研究者詳細 - 國定　勇希

論文 - 國定　勇希

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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