Faculty Profiles - NAGATSUKA Hitoshi

Papers - NAGATSUKA Hitoshi

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ニコチンが口腔癌細胞に与える影響の検討

伊原木聰一郎, 清水理恵子, 奥井達雄, 高畠清文, 河合穂高, 小野喜章, 長塚仁, 佐々木朗

日本口腔科学会雑誌 69 ( 3 ) 235 - 235 2020.9

深層学習を用いた歯科インプラントの分類

吉位和将, 助川信太郎, 原武史, 山下勝督, 中野敬介, 長塚仁, 古木良彦

日本医用画像工学会大会予稿集 39回 35 - 35 2020.9

下顎骨にみられた中心性巨細胞肉芽腫の1例

狩野洋輔, 梅田浩嗣, 内田堅一郎, 中島大輔, 二宮史浩, 長塚仁, 三島克章

日本口腔科学会雑誌 69 ( 3 ) 238 - 238 2020.9

深層学習を用いた歯科インプラントの分類

吉位和将, 助川信太郎, 原武史, 山下勝督, 中野敬介, 長塚仁, 古木良彦

日本医用画像工学会大会予稿集 39回 35 - 35 2020.9

深層学習を用いた歯科インプラントの分類

吉位和将, 助川信太郎, 原武史, 山下勝督, 中野敬介, 長塚仁, 古木良彦

日本医用画像工学会大会予稿集 39回 241 - 245 2020.9

Language：Japanese Publisher：(一社)日本医用画像工学会

インプラントには多くのブランドがあり,メーカーごとに独自に開発されている.患者のインプラントのメンテナンスをする際にはブランドを特定する必要があるが,一人に対して異なるブランドのインプラントが異なる歯科医によって埋入されることが頻繁にあり,歯科医の間で共有される情報がなく特定するのは困難である.歯科パノラマX線画像からは特定に必要な情報を得ることができるが,これを行うには歯科医の努力と経験が必要になる.本研究の目的は,深層学習を用いて歯科パノラマX線画像からインプラントの分類を行い,歯科医や患者の負担軽減に寄与することである.畳み込み層が6つのCNNと,VGG16とVGG19の転移学習及びファインチューニングモデルでの分類精度を評価した.5つのモデルのうちVGG16のファインチューニングが94%と最も高い精度を示し,インプラントの分類において深層学習が有用である可能性が示唆された.(著者抄録)

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Risk Factors for Mandibular Fracture After Marginal Mandibular Resection

Shintaro Sukegawa, Masato Saika, Ryo Tamamura, Norio Yamamoto, Keisuke Nakano, Hitoshi Nagatsuka, Yoshihiko Furuki

The Journal of craniofacial surgery 31 ( 5 ) 1430 - 1433 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

PURPOSE: This study aimed to examine the relationship between post-operative mandibular fractures and its predictable risk factors in patients with marginal mandibular resection. Additionally, the timing of post-operative mandibular fractures was assessed. PATIENTS AND METHODS: Records of 37 patients with mandibular gingival carcinoma who underwent marginal mandibular resection at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from April 2011 to March 2019 were retrospectively analyzed. The following variables were investigated: age, sex, location of carcinoma, tumor size, mandibular height on the surgical and healthy sides, surgical approach, number of residual teeth, post-operative radiotherapy, chemotherapy, and the presence or absence of diabetes and osteoporosis. Various risk factors for post-operative mandibular fractures were statistically investigated. RESULTS: Post-operative mandibular fracture was observed in 5 (13.5%) of the 37 mandibular marginal resection cases. The average residual mandibular height in patients with post-operative mandibular fracture was 8.5 mm. A significant difference in residual mandibular height (P = 0.013) was observed between patients with post-operative mandibular fracture and those with no fracture. The average time to post-operative fracture of the mandible was 305.4 days, and it was found to be correlated to the remaining height of the mandibular body. CONCLUSIONS: A decrease in mandibular height below 9 mm results in post-operative mandibular fracture. Furthermore, a correlation between the height of the mandibular bone and the period until the post-operative mandibular fracture was noted in this study. These findings contribute to the prediction and management of mandibular fractures after mandibular margin resection.

DOI： 10.1097/SCS.0000000000006636

Maxillofacial Trauma Surgery Patients With Titanium Osteosynthesis Miniplates: Remove or Not?

Shintaro Sukegawa, Masanori Masui, Yuka Sukegawa-Takahashi, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

The Journal of craniofacial surgery 31 ( 5 ) 1338 - 1342 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

The authors examined the timing and causes of titanium miniplate removal after maxillofacial trauma surgery. The authors performed a retrospective study of maxillofacial fracture patients in whom maxillofacial osteosynthesis miniplates were inserted or removed at the Kagawa Prefectural Central Hospital, between 2008 and 2017. Predictive variables were age, sex, fracture site distribution, and time to miniplate removal with or without complications in relation to primary outcome variables. Among 185 patients, 440 miniplates were inserted and 272 miniplates were removed. In total, 116 patients (73.4%) had 282 miniplates (64.1%) removed, of which 4.8% fracture sites and 5.7% miniplates were removed because of complications. The mean time to miniplate removal was 630.9 and 258.0 days in patients with and without complications, respectively. There was a statistically significant difference in miniplate removal and miniplate retention relative to age and sex. This difference was not related to the presence or absence of sex- or age-related complications. The miniplates as osteosynthesis material were safe and useful for a long period of time with relatively few complications. Because complications requiring miniplate removal occurred within 1 or after 5 years postoperatively, osteosynthesis miniplate treatments should be decided while considering the patient's age and sex. Long-term follow-up is recommended for miniplates that remain implanted for >1 year.

DOI： 10.1097/SCS.0000000000006352

Biomechanical loading comparison between titanium and bioactive resorbable screw systems for fixation of intracapsular condylar head fractures International journal

Shintaro Sukegawa, Norio Yamamoto, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Takahiro Kanno, Hitoshi Nagatsuka, Yoshihiko Furuki

Materials 13 ( 14 ) 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Osteosynthesis resorbable materials made of uncalcined and unsintered hydroxyapatite (u-HA) particles, poly-L-lactide (PLLA), are bioresorbable, and these materials have feasible bioactive/osteoconductive capacities. However, their strength and stability for fixation in mandibular condylar head fractures remain unclear. This in vitro study aimed to assess the biomechanical strength of u-HA/PLLA screws after the internal fixation of condylar head fractures. To evaluate their biomechanical behavior, 32 hemimandible replicas were divided into eight groups, each consisting of single-screw and double-screw fixations with titanium or u-HA/PLLA screws. A linear load was applied as vertical and horizontal load to each group to simulate the muscular forces in condylar head fractures. Samples were examined for 0.5, 1, 2, and 3-mm displacement loads. Two screws were needed for stable fixation of the mandibular condylar head fracture during biomechanical evaluation. After screw fixation for condylar head fractures, the titanium screws model was slightly more resistant to vertical and horizontal movement with a load for a small displacement than the u-HA/PLLA screws model. There was no statistically significant difference with load for large displacements. The u-HA/PLLA screw has a low mechanical resistance under small displacement loading compared with titanium within the limits of the mandibular head fracture model study.

DOI： 10.3390/ma13143153

Deep neural networks for dental implant system classification International journal

Shintaro Sukegawa, Kazumasa Yoshii, Takeshi Hara, Katsusuke Yamashita, Keisuke Nakano, Norio Yamamoto, Hitoshi Nagatsuka, Yoshihiko Furuki

Biomolecules 10 ( 7 ) 1 - 13 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic radiographs obtained from patients who underwent dental implant treatment at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2019. Five deep CNN models (specifically, a basic CNN with three convolutional layers, VGG16 and VGG19 transfer-learning models, and finely tuned VGG16 and VGG19) were evaluated for implant classification. Among the five models, the finely tuned VGG16 model exhibited the highest implant classification performance. The finely tuned VGG19 was second best, followed by the normal transfer-learning VGG16. We confirmed that the finely tuned VGG16 and VGG19 CNNs could accurately classify dental implant systems from 11 types of panoramic X-ray images.

DOI： 10.3390/biom10070984

口腔扁平上皮癌の腫瘍微小環境における骨髄由来細胞の分化と役割

高畠清文, 河合穂高, Oo May Wathone, 吉田沙織, 大森悠加, 中野敬介, 辻極秀次, 長塚仁

日本口腔科学会雑誌 69 ( 2 ) 132 - 132 2020.7

Patient-derived xenograftモデルを用いた腫瘍間質による腫瘍実質の生物学的性格制御の検討

高畠清文, 河合穂高, 大森悠加, Oo May Wathone, 吉田沙織, 中野敬介, 長塚仁

日本口腔科学会雑誌 69 ( 2 ) 132 - 133 2020.7

Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver International journal

Mariko Seyama, Kaya Yoshida, Kayo Yoshida, Natsumi Fujiwara, Kisho Ono, Takanori Eguchi, Hotaka Kawai, Jiajie Guo, Yao Weng, Yuan Haoze, Kenta Uchibe, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Kuniaki Okamoto, Hirohiko Okamura, Kazumi Ozaki

Biochimica et Biophysica Acta - Molecular Basis of Disease 1866 ( 6 ) 165731 - 165731 2020.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Outer membrane vesicles (OMVs) are nanosized particles derived from the outer membrane of gram-negative bacteria. Oral bacterium Porphyromonas gingivalis (Pg) is known to be a major pathogen of periodontitis that contributes to the progression of periodontal disease by releasing OMVs. The effect of Pg OMVs on systemic diseases is still unknown. To verify whether Pg OMVs affect the progress of diabetes mellitus, we analyzed the cargo proteins of vesicles and evaluated their effect on hepatic glucose metabolism. Here, we show that Pg OMVs were equipped with Pg-derived proteases gingipains and translocated to the liver in mice. In these mice, the hepatic glycogen synthesis in response to insulin was decreased, and thus high blood glucose levels were maintained. Pg OMVs also attenuated the insulin-induced Akt/glycogen synthase kinase-3 β (GSK-3β) signaling in a gingipain-dependent fashion in hepatic HepG2 cells. These results suggest that the delivery of gingipains mediated by Pg OMV elicits changes in glucose metabolisms in the liver and contributes to the progression of diabetes mellitus.

DOI： 10.1016/j.bbadis.2020.165731

Knockout of MMP3 weakens solid tumor organoids and cancer extracellular vesicles International journal

Eman A. Taha, Chiharu Sogawa, Yuka Okusha, Hotaka Kawai, May Wathone Oo, Abdellatif Elseoudi, Yanyin Lu, Hitoshi Nagatsuka, Satoshi Kubota, Ayano Satoh, Kuniaki Okamoto, Takanori Eguchi

Cancers 12 ( 5 ) 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (200–1000 nm) and small EVs (50–200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 led to a significant reduction in tumoroid size and the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. Moreover, CD63, another member of the tetraspanin family, was significantly reduced only in the EVs fractions of the MMP3-KO cells compared to their counterpart. These weakened phenotypes of MMP3-KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3, resulting in increasing the proliferation and tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

DOI： 10.3390/cancers12051260

Secretory Carcinoma of Salivary Gland with High-Grade Histology Arising in Hard Palate: A Case Report

Kiyofumi Takabatake, Keisuke Nakano, Hotaka Kawai, Saori Yoshida, Haruka Omori, May Wathone Oo, Shan Qiusheng, Kenichiro Uchida, Katsuaki Mishima, Hitoshi Nagatsuka

Reports — Medical Cases, Images, and Videos 3 ( 2 ) 6 - 6 2020.3

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Secretory carcinoma (SC) is a recently described salivary gland tumor reported in the fourth edition of World Health Organization classification of head and neck tumors. SC is characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression, and harbors a t(12;15)(p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, SC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretion. SC is generally recognized as low-grade malignancy with low-grade histopathologic features, and metastasis is relatively uncommon. In this case, we described a SC of hard palate that underwent high grade transformation and metastasis to the cervical lymph node in a 54-year-old patient. In addition, this case showed different histological findings between primary lesion and metastasis lesion. Therefore, the diagnosis was confirmed by the presence of ETV6 translocation. Here, we report a case that occurred SC with high-grade transformation in the palate, and a review of the relevant literature is also presented.

DOI： 10.3390/reports3020006

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エナメル上皮腫開窓術の適応に関する組織学的検討

大森悠加, 高畠清文, 河合穂高, 吉田沙織, メイワト・ウ, 浜田芽衣, 中野敬介, 長塚仁

日本病理学会会誌 109 ( 1 ) 316 - 316 2020.3

間葉系幹細胞由来新規幹細胞を用いたモデルラットの脊髄損傷治療

山崎勤, 中野敬介, 長塚仁, 杉野哲造, 笹井紀明, 中西徹

日本薬学会年会要旨集 140年会 28L - am11 2020.3

口腔癌間質細胞が骨髄由来細胞の動員に与える影響

河合穂高, メイワト・ウ, 辻極秀次, 高畠清文, 大森悠加, 藤井昌江, 中野敬介, 長塚仁

日本病理学会会誌 109 ( 1 ) 315 - 315 2020.3

エナメル上皮腫開窓術の適応に関する組織学的検討

大森悠加, 高畠清文, 河合穂高, 吉田沙織, メイワト・ウ, 浜田芽衣, 中野敬介, 長塚仁

日本病理学会会誌 109 ( 1 ) 316 - 316 2020.3

舌扁平上皮癌の浸潤様式(budding)におけるpodoplaninの関わり

浜田芽衣, 蝦原康宏, 永田耕治, 矢野光剛, 小柏靖直, 中平光彦, 菅澤正, 長塚仁, 安田政実

日本病理学会会誌 109 ( 1 ) 395 - 395 2020.3

腫瘍組織に動員される骨髄由来細胞へ腫瘍間質が及ぼす影響の検討

Oo May Wathone, 河合穂高, 吉田沙織, 高畠清文, 中野敬介, 長塚仁

日本口腔診断学会雑誌 33 ( 1 ) 116 - 116 2020.2

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