CBCT images correlates with the cancellous bone around the MC on gross anatomical findings. METHODS: Twenty sides from 10 dry mandibles derived from six females and four males were used for this study. In order to observe the MC distally, the specimen was prepared by the method used in our previous study. The cancellous bone around the MC was observed and classified into three types: type I (trabecular pattern), type II (osteoporotic pattern), and type III (dense/irregular pattern). The mandibles were examined with CBCT and the superior wall of the MC on CBCT was scored as visible or non-visible. Finally, the scores (visible or non-visible) were compared to the type by gross observation. RESULTS: For gross observation, a total of 80 areas were available for this study. The data were added to those from our previous study. As a result, 155 areas on 40 sides were analyzed. In dentulous sections, types I, II, and III were found in 55.8%, 20.9%, and 23.3%, respectively. In edentulous sections, the corresponding percentages were 25.0%, 41.1%, and 33.9%, respectively. The dentulous sections was more likely than edentulous to have a type I mandible in both sexes. More females than males had type II (osteoporotic) mandibles. When the superior wall of the MC was non-visible on CBCT, the cancellous bone was type II in 80%. CONCLUSIONS: We believe the results can easily be applied to preoperative diagnosis with not only radiological but also anatomical evidence. This classification now necessitates clinical trials for further evidence.

DOI： 10.1016/j.aanat.2020.151583

High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4. 査読国際誌

Yumi Sakamoto, Tatsuo Okui, Toshiyuki Yoneda, Shoji Ryumon, Tomoya Nakamura, Hotaka Kawai, Yuki Kunisada, Soichiro Ibaragi, Masanori Masui, Kisho Ono, Kyoichi Obata, Tsuyoshi Shimo, Akira Sasaki

Biochemical and biophysical research communications 531 ( 3 ) 422 - 430 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1016/j.bbrc.2020.07.120

Revisiting major anatomical risk factors of maxillary sinus lift and soft tissue graft harvesting for dental implant surgeons. 査読国際誌

Joe Iwanaga, Tsuyoshi Tanaka, Soichiro Ibaragi, Tatsuo Okui, Junya Hamaguchi, Seiko Min, R Shane Tubbs

Surgical and radiologic anatomy : SRA 42 ( 9 ) 1025 - 1031 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The anatomical variations of the maxillary sinus septa, greater palatine artery, and posterior superior alveolar arteries might cause unexpected complications when they are damaged. Dentists who know these structures well might hope to learn more practical knowledge to avoid and assess injury preoperatively. Therefore, this review paper aimed to review the reported anatomy and variations of the maxillary sinus septa, greater palatine artery/nerve, and posterior superior alveolar artery, and to discuss what has to be assessed preoperatively to avoid iatrogenic injury. To assess the risk of injury of surgically significant anatomical structures in the maxillary sinus and hard palate, the operator should have preoperative three-dimensional images in their mind based on anatomical knowledge and palpation. Additionally, knowledge of the average measurement results from previous studies is important.

DOI： 10.1007/s00276-020-02468-w

頬粘膜に発生した腺房細胞癌の1例本邦における小唾液腺腺房細胞癌に関する文献的検討

小畑協一, 岸本晃治, 小野喜章, 河合穂高, 柴田茜, 奥井達雄, 矢尾真弓, 伊原木聰一郎, 佐々木朗

日本口腔腫瘍学会誌 32 ( 3 ) 77 - 82 2020年9月

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. 査読国際誌

Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

International immunopharmacology 83 106429 - 106429 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1016/j.intimp.2020.106429

Triple knockdown of CDC37, HSP90-alpha and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer. 国際誌

Kisho Ono, Chiharu Sogawa, Hotaka Kawai, Manh Tien Tran, Eman A Taha, Yanyin Lu, May Wathone Oo, Yuka Okusha, Hirohiko Okamura, Soichiro Ibaragi, Masaharu Takigawa, Ken-Ichi Kozaki, Hitoshi Nagatsuka, Akira Sasaki, Kuniaki Okamoto, Stuart K Calderwood, Takanori Eguchi

Journal of extracellular vesicles 9 ( 1 ) 1769373 - 1769373 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

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. Abbreviations: CDC37: cell division control 37; EMT: epithelial-mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour-associated macrophage.

DOI： 10.1080/20013078.2020.1769373

Expression and Role of IL-1 beta Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing 査読国際誌

Tsuyoshi Shimo, Hiroaki Takebe, Tatsuo Okui, Yuki Kunisada, Soichiro Ibaragi, Kyoichi Obata, Naito Kurio, Karnoon Shamsoon, Saki Fujii, Akihiro Hosoya, Kazuharu Irie, Akira Sasaki, Masahiro Iwamoto

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 ( 7 ) 2020年4月

Microsurgical Anatomy of the Superior Wall of the Mandibular Canal and Surrounding Structures: Suggestion for New Classifications for Dental Implantology. 査読国際誌

Joe Iwanaga, Mahindra Kumar Anand, Mitesh N Jain, Mizuki Nagata, Yuki Matsushita, Soichiro Ibaragi, Jingo Kusukawa, R Shane Tubbs

Clinical anatomy (New York, N.Y.) 33 ( 2 ) 223 - 231 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Our goal was to clarify the relationship between the superior wall of the mandibular canal and the presence of teeth. We also sought to study the structural changes of the mandibular canal after tooth loss. Twenty sides from 10 dry mandibles derived from six males and four females were used for this study. The age of the specimens at the time of death ranged from 57 to 91 years. The mandibles were cut in the midline resulting in 20 hemi-mandibles. The presence of teeth (from the second premolar to the third molar) was recorded for each hemi-mandible. The mandibular canal in the body of the mandible was divided into four areas, that is, Areas 1-4. The superior wall of the mandibular canal and a cancellous bone pattern above the mandibular canal were observed. Next, the mandibular canal was horizontally cut at its center and the superior wall of the mandibular canal observed inferiorly. A total of 75 areas (20 dentulous areas and 55 edentulous areas) were produced. The distal view was classified into three groups, Type I (trabecular pattern), Type II (osteoporotic pattern), and Type III (dense/irregular pattern). The Type I pattern was found in 60.0% (12/20) of the dentulous areas and 32.7% of the edentulous areas. While the Type II pattern was found in 15.0% (23/55) of the dentulous areas and 41.8% of the edentulous areas. The inferior view was classified into four groups depending on the surface of the superior wall of the mandibular canal, that is, Class I (trabecular pattern), Class II (osteoporotic pattern), Class III (dense/irregular pattern), and Class IV (smooth).The Class I pattern was seen most frequently (55.0%) in dentulous areas and the Class IV pattern (45.5%) most frequently in edentulous areas. Based on these results, we conclude that the superior wall of the mandibular canal could change following tooth loss. Clin. Anat. 33:223-231, 2020. © 2019 Wiley Periodicals, Inc.

DOI： 10.1002/ca.23456

Surgical resection for advanced bisphosphonate-related osteonecrosis of the jaw associated with fibrous dysplasia: a case report. 査読国際誌

Yurika Murase, Koji Kishimoto, Shoko Yoshida, Yuki Kunisada, Koichi Kadoya, Soichiro Ibaragi, Akira Sasaki

Journal of surgical case reports 2020 ( 3 ) rjaa061 - 3 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1093/jscr/rjaa061

Clinical anatomy of the accessory mandibular foramen: application to mandibular ramus osteotomy. 査読国際誌

Joe Iwanaga, Shogo Kikuta, Soichiro Ibaragi, Koichi Watanabe, Jingo Kusukawa, R Shane Tubbs

Surgical and radiologic anatomy : SRA 42 ( 1 ) 41 - 47 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: An accessory foramen around the mandibular foramen is called an accessory mandibular foramen (AMF). The clinical anatomy of the AMF has not been well described. The aim of this study was to reveal the clinical anatomy of the AMF for a better understanding of its implication during ramus surgeries. METHODS: Twenty-two sides fresh-frozen cadaveric heads with a mean age of 76.2 ± 14.4 years at death underwent dissection. The neurovascular bundles passing through the AMF were observed. Additionally, a hemi-face of a latex injected embalmed cadaver was dissected medially to laterally and the neurovascular bundles of the AMF investigated. RESULTS: A unilateral foramen, bilateral foramina, and absence of foramina were found in 45.4%, 18.2%, and 36.4%, respectively. The origin of the neurovascular bundle entering the AMF was a branch of the maxillary artery in 20% and a tributary of the inferior alveolar vein in 80%. In the latex embalmed cadaver, the AMF was found to contain a branch from the maxillary artery and a tributary of the maxillary vein. CONCLUSION: Given the practical meaning of the specific AMF located in the operative field of the ramus osteotomy, we suggest these be named "foramina for ramus osteotomy."

DOI： 10.1007/s00276-019-02343-3

Methotrexate-Associated Lymphoproliferative Disorder Developed Ectopically in the Maxillary Gingiva and Bilateral Lungs. 査読国際誌

Kyoichi Obata, Tatsuo Okui, Koji Kishimoto, Soichiro Ibaragi, Akira Sasaki

Case reports in medicine 2020 4814519 - 4814519 2020年

記述言語：英語

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.

DOI： 10.1155/2020/4814519

Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. 査読国際誌

Shoji Ryumon, Tatsuo Okui, Yuki Kunisada, Koji Kishimoto, Tsuyoshi Shimo, Kazuaki Hasegawa, Soichiro Ibaragi, Kentaro Akiyama, Nguyen Thi Thu Ha, Nur Mohammad Monsur Hassan, Akira Sasaki

Oncology reports 42 ( 6 ) 2611 - 2621 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Platinum‑based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum‑based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin‑induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

DOI： 10.3892/or.2019.7367

A Case of Pleomorphic Adenoma Originating from Accessory Parotid Gland. 査読国際誌

Tatsuo Okui, Soichiro Ibaragi, Mariko Fujita, Akira Sasaki

Journal of Maxillofacial and Oral Surgery 20 ( 4 ) 573 - 576 2019年5月

Emerging Evidence of Mast Cell Involvement in Oral Squamous Cell Carcinoma 査読

Simon Basha, Nur Mohammad Monsur Hassan, Rahena Akhter, Soichiro Ibaragi, Tatsuo Okui, Stephen Cox, Akira Sasaki

Biomedical Journal of Scientific & Technical Research 16 ( 2 ) 1 - 6 2019年3月

Nicotine exposure induces the proliferation of oral cancer cells through the α7 subunit of the nicotinic acetylcholine receptor. 査読国際誌

Takashi Nishioka, Hiroyuki Tada, Soichiro Ibaragi, Changyan Chen, Takashi Sasano

Biochemical and biophysical research communications 509 ( 2 ) 514 - 520 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Oral cancer and smoking are closely related, because the oral cavity, which is the route of ingestion of tobacco smoke, is in direct contact with the oral mucosa. Nicotine, one of the components of tobacco, can diffuse rapidly to the central nervous system and is responsible for tobacco addiction. Nicotine is present in high concentrations in the bloodstream of smokers; while the addictive effects of this alkaloid have extensively been studied, its effect on tumorigenesis is not clear yet. Therefore, in this study, we examined the effect of nicotine on cell proliferation and the signaling pathways it activates. The human oral squamous cell carcinoma cell line HSC-2 was used as a model system. We demonstrated the correlation between nicotine and epidermal growth factor receptor (EGFR) signaling. Nicotine treatment induced HSC-2 cell proliferation and migration and the phosphorylation of EGFR. Furthermore, nicotine treatment activated the EGFR downstream effectors phosphatidylinositol-3 kinase/AKT and p44/42 mitogen-activated protein kinases (ERK), which, in turn, promoted cell proliferation. Overall, our study suggests that nicotine promotes cell growth and migration through epidermal growth factor (EGF) signaling and plays an important role in oral cancer progression.

DOI： 10.1016/j.bbrc.2018.12.154

Epidemiology of Temporomandibular Disorder in the general population: A systematic review 査読

Joseph Ryan, Rahena Akhter, Nur Hassan, Glen Hilton, James Wickham, Soichiro Ibaragi

Advances in Dentistry & Oral Health 10 ( 3 ) 1 - 13 2019年2月

Anatomy and variations of the lingual frenum and sublingual surface

Shogo Kikuta, Soichiro Ibaragi

Anatomical Variations in Clinical Dentistry 157 - 166 2019年1月

A case of intraoral plasmablastic lymphoma spontaneously regressed after biopsy in HIV-negative patient 査読

Kisho Ono, Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Kyoichi Obata, Mariko Fujita, Akira Sasaki

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 31 ( 4 ) 280 - 283 2019年1月

Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression 査読

Tsuyoshi Shimo, Eiki Koyama, Tatsuo Okui, Masanori Masui, Yuki Kunisada, Soichiro Ibaragi, Norie Yoshioka, Naito Kurio, Shoko Yoshida, Akira Sasaki, Masahiro Iwamoto

IN VIVO 33 ( 1 ) 85 - 91 2019年1月

Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma. 査読国際誌

Rieko Shimizu, Soichiro Ibaragi, Takanori Eguchi, Daisuke Kuwajima, Shinichi Kodama, Takashi Nishioka, Tatsuo Okui, Kyoichi Obata, Kiyofumi Takabatake, Hotaka Kawai, Kisho Ono, Kuniaki Okamoto, Hitoshi Nagatsuka, Akira Sasaki

International journal of oncology 54 ( 1 ) 283 - 294 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.3892/ijo.2018.4631

Solitary Fibrous Tumor Arising in the Buccal Space. 査読国際誌

Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Akira Sasaki

Case reports in medicine 2019 9459837 - 9459837 2019年

記述言語：英語

A 39-year-old Japanese woman presented to the Department of Oral and Maxillofacial Surgery, Okayama University Hospital, with the complaint of a slowly growing buccal mass. The mass was well defined, had rounded margins, and was free from skin and muscles. A color Doppler echographic examination indicated high flow velocity of the blood surrounding the mass. Contrast-enhanced images on CT and contrast-enhanced T1-weighted images on MRI displayed a homogeneous enhanced mass with a well-defined margin. A fine-needle aspiration biopsy and histological examination were performed. On immunohistochemistry, spindle cells were strongly positive for CD34, STAT6, and vimentin and negative for EMA, S100, and α-SMA. The tumor was removed with extracapsular dissection. The tumor was composed of bland spindle cells proliferating in a patternless arrangement with a collagenous background. Most of the tumor mass consisted of hypocellular areas including ectatic blood vessels. A prominent branching vascular pattern was observed. Immunohistochemistry demonstrated that the tumor cells were positive for CD34, STAT6, vimentin, and Bcl-2, and negative for α-SMA, S100, and EMA. Three mitotic cells were observed per 10 high-power fields, and the Ki-67 index was 5.7%. The morphological and immunohistochemical features were consistent with a diagnosis of solitary fibrous tumor.

DOI： 10.1155/2019/9459837

硬性内視鏡下で摘出した上顎洞内異物の1症例

奥井達雄, 西山明慶, 伊原木聰一郎, 佐々木朗

岡山歯学会雑誌 37 ( 2 ) 33 - 35 2018年12月

舌扁平上皮癌における新TNM分類(UICC:第8版)の実用性

吉田祥子, 岸本晃治, 村瀬友里香, 伊原木聰一郎, 吉岡徳枝, 奥井達雄, 長塚仁, 佐々木朗

日本口腔腫瘍学会誌 30 ( 4 ) 151 - 157 2018年12月

Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts. 査読国際誌

Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba

Heliyon 4 ( 11 ) e00979 2018年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

DOI： 10.1016/j.heliyon.2018.e00979

Carcinogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab. 査読国際誌

Toshifumi Fujiwara, Takanori Eguchi, Chiharu Sogawa, Kisho Ono, Jun Murakami, Soichiro Ibaragi, Jun-Ichi Asaumi, Stuart K Calderwood, Kuniaki Okamoto, Ken-Ichi Kozaki

Oral oncology 86 251 - 257 2018年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations. The OSCC-EGFR-EVs were then able to enter into and transform epithelial cells leading to increased mesenchymal traits with increased vimentin and spindle-like shapes. EGF priming of OSCC cells further increased this EMT-initiating effect of the OSCC-EVs. The internalization and pro-EMT effects of the OSCC-EVs were largely blocked by cetuximab. Thus, OSCC-derived EVs transform normal epithelial cells into a mesenchymal phenotype and anti-EGFR therapeutic antibody cetuximab inhibits such a carcinogenic effect of the OSCC-EVs.

DOI： 10.1016/j.oraloncology.2018.09.030

Oral diverticulum. 査読

Koichi Kadoya, Soichiro Ibaragi, Eri Tokunaga, Takayuki Kono, Tatsuo Okui, Akira Sasaki

Journal of general and family medicine 19 ( 6 ) 221 - 222 2018年11月

Fungal metabolite (

Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba

HELIYON 4 ( 11 ) 2018年11月

Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma. 査読国際誌

Kazuaki Hasegawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Hotaka Kawai, Shoji Ryumon, Koji Kishimoto, Yuka Okusha, Nur Mohammad Monsur Hassan, Akira Sasaki

International journal of molecular sciences 19 ( 11 ) 2018年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

DOI： 10.3390/ijms19113317

Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition. 査読国際誌

Toshifumi Fujiwara, Takanori Eguchi, Chiharu Sogawa, Kisho Ono, Jun Murakami, Soichiro Ibaragi, Jun-Ichi Asaumi, Kuniaki Okamoto, Stuart K Calderwood, Ken-Ichi Kozaki

Biochemical and biophysical research communications 503 ( 3 ) 1267 - 1272 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

DOI： 10.1016/j.bbrc.2018.07.035

Ameloblastic fibro-odontoma in a nine-year-old boy 査読

Tatsuo Okui, Soichiro Ibaragi, Tsuyoshi Shimo, Kiyofumi Takabatake, Mariko Fujita, Nur Mohammad Monsur Hassan, Akira Sasaki

Stomatological Disease and Science 2 ( 7 ) 1 - 5 2018年7月

Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling. 査読国際誌

Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki

Journal of cellular biochemistry 119 ( 6 ) 4352 - 4360 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

DOI： 10.1002/jcb.26418

Depletion of lipid efflux pump ABCG1 triggers the intracellular accumulation of extracellular vesicles and reduces aggregation and tumorigenesis of metastatic cancer cells 査読

Matsumoto K, Shimo T, Kurio N, Okui T, Ibaragi S, Kunisada Y, Obata K, Masui M, Pai P, Horikiri Y, Yamanaka N, Takigawa M, Sasaki A

Frontiers in Oncology 119 ( 6 ) 4352 - 4360 2018年6月

Basal cell adenoma arising in the minor salivary gland of the hard palate 査読

Tatsuo Okui, Soichiro Ibaragi, Keisuke Nakano, Yukiko Fujii, Akira Sasaki

Journal of Clinical and Diagnostic Research 12 ( 4 ) ZD04 - ZD05 2018年4月

放射線性下顎骨壊死に関する検討

松崎秀信, 勝井邦彰, 松崎久美子, 津村宗近, 池田篤司, 伊原木聰一郎, 水川展吉, 小野田友男, 浅海淳一, 木股敬裕

頭頸部癌 44 ( 1 ) 57 - 61 2018年4月

Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. 査読国際誌

Ayaka Morisawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Yuka Okusha, Mitsuaki Ono, Thi Thu Ha Nguyen, Nur Mohammad Monsur Hassan, Akira Sasaki

International journal of oncology 52 ( 3 ) 989 - 999 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

DOI： 10.3892/ijo.2018.4242

逆行性超選択的動注化学放射線療法中に腫瘍栄養動脈が閉塞し吻合枝から急速動注した舌癌の1例

伊原木聰一郎, 吉岡徳枝, 奥井達雄, 國定勇希, 志茂剛, 光藤健司, 藤内祝, 佐々木朗

日本口腔腫瘍学会誌 30 ( 1 ) 23 - 27 2018年3月

The Prognostic Implications of Bone Invasion in Gingival Squamous Cell Carcinoma 査読国際誌

Shoko Yoshida, Tsuyoshi Shimo, Yurika Murase, Kiyofumi Takabatake, Koji Kishimoto, Soichiro Ibaragi, Norie Yoshioka, Tatsuo Okui, Hitoshi Nagatsuka, Akira Sasaki

ANTICANCER RESEARCH 38 ( 2 ) 955 - 962 2018年2月

Ameloblastic fibro-odontoma in a 9-year-old boy 査読

Okui T, Ibaragi S, Shimo T, Takabatake K, Fujita M, Hassan NMM, Sasaki A

Stomatological Disease and Science 2 7 2018年

Clinical analysis of osteoradionecrosis of the mandible 査読

Hidenobu Matsuzaki, Kuniaki Katsui, Kumiko Matsuzaki, Munechika Tsumura, Atsushi Ikeda, Soichiro Ibaragi, Nobuyoshi Mizukawa, Tomoo Onoda, Jun-Ichi Asaumi, Yoshihiro Kimata

Japanese Journal of Head and Neck Cancer 44 ( 1 ) 57 - 61 2018年

Palonosetron Prevents Highly Emetogenic Chemotherapy-induced Nausea and Vomiting in Oral Cancer Patients. 査読国際誌

Shinya Sento, Naoya Kitamura, Tetsuya Yamamoto, Koichi Nakashiro, Hiroyuki Hamakawa, Soichiro Ibaragi, Akira Sasaki, Natsumi Takamaru, Yoji Miyamoto, Isamu Kodani, Kazuo Ryoke, Katsuaki Mishima, Yoshiya Ueyama

Anticancer research 37 ( 12 ) 6977 - 6981 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: To evaluate the efficacy of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) in oral cancer patients. PATIENTS AND METHODS: Oral cancer patients receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy were administered. On day 1, 0.75 mg palonosetron was intravenously administrated just before chemotherapy. RESULTS: The primary endpoint was the proportion of patients with a complete response (CR) and the secondary endpoint was the proportion of patients with complete control (CC) during the acute and delayed phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87 courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR and 70 of 87 courses (80.5%) had CC. CONCLUSION: Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.

Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis. 査読国際誌

Hiromasa Kuroda, Naito Kurio, Tsuyoshi Shimo, Kenichi Matsumoto, Masanori Masui, Kiyofumi Takabatake, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Norie Yoshioka, Koji Kishimoto, Hitoshi Nagatsuka, Akira Sasaki

Anticancer research 37 ( 12 ) 6731 - 6737 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS: We found that SHH was highly expressed in human tongue OSCC, whereas patched (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in the microvascular cells in the tumor invasive front. Administration of cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and migration, and reduced aorta vascular length in the rat. CONCLUSION: These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front.

Maxillofacial Fractures in Elderly Patients 査読

Hiroaki Takakura, Tsuyoshi Shimo, Norie Yoshioka, Mayumi Yao, Kyoichi Obata, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Ayaka Morisawa, Akane Shibata, Shoko Yoshida, Yurika Murase, Koji Kishimoto, Akiyoshi Nishiyama, Hiroshi Mese, Akira Sasaki

International Journal of Surgery & Surgical Procedures 2 ( 128 ) 1 - 5 2017年11月

Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma. 査読国際誌

Kyoichi Obata, Tsuyoshi Shimo, Tatsuo Okui, Kenichi Matsumoto, Hiroyuki Takada, Kiyofumi Takabatake, Yuki Kunisada, Soichiro Ibaragi, Norie Yoshioka, Koji Kishimoto, Hitoshi Nagatsuka, Akira Sasaki

Anticancer research 37 ( 11 ) 6119 - 6123 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. MATERIALS AND METHODS: NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. RESULTS: NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. CONCLUSION: NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction.

Perimandibular abscess associated with bisphosphonate-related osteonecrosis of the jaw. 査読

Kazuki Ocho, Masaya Iwamuro, Hideharu Hagiya, Soichiro Ibaragi, Fumio Otsuka

Journal of general and family medicine 18 ( 5 ) 305 - 306 2017年10月

Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma 査読国際誌

Hiroyuki Takada, Soichiro Ibaragi, Takanori Eguchi, Tatsuo Okui, Kyoichi Obata, Masanori Masui, Ayaka Morisawa, Kiyofumi Takabatake, Hotaka Kawai, Norie Yoshioka, Nur Mohammad Monsur Hassan, Tsuyoshi Shimo, Guo-Fu Hu, Hitoshi Nagatsuka, Akira Sasaki

INTERNATIONAL JOURNAL OF ONCOLOGY 51 ( 2 ) 625 - 632 2017年8月

岡山大学病院高度救命救急センターにおける頭部、顎顔面外傷患者の検討

奥井達雄, 伊原木聰一郎, 志茂剛, 森澤綾香, 藤井由紀子, 佐々木朗

岡山歯学会雑誌 36 ( 1 ) 13 - 16 2017年6月

下顎に発生した顎放線菌症の1例本邦における顎放線菌症の過去集計と現状との比較検討

小畑協一, 伊原木聰一郎, 矢尾真弓, 柴田茜, 吉岡徳枝, 志茂剛, 佐々木朗

日本口腔内科学会雑誌 23 ( 1 ) 23 - 27 2017年6月

セツキシマブ投与にてアナフィラキシー様のinfusion reactionを発症したマダニ咬傷既往のある口腔癌患者の1例

矢尾真弓, 志茂剛, 柴田茜, 小畑協一, 吉岡徳枝, 伊原木聰一郎, 藤井由起子, 岸本晃治, 佐々木朗

岡山歯学会雑誌 36 ( 1 ) 1 - 6 2017年6月

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

Masanori Masui, Tsuyoshi Shimo, Norie Yoshioka, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Mayumi Yao, Shoko Yoshida, Yurika Murase, Koji Kishimoto, Akiyoshi Nishiyama, Yoshihiko Soga, Akira Sasaki

2 ( 115 ) 1 - 7 2017年5月

Endoscope-Assisted Transoral Reduction and Internal Fixation of a Mandibular Subcondylar Fracture with a 3D - Shaped Plate 査読

Ibaragi Soichiro, Yoshioka Norie, Kishimoto Koji, Sasaki Akira

International Journal of Contemporary Medical Research 4 ( 2 ) 575 - 577 2017年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Society for Contemporary Medical Research

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.

Orthognathic surgery during breast cancer treatment-A case report 査読国際誌

Tsuyoshi Shimo, Norie Yoshioka, Masahiro Nakamura, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Masanori Masui, Mayumi Yao, Koji Kishimoto, Shoko Yoshida, Akiyoshi Nishiyama, Hiroshi Kamioka, Akira Sasaki

INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS 31 30 - 34 2017年

Tachykinin Receptor 3 Distribution in Human Oral Squamous Cell Carcinoma. 査読国際誌

Kyoichi Obata, Tsuyoshi Shimo, Tatsuo Okui, Kenichi Matsumoto, Hiroyuki Takada, Kiyofumi Takabatake, Yuki Kunisada, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

Anticancer research 36 ( 12 ) 6335 - 6341 2016年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Tachykinin 3 (TAC3) and its preferred tachykinin receptor 3 (TACR3) that are prominently detected in the central nervous system, play significant roles in physiological development and specifically in the human reproductive system. The roles of TAC3/TACR3 in oral squamous cell carcinoma are unknown. MATERIALS AND METHODS: We examined the expression pattern of TAC3/TACR3 in clinically-resected oral squamous cell carcinoma samples using immunohistochemistry and immunofluorescence analysis. RESULTS: We found that even though the expression level of TACR3 was negative in the normal epithelium, it was highly elevated in tumor cells. A more intense signal was observed in the invasive front of tumor cells that had migrated into the mandible bone matrix. TAC3 was not detected in tumor cells, but was expressed in PGP-9.5-positive sensory nerves in the mandible. CONCLUSION: Our results suggest that peripheral sensory nerve-derived TAC3 may affect gingival oral squamous cell carcinoma cells through TACR3 in the bone matrix.

Beckwith-Wiedemann症候群による巨舌に起因する著明な開咬に対して顎矯正手術を施行した1例

吉岡徳枝, 西山明慶, 高橋巧, 伊原木聰一郎, 銅前昇平, 志茂剛, 佐々木朗

日本顎変形症学会雑誌 26 ( 3 ) 228 - 236 2016年8月

Autologous Blood Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation 査読

Norie Yoshioka, Tsuyoshi Shimo, Soichiro Ibaragi, Akira Sasaki

ACTA MEDICA OKAYAMA 70 ( 4 ) 291 - 294 2016年8月

Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma. 査読国際誌

Masanori Masui, Tatsuo Okui, Tsuyoshi Shimo, Kiyofumi Takabatake, Takuya Fukazawa, Kenichi Matsumoto, Naito Kurio, Soichiro Ibaragi, Yoshio Naomoto, Hitoshi Nagatsuka, Akira Sasaki

Anticancer research 36 ( 6 ) 2775 - 81 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma.

当科における舌扁平上皮癌Stage I・II症例の頸部リンパ節後発転移に関する臨床的検討

吉田祥子, 岸本晃治, 村瀬友里香, 銅前昇平, 伊原木聰一郎, 柳文修, 松崎秀信, 志茂剛, 佐々木朗

岡山歯学会雑誌 35 ( 1 ) 13 - 18 2016年6月

福山市民病院歯科口腔外科でのインプラント治療における病診連携の状況について

目瀬浩, 山本大介, 木村周子, 大月要, 伊原木聰一郎, 岸本晃治, 佐々木朗

岡山歯学会雑誌 35 ( 1 ) 19 - 22 2016年6月

Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production. 査読国際誌

Akane Shibata, Soichiro Ibaragi, Hiroki Mandai, Toki Tsumura, Koji Kishimoto, Tatsuo Okui, Nur Mohammad Monsur Hassan, Tsuyoshi Shimo, Kazuhiro Omori, Guo-Fu Hu, Shogo Takashiba, Seiji Suga, Akira Sasaki

Anticancer research 36 ( 5 ) 2161 - 8 2016年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: Head and neck cancers are the fifth most common cancer type worldwide, affecting more than half a million patients annually. Development of effective therapeutic drugs is, therefore, required for this type of disease. This study assessed the effects of synthetic terrein on head and neck cancer. MATERIALS AND METHODS: Synthetic terrein was prepared by using the modified Altenhach's procedure. The effect of synthetic terrein on cell proliferation of head and neck cancer cells and HUVECs was assessed. Angiogenin secretion and ribosome biogenesis were examined by ELISA and silver staining of the nucleolar organizer region. A mouse xenograft model was prepared by inoculating mice with suspensions of cells of the human head and neck cancer cell line OSC-19 subcutaneously into the dorsal region of each mouse. Ki-67, CD31 and angiogenin expression in xenografted tumors was examined by immunohistochemistry. RESULTS: Synthetic terrein inhibited the growth of various head and neck cancer cells. In addition, an in vivo experiment revealed that synthetic terrein inhibited a xenograft tumor growth in athymic mice. Immunohistochemical analysis revealed that expression of Ki-67, CD31 and ANG was down-regulated in synthetic terrein-treated tumors, compared to controls. Synthetic terrein suppressed the ANG secretion and ribosome biogenesis in cancer cells, and cell proliferation in vascular endothelial cells. CONCLUSION: The mechanism underlying the anti-tumor effects of synthetic terrein against head and neck cancer consists of the inhibition of both tumor cell proliferation and angiogenesis via the suppression of ANG production.

ガミースマイルを伴った上顎前突に対して馬蹄形骨切り併用4分割Le Fort I型上顎骨切りを行った1例

西山明慶, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 田井規能, 佐々木朗

日本顎変形症学会雑誌 26 ( 2 ) 129 - 129 2016年5月

The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction 査読国際誌

Tsuyoshi Shimo, Kenichi Matsumoto, Kiyofumi Takabatake, Eriko Aoyama, Yuichiro Takebe, Soichiro Ibaragi, Tatsuo Okui, Naito Kurio, Hiroyuki Takada, Kyoichi Obata, Pai Pang, Masahiro Iwamoto, Hitoshi Nagatsuka, Akira Sasaki

PLOS ONE 11 ( 3 ) e0151731 2016年3月

Detection of sonic hedgehog in patients undergoing orthognathic surgery 査読

Yuki Kunisada, Tsuyoshi Shimo, Masanori Masui, Norie Yoshioka, Soichiro Ibaragi, Kenichi Matsumoto, Tatsuo Okui, Naito Kurio, Shohei Domae, Koji Kishimoto, Akiyoshi Nishiyama, Akira Sasaki

International Journal of Surgery Open 5 1 - 4 2016年

Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction. 査読国際誌

Pai Pang, Tsuyoshi Shimo, Hiroyuki Takada, Kenichi Matsumoto, Norie Yoshioka, Soichiro Ibaragi, Akira Sasaki

Biochemical and biophysical research communications 467 ( 1 ) 21 - 6 2015年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

DOI： 10.1016/j.bbrc.2015.09.139

Familial adenoid cystic carcinoma of sublingual salivary glands 査読

Norie Yoshioka, Hiroshi Mese, Tatsuo Okui, Soichiro Ibaragi, Akira Sasaki

JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY 27 ( 3 ) 353 - 356 2015年5月

早期見学実習の一環として実施した振り返りを取り入れたエスコート実習の評価過去8年間の検討

吉田登志子, 山中玲子, 菅原康代, 伊原木聰一郎, 村上隆, 村田尚道, 志茂剛, 柳田剛志, 縄稚久美子, 星加知宏

日本歯科医学教育学会雑誌 31 ( 1 ) 16 - 24 2015年4月

Expression and Roles of CCN2 in Dental Epithelial Cells 査読

Tsuyoshi Shimo, Eiki Koyama, Naito Kurio, Kenichi Matsumoto, Tatsuo Okui, Soichiro Ibaragi, Norie Yoshioka, Akira Sasaki

IN VIVO 29 ( 2 ) 189 - 195 2015年3月

A case of adenoid cystic carcinoma associated with IgG4-related disease 査読国際誌

Tsuyoshi Shimo, Mayumi Yao, Yuichiro Takebe, Yuko Ono, Kyoichi Obata, Naito Kurio, Soichiro Ibaragi, Norie Yoshioka, Koji Kishimoto, Yoshinobu Yanagi, Hitoshi Nagatsuka, Akira Sasaki

INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS 10 12 - 16 2015年

岡山大学病院口腔がん専門外来と岡山市歯科医師会の連携による口腔がん検診研修会の概要とアンケート結果について

岸本晃治, 岡崎景, 西山明慶, 居樹秀明, 松村達志, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 栗尾奈愛, 矢尾真弓, 小畑協一, 尾野裕子, 志茂剛, 壺内智郎, 飯田征二, 佐々木朗

岡山歯学会雑誌 33 ( 2 ) 23 - 28 2014年12月

Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts. 査読国際誌

Hiroki Mandai, Kazuhiro Omori, Daisuke Yamamoto, Toki Tsumura, Kyouta Murota, Satoshi Yamamoto, Koichi Mitsudo, Soichiro Ibaragi, Akira Sasaki, Hiroshi Maeda, Shogo Takashiba, Seiji Suga

Bioorganic & medicinal chemistry 22 ( 19 ) 5338 - 44 2014年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20 μM and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2-signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p<0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.

DOI： 10.1016/j.bmc.2014.07.047

Neamine inhibits oral cancer progression by suppressing angiogenin-mediated angiogenesis and cancer cell proliferation. 査読国際誌

Koji Kishimoto, Shoko Yoshida, Soichiro Ibaragi, Norie Yoshioka, Guo-Fu Hu, Akira Sasaki

Anticancer research 34 ( 5 ) 2113 - 21 2014年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Angiogenin undergoes nuclear translocation and stimulates ribosomal RNA transcription in both endothelial and cancer cells. Consequently, angiogenin has a dual effect on cancer progression by inducing both angiogenesis and cancer cell proliferation. The aim of this study was to assess whether neamine, a blocker of nuclear translocation of angiogenin, possesses antitumor activity toward oral cancer. MATERIALS AND METHODS: The antitumor effect of neamine on oral cancer cells was examined both in vitro and in vivo. RESULTS: Neamine inhibited the proliferation of HSC-2, but not that of SAS oral cancer cells in vitro. Treatment with neamine effectively inhibited growth of HSC-2 and SAS cell xenografts in athymic mice. Neamine treatment resulted in a significant decrease in tumor angiogenesis, accompanied by a decrease in angiogenin- and proliferating cell nuclear antigen-positive cancer cells, especially of HSC-2 tumors. CONCLUSION: Neamine effectively inhibits oral cancer progression through inhibition of tumor angiogenesis. Neamine also directly inhibits proliferation of certain types of oral cancer cells. Therefore, neamine has potential as a lead compound for oral cancer therapy.

骨髄移植後の慢性GVHD患者に発生した多発性口腔扁平上皮癌の1例

奥井達雄, 目瀬浩, 伊原木聰一郎, 吉岡徳枝, 志茂剛, 佐々木朗

日本口腔外科学会雑誌 60 ( 3 ) 151 - 155 2014年3月

長期経過観察し病理組織学的評価を行った下顎骨線維性異形成症の1例

伊原木聰一郎, 西山明慶, 奥井達雄, 栗尾奈愛, 柴田茜, 岸本晃治, 志茂剛, 佐々木朗

日本口腔診断学会雑誌 27 ( 1 ) 27 - 31 2014年2月

A Case of Fibrous Dysplasia of the Mandible with Histopathological Evaluation after Long-term Observation

SOICHIRO IBARAGI, AKIYOSHI NISHIYAMA, TATSUO OKUI, NAITO KURIO, AKANE SHIBATA, KOJI KISHIMOTO, TSUYOSHI SHIMO, AKIRA SASAKI

Japanese Journal of Oral Diagnosis / Oral Medicine 27 ( 1 ) 27 - 31 2014年

Angiogenin mediates androgen-stimulated prostate cancer growth and enables castration resistance. 査読国際誌

Shuping Li, Miaofen G Hu, Yeqing Sun, Norie Yoshioka, Soichiro Ibaragi, Jinghao Sheng, Guangjie Sun, Koji Kishimoto, Guo-Fu Hu

Molecular cancer research : MCR 11 ( 10 ) 1203 - 14 2013年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

UNLABELLED: The androgen receptor (AR) is a critical effector of prostate cancer development and progression. Androgen-dependent prostate cancer is reliant on the function of AR for growth and progression. Most castration-resistant prostate cancer (CRPC) remains dependent on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of prostate cancer cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. Here, investigation revealed that angiogenin (ANG), a member of the secreted ribonuclease superfamily, is upregulated in prostate cancer and mediates androgen-stimulated rRNA transcription in prostate cancer cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent prostate cancer cells, where it binds to the rDNA promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent prostate cancer cells. Interestingly, ANG also mediates androgen-independent rRNA transcription through a mechanism that involves its constitutive nuclear translocation in androgen-insensitive prostate cancer cells, resulting in a constant rRNA overproduction and thereby stimulating cell proliferation. Critically, ANG overexpression in androgen-dependent prostate cancer cells enables castration-resistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of prostate cancer but also contributes to the transition of prostate cancer from androgen-dependent to castration-resistant growth status. IMPLICATIONS: The ability of angiogenin to regulate rRNA transcription and prostate cancer growth makes it a viable target for therapy.

DOI： 10.1158/1541-7786.MCR-13-0072

エナメル上皮腫摘出後に骨移植と骨延長により骨増量を行ったインプラント治療の1例

伊原木聰一郎, 目瀬浩, 中山周子, 兒玉真一, 奥井達雄, 吉岡徳枝, 岸本晃治, 中妻可奈子, 志茂剛, 佐々木朗

Japanese Journal of Maxillo Facial Implants 12 ( 2 ) 53 - 57 2013年8月

咽頭弁により経鼻挿管困難であった唇顎口蓋裂患者に対し経口挿管で上下顎同時移動術を行った1例

西山明慶, 吉岡徳枝, 伊原木聰一郎, 國定勇希, 福島宏明, 村上隆, 山城隆, 佐々木朗

日本顎変形症学会雑誌 23 ( 2 ) 108 - 108 2013年5月

Novel HSP90 inhibitor NVP-AUY922 enhances the anti-tumor effect of temsirolimus against oral squamous cell carcinoma. 査読国際誌

Tatsuo Okui, Tsuyoshi Shimo, Takuya Fukazawa, Nur Mohammad Monsur Hassan, Tatsuki Honami, Soichiro Ibaragi, Munenori Takaoka, Yoshio Naomoto, Akira Sasaki

Current cancer drug targets 13 ( 3 ) 289 - 99 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Heat shock protein 90 (HSP90) and mammalian target of rapamycin (mTOR) are involved in the molecular pathogenesis of advanced oral squamous cell carcinoma. HSP90 inhibitors are capable of effectively interfering with multiple signaling pathways, including the mTOR signaling pathway. However, the combined effects of HSP90 and mTOR inhibitors on oral squamous cell carcinoma are still unknown. In this study, we investigated the dual treatment of the novel HSP90 inhibitor NVP-AUY922 and temsirolimus against oral squamous cell carcinoma. MATERIALS AND METHODS: The effect of the combination of NVP-AUY922 and temsirolimus on oral squamous cell carcinoma in vitro and in vivo was determined by MTS assay and mouse xenograft models. The effect of the combination on angiogenesis was determined by tube formation assay and angioreactor. RESULTS: The combination treatment of NVP-AUY922 and temsirolimus significantly inhibited the proliferation of SAS oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. We have clearly shown that the combination treatment of NVP-AUY922 and temsirolimus inhibited vascular formation both in vitro and in vivo. Moreover, the combination treatment of NVP-AUY922 and temsirolimus prolonged the survival rate in mice xenografted with oral squamous cell carcinoma. CONCLUSIONS: Here, we showed the activity of a combination of mTOR and HSP90 inhibitors for the treatment of advanced oral squamous carcinoma.

リンパ管新生の分子機構とリンパ浮腫

伊原木聰一郎

上原記念生命科学財団研究報告集 26 1 - 6 2012年12月

Hypoxia-induced up-regulation of angiogenin, besides VEGF, is related to progression of oral cancer. 査読国際誌

Koji Kishimoto, Shoko Yoshida, Soichiro Ibaragi, Norie Yoshioka, Tatsuo Okui, Guo-fu Hu, Akira Sasaki

Oral oncology 48 ( 11 ) 1120 - 7 2012年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Angiogenin (ANG) is a prominent angiogenic factor that has been shown to have a dual effect on tumor progression by inducing both angiogenesis and cancer cell proliferation through stimulating ribosomal RNA transcription in both endothelial cells and cancer cells. In the present study, we investigated the expression profiles of ANG and vascular endothelial growth factor (VEGF) in oral cancer and their correlation with hypoxia and evaluated the possible value of ANG as a therapeutic target for oral cancer. MATERIALS AND METHODS: Immunohistochemistry (IHC), ELISA, real-time RT-PCR and Western blotting were used to examine the expression of ANG, VEGF, and hypoxia-inducible factor 1α (HIF-1α) in oral squamous cell carcinoma (OSCC) specimens and human OSCC cell lines. In order to examine the role of ANG, we knocked down ANG expression in HSC-2 cells by means of plasmid-mediated RNA interference. RESULTS: IHC showed that the expression of ANG was significantly correlated with that of HIF-1α in 50 OSCC specimens (P = 0.031). However, no significant correlation between VEGF and HIF-1α expression was found (P = 0.243). Consistently, ANG secretion increased under hypoxia in all of the 10 OSCC cell lines tested; and a significant increase was observed in 6 of them. In contrast, there was no noticeable increase in VEGF secretion under hypoxia in any of these cell lines. In HSC-2 and SAS OSCC cells, the increase in ANG mRNA expression correlated very well with that of HIF-1α protein expression after hypoxia onset. However, no noticeable increase in VEGF mRNA expression was observed even after 12 h of hypoxia. Down-regulation of ANG expression in HSC-2 cells highly expressing and secreting VEGF inhibited ribosome biogenesis, cell proliferation, tumor angiogenesis, and xenograft growth in athymic mice. CONCLUSION: These results suggest that ANG is up-regulated in the hypoxic environment of oral cancers and that its inhibition can have a therapeutic implication.

DOI： 10.1016/j.oraloncology.2012.05.009

幼児の上顎歯肉に発生した巣状口腔粘液症の1例

伊原木聰一郎, 西山明慶, 吉岡徳枝, 片瀬直樹, 長塚仁, 佐々木朗

日本口腔外科学会雑誌 58 ( 9 ) 546 - 549 2012年9月

後期高齢者口腔扁平上皮癌症例の臨床的検討

吉田祥子, 岸本晃治, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 志茂剛, 西山明慶, 目瀬浩, 佐々木朗

日本口腔腫瘍学会誌 24 ( 3 ) 103 - 111 2012年9月

二つの拡大装置と外科的急速拡大の組み合わせによって治療を行った顔面非対称症例

川邉紀章, 古森紘基, 白賀のり子, 伊原木聰一郎, 吉岡徳枝, 西山明慶, 佐々木朗, 山城隆

日本矯正歯科学会大会プログラム・抄録集 71回 263 - 263 2012年9月

下顎骨腫瘍摘出後の骨折および顔貌変形防止に対するプレートの応用

岸本晃治, 吉田祥子, 銅前昇平, 帆波辰基, 伊原木聰一郎, 奥井達雄, 栗尾奈愛, 中妻可奈子, 佐々木朗

岡山歯学会雑誌 31 ( 1 ) 15 - 19 2012年6月

二つの拡大装置を用いた外科的急速拡大によって上顎歯列弓幅径の改善を行った顔面非対称症例

川邉紀章, 古森紘基, 伊原木聰一郎, 吉岡徳枝, 西山明慶, 佐々木朗, 山城隆

日本顎変形症学会雑誌 22 ( 2 ) 177 - 177 2012年5月

診断力てすと口腔粘膜のびらん

伊原木聰一郎, 佐々木朗

DENTAL DIAMOND 37 ( 1 ) 143 - 144 2012年1月

幼児の上顎歯肉粘液腫の1例

伊原木聰一郎, 西山明慶, 吉岡徳枝, 兒玉真一, 長塚仁, 目瀬浩, 佐々木朗

日本口腔科学会雑誌 61 ( 1 ) 182 - 182 2012年1月

Angiogenin as a molecular target for the treatment of prostate cancer. 査読国際誌

Shuping Li, Soichiro Ibaragi, Guo-Fu Hu

Current cancer therapy reviews 7 ( 2 ) 83 - 90 2011年5月

記述言語：英語

Angiogenin (ANG), a 14 kDa angiogenic ribonuclease, is upregulated in human prostate cancers, especially in hormone refractory diseases, and is the highest upregulated gene in Akt-driven prostate intraepithelial neoplasia (PIN) in mice. ANG has been shown to undergo nuclear translocation in both prostate cancer cells and cancer-associated endothelial cells where it binds to the promoter region of ribosomal DNA (rDNA) and stimulates ribosomal RNA (rRNA) transcription. ANG thus plays an essential role in prostate cancer progression by stimulating both cancer cell proliferation and tumor angiogenesis. A variety of ANG antagonists, including its antisense oligonucleotide, siRNA, soluble binding proteins, monoclonal antibody, enzymatic inhibitors, and nuclear translocation blockers, have all been shown to inhibit prostate cancer in various animal models. Accumulating evidence indicates that ANG is a molecular target for prostate cancer drug development.

Induction of MMP-13 expression in bone-metastasizing cancer cells by type I collagen through integrin α1β1 and α2β1-p38 MAPK signaling. 査読国際誌

Soichiro Ibaragi, Tsuyoshi Shimo, Nur Mohammad Monsur Hassan, Sachiko Isowa, Naito Kurio, Hiroki Mandai, Shinichi Kodama, Akira Sasaki

Anticancer research 31 ( 4 ) 1307 - 13 2011年4月

記述言語：英語

BACKGROUND: Breast cancer cells frequently metastasize to the skeleton and produce and secrete proteinases, such as matrix metalloproteinase-13 (MMP-13), which promote destruction of the bone matrix. However, the mechanism of MMP-13 expression induced in areas of bone metastasis is unknown. Here, the interaction between tumors and type I collagen in bone metastasis was investigated. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with suspensions of cells of the human metastatic breast cancer cell line MDA-MB-231 via the left cardiac ventricle. MMP-13 expression was examined by immunohistochemical, Western blot, and real-time RT-PCR analyses. RESULTS: MMP-13 expression was highly up-regulated in MDA-MB-231 cells, and attachment of these cells to type I collagen and the induction of MMP-13 were down-regulated by treatment with integrin α1, α2 or β1 neutralizing antibodies. The attachment of MDA-MB-231 cells to type I collagen induced the activation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK). Inhibition of FAK and p38 MAPK down-regulated type I collagen-induced MMP-13 expression. CONCLUSION: Our study indicates that metastatic breast cancer cells in the bone microenvironment attached to type I collagen, which stimulated integrins α1β1 and α2β1, via FAK and p38 MAPK pathways, to induce MMP13 expression and further osteolysis.

Parathyroid hormone-related peptide regulates matrix metalloproteinase-13 gene expression in bone metastatic breast cancer cells. 査読国際誌

Soichiro Ibaragi, Tsuyoshi Shimo, Masahiro Iwamoto, Nur Mohammad Monsur Hassan, Shinichi Kodama, Sachiko Isowa, Akira Sasaki

Anticancer research 30 ( 12 ) 5029 - 36 2010年12月

記述言語：英語

BACKGROUND: Breast cancer (BC) cells often metastasize to bone where they express large amounts of parathyroid hormone-related protein (PTHrP). In this study, we investigated the possibility that PTHrP may have roles in breast cancer bone metastasis independently of, or in addition to, its roles in osteoclastic function. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with suspensions of the human BC cell line MDA-MB-231 tumor cells via the left cardiac ventricle. Matrix metalloproteinase-13 (MMP-13) expression in the bone microenvironment was examined by Western blot and Real-time RT-PCR (RT-PCR) analysis, as well as by confocal microscopy. RESULTS: The invading MDA-MB-231 cells contained conspicuous amounts of both PTHrP and MMP-13, an important matrix-degrading enzyme; and treatment of the cells in culture with exogenous PTHrP markedly stimulated MMP13 gene expression. Analysis of signaling mechanisms showed that PTHrP treatment led to rapid increases in the levels of phosphorylated protein kinase C (PKCα) and extracellular signal-regulated kinase (ERK1/2). Pharmacologic inhibition of ERK1/2 and PKC as well as of PKA activities counteracted the PTHrP-dependent stimulation of MMP13 expression. Indeed, pharmacologic activation of PKA or PKC was sufficient for stimulation of MMP13 expression. CONCLUSION: Consistent with these findings, the inhibition of PKC prevented PTHrP-induced activation of ERK1/2, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulator of PKC, up-regulated the PTHrP-induced activation of ERK1/2. Taken together, our data indicate that the MDA-MB-231 breast cancer cells may carry out bone destruction and favor their own metastatic behavior by producing MMP-13. Given that the cells expressed PTHrP and that this factor stimulated MMP-13 expression, metastatic bone destruction may result from a PTHrP autocrine loop involving a PKC-ERK1/2 signaling pathway.

口腔癌切除後の創部に対してポリグリコール酸フェルトとフィブリン糊を併用した被覆法の使用経験

伊原木聰一郎, 岸本晃治, 吉岡徳枝, 銅前昇平, 志茂剛, 中妻可奈子, 辻本紗代子, 栗尾奈愛, 兒玉真一, 武部祐一郎, 堀切優, 柴田茜, 西山明慶, 目瀬浩, 佐々木朗

岡山歯学会雑誌 29 ( 2 ) 107 - 112 2010年12月

PTHrP regulates angiogenesis and bone resorption via VEGF expression. 査読国際誌

Sachiko Isowa, Tsuyoshi Shimo, Soichiro Ibaragi, Naito Kurio, Tatsuo Okui, Kiminori Matsubara, Nur Mohammad Monsur Hassan, Koji Kishimoto, Akira Sasaki

Anticancer research 30 ( 7 ) 2755 - 67 2010年7月

記述言語：英語

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is a key regulator of osteolytic metastasis of breast cancer (BC) cells, but its targets and mechanisms of action are not fully understood. This study investigated whether/how PTHrP (1-34) signaling regulates expression of vascular endothelial growth factor (VEGF) produced by BC cells. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with tumour cell suspensions of the human BC cell line MDA-MB-231 via the left cardiac ventricle. VEGF expression was examined by Western blot and real-time RT-PCR analysis, as well as by confocal microscopy in the bone microenvironment. RESULTS: PTHrP was expressed in cancer cells producing PTH/PTHrP receptor and VEGF that had invaded the bone marrow, and PTHrP was up-regulated VEGF in MDA-MB-231 in vitro. The culture medium conditioned by PTHrP-treated MDA-MB-231 cells stimulated angiogenesis and osteoclastogenesis compared with control medium, giving a response that was inhibited by VEGF-neutralizing antibody treatment. Inhibition of protein kinase C (PKC) prevented PTHrP-induced extracellular signal-regulated kinase (ERK1/2) and p38 activation, and PTHrP-induced VEGF expression. CONCLUSION: PTHrP plays an important role in modulating the angiogenic and bone osteolytic actions of VEGF through PKC-dependent activation of an ERK1/2 and p38 signaling pathway during bone metastasis by breast cancer cells.

Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-beta signalling pathway. 査読国際誌

Takeshi Goda, Tsuyoshi Shimo, Yasuto Yoshihama, Nur Mohammad Monsur Hassan, Soichiro Ibaragi, Naito Kurio, Tatsuo Okui, Tatsuki Honami, Koji Kishimoto, Akira Sasaki

Anticancer research 30 ( 7 ) 2615 - 23 2010年7月

記述言語：英語

BACKGROUND: Gingival squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and this destruction is associated with a worse prognosis. However, the relationship between bone destruction and associated factors is unclear. In this study, the role and diagnostic utility of transforming growth factor-beta (TGF-beta) type I receptor (TbetaRI) in bone destruction of the mandible was investigated. PATIENTS AND METHODS: The expression of TbetaRI was explored by using an immunohistochemical method on paraffin-embedded tissues from 21 cases of mandibular SCC. An inhibitor of the kinase activity of the TbetaRI (TbetaRI-I) was used to assess the role of TbetaRI in bone destruction by a human oral SCC cell line (HSC-2) that highly expresses TbetaRI. RESULTS: TbetaRI-positive signals were closely associated with destructive invasion of the mandible by oral SCC cells. Consistent with these results, TbetaRI-I greatly reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and in vitro. TbetaRI-I treatment reduced the expression of TNF-alpha, RANKL and connective tissue growth factor (CTGF/CCN2), all of which were up-regulated by TGF-beta in HSC-2 cells. CONCLUSION: These data demonstrated an important role for TGF-beta signalling in bone invasion by oral SCC cells, and suggest that the bone destruction is mediated by RANKL, TNF-alpha and CCN2.

Novel transcriptional regulation of CCN2/CTGF by nuclear translocation of MMP3 査読

Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Junji Uehara, Toshihiro Ohgawara, Soichiro Ibaragi, Akira Sasaki, Takuo Kuboki, Masaharu Takigawa

CCN Proteins in Health and Disease: An Overview of the Fifth International Workshop on the CCN Family of Genes 255 - 264 2010年

当科におけるインプラント患者の臨床統計的検討

帆波辰基, 目瀬浩, 西山明慶, 岸本晃治, 塚本剛一, 志茂剛, 吉岡徳枝, 銅前昇平, 中妻加奈子, 辻本紗代子, 伊原木聰一郎, 佐々木朗

岡山歯学会雑誌 28 ( 2 ) 151 - 155 2009年12月

Epithelial-Mesenchymal Transition and Cell Cooperativity in Metastasis 査読国際誌

Takanori Tsuji, Soichiro Ibaragi, Guo-fu Hu

CANCER RESEARCH 69 ( 18 ) 7135 - 7139 2009年9月

当科における口腔扁平上皮癌の治療成績(第1報)

岸本晃治, 吉田祥子, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 志茂剛, 塚本剛一, 西山明慶, 目瀬浩, 松村智弘, 佐々木朗

岡山歯学会雑誌 28 ( 1 ) 43 - 50 2009年6月

Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. 査読国際誌

J Zhou, W Huang, R Tao, S Ibaragi, F Lan, Y Ido, X Wu, Y O Alekseyev, M E Lenburg, G-f Hu, Z Luo

Oncogene 28 ( 18 ) 1993 - 2002 2009年5月

記述言語：英語

AMP-activated protein kinase (AMPK) serves as a fuel-sensing enzyme that is activated by binding of AMP and subsequent phophorylation by upstream kinases such as the tumor suppressor LKB1, when cells sense an increase in the ratio of AMP to ATP. Acute activation of AMPK stimulates fatty acid oxidation to generate more ATP and simultaneously inhibits ATP-consuming processes including fatty acid and protein syntheses, thereby preserving energy for acute cell-surviving program, whereas chronic activation leads to inhibition of cell growth. The goal of the present study is to explore the mechanisms by which AMPK regulates cell growth. Toward this end, we established stable cell lines by introducing a dominant-negative mutant of AMPK alpha1 subunit or its shRNA into the prostate cancer C4-2 cells and other cells, or wild type LKB1 into the lung adenocarcinoma A549 and breast MB-MDA-231 cancer cells, both of which lack functional LKB1. Our results showed that the inhibition of AMPK accelerated cell proliferation and promoted malignant behavior such as increased cell migration and anchorage-independent growth. This was associated with decreased G1 population, downregulation of p53 and p21, and upregulation of S6K, IGF-1 and IGF1R. Conversely, treatment of the C4-2 cells with 5-aminoimidazole-4-carboxamide 1-D-ribonucleoside (AICAR), a prototypical AMPK activator, caused opposite changes. In addition, our study using microarray and RT-PCR revealed that AMPK regulated gene expression involved in tumor cell growth and survival. Thus, our study provides novel insights into the mechanisms of AMPK action in cancer cells and presents AMPK as an ideal drug target for cancer therapy.

DOI： 10.1038/onc.2009.63

われわれの施設における顎変形症治療の実態顎変形症学会2006年度全国調査と比較して

江藤司, 西山明慶, 吉岡徳枝, 伊原木聰一郎, 吉田祥子, 尾野裕子, 佐々木朗

日本顎変形症学会雑誌 19 ( 2 ) 121 - 121 2009年5月

Neamine inhibits prostate cancer growth by suppressing angiogenin-mediated rRNA transcription. 査読国際誌

Soichiro Ibaragi, Norie Yoshioka, Shuping Li, Miaofen G Hu, Saori Hirukawa, Peter M Sadow, Guo-Fu Hu

Clinical cancer research : an official journal of the American Association for Cancer Research 15 ( 6 ) 1981 - 8 2009年3月

記述言語：英語

PURPOSE: Angiogenin (ANG) undergoes nuclear translocation and stimulates rRNA transcription in both prostate cancer cells and endothelial cells. The purpose of this study is to assess the antitumor activity of neamine, a nontoxic degradation product of neomycin that blocks nuclear translocation of ANG. EXPERIMENTAL DESIGN: The anti-prostate cancer activity of neamine was first evaluated in a xenograft animal model. It was then examined in the murine prostate-restricted AKT transgenic mice that develop prostate intraepithelial neoplasia (PIN) owing to AKT transgene overexpression. RESULTS: Neamine inhibits xenograft growth of PC-3 human prostate cancer cells in athymic mice. It blocks nuclear translocation of ANG and inhibits rRNA transcription, cell proliferation, and angiogenesis. Neamine also prevents AKT-induced PIN formation as well as reverses fully developed PIN in murine prostate-restricted AKT mice, accompanied by a decrease in rRNA synthesis, cell proliferation, and angiogenesis and an increase in prostate epithelial cell apoptosis. CONCLUSION: We confirmed that ANG is a molecular target for cancer drug development and that blocking nuclear translocation of ANG is an effective means to inhibit its activity. Our results also suggested that neamine is a lead compound for further preclinical evaluation.

DOI： 10.1158/1078-0432.CCR-08-2593

Angiogenin-stimulated rRNA transcription is essential for initiation and survival of AKT-induced prostate intraepithelial neoplasia. 査読国際誌

Soichiro Ibaragi, Norie Yoshioka, Hiroko Kishikawa, Jamie K Hu, Peter M Sadow, Ming Li, Guo-fu Hu

Molecular cancer research : MCR 7 ( 3 ) 415 - 24 2009年3月

記述言語：英語

Angiogenin (ANG), originally identified as an angiogenic ribonuclease, has recently been shown to play a direct role in prostate cancer cell proliferation by mediating rRNA transcription. ANG is up-regulated in human prostate cancer and is the most significantly up-regulated gene in AKT-driven prostate intraepithelial neoplasia (PIN) in mice. Enhanced cell proliferation in the PIN lesions requires increased ribosome biogenesis, a multistep process involving an orchestrated production of ribosomal proteins and rRNA. AKT is known to enhance ribosomal protein production through the mammalian target of rapamycin pathway. However, it was unknown how rRNA is proportionally increased. Here, we report that ANG is essential for AKT-driven PIN formation and survival. We showed that up-regulation of ANG in the AKT-overexpressing mouse prostates is an early and lasting event. It occurs before PIN initiation and lasts beyond PIN is fully developed. Knocking down ANG expression by intraprostate injection of lentivirus-mediated ANG-specific small interfering RNA prevents AKT-induced PIN formation without affecting AKT expression and its signaling through the mammalian target of rapamycin pathway. Neomycin, an aminoglycoside that blocks nuclear translocation of ANG, and N65828, a small-molecule enzymatic inhibitor of the ribonucleolytic activity of ANG, both prevent AKT-induced PIN formation and reverse established PIN. They also decrease nucleolar organizer region, restore cell size, and normalize luminal architectures of the prostate despite continuous activation of AKT. All three types of the ANG inhibitor suppress rRNA transcription of the prostate luminal epithelial cells and inhibit AKT-induced PIN, indicating an essential role of ANG in AKT-mediated cell proliferation and survival.

DOI： 10.1158/1541-7786.MCR-08-0137

Epithelial-Mesenchymal Transition Induced by Growth Suppressor p12(CDK2-AP1) Promotes Tumor Cell Local Invasion but Suppresses Distant Colony Growth 査読国際誌

Takanori Tsuji, Soichiro Ibaragi, Kaori Shima, Miaofen G. Hu, Miki Katsurano, Akira Sasaki, Guo-fu Hui

CANCER RESEARCH 68 ( 24 ) 10377 - 10386 2008年12月

Nicotine promotes mammary tumor migration via a signaling cascade involving protein kinase C and CDC42. 査読国際誌

Jinjin Guo, Soichiro Ibaragi, Tongbo Zhu, Ling-Yu Luo, Guo-Fu Hu, Petra S Huppi, Chang Yan Chen

Cancer research 68 ( 20 ) 8473 - 81 2008年10月

記述言語：英語

Nicotine, one of the major components in tobacco, is at high concentrations in the bloodstream of cigarette smokers. However, the mechanisms of how nicotine affects tumor development and whether nicotine is a potential carcinogen for malignancies induced by secondhand smoking are not fully understood yet. Here, we investigate the signaling pathways by which nicotine potentiates tumorigenesis in human mammary epithelial-like MCF10A or cancerous MCF7 cells. We show that human MCF10A and MCF7 cells both express four subunits of nicotine acetylcholine receptor (nAChR). The treatment of these cells with nicotine enhances the activity of protein kinase C (PKC) alpha without altering the expression level of this kinase. Nicotine also stimulates [(3)H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting in growth promotion. Importantly, on nicotine treatment, the mobility of MCF10A and MCF7 cells is enhanced, which can be blocked by the addition of nAChR or PKC inhibitor. Experiments using small interfering RNA knockdown or ectopic expression of cdc42 showed that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells. Together, our findings suggest that nicotine, through interacting with its receptor, initiates a signaling cascade that involves PKC and cdc42 and consequently promotes migration in mammary epithelial or tumor cells.

DOI： 10.1158/0008-5472.CAN-08-0131

Novel transcription-factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene. 査読国際誌

Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Junji Uehara, Toshihiro Ohgawara, Soichiro Ibaragi, Akira Sasaki, Takuo Kuboki, Masaharu Takigawa

Molecular and cellular biology 28 ( 7 ) 2391 - 413 2008年4月

記述言語：英語

Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.

DOI： 10.1128/MCB.01288-07

SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion 査読国際誌

Hongyun Wang, Irwin Leav, Soichiro Ibaragi, Michael Wegner, Guo-Fu Hu, Michael L. Lu, Steven P. Balk, Xin Yuan

CANCER RESEARCH 68 ( 6 ) 1625 - 1630 2008年3月

Possible Involvement of p38 MAP Kinase in Retinoidstimulated Expression of Indian Hedgehog in Prehypertrophic Chondrocytes 査読

Tsuyoshi Shimo, Eiki Koyama, Soichiro Ibaragi, Naito Kurio, Daisuke Yamamoto, Tatsuo Okui, Koji Kishimoto, Hiroshi Mese, Akira Sasaki

Oral Science International 5 ( 1 ) 1 - 14 2008年

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

Tsuyoshi Shimo, Shinsuke Matsumura, Soichiro Ibaragi, Sachiko Isowa, Koji Kishimoto, Hiroshi Mese, Akiyoshi Nishiyama, Akira Sasaki

JOURNAL OF CELL COMMUNICATION AND SIGNALING 1 ( 2 ) 103 - 111 2007年9月

Docetaxelにより急性呼吸窮迫症候群(ARDS)が生じた口腔癌肺転移症例

目瀬浩, 吉濱泰斗, 中山周子, 伊原木聰一郎, 佐々木朗

癌と化学療法 34 ( 8 ) 1267 - 1269 2007年8月

Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells 査読国際誌

Takanori Tsuji, Miki Katsurano, Soichiro Ibaragi, Kaori Shima, Akira Sasaki, Guo-fu Hu

BIOCHEMISTRY 46 ( 31 ) 8920 - 8932 2007年8月

末期口腔癌患者の褥瘡に対してチーム医療で取り組んだ1症例査読

梅原亜矢子, 中山周子, 塚本剛一, 矢尾真弓, 伊原木聰一郎, 岸本晃治, 目瀬浩, 佐々木朗

岡山歯学会雑誌 26 ( 1 ) 37 - 40 2007年6月

外科的治療とPaclitaxel,Cisplatin,5-FluorouracilによるAdjuvant Chemotherapyが奏効した下顎歯肉癌肺転移症例査読

塚本剛一, 伊原木聰一郎, 志茂剛, 大山和彦, 岸本晃治, 目瀬浩, 青江基, 木浦勝行, 佐々木朗

癌と化学療法 34 ( 4 ) 597 - 600 2007年4月

Pathogenic role of connective tissue growth factor (CTGF/CCN2) in osteolytic metastasis of breast cancer 査読国際誌

Tsuyoshi Shimo, Satoshi Kubota, Norie Yoshioka, Soichiro Ibaragi, Sachiko Isowa, Takanori Eguchi, Akira Sasaki, Masaharu Takigawa

JOURNAL OF BONE AND MINERAL RESEARCH 21 ( 7 ) 1045 - 1059 2006年7月

顎矯正手術で使用した生体内吸収性高分子材料Poly-L-lactic acid(PLLA)により惹起された非感染性膿瘍の1例査読

伊原木聰一郎, 西山明慶, 小野達生, 小野亜希子, 吉濱泰斗, 佐々木朗

日本口腔科学会雑誌 55 ( 3 ) 196 - 196 2006年7月

当科における口腔扁平上皮癌の術後再発および転移の頻度ならびに時期に関する検討査読

岸本晃治, 西山明慶, 万代とし子, 辻本紗代子, 伊原木聰一郎, 銅前昇平, 佐々木朗

岡山歯学会雑誌 24 ( 2 ) 75 - 80 2005年12月

ポリ-L-乳酸製骨接合プレートを用いたLe Fort I型上顎骨骨切り術の術後安定性について査読

小野達生, 西山明慶, 伊原木聰一郎, 辻本紗代子, 塚本剛一, 目瀬浩, 佐々木朗

日本顎変形症学会雑誌 15 ( 3 ) 177 - 178 2005年12月

下顎前突症患者における中顔面の評価と審美的改善を考慮した術式に関する検討査読

西山明慶, 吉岡徳枝, 小野達生, 伊原木聰一郎, 桂野美貴, 目瀬浩, 佐々木朗

日本口腔科学会雑誌 54 ( 1 ) 90 - 90 2005年1月

当科における顎矯正手術に対する輸血準備に関する検討査読

磯和幸子, 西山明慶, 矢尾真弓, 伊原木聰一郎, 吉岡徳枝, 小野達生, 銅前昇平, 佐々木朗

日本顎変形症学会雑誌 14 ( 3 ) 224 - 224 2004年12月

下顎前方移動術におけるSSROとIVSROの術後安定性に関する検討査読

西山明慶, 吉岡徳枝, 小野達夫, 銅前昇平, 伊原木聰一郎, 矢尾真弓, 磯和幸子, 佐々木朗

日本顎変形症学会雑誌 14 ( 3 ) 246 - 247 2004年12月

舌癌と歯・補綴物などの機械的刺激に関する臨床的観察査読

伊原木聰一郎, 吉濱泰斗, 銅前昇平, 山田庸介, 塚本剛一, 西山明慶, 木村卓爾, 目瀬浩, 佐々木朗

日本口腔腫瘍学会誌 16 ( 3 ) 151 - 151 2004年9月

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