研究者詳細 - 國定　勇希

論文 - 國定　勇希

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

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6月

The maxillary vein: an anatomical narrative review with clinical implications for oral and maxillofacial surgeons

Kazzara Raeburn, Yohei Takeshita, Hiroaki Takakura, Shogo Kikuta, Yuki Kunisada, Soichiro Ibaragi, Rarinthorn Samrid, Marios Loukas, R. Shane Tubbs, Joe Iwanaga

Anatomy & Cell Biology 2025年6月

The greater palatine nerve and artery both supply the maxillary teeth

Joe Iwanaga, Yohei Takeshita, Muralidharan Anbalagan, Binghao Zou, Taku Toriumi, Yuki Kunisada, Soichiro Ibaragi, R. Shane Tubbs

The Journal of the American Dental Association 2025年2月

Lingual nerve revisited-A comprehensive review Part II: Surgery and radiology. 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. 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 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

上顎癒合不全の自然治癒を認めたLe Fort I型骨切り術後Floating Maxillaの2症例

西山明慶, 國定勇希, 竜門省二, 小野喜章, 吉岡徳枝, 伊原木聰一郎

日本顎変形症学会雑誌 34 ( 2 ) 167 - 167 2024年5月

細胞外小胞と銅輸送経路調節を介した頭頸部癌におけるシスプラチン耐性機序の解明

小川辰雄, 小野喜章, 小畑協一, 國定勇希, 奥井達雄, 伊原木聰一郎

頭頸部癌 50 ( 2 ) 159 - 159 2024年5月

美容整形目的に使用されたヒアルロン酸によりオトガイ部の骨吸収をきたした顎変形症の2例

吉岡徳枝, 西山明慶, 國定勇希, 坂本裕美, 小野喜章, 小畑協一

日本口腔診断学会雑誌 37 ( 1 ) 85 - 85 2024年2月

Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells. 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

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

A pancreatic cancer mouse model with human immunity. 国際誌

Norio Miyamura, Kodai Suzuki, Richard A Friedman, Aristidis Floratos, Yuki Kunisada, Kazuya Masuda, Andrew M Lowy, Moriya Tsuji, Kazuki N Sugahara

bioRxiv : the preprint server for biology 2023年5月

記述言語：英語

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a tumor immune microenvironment (TIME) that promotes resistance to immunotherapy. A preclinical model system that facilitates studies of the TIME and its impact on the responsiveness of human PDAC to immunotherapies remains an unmet need. We report a novel mouse model, which develops metastatic human PDAC that becomes infiltrated by human immune cells recapitulating the TIME of human PDAC. The model may serve as a versatile platform to study the nature of human PDAC TIME and its response to various treatments.

DOI： 10.1101/2023.05.24.542127

Tumor-resident regulatory T cells in pancreatic cancer express the αvβ5 integrin as a targetable activation marker. 国際誌

Kodai Suzuki, Yuki Kunisada, Norio Miyamura, Shingo Eikawa, Tatiana Hurtado de Mendoza, Evangeline S Mose, Caisheng Lu, Yukihito Kuroda, Erkki Ruoslahti, Andrew M Lowy, Kazuki N Sugahara

bioRxiv : the preprint server for biology 2023年5月

記述言語：英語

Pancreatic ductal adenocarcinoma (PDAC) has abundant immunosuppressive regulatory T cells (Tregs), which contribute to a microenvironment resistant to immunotherapy. Here, we report that Tregs in the PDAC tissue, but not those in the spleen, express the αvβ5 integrin in addition to neuropilin-1 (NRP-1), which makes them susceptible to the iRGD tumor-penetrating peptide, which targets cells positive for αv integrin- and NRP-1. As a result, long-term treatment of PDAC mice with iRGD leads to tumor-specific depletion of Tregs and improved efficacy of immune checkpoint blockade. αvβ5 integrin + Tregs are induced from both naïve CD4 + T cells and natural Tregs upon T cell receptor stimulation, and represent a highly immunosuppressive subpopulation of CCR8 + Tregs. This study identifies the αvβ5 integrin as a marker for activated tumor-resident Tregs, which can be targeted to achieve tumor-specific Treg depletion and thereby augment anti-tumor immunity for PDAC therapy.

DOI： 10.1101/2023.05.24.542137

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

口腔癌の化学療法中に発症した肺血栓塞栓症の1例

柴田茜, 志茂剛, 岸本晃治, 國定勇希, 目瀬浩, 佐々木朗

日本口腔外科学会雑誌 68 ( 4 ) 193 - 200 2022年4月

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

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

High mobility group box 1は口腔扁平上皮癌の骨破壊を誘発する

坂本裕美, 奥井達雄, 竜門省二, 中村友哉, 國定勇希, 増井正典, 小野喜章, 小畑協一, 伊原木聰一郎, 佐々木朗

日本口腔科学会雑誌 70 ( 2 ) 115 - 115 2021年7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 (Basel, Switzerland) 11 ( 6 ) 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction.

DOI： 10.3390/diagnostics11061044

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

In younger patients of LCH, we should consider that the effectiveness of follow-up without aggressive treatment for SS-type LCH in the oral and maxillofacial bone. However, there are very rare case in which an SS-type LCH recurred after showing a healing tendency. Regular follow-up must be performed even after healing.

DOI： 10.1002/ccr3.4321

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.4321

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

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

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

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

顎骨壊死を伴ったEBV陽性皮膚粘膜潰瘍(EBV-MCU)の2例

竜門省二, 岸本晃治, 奥井達雄, 吉岡徳枝, 小畑協一, 國定勇希, 増井正典, 小野喜章, 伊原木聰一郎, 佐々木朗

日本口腔診断学会雑誌 34 ( 1 ) 71 - 71 2021年2月

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

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

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：Spandidos Publications

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

顎矯正手術における偶発骨折の要因と対応について

吉岡徳枝, 西山明慶, 奥井達雄, 竜門省二, 國定勇希, 伊原木聰一郎, 佐々木朗

日本顎変形症学会雑誌 30 ( 2 ) 136 - 136 2020年5月

Expression and Role of IL-1β 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3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.

DOI： 10.3390/ijms21072365

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

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

当科における著名人のマスコミへの病名公表による受診率の影響について

柴田茜, 岸本晃治, 小畑協一, 國定勇希, 吉岡徳枝, 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 38 ( 2 ) 92 - 92 2019年12月

Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects. 査読国際誌

Yuki Kunisada

International immunology 31 ( 4 ) 187 - 198 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated anti-tumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent. Moreover, the inhibitory effect seen in SCID was abrogated by anti-CD11b antibody injection. PMN-MDSCs were significantly reduced in both spleens and tumors following Met treatment. In TAMs, production of IL-12 and TNF-α, but not IL-10, became apparent, and elevation of MHC class II with reduction of CD206 was observed, indicating a shift from an M2- to M1-like phenotype via Met administration. Metabolically, Met treatment decreased basal respiration and the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) ratio of CD11b+ cells in tumors, but not in the spleen. In addition, decreased reactive oxygen species (ROS) production and proton leakage in MDSCs and TAMs were consistently observed in tumors. Uptake of both 2-deoxy-2-d-glucose (2-NBDG) and BODIPY® decreased in MDSCs, but only BODIPY® incorporation was decreased in TAMs. Overall, our results suggest that Met redirects the metabolism of CD11b+ cells to lower oxidative phosphorylation (OXPHOS) while elevating glycolysis, thereby pushing the microenvironment to a state that inhibits the growth of certain tumors.

DOI： 10.1093/intimm/dxy079

顎放射線菌症治療中に発症した急性出血性直腸潰瘍の1例

長谷川利聡, 奥井達雄, 伊原木聰一郎, 國定勇希, 竜門省二, 佐々木朗

日本口腔外科学会雑誌 65 ( 2 ) 105 - 109 2019年2月

Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression. 査読国際誌

33 ( 1 ) 85 - 91 2019年

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

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

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

Attenuation of CD4(+) CD25(+) Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug 査読国際誌

Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono

EBIOMEDICINE 25 154 - 164 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

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

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: In recent years, patients with orthognathic surgery in middle-aged and elderly people have come to be a more frequent occurrence. Breast cancer is the most frequently diagnosed cancer in woman worldwide, and its prevalence rate is steadily increasing. PRESENTATION OF CASE: We report a case of a 47-year-old Japanese woman in whom left-side breast cancer (Stage 1) was unexpectedly found just before orthognathic surgery in April 2012. Breast-conserving surgery was performed (estrogen receptor+, progesterone receptor+, HER2 -, surgical margin+, sentinel lymph node +) that May. From June to August docetaxel (75mg/m2) and cyclophosphamide (600mg/m2) were administrated four times every 21days and thereafter radiotherapy (total 60Gy) was completed. The cancer surgeon declared the prognosis good and the patient had a strong desire to undergo orthognathic surgery, so in November we performed a bimaxillary osteotomy, and administration of tamoxifen began 6 weeks after the osteotomy. DISCUSSION: There are breast cancer cases in which the prognosis is sufficiently good for a planned orthognathic surgery to proceed. Good communication among surgeons and the patient is important. CONCLUSION: We experienced a case in which breast cancer was found just before the orthognathic surgery; we performed a bimaxillary osteotomy, including follow-up tamoxifen administration, during breast cancer treatment.

DOI： 10.1016/j.ijscr.2016.12.014

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

119 ( 6 ) 4352 - 4360 2017年

Maxillofacial Fractures in Elderly Patients. 査読

2017年

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

Masui M, Shimo T, Yoshioka N, Ibaragi S, Okui T, Kunisada Y, Yao M, Yoshida S, Murase Y, Kishimoto K, Nishiyama A, Soga Y, Sasaki A

International Journal of Surgery & Surgical Procedures 2 ( 1 ) 1 - 7 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

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

２型糖尿病薬メトホルミンの制御性T細胞抑制による抗腫瘍効果. 査読

國定勇希

岡山歯学会雑誌 35 ( 1 ) 2016年

腫瘍局所のmyeloid-derived suppressor cells(MDSCs)に与えるメトホルミン投与の効果

上原健敬, 榮川伸吾, 國定勇希, 渡邉元嗣, 一柳朋子, 山崎千尋, 尾崎敏文, 鵜殿平一郎

日本癌学会総会記事 74回 P - 2109 2015年10月

岡山大学病院腫瘍センターにおけるビスフォスフォネート使用患者に対する当科の取り組み

吉岡徳枝, 矢尾真弓, 曽我賢彦, 杉浦裕子, 柴田茜, 國定勇希, 黒田大雅, 伊原木聰一郎, 目瀬浩, 佐々木朗

日本口腔科学会雑誌 62 ( 1 ) 57 - 57 2013年1月

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