2024/11/22 更新

写真a

ナカノ ケイスケ
中野 敬介
NAKANO Keisuke
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士(歯学) ( 1999年3月   岡山大学 )

  • 修士(学術) ( 1994年3月   北里大学 )

研究分野

  • ライフサイエンス / 病態系口腔科学

所属学協会

  • 日本口腔腫瘍学会

    2020年10月 - 現在

  • 日本臨床細胞学会

    2007年4月 - 現在

  • 日本病理学会

    2007年4月 - 現在

  • 日本臨床口腔病理学会

    2007年4月 - 現在

  • NPO法人口腔がん早期発見システム全国ネットワーク

    2007年1月 - 現在

  • 硬組織再生生物学会

    2000年1月 - 現在

  • 歯科基礎医学会

    2000年1月 - 現在

▼全件表示

委員歴

  • 硬組織再生生物学会   将来検討委員  

    2020年8月 - 現在   

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    団体区分:学協会

  • 日本臨床口腔病理学会   教育委員会  

    2018年6月 - 現在   

  • 日本臨床口腔病理学会   評議員  

    2014年9月 - 現在   

  • 日本病理学会   学術評議員  

    2012年4月 - 現在   

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    団体区分:学協会

  • 歯科基礎医学会   代議員  

    2010年5月 - 現在   

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    団体区分:学協会

 

論文

  • Effect of Scaffold Geometrical Structure on Macrophage Polarization during Bone Regeneration Using Honeycomb Tricalcium Phosphate. 査読 国際誌

    Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Keisuke Nakano, Anqi Chang, Tianyan Piao, Yasunori Inada, Takuma Arashima, Ayumi Morimatsu, Ayumi Tanaka, Hotaka Kawai, Hitoshi Nagatsuka

    Materials (Basel, Switzerland)   17 ( 16 )   2024年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The polarization balance of M1/M2 macrophages with different functions is important in osteogenesis and bone repair processes. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which is a cylindrical scaffold with a honeycomb arrangement of straight pores, and we demonstrated that TCP with 300 and 500 μm pore diameters (300TCP and 500TCP) induced bone formation within the pores. However, the details of the influence of macrophage polarization on bone formation using engineered biomaterials, especially with respect to the geometric structure of the artificial biomaterials, are unknown. In this study, we examined whether differences in bone tissue formation due to differences in TCP geometry were due to the polarity of the assembling macrophages. Immunohistochemistry for IBA-1, iNOS, and CD163 single staining was performed. The 300TCP showed a marked infiltration of iNOS-positive cells, which are thought to be M1 macrophages, during the osteogenesis process, while no involvement of CD163-positive cells, which are thought to be M2 macrophages, was observed in the TCP pores. In addition, 500TCP showed a clustering of iNOS-positive cells and CD163-positive cells at 2 weeks, suggesting the involvement of M2 macrophages in the formation of bone tissue in the TCP pores. In conclusion, we demonstrated for the first time that the geometrical structure of the artificial biomaterial, i.e., the pore size of honeycomb TCP, affects the polarization of M1/2 macrophages and bone tissue formation in TCP pores.

    DOI: 10.3390/ma17164108

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  • Training high-performance deep learning classifier for diagnosis in oral cytology using diverse annotations. 査読 国際誌

    Shintaro Sukegawa, Futa Tanaka, Keisuke Nakano, Takeshi Hara, Takanaga Ochiai, Katsumitsu Shimada, Yuta Inoue, Yoshihiro Taki, Fumi Nakai, Yasuhiro Nakai, Takanori Ishihama, Ryo Miyazaki, Satoshi Murakami, Hitoshi Nagatsuka, Minoru Miyake

    Scientific reports   14 ( 1 )   17591 - 17591   2024年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The uncertainty of true labels in medical images hinders diagnosis owing to the variability across professionals when applying deep learning models. We used deep learning to obtain an optimal convolutional neural network (CNN) by adequately annotating data for oral exfoliative cytology considering labels from multiple oral pathologists. Six whole-slide images were processed using QuPath for segmenting them into tiles. The images were labeled by three oral pathologists, resulting in 14,535 images with the corresponding pathologists' annotations. Data from three pathologists who provided the same diagnosis were labeled as ground truth (GT) and used for testing. We investigated six models trained using the annotations of (1) pathologist A, (2) pathologist B, (3) pathologist C, (4) GT, (5) majority voting, and (6) a probabilistic model. We divided the test by cross-validation per slide dataset and examined the classification performance of the CNN with a ResNet50 baseline. Statistical evaluation was performed repeatedly and independently using every slide 10 times as test data. For the area under the curve, three cases showed the highest values (0.861, 0.955, and 0.991) for the probabilistic model. Regarding accuracy, two cases showed the highest values (0.988 and 0.967). For the models using the pathologists and GT annotations, many slides showed very low accuracy and large variations across tests. Hence, the classifier trained with probabilistic labels provided the optimal CNN for oral exfoliative cytology considering diagnoses from multiple pathologists. These results may lead to trusted medical artificial intelligence solutions that reflect diverse diagnoses of various professionals.

    DOI: 10.1038/s41598-024-67879-w

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  • 【頭頸部腫瘍II-上気道・口腔・顎顔面骨腫瘍-】口腔・歯原性・顎顔面骨腫瘍のWHO分類改訂のポイント

    中野 敬介, 長塚 仁

    病理と臨床   42 ( 7 )   0670 - 0675   2024年7月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • 【頭頸部腫瘍II-上気道・口腔・顎顔面骨腫瘍-】口腔・歯原性・顎顔面骨腫瘍のWHO分類改訂のポイント

    中野 敬介, 長塚 仁

    病理と臨床   42 ( 7 )   0670 - 0675   2024年7月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma. 査読 国際誌

    Htoo Shwe Eain, Hotaka Kawai, Masaaki Nakayama, May Wathone Oo, Toshiaki Ohara, Yoko Fukuhara, Kiyofumi Takabatake, Quisheng Shan, Yamin Soe, Kisho Ono, Keisuke Nakano, Nobuyoshi Mizukawa, Seiji Iida, Hitoshi Nagatsuka

    JCI insight   9 ( 10 )   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro-tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph-circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.

    DOI: 10.1172/jci.insight.174618

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  • 口腔癌間質による腫瘍実質の生物学的性格制御について

    高畠 清文, チャン・アンチ, ピャオ・ティンヤン, リー・ズウシャオ, 河合 穂高, 中野 敬介, 長塚 仁

    日本病理学会会誌   113 ( 1 )   353 - 353   2024年2月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌腫瘍間質が腫瘍関連マクロファージの集簇・分化に与える影響について

    Piao Tianyan, 高畠 清文, Chan Anqi, 河合 穂高, 中野 敬介, 長塚 仁

    岡山歯学会雑誌   42 ( 2 )   70 - 71   2023年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • 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

    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 )   2023年11月

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

    Abstract

    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

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    その他リンク: https://link.springer.com/article/10.1186/s12903-023-03586-8/fulltext.html

  • Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists. 査読 国際誌

    Shintaro Sukegawa, Sawako Ono, Futa Tanaka, Yuta Inoue, Takeshi Hara, Kazumasa Yoshii, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Shimada Katsumitsu, Fumi Nakai, Yasuhiro Nakai, Ryo Miyazaki, Satoshi Murakami, Hitoshi Nagatsuka, Minoru Miyake

    Scientific reports   13 ( 1 )   11676 - 11676   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis.

    DOI: 10.1038/s41598-023-38343-y

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  • 口腔扁平上皮癌の病理組織学的診断におけるAI深層学習補助診断の効果検討

    助川 信太郎, 中野 敬介, 小野 佐和子, 嶋田 勝光, 高畠 清文, 河合 穂高, 村上 聡, 長塚 仁, 三宅 実

    日本口腔科学会雑誌   72 ( 2 )   131 - 132   2023年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 骨髄由来間葉系幹細胞の新規採取技術および骨髄由来間葉系幹細胞移植法の確立

    河合 穂高, メイワトゥ, 高畠 清文, 佐能 彰, 中野 敬介, 宝田 剛, 長塚 仁

    日本口腔科学会雑誌   72 ( 2 )   134 - 134   2023年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • Enzyme-Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem Cells. 査読 国際誌

    Hotaka Kawai, May Wathone Oo, Kiyofumi Takabatake, Ikue Tosa, Yamin Soe, Htoo Shwe Eain, Sho Sanou, Shigeko Fushimi, Shintaro Sukegawa, Keisuke Nakano, Takarada Takeshi, Hitoshi Nagatsuka

    JBMR plus   7 ( 3 )   e10722   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mesenchymal stem cell (MSC) therapy is a promising approach to curing bone diseases and disorders. In treating genetic bone disorders, MSC therapy is local or systemic transplantation of isolated and in vitro proliferated MSC rather than bone marrow transplantation. Recent evidence showed that bone marrow MSC engraftment to bone regeneration has been controversial in animal and human studies. Here, our modified bone marrow transplantation (BMT) method solved this problem. Like routine BMT, our modified method involves three steps: (i) isolation of bone marrow cells from the donor, (ii) whole-body lethal irradiation to the recipient, and (iii) injection of isolated bone marrow cells into irradiated recipient mice via the tail vein. The significant modification is imported at the bone marrow isolation step. While the bone marrow cells are flushed out from the bone marrow with the medium in routine BMT, we applied the enzymes' (collagenase type 4 and dispase) integrated medium to wash out the bone marrow cells. Then, cells were incubated in enzyme integrated solution at 37°C for 10 minutes. This modification designated BMT as collagenase-integrated BMT (c-BMT). Notably, successful engraftment of bone marrow MSC to the new bone formation, such as osteoblasts and chondrocytes, occurs in c-BMT mice, whereas routine BMT mice do not recruit bone marrow MSC. Indeed, flow cytometry data showed that c-BMT includes a higher proportion of LepR+, CD51+, or RUNX2+ non-hematopoietic cells than BMT. These findings suggested that c-BMT is a time-efficient and more reliable technique that ensures the disaggregation and collection of bone marrow stem cells and engraftment of bone marrow MSC to the recipient. Hence, we proposed that c-BMT might be a promising approach to curing genetic bone disorders. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

    DOI: 10.1002/jbm4.10722

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  • CX3CL1の口腔癌リンパ節転移における役割の検討

    河合 穂高, トゥシュ・エイン, 高畠 清文, 中野 敬介, 長塚 仁

    日本病理学会会誌   112 ( 1 )   263 - 263   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Novel Artificial Scaffold for Bone Marrow Regeneration: Honeycomb Tricalcium Phosphate. 査読 国際誌

    Yasunori Inada, Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Keisuke Nakano, Qiusheng Shan, Tianyan Piao, Anqi Chang, Hotaka Kawai, Hitoshi Nagatsuka

    Materials (Basel, Switzerland)   16 ( 4 )   2023年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bone marrow is complex structure containing heterogenetic cells, making it difficult to regenerate using artificial scaffolds. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which is a cylindrical scaffold with a honeycomb arrangement of straight pores, and we demonstrated that TCP with 300 and 500 μm pore diameters (300TCP and 500TCP) induced bone marrow structure within the pores. In this study, we examined the optimal scaffold structure for bone marrow with homeostatic bone metabolism using honeycomb TCP. 300TCP and 500TCP were transplanted into rat muscle, and bone marrow formation was histologically assessed. Immunohistochemistry for CD45, CD34, Runt-related transcription factor 2 (Runx2), c-kit single staining, Runx2/N-cadherin, and c-kit/Tie-2 double staining was performed. The area of bone marrow structure, which includes CD45(+) round-shaped hematopoietic cells and CD34(+) sinusoidal vessels, was larger in 300TCP than in 500TCP. Additionally, Runx2(+) osteoblasts and c-kit(+) hematopoietic stem cells were observed on the surface of bone tissue formed within TCP. Among Runx2(+) osteoblasts, spindle-shaped N-cadherin(+) cells existed in association with c-kit(+)Tie-2(+) hematopoietic stem cells on the bone tissue formed within TCP, which formed a hematopoietic stem cell niche similar to as in vivo. Therefore, honeycomb TCP with 300 μm pore diameters may be an artificial scaffold with an optimal geometric structure as a scaffold for bone marrow formation.

    DOI: 10.3390/ma16041393

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  • 腫瘍微小環境における間質細胞は口腔扁平上皮癌の進行を促進する(Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma) 査読

    Shan Qiusheng, 高畠 清文, 河合 穂高, Oo May Wathone, 稲田 靖則, 中野 敬介, 長塚 仁

    日本口腔診断学会雑誌   36 ( 1 )   79 - 79   2023年2月

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    記述言語:英語   出版者・発行元:(一社)日本口腔診断学会  

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  • 癌の骨破壊病変に対する銅のキレートを応用した治療に関する基礎的検討 査読

    佐々木 朗, 坂本 裕美, 中野 敬介, 金本 栄華, 吉岡 徳枝, 竜門 省二, 西山 明慶, 志茂 剛, 伊原木 聰一郎

    日本口腔診断学会雑誌   36 ( 1 )   56 - 56   2023年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • 癌の骨破壊病変に対する銅のキレートを応用した治療に関する基礎的検討 査読

    佐々木 朗, 坂本 裕美, 中野 敬介, 金本 栄華, 吉岡 徳枝, 竜門 省二, 西山 明慶, 志茂 剛, 伊原木 聰一郎

    日本口腔診断学会雑誌   36 ( 1 )   56 - 56   2023年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • 腫瘍微小環境における間質細胞は口腔扁平上皮癌の進行を促進する(Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma)

    Shan Qiusheng, 高畠 清文, 河合 穂高, Oo May Wathone, 稲田 靖則, 中野 敬介, 長塚 仁

    日本口腔診断学会雑誌   36 ( 1 )   79 - 79   2023年2月

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    記述言語:英語   出版者・発行元:(一社)日本口腔診断学会  

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  • 癌の骨破壊病変に対する銅のキレートを応用した治療に関する基礎的検討

    佐々木 朗, 坂本 裕美, 中野 敬介, 金本 栄華, 吉岡 徳枝, 竜門 省二, 西山 明慶, 志茂 剛, 伊原木 聰一郎

    日本口腔内科学会雑誌   28 ( 2 )   80 - 80   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔内科学会  

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  • Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line-derived xenograft model. 査読 国際誌

    Qiusheng Shan, Kiyofumi Takabatake, Haruka Omori, Hotaka Kawai, May Wathone Oo, Shintaro Sukegawa, Masae Fujii, Yasunori Inada, Sho Sano, Keisuke Nakano, Hitoshi Nagatsuka

    Oncology letters   24 ( 5 )   382 - 382   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue-derived stromal cells (G-SCs and P-SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate-resistant acid phosphatase staining in a cell line-derived xenograft model. The results demonstrated that G-SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC-3 cell line, whereas P-SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC-3 cells. Furthermore, the effects of G-SCs, P-SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)-9, membrane type 1 MMP (MT1-MMP), Snail, parathyroid hormone-related peptide (PTHrP) and receptor activator of NF-κB ligand (RANKL) in HSC-3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G-SCs had a more prominent effect on the expression of MMP-9, MT1-MMP, Snail, PTHrP, and RANKL, whereas P-SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP-9, MT1-MMP and Snail expression. The potential genes underlying the differential effects of G-SCs and P-SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin-dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G-SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P-SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.

    DOI: 10.3892/ol.2022.13502

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  • SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma. 査読 国際誌

    May Wathone Oo, Hotaka Kawai, Htoo Shwe Eain, Yamin Soe, Kiyofumi Takabatake, Sho Sanou, Qiusheng Shan, Yasunori Inada, Masae Fujii, Yoko Fukuhara, Ziyi Wang, Shintaro Sukegawa, Mitsuaki Ono, Keisuke Nakano, Hitoshi Nagatsuka

    Biomedicines   10 ( 11 )   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tumor angiogenesis is one of the hallmarks of solid tumor development. The progressive tumor cells produce the angiogenic factors and promote tumor angiogenesis. However, how the tumor stromal cells influence tumor vascularization is still unclear. In the present study, we evaluated the effects of oral squamous cell carcinoma (OSCC) stromal cells on tumor vascularization. The tumor stromal cells were isolated from two OSCC patients with different subtypes: low invasive verrucous squamous carcinoma (VSCC) and highly invasive squamous cell carcinoma (SCC) and co-xenografted with the human OSCC cell line (HSC-2) on nude mice. In comparison, the CD34+ vessels in HSC-2+VSCC were larger than in HSC-2+SCC. Interestingly, the vessels in the HSC-2+VSCC expressed vascular endothelial cadherin (VE-cadherin), indicating well-formed vascularization. Our microarray data revealed that the expression of extracellular superoxide dismutase, SOD3 mRNA is higher in VSCC stromal cells than in SCC stromal cells. Moreover, we observed that SOD3 colocalized with VE-cadherin on endothelial cells of low invasive stroma xenograft. These data suggested that SOD3 expression in stromal cells may potentially regulate tumor vascularization in OSCC. Thus, our study suggests the potential interest in SOD3-related vascular integrity for a better OSCC therapeutic strategy.

    DOI: 10.3390/biomedicines10112729

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  • Deep learning model for analyzing the relationship between mandibular third molar and inferior alveolar nerve in panoramic radiography. 査読 国際誌

    Shintaro Sukegawa, Futa Tanaka, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Scientific reports   12 ( 1 )   16925 - 16925   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In this study, the accuracy of the positional relationship of the contact between the inferior alveolar canal and mandibular third molar was evaluated using deep learning. In contact analysis, we investigated the diagnostic performance of the presence or absence of contact between the mandibular third molar and inferior alveolar canal. We also evaluated the diagnostic performance of bone continuity diagnosed based on computed tomography as a continuity analysis. A dataset of 1279 images of mandibular third molars from digital radiographs taken at the Department of Oral and Maxillofacial Surgery at a general hospital (2014-2021) was used for the validation. The deep learning models were ResNet50 and ResNet50v2, with stochastic gradient descent and sharpness-aware minimization (SAM) as optimizers. The performance metrics were accuracy, precision, recall, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). The results indicated that ResNet50v2 using SAM performed excellently in the contact and continuity analyses. The accuracy and AUC were 0.860 and 0.890 for the contact analyses and 0.766 and 0.843 for the continuity analyses. In the contact analysis, SAM and the deep learning model performed effectively. However, in the continuity analysis, none of the deep learning models demonstrated significant classification performance.

    DOI: 10.1038/s41598-022-21408-9

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  • Lip pleomorphic adenomas: case series and literature review 査読

    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

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

    DOI: 10.21037/gs-22-308

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  • Elucidation of ameloblastoma fenestration mechanism via HIF-1α(和訳中) 査読

    Inada Yasunori, Takabatake Kiyofumi, Fujii Masae, Tianyan Piao, Angi Chang, Kawai Hotaka, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   31 ( 4 )   272 - 272   2022年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • Effective deep learning for oral exfoliative cytology classification. 査読 国際誌

    Shintaro Sukegawa, Futa Tanaka, Keisuke Nakano, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Sawako Ono, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Scientific reports   12 ( 1 )   13281 - 13281   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The use of sharpness aware minimization (SAM) as an optimizer that achieves high performance for convolutional neural networks (CNNs) is attracting attention in various fields of deep learning. We used deep learning to perform classification diagnosis in oral exfoliative cytology and to analyze performance, using SAM as an optimization algorithm to improve classification accuracy. The whole image of the oral exfoliation cytology slide was cut into tiles and labeled by an oral pathologist. CNN was VGG16, and stochastic gradient descent (SGD) and SAM were used as optimizers. Each was analyzed with and without a learning rate scheduler in 300 epochs. The performance metrics used were accuracy, precision, recall, specificity, F1 score, AUC, and statistical and effect size. All optimizers performed better with the rate scheduler. In particular, the SAM effect size had high accuracy (11.2) and AUC (11.0). SAM had the best performance of all models with a learning rate scheduler. (AUC = 0.9328) SAM tended to suppress overfitting compared to SGD. In oral exfoliation cytology classification, CNNs using SAM rate scheduler showed the highest classification performance. These results suggest that SAM can play an important role in primary screening of the oral cytological diagnostic environment.

    DOI: 10.1038/s41598-022-17602-4

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  • The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery. 査読 国際誌

    Shintaro Sukegawa, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Tomoya Nakamura, Ai Fujimura, Ayaka Fujisawa, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Yumika Mukainaka, Hitoshi Nagatsuka, Yoshihiko Furuki

    Healthcare (Basel, Switzerland)   10 ( 7 )   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8, $905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV.

    DOI: 10.3390/healthcare10071348

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  • Incidence and Risk of Anti-Resorptive Agent-Related Osteonecrosis of the Jaw after Tooth Extraction: A Retrospective Study. 査読 国際誌

    Rieko Shimizu, Shintaro Sukegawa, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Tomoya Nakamura, Ai Fujimura, Ayaka Fujisawa, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Healthcare (Basel, Switzerland)   10 ( 7 )   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bone-modifying agents (BMA) such as bisphosphonates and denosumab are frequently used for the treatment of bone metastases, osteoporosis, and multiple myeloma. BMA may lead to anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). This study aimed to clarify the risk factors for and probabilities of developing ARONJ after tooth extraction in patients undergoing BMA therapy. In this study, the records of 505 target sites of 302 patients undergoing BMA who presented with mandibular fractures at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from March 2014 to January 2022, were retrospectively analyzed for the onset of ARONJ after tooth extraction. The following variables were investigated as attributes: anatomy, health status, and dental treatment. The correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and the factors related to the onset of ARONJ were identified. The incidence rate of ARONJ was found to be 3.2%. Hypoparathyroidism was an important factor associated with ARONJ development. Thus, systemic factors are more strongly related to the onset of ARONJ after tooth extraction than local factors.

    DOI: 10.3390/healthcare10071332

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  • 口腔扁平上皮癌と前駆病変の診断と評価 招待 査読

    中野敬介, 長塚仁

    診断病理   39 ( 3 )   173 - 182   2022年7月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 正常間質組織による口腔扁平上皮癌の生物学的性格制御の可能性 査読

    高畠 清文, 大森 悠加, Shan Qiusheng, 河合 穂高, Oo May Wathone, 稲田 靖則, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   71 ( 2 )   105 - 105   2022年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 口腔癌間質由来のCCL2はCCR2陽性骨髄由来免疫抑制細胞の腫瘍間質への動員に関与する 査読

    河合 穂高, メイ・ワトウ, 高畠 清文, 冨田 秀太, 小野 喜章, 江口 傑徳, 大原 利章, 中野 敬介, 長塚 仁

    日本がん免疫学会総会プログラム・抄録集   26回   91 - 91   2022年6月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • 口腔癌間質由来のCCL2はCCR2陽性骨髄由来免疫抑制細胞の腫瘍間質への動員に関与する 査読

    河合 穂高, メイ・ワトウ, 高畠 清文, 冨田 秀太, 小野 喜章, 江口 傑徳, 大原 利章, 中野 敬介, 長塚 仁

    日本がん免疫学会総会プログラム・抄録集   26回   91 - 91   2022年6月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor‑associated macrophages into the tumor microenvironment of oral squamous cell carcinoma. 査読 国際誌

    Qiusheng Shan, Kiyofumi Takabatake, Hotaka Kawai, May Wathone Oo, Shintaro Sukegawa, Masae Fujii, Keisuke Nakano, Hitoshi Nagatsuka

    International journal of oncology   60 ( 6 )   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tumor‑associated macrophages (TAMs) are linked to the progression of numerous types of cancer. However, the effects of the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC), particularly the cancer stroma on TAMs, remains to be elucidated. In the present study, the effects of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the differentiation, proliferation and migration of macrophages in vitro was assayed using Giemsa staining, and immunofluorescence, MTS and Transwell (migration) assays, respectively. The combined results suggested that both VSCC‑SCs and SCC‑SCs promoted the differentiation of macrophages into M2 type TAMs, as well as the proliferation and migration of macrophages following crosstalk with HSC‑3 cells in vitro. Moreover, the SCC‑SCs exerted a more prominent effect on TAMs than the VSCC‑SCs. Immunohistochemical staining was used to examine the expression of CD34, CD45, CD11b and CD163 to assay the effects of VSCC‑SCs, SCC‑SCs and HDFs on microvessel density (MVD) and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type macrophages. The results suggested that both VSCC‑SCs and SCC‑SCs promoted MVD and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type TAMs into the TME of OSCC following crosstalk with HSC‑3 cells in vivo. The SCC‑SCs exerted a more prominent promoting effect than the VSCC‑SCs. Finally, the potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on the infiltration of TAMs were investigated using microarray analysis. The results revealed that interleukin 1β, bone morphogenetic protein 4, interleukin 6 and C‑X‑C motif chemokine ligand 12 had great potential to mediate the differential effects of VSCC‑SCs and SCC‑SCs on TAM infiltration. On the whole, the findings presented herein, demonstrate that both VSCC‑SCs and SCC‑SCs promote the infiltration of TAMs into the TME of OSCC following crosstalk with HSC‑3 cells; the SCC‑SCs were found to exert a more prominent promoting effect. This may represent a potential regulatory mechanism for the infiltration of TAMs into the TME of OSCC.

    DOI: 10.3892/ijo.2022.5368

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  • Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study. 査読 国際誌

    Shintaro Sukegawa, Rieko Shimizu, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Ai Fujimura, Izumi Yamamoto, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Materials (Basel, Switzerland)   15 ( 9 )   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries.

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  • Identification of osteoporosis using ensemble deep learning model with panoramic radiographs and clinical covariates. 査読 国際誌

    Shintaro Sukegawa, Ai Fujimura, Akira Taguchi, Norio Yamamoto, Akira Kitamura, Ryosuke Goto, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Scientific reports   12 ( 1 )   6088 - 6088   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteoporosis is becoming a global health issue due to increased life expectancy. However, it is difficult to detect in its early stages owing to a lack of discernible symptoms. Hence, screening for osteoporosis with widely used dental panoramic radiographs would be very cost-effective and useful. In this study, we investigate the use of deep learning to classify osteoporosis from dental panoramic radiographs. In addition, the effect of adding clinical covariate data to the radiographic images on the identification performance was assessed. For objective labeling, a dataset containing 778 images was collected from patients who underwent both skeletal-bone-mineral density measurement and dental panoramic radiography at a single general hospital between 2014 and 2020. Osteoporosis was assessed from the dental panoramic radiographs using convolutional neural network (CNN) models, including EfficientNet-b0, -b3, and -b7 and ResNet-18, -50, and -152. An ensemble model was also constructed with clinical covariates added to each CNN. The ensemble model exhibited improved performance on all metrics for all CNNs, especially accuracy and AUC. The results show that deep learning using CNN can accurately classify osteoporosis from dental panoramic radiographs. Furthermore, it was shown that the accuracy can be improved using an ensemble model with patient covariates.

    DOI: 10.1038/s41598-022-10150-x

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  • Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes. 査読 国際誌

    Qiusheng Shan, Kiyofumi Takabatake, Hotaka Kawai, May Wathone Oo, Yasunori Inada, Shintaro Sukegawa, Shigeko Fushimi, Keisuke Nakano, Hitoshi Nagatsuka

    Oncology reports   47 ( 4 )   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts on bone resorption and the activation of HSC‑3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan‑cytokeratin) and tartrate‑resistant acid phosphatase staining. In addition, the expression levels of matrix metalloproteinase (MMP)9, membrane‑type 1 MMP (MT1‑MMP), Snail, receptor activator of NF‑κB ligand (RANKL) and parathyroid hormone‑related peptide (PTHrP) in the bone invasion regions of HSC‑3 cells were examined by immunohistochemistry. The results suggested that both SCC‑SCs and VSCC‑SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1‑MMP, Snail, RANKL and PTHrP. However, SCC‑SCs had a more prominent effect compared with VSCC‑SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC‑SCs and SCC‑SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC‑SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC.

    DOI: 10.3892/or.2022.8292

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  • 口腔癌間質由来のCCL2はCCR2陽性骨髄由来免疫抑制細胞の遊走に関与する 査読

    メイ・ワトウ, 河合 穂高, 高畠 清文, 藤井 昌江, 稲田 靖則, 大森 悠加, 中野 敬介, 長塚 仁

    日本病理学会会誌   111 ( 1 )   277 - 277   2022年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔癌におけるCX3CL1の影響 査読

    トゥ・シュ・エイン, 河合 穂高, 中山 真彰, メイ・ワトウ, 伏見 滋子, 中野 敬介, 飯田 征二, 長塚 仁

    日本病理学会会誌   111 ( 1 )   278 - 278   2022年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔癌と腫瘍間質 招待 査読

    中野敬介, 長塚仁

    病理と臨床   40 ( 2 )   183 - 185   2022年2月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • Heat Shock Protein Overexpression-Mediated Periodontal Ligament Regeneration: A Fundamental Approach to Generate a Potential Biomaterial. 査読 国際誌

    Rina Muraoka, Keisuke Nakano, Toshiyuki Kawakami

    Materials (Basel, Switzerland)   15 ( 3 )   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The periodontal ligament (PDL) is a cell-rich fibrous connective tissue supporting the tooth roots. The tissue helps to maintain homeostasis and exhibits regenerative and repairing ability, which is mediated by the heat shock protein (HSP). Here, we experimentally created PDL tissue with notable ability to regenerate hard tissue and evaluated it as a potential biomaterial. We immunohistochemically examined the mechanical load-induced HSP overexpression in mouse PDL. Following mechanical load application and release, HSP70 localization in the PDL was altered immediately, suggesting that the HSP70 function may differ with the timing of its expression in PDL. HSP70 expressed in the cytoplasm and nucleus of fibroblasts in PDL on the tension side not only participated in periodontium repair, but also functioned as a molecular chaperone during protein expression involved in osteogenesis to restructure injured tissue. This study highlights the potential of artificially created highly functional PDL tissues as biomaterials.

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  • Evaluation of multi-task learning in deep learning-based positioning classification of mandibular third molars. 査読 国際誌

    Shintaro Sukegawa, Tamamo Matsuyama, Futa Tanaka, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Scientific reports   12 ( 1 )   684 - 684   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pell and Gregory, and Winter's classifications are frequently implemented to classify the mandibular third molars and are crucial for safe tooth extraction. This study aimed to evaluate the classification accuracy of convolutional neural network (CNN) deep learning models using cropped panoramic radiographs based on these classifications. We compared the diagnostic accuracy of single-task and multi-task learning after labeling 1330 images of mandibular third molars from digital radiographs taken at the Department of Oral and Maxillofacial Surgery at a general hospital (2014-2021). The mandibular third molar classifications were analyzed using a VGG 16 model of a CNN. We statistically evaluated performance metrics [accuracy, precision, recall, F1 score, and area under the curve (AUC)] for each prediction. We found that single-task learning was superior to multi-task learning (all p < 0.05) for all metrics, with large effect sizes and low p-values. Recall and F1 scores for position classification showed medium effect sizes in single and multi-task learning. To our knowledge, this is the first deep learning study to examine single-task and multi-task learning for the classification of mandibular third molars. Our results demonstrated the efficacy of implementing Pell and Gregory, and Winter's classifications for specific respective tasks.

    DOI: 10.1038/s41598-021-04603-y

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  • Is attention branch network effective in classifying dental implants from panoramic radiograph images by deep learning? 査読 国際誌

    Shintaro Sukegawa, Kazumasa Yoshii, Takeshi Hara, Futa Tanaka, Katsusuke Yamashita, Tutaro Kagaya, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    PloS one   17 ( 7 )   e0269016   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Attention mechanism, which is a means of determining which part of the forced data is emphasized, has attracted attention in various fields of deep learning in recent years. The purpose of this study was to evaluate the performance of the attention branch network (ABN) for implant classification using convolutional neural networks (CNNs). The data consisted of 10191 dental implant images from 13 implant brands that cropped the site, including dental implants as pretreatment, from digital panoramic radiographs of patients who underwent surgery at Kagawa Prefectural Central Hospital between 2005 and 2021. ResNet 18, 50, and 152 were evaluated as CNN models that were compared with and without the ABN. We used accuracy, precision, recall, specificity, F1 score, and area under the receiver operating characteristics curve as performance metrics. We also performed statistical and effect size evaluations of the 30-time performance metrics of the simple CNNs and the ABN model. ResNet18 with ABN significantly improved the dental implant classification performance for all the performance metrics. Effect sizes were equivalent to "Huge" for all performance metrics. In contrast, the classification performance of ResNet50 and 152 deteriorated by adding the attention mechanism. ResNet18 showed considerably high compatibility with the ABN model in dental implant classification (AUC = 0.9993) despite the small number of parameters. The limitation of this study is that only ResNet was verified as a CNN; further studies are required for other CNN models.

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  • Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion. 査読 国際誌

    May Wathone Oo, Hotaka Kawai, Kiyofumi Takabatake, Qiusheng Shan, Htoo Shwe Eain, Shintaro Sukegawa, Keisuke Nakano, Hitoshi Nagatsuka

    Cancers   14 ( 1 )   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tumor stromal components contribute to tumor development and invasion. However, the role of stromal cells in the contribution of bone marrow-derived cells (BMDCs) in oral squamous cell carcinoma (OSCC) invasion is unclear. In the present study, we created two different invasive OSCC patient-derived stroma xenografts (PDSXs) and analyzed and compared the effects of stromal cells on the relation of BMDCs and tumor invasion. We isolated stromal cells from two OSCC patients: less invasive verrucous OSCC (VSCC) and highly invasive conventional OSCC (SCC) and co-xenografted with the OSCC cell line (HSC-2) on green fluorescent protein (GFP)-positive bone marrow (BM) cells transplanted mice. We traced the GFP-positive BM cells by immunohistochemistry (IHC) and detected matrix metalloproteinase 2 (MMP2) expression on BM cells by double fluorescent IHC. The results indicated that the SCC-PDSX promotes MMP2-positive BMDCs recruitment to the invasive front line of the tumor. Furthermore, microarray analysis revealed that the expressions of interleukin 6; IL-6 mRNA and interleukin 1 beta; IL1B mRNA were higher in SCC stromal cells than in VSCC stromal cells. Thus, our study first reports that IL-6 and IL1B might be the potential stromal factors promoting the contribution of MMP2-positive BMDCs to OSCC invasion.

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  • Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

    May Wathone Oo, Hotaka Kawai, Kiyofumi Takabatake, Shuta Tomida, Takanori Eguchi, Kisho Ono, Qiusheng Shan, Toshiaki Ohara, Saori Yoshida, Haruka Omori, Shintaro Sukegawa, Keisuke Nakano, Kuniaki Okamoto, Akira Sasaki, Hitoshi Nagatsuka

    JCI Insight   2021年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Clinical Investigation  

    DOI: 10.1172/jci.insight.148960

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  • 新規生体材料の幾何学的構造制御による象牙質再生

    稲田 靖則, 高畠 清文, 辻極 秀次, 河合 穂高, 中野 敬介, 長塚 仁

    岡山歯学会雑誌   40 ( 2 )   36 - 37   2021年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP 招待 査読

    Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Aki Yoshida, Takayuki Furumatsu, Hotaka Kawai, May Wathone Oo, Keisuke Nakano, Hitoshi Nagatsuka

    Materials   14 ( 23 )   7255   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method

    Kiyofumi Takabatake, Masakazu Matsubara, Eiki Yamachika, Yuki Fujita, Yuki Arimura, Kazuki Nakatsuji, Keisuke Nakano, Histoshi Nagatsuka, Seiji Iida

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   22 ( 22 )   2021年11月

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    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  

    Background: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). Method: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. Results: The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. Conclusion: DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies.

    DOI: 10.3390/ijms222212392

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  • 3次元培養システムを用いた口腔癌の薬剤応答性に対する新規in vitroモデルの検証(A novel 3-dimensional culture system as an in vitro model for drug responsiveness of oral cancer)

    佐藤 晃平, 小野 喜章, 河合 穂高, 中野 敬介, 長塚 仁, 佐々木 朗

    Journal of Oral Biosciences Supplement   2021   200 - 200   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 口腔扁平上皮癌における腫瘍実質の生物学的特性に対する腫瘍間質の影響(Effect of the stroma on the biological characteristics of the parenchyma in oral squamous cell carcinoma)

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

    Journal of Hard Tissue Biology   30 ( 4 )   401 - 401   2021年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • 歯髄由来細胞の分化を制御するためのハニカムTCPの幾何構造(Geometrical structure of honeycomb TCP to control dental pulp-derived cell differentiation)

    Inada Yasunori, Takabatake Kiyofumi, Tsujigiwa Hidetsugu, Kawai Hotaka, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   30 ( 4 )   401 - 401   2021年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • 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

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    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

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  • Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis 国際誌

    Norio Yamamoto, Shintaro Sukegawa, Kazutaka Yamashita, Masaki Manabe, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Toshifumi Ozaki, Keisuke Kawasaki, Hitoshi Nagatsuka, Yoshihiko Furuki, Takashi Yorifuji

    Medicina   57 ( 8 )   846 - 846   2021年8月

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    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  

    Background and Objectives: A few deep learning studies have reported that combining image features with patient variables enhanced identification accuracy compared with image-only models. However, previous studies have not statistically reported the additional effect of patient variables on the image-only models. This study aimed to statistically evaluate the osteoporosis identification ability of deep learning by combining hip radiographs with patient variables. Materials andMethods: We collected a dataset containing 1699 images from patients who underwent skeletal-bone-mineral density measurements and hip radiography at a general hospital from 2014 to 2021. Osteoporosis was assessed from hip radiographs using convolutional neural network (CNN) models (ResNet18, 34, 50, 101, and 152). We also investigated ensemble models with patient clinical variables added to each CNN. Accuracy, precision, recall, specificity, F1 score, and area under the curve (AUC) were calculated as performance metrics. Furthermore, we statistically compared the accuracy of the image-only model with that of an ensemble model that included images plus patient factors, including effect size for each performance metric. Results: All metrics were improved in the ResNet34 ensemble model compared with the image-only model. The AUC score in the ensemble model was significantly improved compared with the image-only model (difference 0.004; 95% CI 0.002–0.0007; p = 0.0004, effect size: 0.871). Conclusions: This study revealed the additional effect of patient variables in identification of osteoporosis using deep CNNs with hip radiographs. Our results provided evidence that the patient variables had additive synergistic effects on the image in osteoporosis identification.

    DOI: 10.3390/medicina57080846

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  • Lymphoepithelial Carcinoma in the Lateral Tongue: The Case Report

    Sawako Ono, Hidenori Marunaka, Hiroyuki Yanai, Hotaka Kawai, Kiyofumi Takabatake, Kenji Nishida, Tomohiro Toji, Keisuke Nakano, Hitoshi Nagatsuka, Tadashi Yoshino

    Reports   4 ( 3 )   24 - 24   2021年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Lymphoepithelial carcinoma (LEC) of the tongue is a rare subtype of squamous cell carcinoma. Histologically, it is an undifferentiated carcinoma with rich lymphocyte and plasma cell infiltration. The most common location for LEC in the head and neck is the salivary glands, and LEC of the oral cavity is extremely rare. The second case report of LEC in the lateral tongue is presented. In addition, a review of the literature was performed, and the relationship between LEC and Epstein–Barr virus infection was considered.

    DOI: 10.3390/reports4030024

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  • The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma. 国際誌

    Haruka Omori, Qiusheng Shan, Kiyofumi Takabatake, Keisuke Nakano, Hotaka Kawai, Shintaro Sukegawa, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka

    Cancers   13 ( 14 )   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Normal stromal cells surrounding the tumor parenchyma, such as the extracellular matrix (ECM), normal fibroblasts, mesenchymal stromal cells, and osteoblasts, play a significant role in the progression of cancers. However, the role of gingival and periodontal ligament tissue-derived stromal cells in OSCC progression is unclear. In this study, the effect of G-SCs and P-SCs on the differentiation, proliferation, invasion, and migration of OSCC cells in vitro was examined by Giemsa staining, Immunofluorescence (IF), (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS), invasion, and migration assays. Furthermore, the effect of G-SCs and P-SCs on the differentiation, proliferation, and bone invasion by OSCC cells in vivo was examined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Finally, microarray data and bioinformatics analyses identified potential genes that caused the different effects of G-SCs and P-SCs on OSCC progression. The results showed that both G-SCs and P-SCs inhibited the differentiation and promoted the proliferation, invasion, and migration of OSCC in vitro and in vivo. In addition, genes, including CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, are probably involved in causing the different effects of G-SCs and P-SCs on OSCC progression. Therefore, as a potential regulatory mechanism, both G-SCs and P-SCs can promote OSCC progression.

    DOI: 10.3390/cancers13143491

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  • ハニカムTCPを用いた細胞外微小環境制御による象牙質再生

    高畠 清文, 辻極 秀次, 吉田 沙織, 稲田 靖則, 河合 穂高, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   70 ( 2 )   127 - 127   2021年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • ハニカムTCPを用いた細胞外微小環境制御による象牙質再生

    高畠 清文, 辻極 秀次, 吉田 沙織, 稲田 靖則, 河合 穂高, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   70 ( 2 )   127 - 127   2021年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • Preparation of Absorption-Resistant Hard Tissue Using Dental Pulp-Derived Cells and Honeycomb Tricalcium Phosphate. 国際誌

    Kiyofumi Takabatake, Keisuke Nakano, Hotaka Kawai, Yasunori Inada, Shintaro Sukegawa, Shan Qiusheng, Shigeko Fushimi, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka

    Materials (Basel, Switzerland)   14 ( 12 )   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In recent years, there has been increasing interest in the treatment of bone defects using undifferentiated mesenchymal stem cells (MSCs) in vivo. Recently, dental pulp has been proposed as a promising source of pluripotent mesenchymal stem cells (MSCs), which can be used in various clinical applications. Dentin is the hard tissue that makes up teeth, and has the same composition and strength as bone. However, unlike bone, dentin is usually not remodeled under physiological conditions. Here, we generated odontoblast-like cells from mouse dental pulp stem cells and combined them with honeycomb tricalcium phosphate (TCP) with a 300 μm hole to create bone-like tissue under the skin of mice. The bone-like hard tissue produced in this study was different from bone tissue, i.e., was not resorbed by osteoclasts and was less easily absorbed than the bone tissue. It has been suggested that hard tissue-forming cells induced from dental pulp do not have the ability to induce osteoclast differentiation. Therefore, the newly created bone-like hard tissue has high potential for absorption-resistant hard tissue repair and regeneration procedures.

    DOI: 10.3390/ma14123409

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  • Biological Effects of Bioresorbable Materials in Alveolar Ridge Augmentation: Comparison of Early and Slow Resorbing Osteosynthesis Materials. 国際誌

    Hotaka Kawai, Shintaro Sukegawa, Keisuke Nakano, Kiyofumi Takabatake, Sawako Ono, Hitoshi Nagatsuka, Yoshihiko Furuki

    Materials (Basel, Switzerland)   14 ( 12 )   2021年6月

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    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 investigate the bone healing properties and histological environment of a u-HA/PLLA/PGA (u-HA-uncalcined and unsintered hydroxyapatite, PLLA-Poly L-lactic acid, PGA-polyglycolic acid) composite device in humans, and to understand the histological dynamics of using this device for maxillofacial treatments. Twenty-one subjects underwent pre-implant maxillary alveolar ridge augmentation with mandibular cortical bone blocks using u-HA/PLLA or u-HA/PLLA/PGA screws for fixation. Six months later, specimens of these screws and their adjacent tissue were retrieved. A histological and immunohistochemical evaluation of these samples was performed using collagen 1a, ALP (alkaline phosphatase), and osteocalcin. We observed that alveolar bone augmentation was successful for all of the subjects. Upon histological evaluation, the u-HA/PLLA screws had merged with the bone components, and the bone was directly connected to the biomaterial. In contrast, direct bone connection was not observed for the u-HA/PLLA/PGA screw. Immunohistological findings showed that in the u-HA/PLLA group, collagen 1a was positive for fibers that penetrated vertically into the bone. Alkaline phosphatase was positive only in the u-HA/PLLA stroma, and the stroma was negative for osteocalcin. In this study, u-HA/PLLA showed a greater bioactive bone conductivity than u-HA/PLLA/PGA and a higher biocompatibility for direct bone attachment. Furthermore, u-HA/PLLA was shown to have the potential for bone formation in the stroma.

    DOI: 10.3390/ma14123286

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  • Multi-Task Deep Learning Model for Classification of Dental Implant Brand and Treatment Stage Using Dental Panoramic Radiograph Images. 国際誌

    Shintaro Sukegawa, Kazumasa Yoshii, Takeshi Hara, Tamamo Matsuyama, Katsusuke Yamashita, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Biomolecules   11 ( 6 )   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It is necessary to accurately identify dental implant brands and the stage of treatment to ensure efficient care. Thus, the purpose of this study was to use multi-task deep learning to investigate a classifier that categorizes implant brands and treatment stages from dental panoramic radiographic images. For objective labeling, 9767 dental implant images of 12 implant brands and treatment stages were obtained from the digital panoramic radiographs of patients who underwent procedures at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2020. Five deep convolutional neural network (CNN) models (ResNet18, 34, 50, 101 and 152) were evaluated. The accuracy, precision, recall, specificity, F1 score, and area under the curve score were calculated for each CNN. We also compared the multi-task and single-task accuracies of brand classification and implant treatment stage classification. Our analysis revealed that the larger the number of parameters and the deeper the network, the better the performance for both classifications. Multi-tasking significantly improved brand classification on all performance indicators, except recall, and significantly improved all metrics in treatment phase classification. Using CNNs conferred high validity in the classification of dental implant brands and treatment stages. Furthermore, multi-task learning facilitated analysis accuracy.

    DOI: 10.3390/biom11060815

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  • White discharge formation following a subepithelial connective tissue graft for anterior fixed partial denture pontics: a case report based on clinical and histological findings.

    Norimi Oda, Mitsuaki Ono, Wataru Sonoyama, Taichiro Morimoto, Ikue Tosa, Shuji Nousho, Keisuke Nakano, Takuo Kuboki

    Journal of prosthodontic research   66 ( 1 )   184 - 192   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PATIENT: A 54-year-old woman presenting with anterior alveolar ridge resorption was submitted to a connective tissue graft (CTG) for esthetic improvement before rehabilitation with a fixed partial denture. Palate-harvested connective tissue was used as a graft after extra-oral removal of the epithelium. Unexpectedly, complete wound healing was not observed. Moreover, 6 months post-surgery, a white discharge was detected at the grafted site. The adjacent tooth showing a root fracture was initially associated with the symptoms and was then extracted. Concomitantly, the unhealed tissue at the grafted site was also excised, leading to temporary symptom resolution. However, the white discharge reappeared after 2 months. The excision area was expanded to remove the grafted tissue entirely, and the wound was completely healed. Since the alveolar ridge resorption had become larger compared to the preoperative condition, the patient was subjected to a second CTG, now using a connective tissue harvested from the palate by a single incision technique. The wound healed uneventfully, and the final prosthesis was delivered 6 months after soft tissu e stabilization. The patient has been followed-up for more than 28 months without any recurrence of white discharge. DISCUSSION: Histopathological and cytological examination detected keratinized epithelial tissues and cells, respectively, in excised tissues and white discharge specimens. Consequently, a possible relationship between white discharge and residual epithelium in the harvested graft was strongly suspected. CONCLUSIONS: Success of the CTG procedure requires careful method selection for tissue transplantation and treatment execution.

    DOI: 10.2186/jpr.JPR_D_20_00115

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  • 口腔がん早期発見のための臨床と細胞診断の架け橋 口腔細胞診による口腔癌および前癌病変の一次スクリーニングの有用性

    助川 信太郎, 小野 早和子, 中野 敬介, 長塚 仁, 古木 良彦

    日本臨床細胞学会雑誌   60 ( Suppl.1 )   120 - 120   2021年5月

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    記述言語:日本語   出版者・発行元:(公社)日本臨床細胞学会  

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  • 【治療方針を変える病理所見 診療ガイドラインと治療戦略】(第1部)臓器別 口腔

    中野 敬介, 長塚 仁

    病理と臨床   39 ( 臨増 )   10 - 17   2021年4月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • CCL2-CCR2 axisを介した癌関連線維芽細胞による骨髄由来細胞の動員

    河合 穂高, メイ・ワトウ, 高畠 清文, 大森 悠加, 中野 敬介, 長塚 仁

    日本病理学会会誌   110 ( 1 )   241 - 241   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • A Case Report of Spindle Cell Carcinoma with Osteoid and Cartilage Formation in the Tongue

    Sawako Ono, Takuma Makino, Hiroyuki Yanai, Hotaka Kawai, Kiyofumi Takabatake, Keisuke Nakano, Kenji Nishida, Kohei Taniguchi, Tomohiro Toji, Hitoshi Nagatsuka, Tadashi Yoshino

    Reports   4 ( 1 )   5 - 5   2021年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Spindle cell carcinoma (SCSCC) with osteoid and/or cartilage formation in the head and neck is rare; only one case was reported in the tongue. Herein, we report an SCSCC with osteoid and cartilage formation of the tongue developed in an 85-year-old man, and then review the report.

    DOI: 10.3390/reports4010005

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  • A Case Report of Primordial Odontogenic Tumor That Required Distinction from a Dentigerous Cyst

    Sawako Ono, Hotaka Kawai, Shintaro Sukegawa, Kiyofumi Takabatake, Keisuke Nakano, Hitoshi Nagatsuka, Tadashi Yoshino

    Reports   4 ( 1 )   4 - 4   2021年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Primordial odontogenic tumor (POT) is a rare odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla and covered by cuboidal to columnar epithelium. We herein report a case of POT in a 14-year-old boy. Computed tomography (CT) exhibited a round cavity with a defined cortical border circumscribing the tooth of the second molar. However, the gross finding was a solid mass, not a cyst. Histologically, the tumor consisted of dental papillalike myxoid connective tissue covered by columnar epithelium. Therefore, although the clinical diagnosis was dentigerous cyst (DC), we diagnosed POT based on histologic findings. Clinical findings of POT resemble DC, but the clinical behavior of POT is different to DC, such as cortical expansion and root resorption of teeth. Therefore, histological differentiation of POT from DC is critical for accurate diagnosis.

    DOI: 10.3390/reports4010004

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  • Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma. 国際誌

    Shunichi Baba, Takumi Akashi, Kou Kayamori, Tomoyuki Ohuchi, Ikuko Ogawa, Nobuhisa Kubota, Keisuke Nakano, Hitoshi Nagatsuka, Hiromasa Hasegawa, Kenichi Matsuzaka, Shohei Tomii, Keisuke Uchida, Noriko Katsuta, Takahiro Sekiya, Noboru Ando, Keiko Miura, Hironori Ishibashi, Yousuke Ariizumi, Takahiro Asakage, Yasuyuki Michi, Hiroyuki Harada, Kei Sakamoto, Yoshinobu Eishi, Kenichi Okubo, Tohru Ikeda

    Pathology international   71 ( 2 )   113 - 123   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.

    DOI: 10.1111/pin.13050

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  • 歯原性腫瘍と歯原性嚢胞にみる疾患概念の変遷

    中野 敬介, 長塚 仁

    病理と臨床   39 ( 2 )   198 - 199   2021年2月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • 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

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  • Feasibility of navigation-assisted bone lid surgery for deeply impacted maxillary tooth - A case report

    Shintaro Sukegawa, Ai Fujimura-Sato, Keisuke Nakano, Hitoshi Nagatsuka, Yoshihiko Furuki

    Annals of Maxillofacial Surgery   11 ( 1 )   176 - 176   2021年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Medknow  

    DOI: 10.4103/ams.ams_370_20

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  • Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process. 国際誌

    Hotaka Kawai, May Wathone Oo, Hidetsugu Tsujigiwa, Keisuke Nakano, Kiyofumi Takabatake, Shintaro Sukegawa, Hitoshi Nagatsuka

    International journal of medical sciences   18 ( 8 )   1824 - 1830   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive functions; these cells play a key role in infection, immunization, chronic inflammation, and cancer. Recent studies have reported that immunosuppression plays an important role in the healing process of tissues and that Treg play an important role in fracture healing. MDSCs suppress active T cell proliferation and reduce the severity of arthritis in mice and humans. Together, these findings suggest that MDSCs play a role in bone biotransformation. In the present study, we examined the role of MDSCs in the bone healing process by creating a bone injury at the tibial epiphysis in mice. MDSCs were identified by CD11b and GR1 immunohistochemistry and their role in new bone formation was observed by detection of Runx2 and osteocalcin expression. Significant numbers of MDSCs were observed in transitional areas from the reactionary to repair stages. Interestingly, MDSCs exhibited Runx2 and osteocalcin expression in the transitional area but not in the reactionary area. And at the same area, cllagene-1 and ALP expression level increased in osteoblast progenitor cells. These data is suggesting that MDSCs emerge to suppress inflammation and support new bone formation. Here, we report, for the first time (to our knowledge), the role of MDSCs in the initiation of bone formation. MDSC appeared at the transition from inflammation to bone making and regulates bone healing by suppressing inflammation.

    DOI: 10.7150/ijms.51946

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  • Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation. 国際誌

    Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Keisuke Nakano, Yasunori Inada, Shan Qiusheng, Hotaka Kawai, Shintaro Sukegawa, Shigeko Fushimi, Hitoshi Nagatsuka

    Materials (Basel, Switzerland)   13 ( 22 )   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recently, dental pulp has been attracting attention as a promising source of multipotent mesenchymal stem cells (MSCs) for various clinical applications of regeneration fields. To date, we have succeeded in establishing rat dental pulp-derived cells showing the characteristics of odontoblasts under in vitro conditions. We named them Tooth matrix-forming, GFP rat-derived Cells (TGC). However, though TGC form massive dentin-like hard tissues under in vivo conditions, this does not lead to the induction of polar odontoblasts. Focusing on the importance of the geometrical structure of an artificial biomaterial to induce cell differentiation and hard tissue formation, we previously have succeeded in developing a new biomaterial, honeycomb tricalcium phosphate (TCP) scaffold with through-holes of various diameters. In this study, to induce polar odontoblasts, TGC were induced to form odontoblasts using honeycomb TCP that had various hole diameters (75, 300, and 500 μm) as a scaffold. The results showed that honeycomb TCP with 300-μm hole diameters (300TCP) differentiated TGC into polar odontoblasts that were DSP positive. Therefore, our study indicates that 300TCP is an appropriate artificial biomaterial for dentin regeneration.

    DOI: 10.3390/ma13225155

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  • Deep Learning for Osteoporosis Classification Using Hip Radiographs and Patient Clinical Covariates. 国際誌

    Norio Yamamoto, Shintaro Sukegawa, Akira Kitamura, Ryosuke Goto, Tomoyuki Noda, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Keisuke Kawasaki, Yoshihiko Furuki, Toshifumi Ozaki

    Biomolecules   10 ( 11 )   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study considers the use of deep learning to diagnose osteoporosis from hip radiographs, and whether adding clinical data improves diagnostic performance over the image mode alone. For objective labeling, we collected a dataset containing 1131 images from patients who underwent both skeletal bone mineral density measurement and hip radiography at a single general hospital between 2014 and 2019. Osteoporosis was assessed from the hip radiographs using five convolutional neural network (CNN) models. We also investigated ensemble models with clinical covariates added to each CNN. The accuracy, precision, recall, specificity, negative predictive value (npv), F1 score, and area under the curve (AUC) score were calculated for each network. In the evaluation of the five CNN models using only hip radiographs, GoogleNet and EfficientNet b3 exhibited the best accuracy, precision, and specificity. Among the five ensemble models, EfficientNet b3 exhibited the best accuracy, recall, npv, F1 score, and AUC score when patient variables were included. The CNN models diagnosed osteoporosis from hip radiographs with high accuracy, and their performance improved further with the addition of clinical covariates from patient records.

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  • Clinical retrospective study of dental implant removal: do patients who require implant removal desire implant prosthesis again?

    Shintaro Sukegawa, Masato Saika, Ryo Tamamura, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL   25 ( 6 )   E784 - E790   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MEDICINA ORAL S L  

    Background: This study investigated the causes of dental implant removal due to complications, and examined whether patients who had dental implant removal desired re-implant prosthesis treatments.Material and Methods: A retrospective case-control study was conducted on patients who had their dental implants removed. We investigated whether the removed dental implant was replaced with other implant prostheses. Age, sex, diabetes, smoking, implant site distribution, reason for implant removal, and blade and root-form implants were categorized as predictive variables. The outcome variable was desire for re-implantation or use of other prosthetic methods after implant removal. A logistic regression model was created to identify patient factors that could predict the re-implantation of dental prostheses after implant removal.Results: A total of 215 dental implants were removed from 143 patients. The most common reason for implant removal was peri-implantitis that was identified in 165 implants. After implant removal, re-implantation was performed in 98 implants (45.6%) Bivariate analyses showed that age, diabetes, implant type, and reason for implant removal were associated with the desire for re-implanted prostheses. The multiple regression model revealed that age, implant type, and reason for implant removal were associated with an increased desire for re-implant prostheses after implant removal.Conclusions: Re-implantation of prostheses after the removal of dental implants was desired by patients who were younger, had implants placed in the root form, and had implants removed due to prosthetic-related complications.

    DOI: 10.4317/medoral.23789

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  • Effect of Honeycomb β-TCP Geometrical Structure on Bone Tissue Regeneration in Skull Defect. 国際誌

    Toshiyuki Watanabe, Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Satoko Watanabe, Ryoko Nakagiri, Keisuke Nakano, Hitoshi Nagatsuka, Yoshihiro Kimata

    Materials (Basel, Switzerland)   13 ( 21 )   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The effect of the geometric structure of artificial biomaterials on skull regeneration remains unclear. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP), which has through-and-through holes and is able to provide the optimum bone microenvironment for bone tissue regeneration. We demonstrated that β-TCP with 300-μm hole diameters induced vigorous bone formation. In the present study, we investigated how differences in hole directions of honeycomb β-TCP (horizontal or vertical holes) influence bone tissue regeneration in skull defects. Honeycomb β-TCP with vertical and horizontal holes was loaded with BMP-2 using Matrigel and Collagen gel as carriers, and transplanted into skull bone defect model rats. The results showed that in each four groups (Collagen alone group, Matrigel alone group, Collagen + BMP group and Matrigel + BMP-2), vigorous bone formation was observed on the vertical β-TCP compared with horizontal β-TCP. The osteogenic area was larger in the Matrigel groups (with and without BMP-2) than in the Collagen group (with and without BMP-2) in both vertical β-TCP and horizontal β-TCP. However, when BMP-2 was added, the bone formation area was not significantly different between the Collagen group and the Matrigel group in the vertical β-TCP. Histological finding showed that, in vertical honeycomb β-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes. Therefore, we can control efficient bone formation by creating a bone microenvironment provided by vertical honeycomb β-TCP. Vertical honeycomb β-TCP has the potential to be an excellent biomaterial for bone tissue regeneration in skull defects and is expected to have clinical applications.

    DOI: 10.3390/ma13214761

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  • Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma. 国際誌

    Kiyofumi Takabatake, Hotaka Kawai, Haruka Omori, Shan Qiusheng, May Wathone Oo, Shintaro Sukegawa, Keisuke Nakano, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka

    International journal of molecular sciences   21 ( 20 )   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor.

    DOI: 10.3390/ijms21207714

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  • Clinical study on primary screening of oral cancer and precancerous lesions by oral cytology. 国際誌

    Shintaro Sukegawa, Sawako Ono, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Diagnostic pathology   15 ( 1 )   107 - 107   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: This study was conducted to compare the histological diagnostic accuracy of conventional oral-based cytology and liquid-based cytology (LBC) methods. METHODS: Histological diagnoses of 251 cases were classified as negative (no malignancy lesion, inflammation, or mild/moderate dysplasia) and positive [severe dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC)]. Cytological diagnoses were classified as negative for intraepithelial lesion or malignancy (NILM), oral low-grade squamous intraepithelial lesion (OLSIL), oral high-grade squamous intraepithelial lesion (OHSIL), or SCC. Cytological diagnostic results were compared with histology results. RESULTS: Of NILM cytology cases, the most frequent case was negative [LBC n = 50 (90.9%), conventional n = 22 (95.7%)]. Among OLSIL cytodiagnoses, the most common was negative (LBC n = 34; 75.6%, conventional n = 14; 70.0%). Among OHSIL cytodiagnoses (LBC n = 51, conventional n = 23), SCC was the most frequent (LBC n = 31; 60.8%, conventional n = 7; 30.4%). Negative cases were common (LBC n = 13; 25.5%, conventional n = 14; 60.9%). Among SCC cytodiagnoses SCC was the most common (LBC n = 16; 88.9%, conventional n = 14; 87.5%). Regarding the diagnostic results of cytology, assuming OHSIL and SCC as cytologically positive, the LBC method/conventional method showed a sensitivity of 79.4%/76.7%, specificity of 85.1%/69.2%, false-positive rate of 14.9%/30.7%, and false-negative rate of 20.6%/23.3%. CONCLUSIONS: LBC method was superior to conventional cytodiagnosis methods. It was especially superior for OLSIL and OHSIL. Because of the false-positive and false-negative cytodiagnoses, it is necessary to make a comprehensive diagnosis considering the clinical findings.

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  • 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年9月

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    記述言語:日本語   出版者・発行元:(一社)日本医用画像工学会  

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  • 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年9月

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    記述言語:日本語   出版者・発行元:(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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  • 下顎臼後部歯肉に発生した周辺性エナメル上皮腫の1例

    武田 斉子, 山近 英樹, 高畠 清文, 中野 敬介, 長塚 仁, 飯田 征二

    日本口腔科学会雑誌   69 ( 3 )   239 - 240   2020年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 下顎臼後部歯肉に発生した周辺性エナメル上皮腫の1例

    武田 斉子, 山近 英樹, 高畠 清文, 中野 敬介, 長塚 仁, 飯田 征二

    日本口腔科学会雑誌   69 ( 3 )   239 - 240   2020年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 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年9月

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    記述言語:日本語   出版者・発行元:(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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  • 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年9月

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    記述言語:日本語   出版者・発行元:(一社)日本医用画像工学会  

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  • Biomechanical Loading Comparison between Titanium and Bioactive Resorbable Screw Systems for Fixation of Intracapsular Condylar Head Fractures. 国際誌

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

    Materials (Basel, Switzerland)   13 ( 14 )   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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.

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  • Deep Neural Networks for Dental Implant System Classification. 国際誌

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

    Biomolecules   10 ( 7 )   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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.

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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年7月

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    掲載種別:研究論文(学術雑誌)  

    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.

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  • 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年7月

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    掲載種別:研究論文(学術雑誌)  

    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.

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  • 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年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 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年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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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

    JOURNAL OF CRANIOFACIAL SURGERY   31 ( 5 )   1430 - 1433   2020年7月

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

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  • 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

    JOURNAL OF CRANIOFACIAL SURGERY   31 ( 5 )   1338 - 1342   2020年7月

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

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  • 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年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 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年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 【免疫組織化学 実践的な診断・治療方針決定のために】(第3部)腫瘍の鑑別に用いられる抗体(各臓器別) 顎口腔領域

    中野 敬介, 長塚 仁

    病理と臨床   38 ( 臨増 )   72 - 77   2020年4月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • 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年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元: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年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 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年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • 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年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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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年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 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年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • CXCR4の阻害が口腔扁平上皮癌の腫瘍血管に与える影響 査読

    吉田 沙織, 河合 穂高, メイ・ワトン・ウ, 常 安き, 浜田 芽衣, 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年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • 口腔扁平上皮癌が作り出す腫瘍微小環境における骨髄由来細胞の役割

    高畠 清文, 吉田 沙織, Oo May Wathone, 大森 悠加, 河合 穂高, 中野 敬介, 長塚 仁

    日本口腔診断学会雑誌   33 ( 1 )   114 - 114   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • 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年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • Clinical retrospective study of dental implant removal: Do patients who require implant removal desire implant prosthesis again?

    Shintaro Sukegawa, Masato Saika, Ryo Tamamura, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Medicina Oral Patologia Oral y Cirugia Bucal   25 ( 6 )   e784 - e790   2020年

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    掲載種別:研究論文(学術雑誌)  

    Background: This study investigated the causes of dental implant removal due to complications, and examined whether patients who had dental implant removal desired re-implant prosthesis treatments. Material and Methods: A retrospective case–control study was conducted on patients who had their dental implants removed. We investigated whether the removed dental implant was replaced with other implant prosthe-ses. Age, sex, diabetes, smoking, implant site distribution, reason for implant removal, and blade and root-form implants were categorized as predictive variables. The outcome variable was desire for re-implantation or use of other prosthetic methods after implant removal. A logistic regression model was created to identify patient factors that could predict the re-implantation of dental prostheses after implant removal. Results: A total of 215 dental implants were removed from 143 patients. The most common reason for implant removal was peri-implantitis that was identified in 165 implants. After implant removal, re-implantation was performed in 98 implants (45.6%). Bivariate analyses showed that age, diabetes, implant type, and reason for implant removal were associated with the desire for re-implanted prostheses. The multiple regression model revealed that age, implant type, and reason for implant removal were associated with an increased desire for re-implant prostheses after implant removal. Conclusions: Re-implantation of prostheses after the removal of dental implants was desired by patients who were younger, had implants placed in the root form, and had implants removed due to prosthetic-related complications.

    DOI: 10.4317/medoral.23789

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  • CXCR4の阻害が口腔扁平上皮癌の腫瘍血管に与える影響 査読

    吉田 沙織, 河合 穂高, ウ・メイ・ワトン, 常 安き, 浜田 芽衣, 高畠 清文, 中野 敬介, 長塚 仁

    日本口腔内科学会雑誌   25 ( 2 )   106 - 106   2019年12月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔内科学会  

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  • Differentiation and roles of bone marrow-derived cells on the tumor microenvironment of oral squamous cell carcinoma. 査読 国際誌

    Chang Anqi, Kiyofumi Takabatake, Hotaka Kawai, May Wathone Oo, Saori Yoshida, Masae Fujii, Haruka Omori, Shintaro Sukegawa, Keisuke Nakano, Hidetsugu Tsujigiwa, Zheng Jinhua, Hitoshi Nagatsuka

    Oncology letters   18 ( 6 )   6628 - 6638   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The stroma affects the properties and dynamics of the tumor. Previous studies have demonstrated that bone marrow-derived cells (BMDCs) possess the capability of differentiating into stromal cells. However, the characteristics and roles of BMDCs in oral squamous cell carcinoma remain unclear. The current study therefore investigated their locations and features by tracing green fluorescent protein (GFP)-labeled BMDCs in a transplantation mouse model. After irradiation, BALB-c nu-nu mice were injected with bone marrow cells from C57BL/6-BALB-C-nu/nu-GFP transgenic mice. These recipient mice were then injected subcutaneously in the head with human squamous cell carcinoma-2 cells. Immunohistochemistry for GFP, Vimentin, CD11b, CD31 and α-smooth muscle actin (SMA), and double-fluorescent immunohistochemistry for GFP-Vimentin, GFP-CD11b, GFP-CD31 and GFP-α-SMA was subsequently performed. Many round-shaped GFP-positive cells were observed in the cancer stroma, which indicated that BMDCs served a predominant role in tumorigenesis. Vimentin(+) GFP(+) cells may also be a member of the cancer-associated stroma, originating from bone marrow. Round or spindle-shaped CD11b(+) GFP(+) cells identified in the present study may be macrophages derived from bone marrow. CD31(+)GFP(+) cells exhibited a high tendency towards bone marrow-derived angioblasts. The results also indicated that spindle-shaped α-SMA(+) GFP(+) cells were not likely to represent bone marrow-derived cancer-associated fibroblasts. BMDCs gathering within the tumor microenvironment exhibited multilineage potency and participated in several important processes, such as tumorigenesis, tumor invasion and angiogenesis.

    DOI: 10.3892/ol.2019.11045

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  • 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

    日本口腔内科学会雑誌   25 ( 2 )   106 - 106   2019年12月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔内科学会  

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  • 口腔扁平上皮癌が作り出す腫瘍微小環境における骨髄由来細胞の役割

    高畠 清文, 吉田 沙織, Oo May Wathone, 大森 悠加, 河合 穂高, 中野 敬介, 長塚 仁

    日本口腔内科学会雑誌   25 ( 2 )   104 - 104   2019年12月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔内科学会  

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  • ハニカムTCPの硬組織形成制御機構解明と臨床応用

    大森 悠加, 高畠 清文, 辻極 秀次, 河合 穂高, 吉田 沙織, Oo May Wathone, 中野 敬介, 長塚 仁

    岡山歯学会雑誌   38 ( 2 )   86 - 87   2019年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • オルガノイドを応用したドラッグリポジショニング開発

    十川 千春, 江口 傑徳, Tran Tien Manh, 石毛 真行, 河合 穂高, 奥舎 有加, 中野 敬介, 十川 紀夫, 小崎 健一, 岡元 邦彰

    岡山歯学会雑誌   38 ( 2 )   89 - 89   2019年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma. 査読 国際誌

    Kiyofumi Takabatake, Tsuyoshi Shimo, Jun Murakami, Chang Anqi, Hotaka Kawai, Saori Yoshida, May Wathone Oo, Omori Haruka, Shintaro Sukegawa, Hidetsugu Tsujigiwa, Keisuke Nakano, Hitoshi Nagatsuka

    International journal of molecular sciences   20 ( 22 )   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.

    DOI: 10.3390/ijms20225779

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  • Advantage of Alveolar Ridge Augmentation with Bioactive/Bioresorbable Screws Made of Composites of Unsintered Hydroxyapatite and Poly-L-lactide. 査読 国際誌

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

    Materials (Basel, Switzerland)   12 ( 22 )   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We studied human bone healing characteristics and the histological osteogenic environment by using devices made of a composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-L-lactide (PLLA). In eight cases of fixation, we used u-HA/PLLA screws for maxillary alveolar ridge augmentation, for which mandibular cortical bone block was used in preimplantation surgery. Five appropriate samples with screws were evaluated histologically and immunohistochemically for runt-related transcription factor 2 (RUNX2), transcription factor Sp7 (Osterix), and leptin receptor (LepR). In all cases, histological evaluation revealed that bone components had completely surrounded the u-HA/PLLA screws, and the bone was connected directly to the biomaterial. Inflammatory cells did not invade the space between the bone and the u-HA/PLLA screw. Immunohistochemical evaluation revealed that many cells were positive for RUNX2 or Osterix, which are markers for osteoblast and osteoprogenitor cells, in the tissues surrounding u-HA/PLLA. In addition, many bone marrow-derived mesenchymal stem cells were notably positive for both LepR and RUNX2. The u-HA/PLLA material showed excellent bioactive osteoconductivity and a highly biocompatibility with bone directly attached. In addition, our findings suggest that many bone marrow-derived mesenchymal stem cells and mature osteoblast are present in the osteogenic environment created with u-HA/PLLA screws and that this environment is suitable for osteogenesis.

    DOI: 10.3390/ma12223681

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  • 高転移臓器における転移促進的微小環境の性質の検討

    河合 穂高, 信長 ひかり, Oo May Wathone, 吉田 沙織, 大森 悠加, 高畠 清文, 中野 敬介, 辻極 秀次, 長塚 仁

    Journal of Oral Biosciences Supplement   2019   261 - 261   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • エナメル上皮腫における細胞診の有用性

    藤井 昌江, 高畠 清文, 河合 穂高, 吉田 沙織, 大森 悠加, 中野 敬介, 長塚 仁

    日本臨床細胞学会雑誌   58 ( Suppl.2 )   716 - 716   2019年10月

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    記述言語:日本語   出版者・発行元:(公社)日本臨床細胞学会  

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  • 新しい腫瘍オルガノイド多元評価システムの開発

    十川 チハル, 江口 傑徳, 大山 和美, 奥舎 有加, 中野 敬介, 十川 紀夫, 岡元 邦彰

    Journal of Oral Biosciences Supplement   2019   165 - 165   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 骨・軟骨形成に対するハニカムTCPの幾何学的構造の影響の解析と臨床応用(Analysis of the geometrical structure effect of honeycomb TCP on bone and cartilage formation and clinical application)

    Takabatake Kiyofumi, Tsujigiwa Hidetsugu, Kawai Hotaka, Yoshida Saori, Omori Haruka, Nakano Keisuke, Kawakami Toshiyuki, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   28 ( 4 )   395 - 395   2019年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • コレステリン肉芽腫の骨髄由来免疫抑制細胞(MDSC)の免疫組織化学的検討(Immunohistohemical examination of Myeloid-derived suppressor cells(MDSC) of cholesterol granuloma)

    Nakano Keisuke, Kawai Hotaka, Takabatake Kiyofumi, Yoshida Saori, Omori Haruka, Nagatsuka Hitoshi, Kawakami Toshiyuki

    Journal of Hard Tissue Biology   28 ( 4 )   395 - 395   2019年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • An in vitro Three-Dimensional Co-Culture System for Ameloblastoma Modelling 査読

    Soo Leng Lee, Zainal Ariff Abdul Rahman, Hidetsugu Tsujigiwa, Mei Hamada, Kiyofumi Takabatake, Keisuke Nakano, Hitoshi Nagatsuka, Chong Huat Siar

    SAINS MALAYSIANA   48 ( 8 )   1697 - 1706   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:UNIV KEBANGSAAN MALAYSIA  

    Ameloblastoma, the most clinically significant odontogenic epithelial tumor, is a locally-invasive and destructive lesion in the jawbones. However, the nature of this infiltrativeness and destructive behavior remains ill-understood. To address this, we established an in vitro three-dimensional (3D) co-culture system to simulate an amelobastoma disease model aimed at investigating the interactions between tumor cells and osteoblasts. Osteoblastic cell lines (KUSA/A1 and mc3T3-E1) and one stromal cell line (ST2) were separately co-seeded with ameloblastoma-derived cell line (AM-1) in a collagen scaffold (representing the extracellular bone matrix) and incubated with mineralization medium. Inununohistochemistry, double immunofluorescence and mineralization assay were performed. Only Am-1/KUsA-A1 co-culture showed a significant increase in Am-1 cell count, suggesting that heterotypic cell-cell interaction promotes tumoral cell growth, while formation of visible Am-1 epithelial nest-like structures resembling ameloblastoma cells in their native state, suggest morphodffferentiation. A RANK-high, RANKL-low and osteoprotegerin-low immunoprofile in co-culture AM-1 cells implies deregulated osteoclastogenesis. Mineralization assays showed diminished calcification in Am-1/KUSA-A1 co-culture extracellular matrix suggesting an altered local bone metabolism. In contrast, KUSA/A1 monocultures showed abundant extracellular matrix calcification. Taken together, these results suggest that a 3D co-culture system as an amelobastoma disease model provides insights that bidirectional ameloblastoma-osteoblastic interactions might play a role in modulating tumor growth and osteoclastogenesis.

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  • Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer. 査読 国際誌

    Saori Yoshida, Hotaka Kawai, Takanori Eguchi, Shintaro Sukegawa, May Wathone Oo, Chang Anqi, Kiyofumi Takabatake, Keisuke Nakano, Kuniaki Okamoto, Hitoshi Nagatsuka

    Cells   8 ( 7 )   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To uncover the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as tumor angiogenic inhibition triggered necrosis (TAITN), which was induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic areas with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.

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  • ハニカムTCPの幾何学構造による血管新生を介した選択的骨・軟骨組織形成制御

    高畠 清文, 辻極 秀次, 浜田 芽衣, 河合 穂高, 吉田 沙織, 大森 悠加, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   68 ( 2 )   179 - 179   2019年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • Biomechanical Loading Comparison between Titanium and Unsintered Hydroxyapatite/Poly-L-Lactide Plate System for Fixation of Mandibular Subcondylar Fractures. 査読 国際誌

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

    Materials (Basel, Switzerland)   12 ( 9 )   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteosynthesis absorbable materials made of uncalcined and unsintered hydroxyapatite (u-HA) particles, poly-l-lactide (PLLA), and u-HA/PLLA are bioresorbable, and these plate systems have feasible bioactive osteoconductive capacities. However, their strength and stability for fixation in mandibular subcondylar fractures remain unclear. This in vitro study aimed to assess the biomechanical strength of u-HA/PLLA bioresorbable plate systems after internal fixation of mandibular subcondylar fractures. Tensile and shear strength were measured for each u-HA/PLLA and titanium plate system. To evaluate biomechanical behavior, 20 hemimandible replicas were divided into 10 groups, each comprising a titanium plate and a bioresorbable plate. A linear load was applied anteroposteriorly and lateromedially to each group to simulate the muscular forces in mandibular condylar fractures. All samples were analyzed for each displacement load and the displacement obtained by the maximum load. Tensile and shear strength of the u-HA/PLLA plate were each approximately 45% of those of the titanium plates. Mechanical resistance was worst in the u-HA/PLLA plate initially loaded anteroposteriorly. Titanium plates showed the best mechanical resistance during lateromedial loading. Notably, both plates showed similar resistance when a lateromedially load was applied. In the biomechanical evaluation of mandibular condylar fracture treatment, the u-HA/PLLA plates had sufficiently high resistance in the two-plate fixation method.

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  • Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics. 査読 国際誌

    Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Saori Yoshida, Hatsuhiko Maeda, Toshiyuki Kawakami, Hitoshi Nagatsuka

    International journal of molecular sciences   20 ( 8 )   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Histopathological findings of oral neoplasm cell differentiation and metaplasia suggest that tumor cells induce their own dedifferentiation and re-differentiation and may lead to the formation of tumor-specific histological features. Notch signaling is involved in the maintenance of tissue stem cell nature and regulation of differentiation and is responsible for the cytological regulation of cell fate, morphogenesis, and/or development. In our previous study, immunohistochemistry was used to examine Notch expression using cases of odontogenic tumors and pleomorphic adenoma as oral neoplasms. According to our results, Notch signaling was specifically associated with tumor cell differentiation and metaplastic cells of developmental tissues. Notch signaling was involved in the differentiation of the ductal epithelial cells of salivary gland tumors and ameloblast-like cells of odontogenic tumors. However, Notch signaling was also involved in squamous metaplasia, irrespective of the type of developmental tissue. In odontogenic tumors, Notch signaling was involved in epithelial-mesenchymal interactions and may be related to tumor development and tumorigenesis. This signaling may also be associated with the malignant transformation of ameloblastomas. Overall, Notch signaling appears to play a major role in the formation of the characteristic cellular composition and histological features of oral neoplasms, and this involvement has been reviewed here.

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  • 動物モデルを用いた高転移臓器における転移促進的微小環境の検討

    河合 穂高, 辻極 秀次, メイワト・ウ, 吉田 沙織, 高畠 清文, 中野 敬介, 長塚 仁

    日本病理学会会誌   108 ( 1 )   293 - 293   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌におけるCXCR4の腫瘍血管新生への関与

    吉田 沙織, 河合 穂高, Chang Anqi, 高畠 清文, 浜田 芽衣, 藤井 昌江, 中野 敬介, 長塚 仁

    日本病理学会会誌   108 ( 1 )   335 - 335   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • In Vivo Tissue Response of Endodontic Bio-ceramic Materials

    Teresita Romano, Maria Victoria Jammal, Keisuke Nakano, Ana Garcia Rusco, Jorge Olmos Fassi, Silvia Kozuszko, Kiyofumi Takabatake, Hitoshi Nagatsuka, Liliana Raquel Missana

    JOURNAL OF HARD TISSUE BIOLOGY   28 ( 1 )   1 - 6   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    In order to evaluate the biocompatibility and mineral repair capacity, mineral trioxide aggregate (MTA), portland cement normal setting (PCn) and fast setting (PCt) and calcium hydroxide-based paste (Calen) filled silicone tube were implanted into the dorsal subcutaneous connective tissues of 25 Wistar rats. Animals were euthanized at 24, 72 hours, 7, 15 and 30 days. Implants with surrounding tissues were fixed with 10% buffer formaldehyde and processed for histological routine techniques. Slides (5 pm serial cuts) were stained with H&E and Von Kossa stains for morphological, qualitative and quantitative analysis by light microscopy. Calen showed severe and moderate inflammatory response and granulomatons reaction with psammoma body-like formation. PCn and MTA have similar behavior, with mild inflammatory reaction from 8% and 4%, respectively. Even though, PCn and MTA demonstrated analogous biological reaction, MTA developing thick artificial mineral precipitation (p = 0,007). All sealers demonstrated a similar inflammatory response at all time periods studied (p = 0.678).

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  • Do the Presence of Mandibular Third Molar and the Occlusal Support Affect the Occurrence and the Mode of Mandibular Condylar Fractures? 査読

    Sukegawa Shintaro, Saika Masato, Kanno Takahiro, Nakano Keisuke, Takabatake Kiyofumi, Kawai Hotaka, Nagatsuka Hitoshi, Furuki Yoshihiko

    JOURNAL OF HARD TISSUE BIOLOGY   28 ( 4 )   377 - 382   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.28.377

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  • Feasible Advantage of Bioactive/Bioresorbable Devices Made of Forged Composites of Hydroxyapatite Particles and Poly-L-lactide in Alveolar Bone Augmentation: A Preliminary Study. 査読 国際誌

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

    International journal of medical sciences   16 ( 2 )   311 - 317   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose: We aimed to document the clinical usefulness of uncalcined and unsintered hydroxyapatite (u-HA) particles and poly-L-lactide (PLLA) composite materials and their advantageous properties. Methods: Between April 2016 and March 2018, five patients required anterior maxillary alveolar ridge augmentation using fixation with u-HA/PLLA screws for an onlay block bone graft harvested from the mandibular ramus at our institute. Bone biopsies were obtained from the dental implantation site following bone healing for histomorphometric and immunohistochemical (IHC) measurements. Results: Many stromal cells were positive for Osterix, RUNX2, and SOX9 but were negative for CD68. On cell counting, based on IHC staining for Osterix, RUNX2, SOX9 and CD68 from peripheral u-HA/PLLA screw or bone areas, both areas consistently showed no significant difference in terms of Osterix, RUNX2, and SOX9. Hematoxylin-eosin staining revealed direct bone connection to the biomaterials, and no inflammatory cells infiltrated the areas surrounding the bone or artificial material. Area between the bone and u-HA/PLLA screw was seamless with no boundary. Round small cells and immature fibroblasts were noted. The new bone showed the presence of bone lamellae, normal osteocytes, and osteoblasts. Conclusion: The u-HA/PLLA materials showed excellent biodegradability and bioactive osteoconductivity. In addition, this material induced no apparent inflammatory or foreign body reactions following implantation, and it directly bonded to the human bone. Therefore, this u-HA/PLLA material seems ideal and most suitable for use as a substitute for osteosynthesis.

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  • Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma. 査読 国際誌

    Sawako Ono, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka

    International journal of medical sciences   16 ( 5 )   766 - 773   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Yes-associated protein (YAP) is a candidate oncogene in various human cancers, and recently, it has been reported that YAP expression and its activity was enhanced by ΔNp63. However, the role of YAP and ΔNp63 expression in carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has been unknown. Therefore, we investigated how YAP and ΔNp63 influence carcinogenesis and progression of OSCC. Methods: We performed immunohistochemical analyses in whole tissue samples to investigate YAP and ΔNp63 expression in normal oral mucosa, epithelial hyperplasia, oral epithelial dysplasia (OED; low/high grade), carcinoma in situ (CIS), and OSCC. Furthermore, in OSCC, we analyzed clinical significance by using Kaplan-Meier survival analysis. Results: In normal oral mucosa and epithelial hyperplasia, YAP expression was primarily confined to the basal and parabasal layers, but YAP expression was elevated in OED, CIS, and OSCC. In OED, YAP and ΔNp63 expression levels were markedly higher in high grade than in low grade. In OSCC groups, YAP and ΔNp63 expression patterns tended to differ according to histopathological differentiation of OSCC. Furthermore, the YAP high expression group, which showed YAP staining in >50% positive cells with strong cytoplasmic staining or >10% positive cells with nuclear reactivity, showed a tendency to have a poor survival rate. Conclusion: YAP and ΔNp63 expression levels correlated with grade of oral OED. Additionally, YAP expression was associated with OSCC survival rate. Our results suggested that YAP and ΔNp63 expression might serve as predictive markers to distinguish OSCC development and progression.

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  • In vivo tissue response of endodontic bio-ceramic materials

    Teresita Romano, María Victoria Jammal, Keisuke Nakano, Ana García Rusco, Jorge Olmos Fassi, Silvia Kozuszko, Kiyofumi Takabatake, Hitoshi Nagatsuka, Liliana Raquel Missana

    Journal of Hard Tissue Biology   28 ( 1 )   1 - 6   2019年

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    掲載種別:研究論文(学術雑誌)  

    In order to evaluate the biocompatibility and mineral repair capacity, mineral trioxide aggregate (MTA), portland cement normal setting (PCn) and fast setting (PCf) and calcium hydroxide-based paste (Calen) filled silicone tube were implanted into the dorsal subcutaneous connective tissues of 25 Wistar rats. Animals were euthanized at 24, 72 hours, 7, 15 and 30 days. Implants with surrounding tissues were fixed with 10% buffer formaldehyde and processed for histological routine techniques. Slides (5 µm serial cuts) were stained with H&E and Von Kossa stains for morphological, qualitative and quantitative analysis by light microscopy. Calen showed severe and moderate inflammatory response and granuloma-tous reaction with psammoma body-like formation. PCn and MTA have similar behavior, with mild inflammatory reaction from 8% and 4%, respectively. Even though, PCn and MTA demonstrated analogous biological reaction, MTA developing thick artificial mineral precipitation (p = 0,007). All sealers demonstrated a similar inflammatory response at all time periods studied (p = 0.678).

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  • ハニカムTCP構造の幾何学構造が骨・軟骨形成および血管新生に及ぼす影響(Effects of the geometrical structure of a honeycomb TCP structure on bone and cartilage formation and angiogenesis)

    Matsuda Hiroyuki, Takabatake Kiyofumi, Tsujigiwa Hidetsugu, Kawai Hotaka, Yoshida Saori, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   27 ( 4 )   367 - 367   2018年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • 口腔扁平上皮癌における腫瘍間質による腫瘍生物学特性の制御(Control of tumor biological character by tumor stroma in oral squamous cell carcinoma)

    Takabatake Kiyofumi, Kawai Hotaka, Yoshida Saori, Matsuda Hiroyuki, Fujii Masae, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   27 ( 4 )   365 - 366   2018年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells. 査読 国際誌

    Yuka Okusha, Takanori Eguchi, Chiharu Sogawa, Tatsuo Okui, Keisuke Nakano, Kuniaki Okamoto, Ken-Ichi Kozaki

    Journal of cellular biochemistry   119 ( 9 )   7363 - 7376   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells.

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  • 肺癌移植マウスを用いた高転移臓器における骨髄由来細胞の局在と役割の検討

    河合 穂高, 辻極 秀次, 信長 ひかり, 高畠 清文, 中野 敬介, 長塚 仁

    日本がん免疫学会総会プログラム・抄録集   22回   97 - 97   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Cell supplying to the experimentally induced absorbable suture thread foreign body granuloma from the bone marrow tissues

    Y. Nakayasu, S. Aoki, M. Shoumura, N. Osuga, N. Okafuji, K. Nakano, H. Nagatsuka, H. Tsujigiwa, Toshiyuki Kawakami

    International Journal of Dentistry and Oral Science   5 ( 6 )   641 - 644   2018年6月

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    掲載種別:研究論文(学術雑誌)  

    Using the experimental system of GFP (Green florescence Protein) bone marrow transplanted rats, we implanted the Vicryl absorbable suture thread in subcutaneous tissue and examined the formation of foreign body granuloma histopathologically. We also compared the main cellular components, namely, the macrophage and foreign body giant cell immunohistochemically using GFP to confirm their origin. Histologically, the disintegrated suture thread was observed as a circular in void surrounded by the proliferation of macrophages and foreign body giant cells. Fibrous connective tissue including the fibroblasts was interposed among large masses. Even after 6 months, some clusters considered to be residues of macrophages that grew on the suture were still remained. Immunohistochemical examination of GFP showed that all proliferated macrophages and foreign body giant cells were GFP-positive. However, the relatively thin fibrous tissues formed on the outermost layer of the granulation tissue growth were mostly GFP-negative. Based on the results of the experiment, the macrophages and foreign body giant cells that are GFP-positive were derived from the mesenchymal tissue of transplanted bone marrow tissues.

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Clinical and Diagnostic Research  

    Basal Cell Adenoma (BCA) is an extremely rare benign salivary gland tumour that usually arises in the parotid gland. The incidence of BCA is 1%-3% of all salivary gland tumours. Here, we report an extremely rare case of BCA arising in the minor salivary gland of the hard palate of a young man.

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  • Characterization and potential roles of bone marrow-derived stromal cells in cancer development and metastasis. 査読 国際誌

    Hotaka Kawai, Hidetsugu Tsujigiwa, Chong Huat Siar, Keisuke Nakano, Kiyofumi Takabatake, Masae Fujii, Mei Hamada, Ryo Tamamura, Hitoshi Nagatsuka

    International journal of medical sciences   15 ( 12 )   1406 - 1414   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: The tumor microenvironment and its stromal cells play an important role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a rich source of hematopoietic and mesenchymal stem cells, putatively contribute to this tumoral stroma. However their characteristics and roles within the tumor microenvironment are unclear. In the present study, BMDCs in the tumor microenvironment were traced using the green fluorescent protein (GFP) bone marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued by bone marrow transplantation from GFP-transgenic mice. Lewis lung cancer cells were inoculated into the mice to generate subcutaneous allograft tumors or lung metastases. Confocal microscopy, immunohistochemistry for GFP, α-SMA, CD11b, CD31, CD34 and CD105, and double-fluorescent immunohistochemistry for GFP-CD11b, GFP-CD105 and GFP-CD31 were performed. Results: Round and dendritic-shaped GFP-positive mononuclear cells constituted a significant stromal subpopulation in primary tumor peripheral area (PA) and metastatic tumor area (MA) microenvironment, thus implicating an invasive and metastatic role for these cells. CD11b co-expression in GFP-positive cells suggests that round/dendritic cell subpopulations are possibly BM-derived macrophages. Identification of GFP-positive mononuclear infiltrates co-expressing CD31 suggests that these cells might be BM-derived angioblasts, whereas their non-reactivity for CD34, CD105 and α-SMA implies an altered vascular phenotype distinct from endothelial cells. Significant upregulation of GFP-positive, CD31-positive and GFP/CD31 double-positive cell densities positively correlated with PA and MA (P<0.05). Conclusion: Taken together, in vivo evidence of traceable GFP-positive BMDCs in primary and metastatic tumor microenvironment suggests that recruited BMDCs might partake in cancer invasion and metastasis, possess multilineage potency and promote angiogenesis.

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  • The Role of Bone Marrow-Derived Cells during Ectopic Bone Formation of Mouse Femoral Muscle in GFP Mouse Bone Marrow Transplantation Model. 査読 国際誌

    Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Yu Song, Hiroyuki Matsuda, Hotaka Kawai, Masae Fujii, Mei Hamada, Keisuke Nakano, Toshiyuki Kawakami, Hitoshi Nagatsuka

    International journal of medical sciences   15 ( 8 )   748 - 757   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Multipotential ability of bone marrow-derived cells has been clarified, and their involvement in repair and maintenance of various tissues has been reported. However, the role of bone marrow-derived cells in osteogenesis remains unknown. In the present study, bone marrow-derived cells during ectopic bone formation of mouse femoral muscle were traced using a GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) mice were transplanted into C57BL/6 J wild type mice. After transplantation, insoluble bone matrix (IBM) was implanted into mouse muscle. Ectopic bone formation was histologically assessed at postoperative days 7, 14, and 28. Immunohistochemistry for GFP single staining and GFP-osteocalcin double staining was then performed. Bone marrow transplantation successfully replaced hematopoietic cells with GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts and osteocytes involved in ectopic bone formation were GFP-negative, whereas osteoclasts and hematopoietic cells involved in bone formation were GFP-positive. These results indicate that bone marrow-derived cells might not differentiate into osteoblasts. Thus, the main role of bone marrow-derived cells in ectopic osteogenesis may not be to induce bone regeneration by differentiation into osteoblasts, but rather to contribute to microenvironment formation for bone formation by differentiating tissue stem cells into osteoblasts.

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  • Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment. 査読 国際誌

    Takanori Eguchi, Chiharu Sogawa, Yuka Okusha, Kenta Uchibe, Ryosuke Iinuma, Kisho Ono, Keisuke Nakano, Jun Murakami, Manabu Itoh, Kazuya Arai, Toshifumi Fujiwara, Yuri Namba, Yoshiki Murata, Kazumi Ohyama, Manami Shimomura, Hirohiko Okamura, Masaharu Takigawa, Tetsuya Nakatsura, Ken-Ichi Kozaki, Kuniaki Okamoto, Stuart K Calderwood

    PloS one   13 ( 2 )   e0191109   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science  

    Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.

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  • In Vitro Efficacy of CaCO3 Content in CaTiO3-CaCO3 Composites for Bone Growth 査読

    Rodriguez Andrea Paola, Sanchez Maria Alejandra, Felice Betiana, Zamora Martin Lucas, Tsujigiwa Hidetsugu, Takabatake Kiyofumi, Kawai Hotaka, Nakano Keisuke, Nagatsuka Hitoshi

    JOURNAL OF HARD TISSUE BIOLOGY   27 ( 3 )   250 - 256   2018年

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    掲載種別:研究論文(学術雑誌)  

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  • Effects of the Geometrical Structure of a Honeycomb TCP on Relationship between Bone / Cartilage Formation and Angiogenesis. 査読 国際誌

    Hiroyuki Matsuda, Kiyofumi Takabatake, Hidetsugu Tsujigiwa, Satoko Watanabe, Satoshi Ito, Hotaka Kawai, Mei Hamada, Saori Yoshida, Keisuke Nakano, Hitoshi Nagatsuka

    International journal of medical sciences   15 ( 14 )   1582 - 1590   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A number of biomaterials have been developed, some of which already enjoy widespread clinic use. We have devised a new honeycomb tricalcium phosphate (TCP) containing through-and-through holes of various diameters to control cartilage and bone formation. However, the way in which the geometric structure of the honeycomb TCP controls cartilage and bone tissue formation separately remains unknown. In addition, an association has been reported between bone formation and angiogenesis. Therefore, in the present study, we investigated the relationship between angiogenesis and various hole diameters in our honeycomb TCP over time in a rat ectopic hard tissue formation model. Honeycomb TCPs with hole diameters of 75, 300, and 500 μm were implanted into rat femoral muscle. Next, ectopic hard tissue formation in the holes of the honeycomb TCP was assessed histologically at postoperative weeks 1, 2, and 3, and CD34 immunostaining was performed to evaluate angiogenesis. The results showed that cartilage formation accompanied by thin and poor blood vessel formation, bone marrow-like tissue with a branching network of vessels, and vigorous bone formation with thick linear blood vessels occurred in the TCPs with 75-μm, 300-μm, and 500-μm hole diameters, respectively. These results indicated that the geometrical structure of the honeycomb TCP affected cartilage and bone tissue formation separately owing to the induced angiogenesis and altered oxygen partial pressure within the holes.

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  • Significance of PD-L1 Expression in Tongue Cancer Development. 査読 国際誌

    Saori Yoshida, Hitoshi Nagatsuka, Keisuke Nakano, Yasunao Kogashiwa, Yasuhiro Ebihara, Mitsutake Yano, Masanori Yasuda

    International journal of medical sciences   15 ( 14 )   1723 - 1730   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims: Immunohistochemistry of PD-L1 has been recently established as a surrogate method to predict if immunotherapy targeting PD-L1/PD-1 has a significant effect on suppression of cancers such as lung non-small cell carcinoma, melanoma, and renal cell carcinoma. Here we performed immunohistochemistry for PD-L1 expression in squamous cell carcinoma (SCC) of the tongue to investigate the potential correlation between PD-L1 expression and clinicopathological factors and whether PD-L1 expression would be associated with prognosis. Methods: Tissue microarray cores of paraffin-embedded blocks from 135 cases with surgically resected tongue SCC were immunohistochemically analysed for PD-L1 expression. Results: We observed a positive correlation between PD-L1 expression and tongue SCC pT1 and pT2 tumours, but a negative correlation with pT2, pT3 and pT4 tumours. We also observed a positive correlation with lymph node metastasis. However, no positive correlation was demonstrated between PD-L1 expression and overall survival. Conclusions: PD-L1 tends to be overexpressed at the early stage of tongue SCC, showing a close correlation with initial development of tongue. However, PD-L1 expression may not affect prognosis.

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  • Pathological and Clinical Study of Japanese Ameloblastic Fibro-Odontomas 査読

    Sukegawa Shintaro, Nakano Keisuke, Kanno Takahiro, Kawai Hotaka, Matsumoto Kenichi, Sukegawa-Takahashi Yuka, Masui Masanori, Furuki Yoshihiko

    JOURNAL OF HARD TISSUE BIOLOGY   26 ( 4 )   425 - 430   2017年10月

  • Antibacterial Activity and Biocompability of Zinc Oxide and Graphite Particles as Endodontic Materials 査読

    Silvia Noemi Kozuszko, Maria Alejandra Sanchez, Maria Ines Gutierrez de Ferro, Ana Maria Sfer, Ana Paula Moreno Madrid, Kiyofumi Takabatake, Keisuke Nakano, Hitoshi Nagatsuka, Andrea Paola Rodriguez

    JOURNAL OF HARD TISSUE BIOLOGY   26 ( 4 )   311 - 318   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The aim of this work is to evaluate the antibacterial effect and biocompatibility of zinc oxide (ZnO) nanopaticles and graphite-type carbon (Gt) microparticles commercial powders. SEM analysis was performed to assess particles morphology. The antibacterial behavior was studied against Staphylococcus aureus (Staph. Aureus) (bacterial strain ATCC 29213) and TEM analysis of bacteria was performed to determine ultrastructural alterations; in addition, biocompatibility was evaluated in subcutaneous tissue of Wistar rats at 3, 7 and 28 d. ZnO and Gt powders exhibited antibacterial activity while TEM images of Staph. aureus showed membrane disruption followed by the release of internal content. Also, an electron-light region within the cytoplasm was observed for microorganisms treated with ZnO. Regarding biocompatibility, Gt samples induced a foreign body reaction response with presence of giant cells whereas ZnO samples showed fibroblastic connective tissue with chronic inflammatory cells and new small vessels. Also, collagen fibers and lack of capsule was observed by Trichome Masson stain. Thus, ZnO improved wound healing by enhancing tissue regeneration in contrast with calcium hydroxide control sample response which showed a fibrous tissue scar. Hence, ZnO nano-powder seems to be a potential material in the regenerative endodontic field.

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  • 腫瘍移植マウスを用いた、遠隔臓器に含まれる骨髄由来細胞の局在同定(Localization of bone marrow-derived cells of distant organs using tumor transplanted mouse)

    Kawai Hotaka, Tsujigiwa Hidetsugu, Nobunaga Hikari, Takabatake Kiyofumi, Nakano Keisuke, Matsuda Hiroyuki, Fushimi Shigeko, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   26 ( 4 )   438 - 438   2017年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • 細胞内におけるマトリックスメタロプロテアーゼ(MMP)の役割

    江口 傑徳, 奥舎 有加, 中野 敬介, 久保田 聡, 滝川 正春, カルダーウッド・スチュアート, 小崎 健一

    Journal of Oral Biosciences Supplement   2017   249 - 249   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Mmp遺伝子を標的とし、高転移性癌細胞の生存と転移を抑制する

    奥舎 有加, 江口 傑徳, 十川 千春, 中野 敬介, 岡元 邦彰, 小崎 健一

    Journal of Oral Biosciences Supplement   2017   378 - 378   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Cytoplasmic ABCG2 and Podoplanin Expression in Oral Squamous Cell Carcinoma Correlates with Lymph Node Metastasis 査読

    Han Liu, Shilin Xia, Lei Zhu, Nan Li, Qian Yang, Yan Dong, Keisuke Nakano, Hitoshi Nagatsuka, Jing Xiao

    JOURNAL OF HARD TISSUE BIOLOGY   26 ( 3 )   268 - 273   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The cervical lymph node metastasis of Oral Squamous Cell Carcinoma (OSCC) has been considered to be the main causes of death. The aim of our study was to clarify the expression pattern of ABCG2 and podoplanin in OSCC tissues and corresponding cervical lymph node, and evaluate the diagnostic value of ABCG2 and podoplanin in OSCC for tumorigenesis, histological stage and clinical prognosis. ABCG2 showed a mixed membranous and cytoplasmic pattern of staining in specific regions of stratum corneum and the center of well differentiated cancer nest, while only expressed in cytoplasm of poorly differentiated tumor nests. Podoplanin showed strong staining in LV endothelia, the periphery of well differentiated cancer nests, and tumor stromal fibroblasts surrounding tumor nests. The expression of ABCG2, especially cytoplasmic ABCG2, and podoplanin protein showed significantly higher tendency to lymph node metastasis (P&lt;0.05). Meanwhile, podoplanin positive rate increased with the decreasing degree of histological differentiation (P&lt;0.05). ABCG2 and podoplanin expression pattern is correlated with lymph node metastasis of OSCC. This result suggested that cytoplasmic ABCG2 with podoplanin have clinical potential in reliable molecule diagonsis for OSCC.

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  • Characteristics of Clinical and Imaging Findings of Epidermoid Cysts under the Skin of the Mental Region 査読

    Keiichi Uchida, Keisuke Nakano, Masaki Takada, Noriyuki Sugino, Hiromasa Hasegawa, Yoshizawa Michiko, Hideaki Kagami, Akira Taguchi

    JOURNAL OF HARD TISSUE BIOLOGY   26 ( 3 )   305 - 308   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Epidermoid cyst often arises in the floor of oral cavity; however, it is relatively rare to arise subcutaneously in the mental region. We reported characteristics of clinical and imaging findings of epidermoid cysts under the skin of the mental region. The patient was a 53-year-old male. He complained of a subcutaneous mass without pain in the left mental region. A palpable soft and movable thumb-sized mass without pain was observed at the first examination. Ultrasound examination revealed a well-demarcated mass with heterogenous hyper-echoic internal echo and posterior echo enhancement. On power Doppler sonography, a small amount of blood supply was found around the periphery of the mass. Plain CT scan revealed a globular soft-tissue mass with peripheral high and central low CT values area. The mass was removed under local anesthesia using intraoral approach. A histopathologic diagnosis was epidermoid cyst. Recurrence is not observed 2 years after surgery. There were only 3 reports of epidermoid cysts in the mental region, including our case in Japan, clinically characteristics of age ranging 20 to 66 years of age and the mean age of 46 years, with 2 males and 1 female. The size was from 20 mm to 12 mm in diameter and from the tip of a thumb up to the tip of a small finger. Ultrasound images of the inside of epidermoid cysts that we experienced this time showed enhancement of relatively uniform hyperechoic image and posterior echo, which was characteristically slightly different from findings of epidermoid cysts generally reported.

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  • Parenchyma-stromal interactions induce fibrosis by secreting CCN2 and promote osteoclastogenesis by stimulating RANKL and CD68 through activated TGF-β/BMP4 in ameloblastoma. 査読 国際誌

    Takebe Y, Tsujigiwa H, Katase N, Siar CH, Takabatake K, Fujii M, Tamamura R, Nakano K, Nagatsuka H

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   46 ( 1 )   67 - 75   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • GFPマウス骨髄移植モデルの異所性骨形成における骨髄由来細胞の役割(The role of bone marrow-derived cells in ectopic bone regeneration in the GFP mouse bone marrow transplantation model)

    Yu Song, Takabatake Kiyofumi, Tsujigiwa Hidetsugu, Matsuda Hiroyuki, Kawai Hotaka, Yoshida Saori, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   25 ( 4 )   458 - 458   2016年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • エナメル上皮腫において間質特性をもたらすCCN2とYAP局在化の解析(Analyzing the localization of CCN2 and YAP which effect the stromal properties in ameloblastoma)

    Hamada Mei, Takabatake Kiyofumi, Tsujigiwa Hidetsugu, Fujii Masae, Ono Sawako, Nobunaga Hikari, Nakano Keisuke, Nagatsuka Hitoshi

    Journal of Hard Tissue Biology   25 ( 4 )   460 - 461   2016年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • Cell migration and differentiation of GFP transplanted bone marrow-derived-cells into periodontal polyp in mice 査読

    Matsuda S, Shoumura M, Osuga N, Tsujigiwa H, Nakano K, Okafuji N, Ochiai T, Hasegawa H, Kawakami T

    ORAL DISEASES   22   11   2016年9月

  • 移植骨髄由来細胞の口蓋腺への遊走と細胞分化

    大谷 友加里, 玉村 亮, 河野 哲朗, 鈴木 久仁博, 中野 敬介, 長塚 仁, 辻極 秀次, 岡田 裕之

    Journal of Oral Biosciences Supplement   2016   352 - 352   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Three-Dimensional Cell Culture at the Frontiers of in Vitro Cancer Research: Present Perspectives

    Soo LL, Zainal AA, Hidetsugu T, Takabatake K, Nakano K, Chai WL, Nagatsuka H, Siar CH

    Annals of Dentistry   23 ( 1 )   1 - 10   2016年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Univ. of Malaya  

    DOI: 10.22452/adum.vol23no1.1

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  • Migration and Differentiation of GFP-transplanted Bone Marrow-derived Cells into Experimentally Induced Periodontal Polyp in Mice. 査読 国際誌

    Saeka Matsuda, Masahito Shoumura, Naoto Osuga, Hidetsugu Tsujigiwa, Keisuke Nakano, Norimasa Okafuji, Takanaga Ochiai, Hiromasa Hasegawa, Toshiyuki Kawakami

    International journal of medical sciences   13 ( 7 )   500 - 6   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    Perforation of floor of the dental pulp is often encountered during root canal treatment in routine clinical practice of dental caries. If perforation were large, granulation tissue would grow to form periodontal polyp. Granulation tissue consists of proliferating cells however their origin is not clear. It was shown that the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow. Hence, this study utilized GFP bone marrow transplantation mouse model. The floor of the pulp chamber in maxillary first molar was perforated using ½ dental round bur. Morphological assessment was carried out by micro CT and microscopy and GFP cell mechanism was further assessed by immunohistochemistry using double fluorescent staining with GFP-S100A4; GFP-Runx2 and GFP-CD31. Results of micro CT revealed alveolar bone resorption and widening of periodontal ligament. Histopathological examination showed proliferation of fibroblasts with some round cells and blood vessels in the granulation tissue. At 2 weeks, the outermost layer of the granulation tissue was lined by squamous cells with distinct intercellular bridges. At 4 weeks, the granulation tissue became larger than the perforation and the outermost layer was lined by relatively typical stratified squamous epithelium. Double immunofluorescent staining of GFP and Runx2 revealed that both proteins were expressed in spindle-shaped cells. Double immunofluorescent staining of GFP and CD31 revealed that both proteins were expressed in vascular endothelial cells in morphologically distinct vessels. The results suggest that fibroblasts, periodontal ligament fibroblasts and blood vessels in granulation tissue were derived from transplanted-bone marrow cells. Thus, essential growth of granulation tissue in periodontal polyp was caused by the migration of undifferentiated mesenchymal cells derived from bone marrow, which differentiated into fibroblasts and later on differentiated into other cells in response to injury.

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  • Functional Role of HSP47 in the Periodontal Ligament Subjected to Occlusal Overload in Mice. 査読 国際誌

    Hiroaki Mimura, Tatsuo Takaya, Saeka Matsuda, Keisuke Nakano, Rina Muraoka, Mihoko Tomida, Norimasa Okafuji, Takeo Fujii, Toshiyuki Kawakami

    International journal of medical sciences   13 ( 4 )   248 - 54   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    We carried out an experiment to induce traumatic occlusion in mice periodontal tissue and analyzed the expression of HSP47. Continuous traumatic occlusion resulted to damage and remodeling of periodontal ligament as well as increase in osteoclasts and bone resorption. Four days after traumatic occlusion, osteoclasts did not increase but Howship's lacunae became enlarged. That is, the persistent occlusal overload can destroy collagen fibers in the periodontal ligament. This was evident by the increased in HSP47 expression with the occlusal overload. HSP47 is maintained in fibroblasts for repair of damaged collagen fibers. On the other hand, osteoclasts continue to increase although the load was released. The osteoclasts that appeared on the alveolar bone surface were likely due to sustained activity. The increase in osteoclasts was estimated to occur after load application at day 4. HSP47 continued to increase until day 6 in experiment 2 but then reduced at day 10. Therefore, HSP47 appears after a period of certain activities to repair damaged collagen fibers, and the activity was returned to a state of equilibrium at day 30 with significantly diminished expression. Thus, the results suggest that HSP47 is actively involved in homeostasis of periodontal tissue subjected to occlusal overload.

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  • Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice. 査読 国際誌

    Kenzo Sakai, Keisuke Nakano, Saeka Matsuda, Hidetsugu Tsujigiwa, Takanaga Ochiai, Masahito Shoumura, Naoto Osuga, Hiromasa Hasegawa, Toshiyuki Kawakami

    International journal of medical sciences   13 ( 3 )   220 - 4   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    In this study, cholesterin was implanted in the subcutaneous tissue in mice to induce the formation of cholesterol granuloma. Histological examination was carried out to determine the type and source of cells. The tissue surrounding the embedded cholesterin was examined histologically within the period of 6 months. Cell differentiation in cholesterol granulomas was investigated using ddY mice and GFP bone marrow transplanted mice. Cholesterin was embedded in mice subcutaneously and histopathological examination was carried out in a period of 6 months. Results showed that at 2 weeks, cholesterin was replaced partly by granulation tissues. The majority of cells in the granulation tissues were macrophages and foreign body giant cells and the center consists of small amount of fibroblasts, collagen fibers and capillaries. At 3 months, more granulation tissue was observed compared to 2 weeks. Similar cells were observed, however, there were more fibroblasts, collagen bundles and capillaries present compared to 2 weeks. At 6 months, the cholesterin was mostly substituted by fibrous tissues consisting mainly of fibroblasts and collagen fibers with some macrophages and foreign body giant cells. Specifically, the outer part of the tissue consists of fibroblasts, collagen bundles and capillaries and the inner portion is filled with collagen bundles. Immunohistochemistry revealed that macrophages and foreign body giant cells were positive to GFP and CD68 although the fibroblasts and capillaries in the outer portion of cholesterol granulomas were GFP negative. Some spindle shape fibroblasts were also GFP positive. Immunofluorescent double staining revealed that cells lining the blood vessels were both positive to GFP and CD31 indicating that those were endothelial cells and were actually derived from the transplanted bone marrow cells. The results suggest that macrophages, foreign body giant cells as well as fibroblasts and capillary endothelial cells are bone marrow derived mesenchymal cells.

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  • Pathological Examination of Experimentally Induced Periodontal Polyp in Mice 査読

    Saeka Matsuda, Yukiko Yokoi, Keita Moriyama, Masahito Shoumura, Naoto Osuga, Keisuke Nakano, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   24 ( 4 )   397 - 400   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The mechanism in the formation of periodontal polyp has been established in several histological studies but details on cell differentiation and/or proliferation have not been elucidated. In the present study, we established a convenient and possible experimental system using ddY mice. Briefly, pentobarbital sodium (Somnopentyl) was injected into the abdominal cavity of the mouse followed by access cavity preparation on maxillary first molar using low speed 1/2 round bur (Merufa Inc), exposing the pulp and then allowed to perforate the floor of the pulp chamber. Observation was done over time until 6 months using micro CT (m_CT) image photography. Results with transmission image using m_CT showed the expansion in the width of the periodontal ligament in the furcation area. The lesion was excised as one mass and examined histopathologically. The granulation tissue was covered with stratified squamous epithelium. The present experimental technique has been confirmed to be effective in analyzing the formation of periodontal polyp induced by mechanical perforation.

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  • Role of extracytoplasmic function sigma factors in biofilm formation of Porphyromonas gingivalis. 査読 国際誌

    Satosu Onozawa, Yuichiro Kikuchi, Kazuko Shibayama, Eitoyo Kokubu, Masaaki Nakayama, Tetsuyoshi Inoue, Keisuke Nakano, Yukinaga Shibata, Naoya Ohara, Koji Nakayama, Kazuyuki Ishihara, Toshiyuki Kawakami, Hiromasa Hasegawa

    BMC oral health   15   4 - 4   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    BACKGROUND: Porphyromonas gingivalis has been implicated as a major pathogen in the development and progression of chronic periodontitis. P. gingivalis biofilm formation in the subgingival crevice plays an important role in the ability of the bacteria to tolerate stress signals outside the cytoplasmic membrane. Some bacteria use a distinct subfamily of sigma factors to regulate their extracytoplasmic functions (the ECF subfamily). The objective of this study was to determine if P. gingivalis ECF sigma factors affect P. gingivalis biofilm formation. METHODS: To elucidate the role of ECF sigma factors in P. gingivalis, chromosomal mutants carrying a disruption of each ECF sigma factor-encoding gene were constructed. Bacterial growth curves were measured by determining the turbidity of bacterial cultures. The quantity of biofilm growing on plates was evaluated by crystal violet staining. RESULTS: Comparison of the growth curves of wild-type P. gingivalis strain 33277 and the ECF mutants indicated that the growth rate of the mutants was slightly lower than that of the wild-type strain. The PGN_0274- and PGN_1740-defective mutants had increased biofilm formation compared with the wild-type (p < 0.001); however, the other ECF sigma factor mutants or the complemented strains did not enhance biofilm formation. CONCLUSION: These results suggest that PGN_0274 and PGN_1740 play a key role in biofilm formation by P. gingivalis.

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  • Notch as a Possible Cell Differentiation Factor in Pleomorphic Adenomas. 査読 国際誌

    Keisuke Takamine, Yukiko Ueda, Keisuke Nakano, Takanaga Ochiai, Yoshihiko Sugita, Katsutoshi Kubo, Hatsuhiko Maeda, Hiromasa Hasegawa, Toshiyuki Kawakami

    International journal of medical sciences   12 ( 10 )   759 - 63   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    The expression of Notch in 30 cases of pleomorphic adenoma was examined by immunohistochemistry. Comparing the results of our study with previous literatures, from the partial CK7 expression and substantial Notch expression in ductal epithelial cells as well as the Notch expression in solid tumor nests, it can be inferred that Notch is involved in cell differentiation. CK13 expression was observed in cells undergoing squamous metaplasia and Notch expression was seen in the nucleus of basal and squamous cells. The intense Notch expression in basal cells and weak expression in squamous cells suggests that Notch is involved in the differentiation from basal to squamous cell. Moreover, the loss of nuclear expression on the inner layer would signify that differentiation is about to end or has been terminated. Notch was expressed in the cytoplasm of cartilage cells and in the cell membrane of mucous cells but not in the nucleus indicating that differentiation has been concluded. Notch involvement is suspected in cell differentiation in areas showing ductal structures and squamous metaplasia. In summary, Notch is involved in cell differentiation of ductal cells in PA. Nuclear expression was shown in tumor cells in solid nests and surrounding structures. Moreover, Notch is expressed by basal cells undergoing squamous metaplasia suggesting the participation of Notch in cell differentiation in PA.

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  • Histological Evaluation of Periodontal Ligament in Response to Orthodontic Mechanical Stress in Mice. 査読 国際誌

    Keiko Kaneko, Saeka Matsuda, Rina Muraoka, Keisuke Nakano, Takami Iwasaki, Mihoko Tomida, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Toshiyuki Kawakami

    International journal of medical sciences   12 ( 9 )   689 - 94   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    The purpose of the study was to determine the cell dynamics in periodontal ligament in response to mechanical stress during orthodontic movement. Following Waldo's method, a square sheet of rubber dam was inserted in between the first and second maxillary molars in 10 ddY mice leaving the stress load for 3 hours. After 3 days and at 1 week, cell count on pressure and tension sides of the periodontal ligament was determined. Furthermore, the type of cell present after mechanical stress was identified using GFP bone marrow transplantation mouse model. Immunohistochemistry was carried out at 0 min (immediately after mechanical stress), 24 hours, 1 week, 2 weeks and 6 months. Temporal changes in the expression of GFP-positive bone marrow derived cells were examined. Moreover, double immunofluorescent staining was performed to determine the type of cell in the periodontal ligament. Cell count on the tension side tremendously increased 3 days after mechanical stress. At 1 week, spindle and round cell count increased compared to the control group. These changes were observed on both tension and pressure sides. Cell count on pressure side at 3 days (22.11+/-13.98) and at 1 week (33.23+/-11.39) was higher compared to the control group (15.26+/-8.29). On the tension side, there was a significantly increased at 3 days (35.46+/-11.85), but decreased at 1 week (29.23+/-13.89) although it is still higher compared to the control group (AD+/-SD: 10.37+/-8.69). Using GFP bone marrow transplantation mouse model, GFP positive cell count increased gradually over time in 6 months. GFP positive cells were also positive to CD31, CD68 and Runx2 suggesting that fibroblasts differentiated into osteoclasts and tissue macrophages. In conclusion, mechanical stress during orthodontic movement promoted the increase in the number of cells in the periodontal ligament on both tension and pressure sides. The increase in the number of cells in the periodontal ligament is believed to be due to the migration and cell division of undifferentiated mesenchymal cells.

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  • Cytological Kinetics of Periodontal Ligament in an Experimental Occlusal Trauma Model. 査読 国際誌

    Tatsuo Takaya, Hiroaki Mimura, Saeka Matsuda, Keisuke Nakano, Hidetsugu Tsujigiwa, Mihoko Tomida, Norimasa Okafuji, Takeo Fujii, Toshiyuki Kawakami

    International journal of medical sciences   12 ( 7 )   544 - 51   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    Using a model of experimental occlusal trauma in mice, we investigated cytological kinetics of periodontal ligament by means of histopathological, immunohistochemical, and photographical analysis methods. Periodontal ligament cells at furcation areas of molar teeth in the experimental group on day 4 showed a proliferation tendency of periodontal ligament cells. The cells with a round-shaped nucleus deeply stained the hematoxylin and increased within the day 4 specimens. Ki67 positive nuclei showed a prominent increase in the group on days 4 and 7. Green Fluorescent Protein (GFP) positivity also revealed cell movement but was slightly slow compared to Ki67. It indicated that restoration of mechanism seemed conspicuous by osteoclasts and macrophages from bone-marrow-derived cells for the periodontal ligament at the furcation area. It was suggested that the remodeling of periodontal ligament with cell acceleration was evoked from the experiment for the group on day 4 and after day 7. Periodontal ligament at the furcation area of the molar teeth in this experimental model recovered using the cells in situ and the bone-marrow-derived cells.

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  • Mouse Subcutaneous Tissue Reaction to Calcium Hydroxide-based Root Canal Filling Material 査読

    Masahito Shoumura, Saeka Matsuda, Naoto Osuga, Keisuke Nakano, Hidetsugu Tsujigiwa, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   23 ( 4 )   435 - 438   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Mouse subcutaneous tissue reaction to an embedded calcium hydroxide-based root canal filling material was analyzed histopathologically. After the material was placed within the mouse dorsal subcutaneous tissues, we performed examinations using histopathological, histochemical and immunohistochemical techniques. Two weeks after embedment, the proliferation of granulation tissue had already begun to surround the calcification. Most of the cells observed were macrophages. Likewise, multinucleated giant cells increased significantly. The multinucleated giant cells were observed as two types. In one, the centers of the giant cells were vacuoles, while in the others there were deeply stained calcifications with hematoxylin. Twelve weeks after embedment of the materials, further growth of multinucleated giants cells were sighted. Histochemically, von Kossa-stain-positive granules were observed within the macrophages and multinucleated giant cells as black fine granules. According to the TRAP stained specimens, the multinucleated giant cells especially reacted strongly at 4 weeks. However, the reaction became very weak at 12 weeks. CD68 immunohistochemical staining showed positive reactions in the cytoplasm of the proliferating macrophages and multinucleated giant cells. These results suggest that multinucleated giant cells are present in the surrounding tissues due to implantation of the calcium hydroxide-based root canal filling material, and that the presence of ACP in the cells is due to ingested calcium during active phagocytosis, which would disappear later on.

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  • 移植骨髄由来細胞の歯周組織への遊走と細胞分化(Transplanted bone marrow-derived cell migration into periodontal tissue and cell differentiation)

    Tsujigiwa Hidetsugu, Muraoka Rina, Nakano Keisuke, Tomida Mihoko, Takabatake Kiyofumi, Tamamura Ryo, Nagatsuka Hitoshi, Kawakami Toshiyuki

    Journal of Hard Tissue Biology   23 ( 4 )   470 - 470   2014年10月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • Experimental Model of Occlusal Trauma in Mouse Periodontal Tissues 査読

    Takeo Fujii, Tatsuo Takaya, Hiroaki Mimura, Naoto Osuga, Saeka Matsuda, Keisuke Nakano

    JOURNAL OF HARD TISSUE BIOLOGY   23 ( 3 )   377 - 380   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The aim of this study was to establish a model, which can be used to investigate the response of periodontal tissues to excessive occlusal loading in mice by observing histopathological changes. The experiment was performed on ten 7-week-old ddY male mice. Under general anesthesia by intraperitoneal injection pentobarbital sodium, a micro-plus-screwpin (head part, 1.7mm in diameter, thickness 0.5mm thickness) was screwed into the pulp cavity of the upper-left-first molar. R_mCT images of the experimental site indicated the occlusal contact position between the upper- and lower-left-first molars during the experimental periods. A micro-plus-screwpin was maintained at a constant position on the occlusal surface throughout the experimental period. Histopathological changes of the periodontal ligament at the furcation lesion of the lower-left-first molar and its surrounding periodontal tissues were observed under a light microscope. The densities of deeply dyeing cells in hematoxylin staining with a round-shaped nucleus were increased in the periodontal ligament, with a peak effect of day 4. Multinucleated giant cells appeared in the central lesion of the periodontal ligament on day 7. The distribution of resorption on the surface of both of the cementum and the alveolar bone was accompanied by multinucleated giant cells, which expanded rapidly from day 7 to day 14. These results showed that histopathological changes of periodontal tissues to excessive occlusal load were observed at the furcation area of molar teeth. The present method confirmed the effectiveness of the experimental model to examine the occlusal trauma on periodontal tissues produced by excessive occlusal load.

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  • Wnt signaling as a possible promoting factor of cell differentiation in pleomorphic adenomas. 査読 国際誌

    Yukiko Okuda, Keisuke Nakano, Koji Suzuki, Yoshihiko Sugita, Katsutoshi Kubo, Hatsuhiko Maeda, Norimasa Okafuji, Hiromasa Hasegawa, Toshiyuki Kawakami

    International journal of medical sciences   11 ( 9 )   971 - 8   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the 'mixed' differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.

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  • Establishment of Experimental Periapical Inflammatory Lesions in Mice 査読

    Naoto Osuga, Saeka Matsuda, Masahito Shoumura, Keita Moriyama, Yukiko Yokoi, Keisuke Nakano, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   22 ( 4 )   517 - 520   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Although studies on the formation of apical periodontitis have somehow been carried out but detailed cellular dynamics remain unclear. We recently established an experiment that could easily be performed using ddY mice. First, under general anesthesia using isoflurane inhalation, the coronal portion of the maxillary first molar was penetrated using a round bur and drill with water irrigation causing pulp exposure until the root apex. Micro computed tomography (R_mCT) was taken over time during observation. Four weeks later, R_mCT confirmed the presence of a radiolucent image at the apex of the tooth, which was then removed for histological examination. The results showed that granulation tissue with fibrosis had gradually formed at the periphery of the abscess. The present method confirmed the effectiveness of the experimental mode to exmine the formation of chronic inflammatory lesions at the root apex.

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  • Expression of TRAF6 Protein and TRAF6 mRNA during Different Stages of Deciduous Tooth Root Physiological Absorption 査読

    Guirong Zhang, Linxi Zhou, Koji Ito, Yoshihiko Sugita, Keisuke Nakano, Hatsuhiko Maeda, Xue Wang, Minghua Wang

    JOURNAL OF HARD TISSUE BIOLOGY   22 ( 1 )   1 - 6   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The expression of TRAF6 protein and TRAF6 mRNA during different stages of deciduous tooth root physiological absorption was observed. Deciduous teeth with physiological absorption period were divided into 3 groups according to the length of deciduous tooth root absorption: early stage of deciduous tooth root physiological absorption (I group), intermediate stage of deciduous teeth roots' physiological absorption (II group), final stage of deciduous tooth root physiological absorption (III group). TRAF6 antibody and TRAF6 hybridization in situ agent were used to detect the expression of TRAF6 protein and TRAF6 mRNA of odontoclasts of deciduous teeth with different physiological absorption stages. Im-pro-plas 6.0 analytical system software was used to measure the optical density of odontoclasts stained in three groups. SPSS13.0 software was used to analyze the regularity of expression. Optical density value of TRAF6 immunohistochemistry stain and TRAF6 mRNA in situ hybridization stain of odontoclasts was larger in I and II group compared with the value in III group. It indicated that odontoclasts in early and intermediate stages showed more activity than in the final stage. Expression of TRAF6 protein and TRAF6 mRNA during different stages of deciduous tooth root physiological absorption was consistent with the activity of odontoclast.

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  • Promotion of transplanted bone marrow-derived cell migration into the periodontal tissues due to orthodontic mechanical stress. 査読 国際誌

    Mihoko Tomida, Hidetsugu Tsujigiwa, Keisuke Nakano, Rina Muraoka, Takami Nakamura, Norimasa Okafuji, Hitoshi Nagatsuka, Toshiyuki Kawakami

    International journal of medical sciences   10 ( 10 )   1321 - 6   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Ivyspring International Publisher  

    BACKGROUND: Bone marrow-derived cells (BMCs) have abilities of cell migration and differentiation into tissues/organs in the body and related with the differentiation of teeth or periodontal tissue including fibroblasts. Then, we examined the effect of orthodontic mechanical stress to the transplanted BMC migration into periodontal tissues using BMC transplantation model. MATERIAL AND METHOD: BMC from green fluorescence protein (GFP) transgenic mice were transplanted into 8-week-old female C57BL/6 immunocompromised recipient mice, which had undergone 10 Gy of lethal whole-body-irradiation. Five mice as experimental group were received orthodontic mechanical stress using separator between first molar (M1) and second molar (M2) 1 time per week for 5 weeks and 5 mice as control group were not received mechanical stress. The maxilla with M1 and M2 was removed and was immunohistochemically analyzed using a Dako Envision + Kit-K4006 and a primary anti-GFP-polyclonal rabbit antibody. Immunohistochemically stained was defined as positive area and the pixel number of positive area in the periodontal tissue was compared with the previously calculated total pixel number of the periodontal tissue. RESULTS: The immunohistochemistry revealed that GFP positive cells were detected in the periodontal tissues, both in the experimental and control specimens. The ratio of pixel number in the examination group showed 5.77 ± 3.24 % (mean ± SD); and that in the control group, 0.71 ± 0.45 % (mean ± SD). The examination group was significantly greater than that of control group (Mann-Whitney U test: p<0.001). CONCLUSION: These results suggest that orthodontic mechanical stress accelerates transplanted BMC migration into periodontal tissues.

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  • Heat shock protein27 expression and cell differentiation in ameloblastomas. 査読 国際誌

    Muneteru Fujita, Keisuke Nakano, Ariyoshi Funato, Yoshihiko Sugita, Toshikatsu Kubo, Hatsuhiko Maeda, Norimasa Okafuji, Hiromasa Hasegawa, Toshiyuki Kawakami

    International journal of medical sciences   10 ( 10 )   1271 - 7   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Ivyspring International Publisher  

    The expression of HSP27 and some CKs were examined the 40 cases of typical solid/multicystic ameloblastoma using immunohistochemical techniques. In order to examine the relevance of HSP in cell differentiation, we focused on the cytoskeletal expression of CK. CK19 is a marker of typical odontogenic epithelium widely observed in follicular and plexiform types of ameloblastomas. Since staining with CK14 is one of the measures of the differentiation potential of squamous cells and is extensively expressed in both follicular and plexiform types, it implies that squamous differentiation of each type can occur. CK8 was strongly detected in tumor nests in plexiform type but weakly detected in follicular type. It was considered that the expression of HSP27 in plexiform type correlated with the expression of CK8 suggesting that HSP27 might have regulated the expression of CK8.

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  • HSP70 expression in the mouse dental pulp after immediate teeth separation

    Keisuke Nakano, Shinnosuke Saito, Atsushi Nabeyama, Shintaro Oishi, Masahiro Sato, Yukiko Yokoi, Naoto Osuga, Norimasa Okafuji, Toshiyuki Kawakami

    Journal of Hard Tissue Biology   22 ( 1 )   7 - 11   2013年

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    掲載種別:研究論文(学術雑誌)  

    We examined the change of HSP70 expression in the mouse dental pulp which was exposed to experimental teeth separation by immunohistochemistry as a model for conservative dental treatment. Eight week-old 18 male ddY mice were used and a wedge was inserted between upper 1st and 2nd molars for 3 hours. In the experimental group, HSP70 expression increased in the dental pulp tissues. The expression was the greatest at 24 hours after which it gradually decreased to become similar to the level of the control group at 1 week. These results suggest that when immunohistochemical expression of HSP70 is used as an index, almost no severe damage occurs upon clinical application of a wedge insertion. © 2013 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.

    DOI: 10.2485/jhtb.22.7

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  • Transplanted Bone Marrow-Derived Cell Migration Into Periodontal Tissues Induced by Orthodontic Mechanical Stress 査読

    Tomida M, Tsujigiwa H, Nakano K, Muraoka R, Nagatsuka H, Kawakami T

    TRANSPLANTATION   94 ( 10 )   555   2012年11月

  • Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma. 査読 国際誌

    Chong Huat Siar, Hitoshi Nagatsuka, Phuu Pwint Han, Rosario Rivera Buery, Hidetsugu Tsujigiwa, Keisuke Nakano, Kok Han Ng, Toshiyuki Kawakami

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   41 ( 4 )   332 - 9   2012年4月

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    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  

    BACKGROUND: Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are detected in this tumor. The activity of other Wnt members remains unclarified. MATERIALS AND METHODS: Canonical (Wnts-1, -2, -3, -8a, -8b, -10a, and -10b), non-canonical (Wnts-4, -5a, -5b, -6, 7a, -7b, and -11), and indeterminate groups (Wnts-2b and -9b) were examined immunohistochemically in 72 cases of ameloblastoma (19 unicystic [UA], 35 solid/multicystic [SMA], eight desmoplastic [DA], and 10 recurrent [RA]). RESULTS: Canonical Wnt proteins (except Wnt-10b) were heterogeneously expressed in ameloblastoma. Their distribution patterns were distinctive with some overlap. Protein localization was mainly membranous and/or cytoplasmic. Overexpression of Wnt-1 in most subsets (UA = 19/19; SMA = 35/35; DA = 5/8; RA = 7/10) (P < 0.05), Wnt-3 in granular cell variant (n = 3/3), and Wnt-8b in DA (n = 8/8) was key observations. Wnts-8a and -10a demonstrated enhanced expression in tumoral buddings and acanthomatous areas. Non-canonical and indeterminate Wnts were absent except for limited Wnt-7b immunoreactivity in UA (n = 1/19) and SMA (n = 1/35). Stromal components expressed variable Wnt positivity. CONCLUSION: Differential expression of Wnt ligands in different ameloblastoma subtypes suggests that the canonical and non-canonical Wnt pathways are selectively activated or repressed depending on the tumor cell differentiation status. Canonical Wnt pathway is most likely the main transduction pathway while Wnt-1 might be the key signaling molecule involved in ameloblastoma tumorigenesis.

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  • Immunohistochemical Changes of Heat Shock Protein 27 Expression in the Mouse Periodontal Tissues Exposed to Orthodontic Mechanical Stress 査読

    Maki Tomoda, Keisuke Nakano, Rina Muraoka, Hirokazu Matsuda, Kazuhiro Yamada, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   21 ( 1 )   43 - 50   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Orthodontic mechanical stress was exposed on mouse molars and histopathological changes as well as the expressions of HSP27 and p-HSP27 in the periodontal tissues were examined after removal of mechanical stress. The increased in mechanical stress up to 3 hours led to pathological changes that caused a space in between stretched periodontal ligament fibrous bundles and fibroblasts as well as narrowing of the periodontal ligament space. Degenerative changes were also occurred in the pressure side. Pathological changes did not only occur due to mechanical stress but also at the time of the release of mechanical stress exposure which increased over time. In the control group, both HSP27 and p-HSP27 were negative in the pressure side after mechanical stress was released 3 hours later. On the other hand, the tension side showed a strong positive reaction. The proteins were also expressed after 20 min, 1 hour, 3 hours and 9 hours. The strongest expression was observed 24 hours. A decreased in the intensity of expression was observed 3 days and 1 week later. The results suggest that HSP27 plays an important role in the recovery of injured cells in the periodontal tissues.

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  • Immunohistochemical expression of osterix appearing in the mouse orthodontic periodontal tension sides

    Toshihisa Harada, Keisuke Nakano, Hirokazu Matsuda, Rina Muraoka, Maki Tomoda, Yukiko Yokoi, Kazuhiro Yamada, Norimasa Okafuji

    Journal of Hard Tissue Biology   21 ( 3 )   321 - 328   2012年

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    掲載種別:研究論文(学術雑誌)  

    Early changes of Osterix expression were examined by immunohistochemistry (IHC) and fluorescent immunohistochemistry (FIHC) in mouse periodontal ligament exposed to experimentally induced orthodontic mechanical stress. Eight-week-old ddY mice were used as experimental animals. To provide continuous orthodontic mechanical stress on the periodontal ligament, a rubber dam sheet was placed between the upper molars of the mice. At 20 min, 1 h, 3 h, 9 h and 24 h after the insertion, related parts of the animal tissues were evaluated by IHC and FIHC regarding Osterix and Runx2 expressions. In the 3-h and 9-h experimental groups, orthodontic tension sites reacted positively. The positive reactions became weak in the experimental group at 24-h. The results suggest that Osterix acts as one of the key factors of osteogenic cell differentiation, which expresses the following after the expression of Runx2, down-steam of Runx2. © 2012 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.

    DOI: 10.2485/jhtb.21.321

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  • Immunohistochemical Observation of HSP27 in Ameloblastomas 査読

    Muneteru Fujita, Keisuke Nakano, Hatsuhiko Maeda, Waka Yoshida, Ryota Torii, Masanori Yoshiyama, Norimasa Okafuji, Hiromasa Hasegawa, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   20 ( 4 )   289 - 294   2011年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    We examined expression of Heat Shock Protein 27 (HSP27) molecules, in 10 cases of typical solid/multicystic ameloblastoma, by means of immunohistochemistry. In general, HSP27 and pHSP27 positive staining products were frequently detected in the cytoplasms of the neoplastic cells. The expression pattern and/or strength are slightly different according to the cytological features of ameloblastomas. The immunohistochemical staining results suggest that the expression of HSP27 and pHSP27 is considered to be involved in neoplastic transformation of odontogenic epithelial cells.

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  • A Consideration on the Role of HSP70 Appearing in the Periodontal Tissues due to Experimental Orthodontic Force 査読

    Rina Muraoka, Keisuke Nakano, Hirokazu Matsuda, Maki Tomoda, Norimasa Okafuji, Kazuhiro Yamada, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   20 ( 4 )   275 - 281   2011年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    We examined immunohistochemical expressions of HSP70 and p-HSP70 in the orthodontic periodontal tissues. In the control group, the HSP70 and p-HSP70 expression was observed in the periodontal ligament fibroblasts and that was kept in low levels. In the experimental group, the strong expression of HSP70 was detected according to over time. However, p-HSP70 expression was a bit delayed. The data suggests that HSP70 has been closely involved in the repair of tissue to maintain homeostasis of the periodontal tissues by the activation of periodontal ligament fibroblasts. Farthermore, the data also suggests that HSP70 act as a molecular chaperone of osteogenesis through an activation of osteoblasts.

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  • HISTOPATHOLOGICAL SAFETY EVALUATION OF NEWLY-DEVELOPED MGO SEALER 査読

    K. Nakano, M. Tomida, M. Sato, S. Matsuura, A. Yamamoto, E. Kasahara, T. Kawakami

    EUROPEAN JOURNAL OF MEDICAL RESEARCH   16 ( 12 )   526 - 530   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:I HOLZAPFEL VERLAG GMBH  

    We aimed to evaluate the subcutaneous tissue reaction to a newly-developed MgO Sealer for root canals. We injected the experimental material and three existing control materials into the dorsal area of 43 male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding sites was removed and histopathological examination was performed. The results demonstrate that the basic histopathological reaction is the formation of fibrous capsules consisting of granulation tissue around the experimental and control embedded materials. Based on our results, we believe that the newly-developed MgO Sealer is as safe as the existing control materials and can be considered for dental use as a root canal sealer.

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  • Expression of Chromogranin A in the Mouse Dental Pulp and Periodontal Tissues 査読

    Masahiro Sato, Keisuke Nakano, Shinnosuke Saito, Atsushi Nabeyama, Norimasa Okafuji, Akio Yamamoto, Etsuo Kasahara, Hiromasa Hasegawa, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   20 ( 4 )   295 - 299   2011年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    We examined immunohistochemical expression of Chromogranin A (CgA) in the mouse dental pulp and the periodontal tissues, which exposed to 3 hours immediate teeth separation. In the experimental group, CgA positive staining products were frequently detected in the periodontal fibroblasts and endothelial cells, and also detected in the dental pulp cells. The positive reactions were stronger than that of control specimens. The data suggests that induced expression was due to the mechanical stress of wedge insertion.

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  • Immunohistochemical expression of heat shock protein27 in the mouse dental pulp after immediate teeth separation

    S. Saito, K. Nakano, A. Nabeyama, M. Sato, N. Okafuji, A. Yamamoto, E. Kasahara, Toshiyuki Kawakami

    European Journal of Medical Research   16 ( 11 )   495 - 500   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central Ltd.  

    Aim: After immediate teeth separation, expression of HSP27 in the mouse dental pulp was examined. Immunohistochemistry was performed to examine the incidence of HSP27 expression. Materials and methods: A total of 36 8-week-old ddY mice were used as experimental subjects and a wedge was inserted in between maxillary right molars. The wedge was removed 30 min or 3 h after insertion. Animals were immediately sacrificed after the removal of wedge or until 1 week later and serial sections from paraffin-embedded tissues were prepared. Immunohistochemistry was carried out to examine the expression of HSP27. The untreated side served as the control. Results: In the control group, the endothelial cells and some pulp fibroblasts weakly expressed HSP27 suggesting that the expression is due to mechanical stress brought about by physiological masticatory force and pressure from the tongue. In both 30 min and 3 h experimental groups, HSP27 expression was highest at 24 h after wedge removal and the expression remained the same or started to decrease thereafter. The expression decreased at the same level as that of the control group 1 week after wedge removal. Conclusion: HSP27 may serve as an indicator of stimulus strong enough to show its expression. © I. Holzapfel Publishers 2011.

    DOI: 10.1186/2047-783x-16-11-495

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  • Immunohistochemical expression of hard tissue related factors in the mouse dental pulp after immediate teeth separation

    A. Nabeyama, K. Nakano, S. Saito, M. Sato, N. Okafuji, A. Yamamoto, E. Kasahara, Toshiyuki Kawakami

    European Journal of Medical Research   16 ( 11 )   507 - 513   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central Ltd.  

    We examined change of Runx2 and ALP expression in mouse tooth pulp which exposed to teeth separation experiment by immunohistochemistry as a model for conservative dentistry treatment. 8-week-old 36 male ddY mice were used and wedge was inserted between upper 1st and 2nd molars. The wedge was removed 30 minutes as well as 3 hours after the insertion and the samples were prepared extending up to 1 week of time period for regular histopathological and immunohistochemical examinations for ALP and Runx2 expression. The opposite sides without wedge insertion were taken as controls. In the control group pulp, weak expressions of Runx2 and ALP in the vessel endothelial cells as well as the pulp cells were revealed, suggesting the appearance of these genes upon mechanical stress induced by mastication and tongue pressure etc. On the other hand in the experiment group, Runx2 expression increased both in 30-minute and 3-hour teeth separation group. The expression became maximum at 24 hours. Then it gradually decreased and became similar level with the control group at 1-week after the wedge insertion. Similarly ALP expression increased after the wedge insertion and was maximum at 24 hours and then gradually decreased to the levels similar with the control group. These results suggest that when immunohistochemical expression of Runx2 as well as ALP was used as an index, no severe damage occur upon clinical application of wedge insertion. © I. Holzapfel Publishers 2011.

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  • Strawberry gingivitis as the first presenting sign of Wegener's granulomatosis: report of a case. 国際誌

    C H Siar, K B Yeo, K Nakano, H Nagatsuka, H Tsujigiwa, M Tomida, K H Ng, Toshiyuki Kawakami

    European journal of medical research   16 ( 7 )   331 - 4   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Wegener's granulomatosis is a rare multi-system disease characterized by the classic triad of necrotizing granulomas affecting the upper and lower respiratory tracts, disseminated vasculitis and glomerulonephritis. Oral lesions as a presenting feature are only encountered in 2% of these cases. Hyperplastic gingival lesions or strawberry gingivitis, is a characteristic sign of Wegener's granulomatosis. The latter consists of reddish-purple exophytic gingival swellings with petechial haemorrhages thus resembling strawberries. Recognition of this feature is of utmost importance for timely diagnosis and definitive management of this potentially fatal disease. A case of strawberry gingivitis as the first presenting sign of Wegener's granulomatosis affecting a 50-year-old Malay male is reported here. The differential diagnosis of red lesions that may present in the gingiva is discussed.

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  • HISTOPATHOLOGICAL EXAMINATION OF NEWLY-DEVELOPED ADHESIVE SILICONE DENTURE RELINING MATERIAL 査読

    M. Tomida, K. Nakano, M. Sato, S. Matsuura, T. Kawakami

    EUROPEAN JOURNAL OF MEDICAL RESEARCH   16 ( 7 )   328 - 330   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:I HOLZAPFEL VERLAG GMBH  

    We aimed to evaluate the subcutaneous tissue reaction to a newly developed adhesive silicone denture relining material, SG, (Neo Dental Chemical Products Co., Ltd. Tokyo, Japan). We embedded the experimental material SG and another existing control material, Roeko Seal (RS), in the dorsal area of 22 male ddY mice. One week and 12 weeks after the embedding, the tissues surrounding the embedded materials were removed and a histopathological examination was performed. The results demonstrate that the basic histopathological aspects are the formation of granulation tissue and the change of the tissue to fibrous capsule over time. The results suggests that the newly-developed SG is safe as compared with the control RS, whose composition is similar.

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  • COMPARATIVE EXAMINATION OF SUBCUTANEOUS TISSUE REACTION TO HIGH MOLECULAR MATERIALS IN MEDICAL USE 査読

    M. Tomida, K. Nakano, S. Matsuura, T. Kawakami

    EUROPEAN JOURNAL OF MEDICAL RESEARCH   16 ( 6 )   249 - 252   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:I HOLZAPFEL VERLAG GMBH  

    Polypropylene (PP), Polyethylene (PE) and polytetrafluoroethylene (FE) are high molecular materials in medical use. They are also used as the negative control materials for ISO 10993-6 international standard biological evaluation of medical devices. We examined tissue reactions to these materials embedded subcutaneously in the dorsal area of male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding site was removed and then histopathological examination was performed. Our results demonstrate that the basic histopathological reaction is the formation of fibrous capsule consisting of granulation tissue around the embedded materials. Based on our results, we believe that the high molecular materials such as, PP, PE and FE, can be considered for medical use as a biomaterials within the body.

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  • IMMUNOHISTOCHEMICAL LOCALIZATION OF NOTCH SIGNALING MOLECULES IN AMELOBLASTOMAS 査読

    E. Muraki, K. Nakano, H. Maeda, M. Takayama, M. Jinno, K. Kubo, W. Yoshida, H. Hasegawa, T. Kawakami

    EUROPEAN JOURNAL OF MEDICAL RESEARCH   16 ( 6 )   253 - 257   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:I HOLZAPFEL VERLAG GMBH  

    We examined Notch signaling molecules, Notch1 and Jagged1, in serial large cases of typical solid/multicystic ameloblastoma. In general, Notch positive staining products were frequently detected in the cytoplasms of the cells. In the same cells, Jagged positive staining were also frequently observed, while only occasionally positive in peripheral cells, especially in cuboidal cells. The results showed that these morphogenesis regulation factors are closely related to cytological differentiation in neoplastic cells of ameloblastoma. The Notch and Jagged positive-cell ratios were frequently positive, and the ratios were nearly the same between the varied histopathological, cytological patterns. However, the less-differentiated cells were fewer in number than that of well-differentiated cells.

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  • Transplanted bone marrow derived cells differentiated to tooth, bone and connective tissue in mice. 査読

    Tsujigiwa H, Katase N, Sathi GA, Buery RR, Hirata Y, Kubota M, Nakano K, Kawakami T, Nagatsuka H

    J Hard Tissue Biol.   20 ( 2 )   147 - 151   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.20.147

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  • L929 cell adhesion on the surface oxidized NiTi shape memory alloy 査読

    Ying Na, Qiang Wang, Keisuke Nakano, Mihoko Tomida, Toshiyuki Kawakami, Yang Zhang

    Journal of Hard Tissue Biology   20 ( 1 )   53 - 58   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Oxide film was obtained on a NiTi shape memory alloy by a chemical method. In vitro bioactivity of the oxidized NiTi shape memory alloy was studied. Cell culture showed that both non-oxidized and oxidized NiTi shape memory alloy did not have cell toxicity while the oxidized displayed higher cell viability. More L929 cells were found to adhere and proliferate on the oxidized samples surface than that on the non-oxidized. Cell number increased slowly for the test alloy samples'. Oxidized NiTi shape memory alloy possesses equal cell-activating properties to the pure titanium. More intercellular substance was observed for the cells on the oxidized NiTi alloy. The oxidized NiTi alloy shows better cell response than the non-oxidized. Surface oxidation improves the bioactivity of NiTi shape memory alloy. © 2011 The Hard Tissue Biology Network Association.

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  • Immunohistochemical Expression of Notch Signaling in Calcifying Cystic Odontogenic Tumor 査読

    Kawakami T, Siar C. H, Nakano K, Tomida M, Matsuura S, Tsujigiwa H, Nagatsuka H

    ORAL DISEASES   16 ( 6 )   517 - 518   2010年9月

  • Differential expression of Notch receptors and their ligands in desmoplastic ameloblastoma. 査読 国際誌

    Chong Huat Siar, Keisuke Nakano, Phuu Pwint Han, Hitoshi Nagatsuka, Kok Han Ng, Toshiyuki Kawakami

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   39 ( 7 )   552 - 8   2010年8月

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    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-BLACKWELL  

    BACKGROUND: In mammals, the Notch gene family encodes four receptors (Notch1-4), and all of them are important for cell fate decisions. Notch signaling pathway plays an essential role in tooth development. The ameloblastoma, a benign odontogenic epithelial neoplasm, histologically recapitulates the enamel organ at bell stage. Notch has been detected in the plexiform and follicular ameloblastoma. Its activity in the desmoplastic ameloblastoma is unknown. METHOD: Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) were examined immunohistochemically in 10 cases of desmoplastic ameloblastoma. RESULTS: Ameloblastoma tumor epithelium demonstrated positive expression for Notch1 (n = 5/10), Notch3 (n = 8/10), Notch4 (n = 10/10), Jagged1 (n = 6/10) and Delta1 (n = 5/10), but no reactivity for Notch2 (n = 10/10) and Jagged2 (10/10). Expression patterns were distinct with some overlap. Positive activity was detected largely in the cell membrane and cytoplasm of peripheral and central neoplastic epithelial cells, and sometimes in the nucleus. Staining score was highest for Notch4. Stromal components namely endothelial cells and fibroblasts showed overexpression for Notch4 but were mildly or non-reactive for the other Notch members and their ligands. CONCLUSIONS: These findings suggest that Notch receptors and their ligands may play differing roles during the development of the desmoplastic ameloblastoma with Notch4 probably playing a greater role in the acquisition of tissue-specific cellular characteristics in the desmoplastic ameloblastoma.

    DOI: 10.1111/j.1600-0714.2009.00871.x

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  • Notch4 overexpression in ameloblastoma correlates with the solid/multicystic phenotype. 査読 国際誌

    Chong Huat Siar, Hitoshi Nagatsuka, Kee Seng Chuah, Rosario Santos Rivera, Keisuke Nakano, Kok Han Ng, Toshiyuki Kawakami

    Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics   110 ( 2 )   224 - 33   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    OBJECTIVE: Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance. METHODS: Notch receptors (Notch1, 2, 3, 4) and ligands (Jagged1, 2, and Delta1) were examined immunohistochemically in SA (n = 23), UA (n = 22), and RA (n = 19). RESULTS: Notch4 overexpression in SA (n = 19/23; 82.6%) compared with UA (n = 1/22; 4.5%) or RA (n = 10/19; 52.6%) (P < .05) suggests positive correlation between Notch4 signaling and ameloblastomas with a solid/multicystic phenotype. Ligand (Jagged1 and Delta1) underexpression compared with their receptors (Notch1, 3, 4) (P < .05) and nonreactivity for Notch2 and Jagged2 in all 3 subsets suggests that ameloblastoma epithelium belongs to an earlier stage of differentiation (equivalent to inner enamel epithelium of developing tooth germ) before lineage commitment. CONCLUSION: Present findings suggest that Notch signaling molecules may play differing roles in the acquisition of different ameloblastoma phenotypes.

    DOI: 10.1016/j.tripleo.2010.03.009

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  • Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1. 査読 国際誌

    C H Siar, Keisuke Nakano, K H Ng, M Tomida, H Nagatsuka, T Kawakami

    European journal of medical research   15 ( 4 )   180 - 4   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:I HOLZAPFEL VERLAG GMBH  

    BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown. CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2. CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.

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  • Possibility of Odontoblasts Activity Up-Regulation due to Orthodontic Mechanical Stress in Mice 査読

    Keisuke Nakano, Rina Muraoka, Mihoko Tomida, Sachiko Matsuura, Norimasa Okafuji, Chong Huat Siar, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   19 ( 1 )   13 - 16   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Using Waldo's method in mice, we examined the immunohistochemical expression of Runx2 and alkaline phosphatase (ALP) appearing in dental pulp cells, especially in odontoblasts, just after receiving experimental orthodontic mechanical stress, using Waldo's method in mice. The examination results demonstrated that some dental root pulp cells, especially some odontoblasts, expressed the Runx2 and ALP in a comparatively short time after receiving the stress. The results suggest that the stress may cause odontoblast activity up-regulation.

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  • Immunohistochemical Observation of BMP in the Mouse Orthodontic Periodontal Tension Sides 査読

    Hirokazu Matsuda, Rina Muraoka, Maki Tomoda, Keisuke Nakano, Norimasa Okafuji, Kazuhiro Yamada, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   18 ( 4 )   181 - 184   2009年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    The purpose of this examination was to in vestigate the expression of BMP-2 and -4 in mouse orthodontic periodontal tension sides exposed orthodontic mechanical stress using the method of Waldo Immnohistochemically, in the experimental group. strong expression of BMP-2 and -4 were observed in the periodontal tension sides at 20minutes The results strongly suggested that the BMP-2 and -4 promoted the Runx2 expression for osteoblastic differention in the orthodontic periodontal tension sides at the early stage after receiving of the mechanical stress

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  • Expression of HSP in Dental Root Pulp Cells due to Experimental Orthodontic Mechanical Stress 査読

    Keisuke Nakano, Rina Muraoka, Mihoko Tomida, Sachiko Matsuura, Norimasa Okafuji, Chong Huat Siar, Toshiyuki Kawakami

    JOURNAL OF HARD TISSUE BIOLOGY   18 ( 3 )   127 - 130   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Using immunohistochemical techniques, we examined the expression of heat shock protein (HSP) appearing in murine dental pulp cells after the application of experimental orthodontic mechanical stress We used Waldo's method, and the results demonstrate that the dental root pulp cells expressed HSP in a comparatively short time after stress The results suggest that FISP works as one of the mechanisms to maintain homeostasis

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  • Immunohistochemical characteristics of odontogenic neoplasms and their physiological counterparts. 査読

    Nakano K, Nagatsuka H, Tsujigiwa H, Gunduz M, Katase N, Siar CH, Kawakami T

    J Hard Tissue Biol.   17 ( 3 )   79 - 90   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.17.79

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  • Cell differentiation of neoplastic cells originating in the oral and craniofacial regions

    Toshiyuki Kawakami, Hitoshi Nagatsuka, Keisuke Nakano, Takako Shimizu, Hidetsugu Tsujigiwa, Hiromasa Hasegawa, Noriyuki Nagai

    Cell Differentiation of Research Developments   1 - 30   2008年1月

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    掲載種別:論文集(書籍)内論文  

    Development of the oral and craniofacial region is a complex and fascinating set of processes which require a sequential integration of numerous biological steps. For medical and dental doctors, interest is particularly high in this region, because it is composed of three blastoderms - ectoderm, mesoderm, and endoderm - as well as neural crest cells. There are many different types of neoplasms in this region. In general, proliferation, development and cytological differentiation of the neoplastic cells reflect the normal physiological development of the outbreak mother cells and/or tissues. Collected human neoplasm cases, such as osteosarcoma appearing in the oral and craniofacial region, are examined regarding the immunohistochemical expression of some morphogenesis regulation factors. Furthermore, examination of Notch signaling is also conducted for some odontogenic neoplasms. This chapter mainly describes the examination results of some morphogenesis regulation factors, such as Notch signaling, in the neoplastic cells originating in the oral and craniofacial region, especially in the odontogenic neoplasms, in both well-differentiated and poorly-differentiated neoplasms of tooth germ enamel organ-derived neoplasm. In general, these morphogenesis regulation factors are responsible for cytological regulation of cell fate, morphogenesis and/or development. The results suggest that these factors play some role in cytological differentiation or acquisition of tissue specific characteristics in neoplastic cells. Furthermore, there would appear to be a relationship between the cytological differentiation in the oral and craniofacial neoplastic cells and the physiological development and differentiation of their originating mother cells and tissues of the oral and craniofacial region. © 2007 by Nova Science Publishers, Inc. All rights reserved.

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  • Notch signaling in mandibular condylar cartilage development(Poster Session,The 16th Annual Meeting of the Society for Hard Tissue Regenerative Biology in Matsumoto Dental University)

    Shimizu Takako, Nakano Keisuke, Tsujigiwa Hidetsugu, Nagatsuka Hitoshi, Watanabe Takehiro, Okafuji Norimasa, Kurihara Saburo, Hasegawa Hiromasa, Nagai Noriyuki, Kawakam Toshiyuki

    Journal of Hard Tissue Biology   16 ( 3 )   154 - 155   2007年12月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

    DOI: 10.2485/jhtb.16.147

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    その他リンク: http://search.jamas.or.jp/link/ui/2008174255

  • Immunohistochemical characteristics of bone forming cells in pleomorphic adenoma. 査読 国際誌

    Keisuke Nakano, Takehiro Watanabe, Takako Shimizu, Toshiyuki Kawakami

    International journal of medical sciences   4 ( 5 )   264 - 6   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Ivyspring International Publisher  

    Histopathological and immunohistochemical examinations were carried out in a case of pleomorphic adenoma with bone formation, occurring in the chin of a 34-year-old Japanese man. Examination results showed the modified neoplastic myoepithelial cells reacted positively to S-100 protein. The S-100-positive modified neoplastic myoepithelial cells were proliferated in the closely related area of the bone tissue. Furthermore, positive reaction was detected in the bone forming cells: osteoblasts and osteocytes. These cells also reacted positively to Runx2 as a marker of bone forming cells. These results suggest that the origin of the bone forming cells in this case of pleomorphic adenoma was modified neoplastic myoepithelial cells.

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  • Wnt5a overexpression in thick primary oral mucosal melanomas; Implications for its role in tumor progression. 査読

    Xiao J, Nagatsuka H, Siar CH, Ng KH, Tamamura R, Rivera RS, Katase N, Inoue M, Setsu K, Nakano K, Kawakami T, Nagai N

    J Hard Tissue Biol.   16 ( 2 )   79 - 86   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.16.79

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  • Role of heparanase in release of hepalan sulphate binding growth factors in odontogenic tumors. 査読

    Han PP, Nagatsuka H, Tamamura R, Katase N, Lefeuvre M, Hu HL, Takagi S, Ishida N, Nakano K, Kawakami T, Gunduz M

    J Hard Tissue Biol.   16 ( 1 )   23 - 30   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.16.23

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  • Histopathological study of matrix mineralization by osteoblastic-like and odontoblastic-like cells in diffusion chamber. 査読

    Rodriguez AP, Borkosky SS, Han PP, Tsujigiwa H, Takagi T, Sathi GS, Lee YJ, Katase N, Okauchi M, Nakano K, Xiao J

    J Hard Tissue Biol.   15 ( 1 )   6 - 10   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.15.6

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  • Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas. 国際誌

    Kimihide Kusafuka, Keisuke Nakano, Yuji Hiraki, Chisa Shukunami, Hitoshi Nagatsuka, Noriyuki Nagai, Tamiko Takemura, Yutaku Sakaguchi, Kazuichi Okazaki, Michi Kusafuka, Hiroko Hisha, Susumu Ikehara

    Virchows Archiv : an international journal of pathology   446 ( 1 )   34 - 40   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pleomorphic adenoma is the most common epithelial tumor in the salivary glands. This tumor frequently exhibits "mesenchyme"-like components, including myxoid or chondroid areas. Recently, using immunohistochemical techniques, we reported that cartilage-specific matrix protein, chondromodulin-I (ChM-I), was deposited on the inter-territorial matrix of the chondroid area in salivary pleomorphic adenomas and that ChM-I, which is also a strong angio-inhibitory factor, plays an important role in the avascular nature of the chondroid area and the chondroid formation in this type of tumor. To elucidate which cells express ChM-I mRNA in pleomorphic adenomas, we examined the expression and localization of ChM-I mRNA in this type of tumor using an in situ hybridization technique. Immunoreactivity for ChM-I was observed in the inter-territorial matrix of the chondroid area, especially around the lacunae, and in the cytoplasm of neoplastic myoepithelial cells of the myxoid element of pleomorphic adenomas. On in situ hybridization analysis, strong signals for ChM-I mRNA were detected in the cytoplasm of the lacuna cells of the chondroid element, and moderate to marked signals were observed in the cytoplasm of the neoplastic myoepithelial cells of the myxoid element. Signals for ChM-I mRNA were also seen in the cytoplasm of the spindle-shaped neoplastic myoepithelial cells in the transitional areas between the myxoid and chondroid elements of this tumor. Signals for ChM-I mRNA were not seen in the inner ductal cells or the fibrous element. These findings indicate that lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA and that mature ChM-I, which lacuna cells and neoplastic myoepithelial cells translate, is deposited in the chondroid matrix of pleomorphic adenomas. In conclusion, lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA ectopically in pleomorphic adenoma, and this plays an important role in chondroid formation and hypovascularity in this type of tumor.

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  • Elemental sulphur and alkali elutable melanin detected in oral melanosis and malignant melanoma by energy-filtering transmission electron microscopy. 査読 国際誌

    Noriyuki Nagai, You-Jin Lee, Noriyuki Nagaoka, Mehmet Gunduz, Keisuke Nakano, Tetsundo Nojima, Hidetsugu Tsujigiwa, Esra Gunduz, Chong Huat Siar, Hitoshi Nagatsuka

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   31 ( 8 )   481 - 7   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The morphology and contents of melanosomes are important features for differentiating melanocyte-derived melanotic lesions such as melanosis and malignant melanoma. METHODS: In this study, we attempted to elucidate the structure of melanin and sulphur content in oral melanosis and malignant melanomas by ultrastructural analysis. RESULTS: In oral melanosis, the essential pathological findings were overproduction of eumelanin and discharge of melanin into keratinocytes. In malignant melanoma in situ, pleomorphic and ellipsoid abnormal melanosomes with an increase in sulphur content and alkali elution rate were detected. In invasive malignant melanoma, the irregular ellipsoid and spheroid melanosomes existing either as discrete bodies or compound melanosomes with furtherly increased sulphur content and alkali elution were detected. CONCLUSIONS: Our findings suggest that abnormal melanosome morphology and high sulphur content are predictive markers for assessment of early or precancerous melanotic lesions and malignant melanoma.

    DOI: 10.1034/j.1600-0714.2002.00010.x

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  • Distribution of basement membrane type IV collagen alpha chains in ameloblastoma: an immunofluorescence study. 国際誌

    Keisuke Nakano, Chong Huat Siar, Noriyuki Nagai, Ichiro Naito, Yoshikazu Sado, Hitoshi Nagatsuka, Choufuku Hoh, Katsuhiro Kurada, Hidetsugu Tsujigiwa, Mehmet Gunduz

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   31 ( 8 )   494 - 9   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Type IV collagen, a heterotrimeric molecule that exists in six genetically distinct forms, alpha1(IV)-alpha6(IV) is a major structural component of basement membrane (BM) and acts as a scaffold for other BM constituents. METHODS: Indirect immunofluorescence using alpha chain-specific monoclonal antibodies was employed to clarify basement membrane (BM) collagen IV distribution in two ameloblastoma, and for comparison, on oral mucosa and tooth germ. RESULTS: Ameloblastoma BM expressed five of six genetically distinct forms of collagen IV: alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains occurred as intense linear stainings without disruption around neoplastic epithelium, and this expression pattern was fundamentally similar to oral mucosa BM; alpha4(IV) expression was rare and occurred around nests of primitive tumor cells or potentially invasive sites. The tooth germ demonstrated a stage- and position-specific collagen IV distribution: the inner enamel epithelium BM expressed alpha1(IV), alpha2(IV), and alpha4(IV) except in the cuspal predentine region; and the outer enamel epithelium BM expressed alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains. CONCLUSIONS: Results suggest that collagen IV alpha chain distribution in ameloblastoma BM plays an important role in tumor cytodifferentiation and progression.

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  • Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development. 査読

    Nagai N, Nakano K, Sado Y, Naito I, Gunduz M, Tsujigiwa H, Nagatsuka H, Ninomiya Y, Siar CH

    The International journal of developmental biology   45 ( 7 )   827 - 831   2001年10月

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    掲載種別:研究論文(学術雑誌)  

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  • 骨内歯科インプラント植立実験における牛骨BMP-多孔体アパタイト複合体による顎骨欠損部再生効果について

    緒方 一昌, 譚 軍, 緒方 哲郎, 河野 渡, 春次 賢太郎, 加納 邦弘, 中野 敬介, 衣田 圭宏, 井上 正久

    日本口腔インプラント学会誌 = Journal of Japanese Society of Oral Implantology   10 ( 3 )   272 - 279   1997年9月

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    記述言語:日本語   出版者・発行元:公益社団法人 日本口腔インプラント学会  

    Hydroxyapatite (HAP) is considered one of the best bioactive ceramics because of high bone conduction/induction in osteogenic tissue. Although it has several characteristics of an ideal bone substitute, it does not have bone induction in heterogenous tissue. On the other hand, partially-purified bone morphogenetic protein (BMP), which contains BMP-2 and can induce differentiation of mesenchymal cells into osteoblast, was extracted from bovine bone matrix. In this study, porous HAP-BMP complex was inserted into the bone defect in case of HAP-coated implant, an integral implant system for the dog mandible.<br/> The results showed significant increases in the height and the area of the new bone in the porous HAP-BMP complex experimental group as compared with the control group. From the results above, it was considered that porous HAP-BMP composite maintains the thickness of regenerated tissue of the bone defect around implant.

    DOI: 10.11237/jsoi.10.272

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  • 分子量早期限定部分精製BMPの性状と骨I型コラーゲンキャリア

    永井 教之, 村田 勝, 辻極 秀次, 井上 正久, 長塚 仁, 中野 敬介, 赤木 巧, 衣田 圭宏, 完山 学, 秦 春林, 張 紹全, 此内 浩信, 韓 松, 黄 炳珍, 譚 軍, 劉 桂需, GOMAH Atia, 日比 一光

    Journal of hard tissue biology = 日本硬組織研究技術学会雑誌   5 ( 2 )   163 - 173   1996年9月

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    記述言語:日本語   出版者・発行元:日本硬組織研究技術学会  

    A modofied method was established to extracted BMP from bovine bone. SDS-PAGE and Westen blotting were apllied to analize the components of this partially purified BMP. In addition the amino acid sequence was studied using protein sequencer to analyze the unknown bands. Type I collagen derived from bone was used as a carrier whose properties and advantages were studied. The following conclusions are made from this study. 1. The limitation of molecluar weight in tbe early step of BMP purification procedure improves purification efficiency and stability, which makes the applicadon of BMP in big animalos possible. 2. In this method the purified BMP product also contains histone H3, histone 2B and other unknown proteins as well as BMP-2. 3. The atelocollagen derived from bone has proved to be an useful carrier for BMP. This carrier shows characteristics of self absorption and recalcification when embedded in tissues. 4. The minimun bone induction dose of BMP at each step (G-Ext:500μg, Hep:30μg, S200:50μg) and the optimal bone induction dose(G-Ext:5.0mg, Hep:2.0mg, S200:0.3mg) are determined, which makes the applicalion of BMP in cellular biology possible.

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  • アパタイト : 骨結合界面の初期石灰化とBMPによる異所性骨誘導

    永井 教之, 長塚 仁, 井上 正久, 村田 勝, 赤木 巧, 辻極 秀次, 中野 敬介, 馬渕 優, 寒河江 登志朗, 高木 亨, 久保木 芳徳

    Journal of hard tissue biology = 日本硬組織研究技術学会雑誌   4 ( 3 )   79 - 90   1995年11月

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    記述言語:日本語   出版者・発行元:日本硬組織研究技術学会  

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書籍等出版物

  • 口腔癌 = Oral cancer

    中野敬介, 長塚, 仁( 担当: 共著 ,  範囲: 上巻:4章:各種口腔癌と歯原生腫瘍の病理 p39-52)

    医歯薬出版  2023年9月  ( ISBN:9784263423158

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    総ページ数:xvi, 396p   記述言語:日本語

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  • Clinical Concepts and Practical Management Techniques in Dentistry

    Toshiyuki Kawakami, Kiyofumi Takabatake, Hotaka Kawai, Keisuke Nakano, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka( 担当: 分担執筆 ,  範囲: Chapter 5: Regeneration of Dentin Using Stem Cells Present in the Pulp)

    IntechOpen  2022年1月  ( ISBN:9781839628429

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  • Inflammation and Oral Cancer From Bench to Bedside 1st Edition

    Keisuke Nakano, Hitoshi Nagatsuka( 担当: 分担執筆 ,  範囲: 2. Diagnosis of oral squamous cell carcinomas and precancerous lesions : pp.19-40)

    Academic Press is an imprint of Elsevier  2021年9月 

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  • 新口腔病理学

    下野, 正基, 田中, 昭男( 担当: 分担執筆)

    医歯薬出版  2021年3月  ( ISBN:9784263458594

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    総ページ数:xix, 363p   記述言語:日本語

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  • Regeneration of Dentin Using Stem Cells Present in the Pulp

    Toshiyuki Kawakami, Kiyofumi Takabatake, Hotaka Kawai, Keisuke Nakano, Hidetsugu Tsujigiwa and Hitoshi Nagatuka( 担当: 共著)

    IntechOpen  2021年1月 

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    記述言語:英語

    DOI: 10.5772/intechopen.9

  • 病理組織の見方と鑑別診断

    吉野, 正, 小田, 義直, 坂元, 亨宇, 森井, 英一, 赤木, 忠厚, 松原, 修, 真鍋, 俊明( 担当: 分担執筆)

    医歯薬出版  2020年12月  ( ISBN:9784263731970

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    総ページ数:xxii, 740p   記述言語:日本語

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  • 口腔がん早期発見のための口腔細胞診入門 : 歯科医院で取り組むLBC

    田沼, 順一, 松坂, 賢一( 担当: 分担執筆)

    医歯薬出版  2020年12月  ( ISBN:9784263462188

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    総ページ数:111p   記述言語:日本語

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  • 口腔外科学

    白砂, 兼光, 古郷, 幹彦( 担当: 分担執筆)

    医歯薬出版  2020年2月  ( ISBN:9784263458433

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    総ページ数:xx, 862p   記述言語:日本語

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MISC

  • エナメル上皮腫が分泌するCCN2による腫瘍間質を介した骨吸収に及ぼす影響

    武部祐一郎, 辻極秀次, 高畠清文, 稲田靖則, 藤井昌江, 河合穂高, 中野敬介, 長塚仁

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   41st   2023年

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  • エナメル上皮腫におけるHIF-1を介した開窓術作用機序の解明

    稲田靖則, 高畠清文, 藤井昌江, 伏見滋子, 中野敬介, 長塚仁

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   41st   2023年

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  • ハニカム構造を有するTCPを応用した骨髄組織誘導

    稲田靖則, 高畠清文, 辻極秀次, 河合穂高, 中野敬介, 長塚仁

    日本口腔科学会学術集会プログラム・抄録集   77th   2023年

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  • HIF-1αを介したエナメル上皮腫開窓術作用機序の解明

    高畠清文, 稲田靖則, 藤井昌江, 河合穂高, 中野敬介

    日本口腔科学会学術集会プログラム・抄録集   77th   2023年

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  • 口腔扁平上皮癌の腫瘍血管形成におけるCXCR4の役割の検討

    SOE Yamin, 河合穂高, EAIN Htoo Shwe, 高畠清文, 吉田沙織, 佐能彰, 佐能彰, 森松歩, 中野敬介, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   34th   2023年

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  • 深層学習を用いた歯科パノラマX線画像における歯科インプラントの製品名と治療段階の自動分類法

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

    電子情報通信学会技術研究報告(Web)   120 ( 431(MI2020 47-97) )   2021年

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  • 口腔細胞診による口腔癌および前癌病変の一次スクリーニングの有用性

    助川信太郎, 小野早和子, 中野敬介, 長塚仁, 古木良彦

    日本臨床細胞学会雑誌(Web)   60   2021年

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  • 口腔扁平上皮癌における間質細胞が与える骨髄由来細胞の動員への影響

    河合穂高, MAY Oo Wathone, 高畠清文, 伏見滋子, 稲田靖則, 中野敬介, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   31st   2020年

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  • 口腔扁平上皮癌におけるCXCR4の腫瘍血管での役割

    大森悠加, 河合穂高, 吉田沙織, 藤井昌江, SHAN Qiusheng, SHAN Qiusheng, 高畠清文, 中野敬介, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   31st   2020年

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  • 下顎臼後部歯肉に発生した周辺性エナメル上皮腫の1例

    武田斉子, 山近英樹, 高畠清文, 中野敬介, 長塚仁, 飯田征二

    日本口腔科学会雑誌(Web)   69 ( 3 )   2020年

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  • 口腔扁平上皮癌におけるCXCR4阻害の抗腫瘍血管治療の有用性の検討

    河合穂高, 吉田沙織, 高畠清文, 中野敬介, 長塚仁

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   38th   2020年

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  • ハニカムTCPの幾何学構造による血管新生を介した選択的骨・軟骨組織形成制御

    高畠 清文, 辻極 秀次, 浜田 芽衣, 河合 穂高, 吉田 沙織, 大森 悠加, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   68 ( 2 )   179 - 179   2019年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 口腔扁平上皮癌におけるCXCR4の腫瘍血管新生への関与

    吉田 沙織, 河合 穂高, Chang Anqi, 高畠 清文, 浜田 芽衣, 藤井 昌江, 中野 敬介, 長塚 仁

    日本病理学会会誌   108 ( 1 )   335 - 335   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 動物モデルを用いた高転移臓器における転移促進的微小環境の検討

    河合 穂高, 辻極 秀次, メイワト・ウ, 吉田 沙織, 高畠 清文, 中野 敬介, 長塚 仁

    日本病理学会会誌   108 ( 1 )   293 - 293   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • ハニカムTCPの幾何学構造による血管新生を介した選択的骨・軟骨組織形成制御

    高畠清文, 辻極秀次, 浜田芽衣, 河合穂高, 吉田沙織, 大森悠加, 中野敬介, 長塚仁

    日本口腔科学会学術集会プログラム・抄録集   73rd   252   2019年

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  • 頭頸部領域再建におけるハニカムTCPの硬組織再生メカニズム解明と臨床応用の検討

    高畠清文, 辻極秀次, 河合穂高, 吉田沙織, 大森悠加, 中野敬介, 川上敏行, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   28th   2019年

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  • コレステリン肉芽腫における骨髄由来免疫抑制細胞(MDSC)の免疫組織化学的検討

    中野敬介, 河合穂高, 高畠清文, 吉田沙織, 大森悠加, 長塚仁, 川上敏行

    硬組織再生生物学会学術大会・総会プログラム・抄録集   28th   2019年

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  • エナメル上皮腫における細胞診の有用性

    藤井昌江, 高畠清文, 河合穂高, 吉田沙織, 大森悠加, 中野敬介, 長塚仁

    日本臨床細胞学会雑誌(Web)   58   2019年

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  • 高転移臓器における転移促進的微小環境の性質の検討

    河合穂高, 信長ひかり, MAY Wathone Oo, 吉田沙織, 大森悠加, 高畠清文, 中野敬介, 辻極秀次, 長塚仁

    Journal of Oral Biosciences Supplement (Web)   2019   2019年

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  • 新しい腫瘍オルガノイド多元評価システムの開発

    十川チハル, 江口傑徳, 江口傑徳, 大山和美, 奥舎有加, 中野敬介, 十川紀夫, 岡元邦彰

    Journal of Oral Biosciences Supplement (Web)   2019   2019年

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  • 口腔扁平上皮癌におけるPD-L1発現傾向の臨床病理学的解析

    吉田 沙織, 浜田 芽衣, 藤井 昌江, 河合 穂高, 高畠 清文, 中野 敬介, 長塚 仁, 安田 政実

    岡山歯学会雑誌   37 ( 2 )   86 - 86   2018年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • 癌の治療抵抗性と転移におけるHSP90およびMMP3の役割

    江口 傑徳, 小野 喜章, 奥舎 有加, 十川 千春, 内部 健太, 中野 敬介, 奥井 達雄, 滝川 正春, 岡元 邦彰, カルダーウッド・スチュアート

    Journal of Oral Biosciences Supplement   2018   142 - 142   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 核内およびエクソソーム中に存在するMMPs/PEXの癌進展における役割とその抑制

    奥舎 有加, 江口 傑徳, 十川 千春, 小野 喜章, 奥井 達雄, 中野 敬介, 岡元 邦彰

    Journal of Oral Biosciences Supplement   2018   150 - 150   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 口腔扁平上皮癌診断・治療における分子シャペロンHSP90含有細胞外小胞の可能性

    小野 喜章, 江口 傑徳, 十川 千春, 奥舎 有加, 河合 穂高, 中野 敬介, 佐々木 朗, 岡元 邦彰, 小崎 健一

    Journal of Oral Biosciences Supplement   2018   333 - 333   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ハニカムTCPを用いた硬組織形成制御における血管新生について

    松田 寛之, 高畠 清文, 辻極 秀次, 浜田 芽衣, 河合 穂高, 吉田 沙織, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   67 ( 2 )   160 - 160   2018年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 肺癌移植マウス高転移臓器における骨髄由来細胞の局在と役割の検討

    河合 穂高, 辻極 秀次, 藤井 昌江, 高畠 清文, 中野 敬介, 吉田 沙織, 浜田 芽衣, 長塚 仁

    日本病理学会会誌   107 ( 1 )   299 - 299   2018年4月

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  • 食道扁平上皮癌におけるPD‐L1の発現と進行との関係性

    吉田沙織, 長塚仁, 浜田芽衣, 中野敬介, 榊美佳, 永田耕治, 藤野節, 新井栄一, 長谷部孝裕, 安田政実

    日本病理学会会誌   107 ( 1 )   354 - 354   2018年4月

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  • 肺癌移植マウス高転移臓器における骨髄由来細胞の局在と役割の検討

    河合 穂高, 辻極 秀次, 藤井 昌江, 高畠 清文, 中野 敬介, 吉田 沙織, 浜田 芽衣, 長塚 仁

    日本病理学会会誌   107 ( 1 )   299 - 299   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 舌縁部に生じた無色素性悪性黒色腫の1例

    岡田 亜由美, 池田 篤司, 山近 英樹, 中野 敬介, 久富 美紀, 岡田 俊輔, 森谷 徳文, 石田 展久, 仲田 直樹, 松原 正和, 飯田 征二

    日本口腔診断学会雑誌   31 ( 1 )   121 - 121   2018年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • ハニカムTCPの幾何学構造が硬組織形成における血管新生に与える影響について

    松田寛之, 高畠清文, 辻極秀次, 河合穂高, 吉田沙織, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   27th   41   2018年

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    記述言語:日本語  

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  • 口腔扁平上皮癌における腫瘍間質による腫瘍実質の生物学的性格制御について

    高畠清文, 河合穂高, 吉田沙織, 松田寛之, 藤井昌江, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   27th   32   2018年

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    記述言語:日本語  

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  • ハニカムTCPを用いた硬組織形成制御における血管新生について

    松田寛之, 高畠清文, 辻極秀次, 浜田芽衣, 河合穂高, 吉田沙織, 中野敬介, 長塚仁

    日本口腔科学会雑誌(Web)   67 ( 2 )   2018年

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  • 核内およびエクソソーム中に存在するMMPs/PEXの癌進展における役割とその抑制

    奥舎有加, 江口傑徳, 江口傑徳, 十川千春, 小野喜章, 小野喜章, 奥井達雄, 中野敬介, 岡元邦彰

    Journal of Oral Biosciences Supplement (Web)   2018   2018年

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  • 転移性の異なる細胞株を用いた核内MMP3の機能解析とその役割

    奥舎有加, 江口傑徳, 十川千春, 奥井達雄, 中野敬介, 小崎健一, 岡元邦彰

    日本薬理学会近畿部会プログラム・要旨集   133rd   2018年

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  • 口腔扁平上皮癌診断・治療における分子シャペロンHSP90含有細胞外小胞の可能性

    小野喜章, 江口傑徳, 江口傑徳, 十川千春, 奥舎有加, 河合穂高, 中野敬介, 佐々木朗, 岡元邦彰, 小崎健一

    Journal of Oral Biosciences Supplement (Web)   2018   2018年

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  • 癌の治療抵抗性と転移におけるHSP90およびMMP3の役割

    江口傑徳, 江口傑徳, 小野喜章, 小野喜章, 奥舎有加, 十川千春, 内部健太, 中野敬介, 中野敬介, 奥井達雄, 滝川正春, 岡元邦彰, CALDERWOOD SK

    Journal of Oral Biosciences Supplement (Web)   2018   2018年

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    岡田亜由美, 池田篤司, 山近英樹, 中野敬介, 久富美紀, 岡田俊輔, 森谷徳文, 石田展久, 仲田直樹, 松原正和, 飯田征二

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  • 動物モデルを用いた,腫瘍微小環境における骨髄由来細胞の動態

    藤井昌江, 河合穂高, 辻極秀次, 玉村亮, 浜田芽衣, 小野早和子, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   26th   58   2017年8月

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  • マウス肺癌移植モデルにおける骨髄由来細胞の全身的局在と役割

    河合穂高, 辻極秀次, 信長ひかり, 高畠清文, 中野敬介, 松田寛之, 伏見滋子, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   26th   57   2017年8月

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  • ハニカムTCPを用いた幾何学構造による骨・軟骨組織再生メカニズムの解明

    高畠 清文, 辻極 秀次, 浜田 芽衣, 松田 寛之, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   66 ( 2 )   177 - 177   2017年7月

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  • エナメル上皮線維腫におけるWntとβ-cateninの発現

    中野 敬介, 高畠 清文, 杉田 好彦, 久保 勝俊, 前田 初彦, 川上 敏行, 長塚 仁

    日本病理学会会誌   106 ( 1 )   423 - 423   2017年3月

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  • 三次元共培養法を用いたエナメル上皮腫細胞および間質細胞の相互作用解析

    浜田芽衣, 辻極秀次, SIAR Chong Huat, LEE Soo Leng, 高畠清文, 中野敬介, 長塚仁

    日本病理学会会誌   106 ( 1 )   323   2017年3月

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  • 口腔扁平上皮癌の癌化過程におけるYAPおよび関連因子の検討

    小野 早和子, 中野 敬介, 高畠 清文, 河合 穂高, 吉田 沙織, 浜田 芽衣, 藤井 昌江, 信長 ひかり, 辻極 秀次, 長塚 仁

    日本病理学会会誌   106 ( 1 )   298 - 298   2017年3月

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  • 口蓋腫瘍の1例

    高畠清文, 中野敬介, 河合穂高, 浜田芽衣, 藤井昌江, 内田堅一郎, 三島克章, 上山吉哉, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   28th   58 (WEB ONLY)   2017年

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  • Mmp遺伝子を標的とし,高転移性癌細胞の生存と転移を抑制する

    奥舎有加, 江口傑徳, 十川千春, 中野敬介, 岡元邦彰, 小崎健一

    Journal of Oral Biosciences Supplement (Web)   2017   2017年

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  • 転移性の異なる癌細胞株の網羅的遺伝子発現解析による浸潤・転移促進因子の探索と機能解明

    奥舎有加, 江口傑徳, 十川千春, 中野敬介, 小崎健一, 岡元邦彰

    硬組織再生生物学会学術大会・総会プログラム・抄録集   26th   2017年

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  • 細胞内におけるマトリックスメタロプロテアーゼ(MMP)の役割

    江口傑徳, 江口傑徳, 奥舎有加, 中野敬介, 久保田聡, 滝川正春, CALDERWOOD SK, 小崎健一

    Journal of Oral Biosciences Supplement (Web)   2017   2017年

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  • 口腔細胞診における細胞採取方法の検討

    藤井 昌江, 井口 貴之, 硲 雄麻, 河合 穂高, 中野 敬介

    日本臨床細胞学会雑誌   55 ( Suppl.2 )   568 - 568   2016年10月

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    記述言語:日本語   出版者・発行元:(公社)日本臨床細胞学会  

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  • エナメル上皮腫間質性状とCCN2およびYAP局在の分析

    浜田芽衣, 高畠清文, 辻極秀次, 藤井昌江, 小野早和子, 信長ひかり, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   25th   44   2016年7月

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  • GFP骨髄移植マウスの異所性骨形成における骨髄由来細胞の関与について

    SONG Yu, 高畠清文, 辻極秀次, 松田寛之, 河合穂高, 吉田沙織, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   25th   34   2016年7月

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  • 異所性骨形成微小環境における骨髄幹細胞の関与

    高畠 清文, 松田 寛之, 辻極 秀次, 于 淞, 藤井 昌江, 中野 敬介, 長塚 仁

    日本口腔科学会雑誌   65 ( 2 )   198 - 198   2016年7月

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  • 口腔扁平上皮癌におけるYAPの発現

    小野 早和子, 中野 敬介, 高畠 清文, 河合 穂高, 吉田 沙織, 浜田 芽衣, 藤井 昌江, 信長 ひかり, 辻極 秀次, 長塚 仁

    日本病理学会会誌   105 ( 1 )   420 - 420   2016年4月

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  • エナメル上皮線維腫におけるWntの免疫組織化学的検討

    中野敬介, 高畠清文, 浜田芽衣, 藤井昌江, 吉田和加, 杉田好彦, 久保勝俊, 前田初彦, 川上敏行, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   27th   161 (WEB ONLY)   2016年

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  • 腫瘍微小環境における骨髄由来細胞の組織学的検討

    河合 穂高, 玉村 亮, 藤井 昌江, 高畠 清文, 松田 寛之, 吉田 沙織, 辻極 秀次, 中野 敬介, 長塚 仁

    岡山歯学会雑誌   34 ( 2 )   73 - 74   2015年12月

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  • ハニカムβ-TCPを用いた骨・軟骨組織形成制御

    高畠 清文, 辻極 秀次, 于 淞, 伊藤 聡, 松田 寛之, 河合 穂高, 信長 ひかり, 中野 敬介, 長塚 仁

    岡山歯学会雑誌   34 ( 2 )   75 - 75   2015年12月

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  • ハニカムβ‐TCPを用いた象牙芽細胞様細胞の誘導

    吉田沙織, 辻極秀次, 高畠清文, 河合穂高, 中野敬介, 玉村亮, 川上敏行, 長塚仁

    Journal of Oral Biosciences Supplement (Web)   2015   ROMBUNNO.P1‐88 (WEB ONLY) - 332   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ハニカムβ-TCPを用いた象牙芽細胞様細胞の誘導

    吉田 沙織, 辻極 秀次, 高畠 清文, 河合 穂高, 中野 敬介, 玉村 亮, 川上 敏行, 長塚 仁

    Journal of Oral Biosciences Supplement   2015   332 - 332   2015年9月

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  • ハニカムβ‐TCPの孔径による硬組織再生制御

    YU Song, 高畠清文, 辻極秀次, 伊藤聡, 松田寛之, 信長ひかり, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   24th   38   2015年8月

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  • 多形腺腫におけるYAPとCCN2の発現

    小野早和子, 中野敬介, 高畠清文, 河合穂高, 吉田沙織, 浜田芽衣, 辻極秀次, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   24th   33   2015年8月

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  • GFP骨髄移植マウスを用いた,異所性骨形成過程における骨髄由来細胞の役割の検討

    松田寛之, 辻極秀次, 高畠清文, 伊藤聡, 藤井昌江, 中野敬介, 長塚仁

    硬組織再生生物学会学術大会・総会プログラム・抄録集   24th   34   2015年8月

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  • 上顎に生じた傍骨性骨軟骨異型増生の一例(A case of bizarre parosteal osteochondromatous proliferation(BPOP, Nora's lesion) of the maxilla)

    永山 元彦, 落合 隆永, 中野 敬介, 中尾 寿奈, 江原 道子, 長谷川 博雅, 田沼 順一

    日本病理学会会誌   104 ( 1 )   471 - 471   2015年3月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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  • 多形腺腫の細胞分化におけるNotchシグナルの関与

    中野敬介, 高畠清文, 信長ひかり, 河合穂高, 落合隆永, 杉田好彦, 久保勝俊, 前田初彦, 川上敏行, 長塚仁

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   26th   121 (WEB ONLY)   2015年

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  • 骨治癒過程における骨髄由来細胞の関与

    河合 穂高, 辻極 秀次, 伊藤 聡, 中野 敬介, 于 淞, 川上 敏行, 長塚 仁

    Journal of Oral Biosciences Supplement   2013   120 - 120   2013年9月

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  • Strawberry gingivitis as the first presenting sign of Wegener’s granulomatosis: Report of a case.

    Siar CH, Yeo KB, Nakano K, Nagatsuka H, Tsujigiwa H, Tomida M, Ng KH, Kawakami T

    Eur J Med Res   16 ( 7 )   331 - 334   2011年

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  • Co-expression of BMP-2 and -7 in the tumoral epithelium of CEOT with selective BMP-7 expression in amyloid materials.

    Siar CH, Nakano K, Han PP, Tomida M, Tsujigiwa H, Nagatsuka H, Ng KH, Kawakami T

    J Hard Tissue Biol   20 ( 2 )   125 - 132   2011年

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  • Transplanted bone marrow-derived cell migration into periodontal tissues and cell differentiation.

    Muraoka R, Tsujigiwa H, Nakano K, Katase N, Tamamura R, Tomida M, Okafuji N, Nagatsuka H, Kawakami T

    J Hard Tissue Biol   20 ( 4 )   301 - 306   2011年

  • Notch signaling and ghost cell fate in the calcifying cystic odontogenic tumor.

    Siar CH, Kawakami T, Buery RR, Nakano K, Tomida M, Tsujigiwa H, Han PP, Nagatsuka H, Ng KH

    Eur J Med Res   16 ( 11 )   501 - 506   2011年

  • A case of histiocytic sarcoma localized in the maxillary gingiva

    T. Ochiai, K. Nakano, T. Kawakami, H. Hasegawa

    ORAL DISEASES   16 ( 6 )   561 - 561   2010年9月

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  • Immunohistochemical study of Notch signaling proteins in the calcifying epithelial odontogenic tumor (Pindborg Tumor).

    Siar CH, Chuah KS, Nakano K, Rivera RS, Tsujigiwa H, Nagatsuka H, Ng KH, Kawakami T

    J Hard Tissue Biol   19 ( 3 )   167 - 174   2010年

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  • Immunohistochemical observation of Notch signaling in a case of calcifying cystic odontogenic tumor.

    Nakano K, Siar CH, Tomida M, Matsuura S, Tsujigiwa H, Nagatsuka H, Kawakami T

    J Hard Tissue Biol   19 ( 3 )   147 - 152   2010年

  • Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor.

    Siar CH, Ha KO, Aung LO, Nakano K, Tsujigiwa H, Nagatsuka H, Ng KH, Kawakami T

    Eur J Med Res   15 ( 10 )   456 - 460   2010年

  • An unsuspected ameloblastoma in the subpontic region of the mandible with consideration of pathogenesis from the radiographic course.

    Siar CH, Nakano K, Chelvanayagam PI, NG KH, Nagatsuka H, Kawakami T

    Eur J Med Res   2010年

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  • Angiogenic squamous dysplasia-like phenomenon in oral epithelial precursor lesions.

    Siar CH, Oo VP, Nagatsuka H, Nakano K, Ng KH, Kawakami T

    Eur J Med Res   14 ( 7 )   315 - 319   2009年

  • Histopathological and immunohistochemical background of orthodontic treatment.

    Kawakami T, Nakano K, Shimizu T, Kimura A, Okafuji N, Tsujigiwa H, Hasegawa H, Nagatsuka H

    Int J Med Biol Front   2009年

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  • Wingless-type protein-1 (Wnt-1) expression in primary conventional and unicystic ameloblastomas and their recurrent tumors.

    Chuah KS, Siar CH, Nakano K, Nagatsuka H, Khoo SP, Ng KH, Kawakami T

    J Hard Tissue Biol   18 ( 2 )   63 - 70   2009年

  • Gene expression of Jagged2 in mandibular condylar cartilage development.

    Shimizu T, Tsujigiwa H, Nagatsuka H, Nakano K, Okafuji N, Kurihara S, Nagai N, Kawakami T

    Eur J Med Res   13 ( 1 )   1 - 3   2008年

  • Notch signaling in benign and malignant ameloblastic neoplasms.

    Nakano K, Siar CH, Tsujigiwa H, Nagatsuka H, Nagai N, Kawakami T

    Eur J Med Res   13 ( 10 )   476 - 480   2008年

  • Notch signaling in malignant tranceforming of odontogenic tumor(Oral Session,The 16th Annual Meeting of the Society for Hard Tissue Regenerative Biology in Matsumoto Dental University)

    Nakano Keisuke, Nagatsuka Hitoshi, Tsujigiwa Hidetsugu, Shimizu Takako, CH Siar, Nagai Noriyuki, Kawakami Toshiyuki

    Journal of hard tissue biology   16 ( 3 )   151 - 152   2007年12月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • A basic research of CaTiO_3-C as a coating material for implants(Oral Session,The 16th Annual Meeting of the Society for Hard Tissue Regenerative Biology in Matsumoto Dental University)

    Hu HaiLong, Okauchi Mika, Tamamura Ryo, Rodrigez Andrea Paola, Inoue Miho, Nakano Keisuke, Sagae Toshiro, Nagatsuka Hitoshi, Takagi Toru, Nagai Noriyuki

    Journal of hard tissue biology   16 ( 3 )   149 - 149   2007年12月

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  • Origin of osteoblasts involved in the mechanisn of ectopic bone formation induced by KUSA/A1 cells with honeycomb carrier.

    Rodriguez AP, Nagatsuka H, Tsujigiwa H, Han PP, Hu H, Okauchi M, Tamamura R, Borkosky S, Nakano K, Nagai N

    J Hard Tissue Biology   16 ( 2 )   75 - 78   2007年

  • Notch signaling in mandibular condylar cartilage development.

    Shimizu T, Nakano K, Tsujigiwa H, Nagatsuka H, Watanabe T, Okafuji N, Kurihara S, Hasegawa H, Nagai N, Kawakami T

    Eur J Med Res   12 ( 10 )   515 - 519   2007年

  • Development of CaTiO_3-C coating material for dental implant(5th Asian Science Seminar,Session 1)

    Okauchi Mika, Tamamura Ryo, Ryuu Ko Kai, Rui Kan, Xiao Jing, Nakano Keisuke, Nagaoka Noriyuki, Kanata Katsunori, Takagi Toru, Akao Masaru, Nagai Noriyuki

    Journal of hard tissue biology   15 ( 3 )   107 - 107   2006年12月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • マウス歯胚とヒト歯胚の基底膜におけるIV型コラーゲンα鎖の局在

    片瀬 直樹, 長塚 仁, 中野 敬介, 岡内 美佳, グンデゥズ・メーメット, 玉村 亮, 永井 教之

    Journal of Oral Bioscience   47 ( Suppl )   122   2005年9月

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  • Localization of type IV collagen alpha chains in tooth germ development

    Katase N, Nagatsuka H, Nakano K, Tamamura R, Xie W, Matsuoka Y, Nagai N

    Journal of Hard Tissue Biology   14 ( 2 )   124 - 125   2005年9月

  • Expression of Hsp70 in Acute Lung Injury Induced by Lipopolysaccharide

    Kang Jin, Yun Yu Dong, Nakano Keisuke, Nagai Noriyuki

    Journal of hard tissue biology   14 ( 1 )   28 - 31   2005年7月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

    We examined the expression of HSP70 in acute lung injury induced by lipopolysaccharide (LPS), in order to explore the mechanism of HSP70 in acute lung injury. Using an acute lung injury model in Wistar rats, we observed the in vivo HSP70 expression by immunohistochemistry and Western blot. After exposure to LPS, the level of HSP70 increased above the control level at 1 hour, reached the maximum level at 2 hours, and returned to the control level by 6 hours. Our study suggested that the expression of HSP70 is involved in the protection of acute lung injury induced by LPS.

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    その他リンク: http://search.jamas.or.jp/link/ui/2006294927

  • Localization of type IV collagen alpha chains in the basement membrane of ameloblastoma, tooth germ and oral mucosa by using indirect immunofluorescence.

    Kou H, Borkosky SS, Nagatsuka H, Tamamura R, Nakano K, Nagai N

    J Hard Tissue Biol   14 ( 2 )   235 - 236   2005年

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

    DOI: 10.2485/jhtb.14.235

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    その他リンク: http://search.jamas.or.jp/link/ui/2007049540

  • Gene expression of matrix proteins in Cbfal- knockout mice(2nd ASIAN SCIENCE SEMINAR IN OKAYAMA 2003)

    Rivera Rosario, Nagatsuka Hitoshi, Tsujigiwa Hidetsugu, Nakano Keisuke, Huang Bingzhen, Nagai Noriyuki

    Journal of hard tissue biology   12 ( 2 )   73 - 73   2003年12月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • Angioarchitecture of primary oral malignant melanomas. 国際誌

    You-Jin Lee, Noriyuki Nagai, Chong-Huat Siar, Keisuke Nakano, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Cheng-Hsiung Roan, Mehmet Gunduz

    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society   50 ( 11 )   1555 - 62   2002年11月

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    記述言語:英語  

    Angiogenesis is an essential process in the progression of malignant tumors. However, little is known of the angioarchitecture in primary oral malignant melanoma. We sought to determine this by the use of periodic acid-Schiff (PAS) stain, endothelial markers (CD34, CD105) and laminin, and by transmission electron microscopy in two cases. The results demonstrated that endothelium-lined vessels dominated the tumor microvasculature and these stained positively for PAS, laminin, and endothelial markers. Mosaic and tumor-lined vessels were infrequently encountered. Most PAS-positive patterned networks and loops ultrastructurally represented intratumor microhemorrhages that probably arose secondary to tumor vessel leakiness. Vascular channels of the vasculogenic mimicry type were rare. They stained for laminin but not for endothelial markers.

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  • Differential expression of collagen IV alpha1 to alpha6 chains in basement membranes of benign and malignant odontogenic tumors. 国際誌

    Hitoshi Nagatsuka, Chong Huat Siar, Keisuke Nakano, Hidetsugu Tsujigiwa, Mehmet Gunduz, Hoh Choufuku, You-Jin Lee, Ichiro Naito, Yoshikazu Sado, Noriyuki Nagai

    Virchows Archiv : an international journal of pathology   441 ( 4 )   392 - 9   2002年10月

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    記述言語:英語  

    Type IV collagen, the major component of basement membrane (BM), demonstrates a stage- and position-specific distribution of its isoforms during tooth development. To determine its localization in BM of odontogenic neoplasms, immunohistochemistry using six anti-alpha(IV) chain-specific monoclonal antibodies was performed. Results disclosed that BM demonstrated an irregular alpha(IV) chain profile in malignant odontogenic tumors as compared to benign odontogenic neoplasms. No alpha3(IV) chains were detected. Expression of alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) chains was stronger in desmoplastic ( n=3) than in ordinary (n=5) ameloblastomas. The adenomatoid odontogenic tumor ( n=2) distinctly expressed these chains in BM of cribriform areas and hyaline materials (which was also alpha4(IV)-positive), but weakly around epithelial whorls/rosettes/nests and mineralized foci. These five chains also stained BM and tumor cells of ameloblastic fibroma ( n=3) and ameloblastic fibro-odontosarcoma (n=1), but not the inductive hard tissues. Ameloblastic carcinoma ( n=2) showed specific alpha1(IV)/alpha2(IV) chain loss, while primary intraosseous carcinoma ( n=1) demonstrated a discontinuous alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) staining pattern. The present results suggest that modification and remodeling of BM collagen IValpha chains occur during odontogenic neoplasms' progression.

    DOI: 10.1007/s00428-002-0658-1

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  • 口腔扁平上皮癌におけるIV型コラーゲンα鎖の免疫組織化学的検討

    玉村 亮, 中野 敬介, 辻極 秀次, 長塚 仁, 井上 正久, Siar Chong Haut, 永井 教之

    歯科基礎医学会雑誌   43 ( 5 )   630 - 630   2001年8月

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    記述言語:日本語   出版者・発行元:歯科基礎医学会  

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  • Quantitation of epidermal growth factor gene amplification by competitive polymerase reaction in premalignant and malignant oral epithelial lesions

    Nagatsuka, H, Ishiwari, Y, Tsujigiwa, H, Nakano, K, Nagai, N

    Oral Oncology   37 ( 7 )   599 - 604   2001年

  • Effect of Immobilized rhBMP- 2/Collagen on ST2Cell.

    Tsujigiwa, H, Nagatsuka, H, Ishiwari, Y, Nakano, K, Viloria, I.L, Palmario, G.B, hay, S.H, Lee, J.I, Termvidchakorn, O, Nagai, N

    Journal of Dental Research   2001年

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  • 25:Quantitation of epidermal growth factor receptor gene amplification in premalignant and malignant oral epithelia

    Nagatsuka H, Ishiwari Y, Nakano K, Tsujigiwa H, Nagai N

    Oral medicine & pathology   5 ( 2 )   122 - 122   2000年12月

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    記述言語:英語   出版者・発行元:特定非営利活動法人日本臨床口腔病理学会  

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  • マウスストローマ培養細胞(ST2)におけるコラーゲン/BMP-2固定化効果の検討

    辻極 秀次, 長塚 仁, 石割 裕三, 中野 敬介, 永井 教之

    歯科基礎医学会雑誌   42 ( 5 )   450 - 450   2000年8月

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    記述言語:日本語   出版者・発行元:歯科基礎医学会  

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  • 歯胚およびエナメル上皮腫の基底膜におけるIV型コラーゲンα鎖の局在

    中野 敬介, 喜多村 佳子, 辻極 秀次, 石割 裕三, 長塚 仁, 中川 敏浩, 山本 茂久, 永井 教之

    歯科基礎医学会雑誌   42 ( 5 )   408 - 408   2000年8月

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    記述言語:日本語   出版者・発行元:歯科基礎医学会  

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  • Age and magnetic effects on ectopic bone formation induced by purified bone morphogenetic protein

    Nagai, N, Inoue, M, Nagatsuka, H, Ishiwari, Y, Tsujigiwa, H, Nakano, K, Nagaoka, N

    Pathophysiology   7 ( 2 )   107 - 114   2000年

  • rhBMP-2/I型アテロコラーゲン複合体の化学的固定化による異所性骨誘導の検討

    永井教之, 譚 軍, 長塚 仁, 石割裕三, 辻極秀次, 中野敬介

    岡山歯学会雑誌   2000年

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  • 口腔粘膜扁平上皮癌発生における表皮増殖因子受容体の遺伝子増幅に関する研究

    永井教之, 劉 桂需, 石割裕三, 辻極秀次, 中野敬介, 長塚 仁

    岡山歯学会雑誌   2000年

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  • Detection of mRNA in hard tissue using in situ hybridization

    Ishiwari,Y, Nagatsuka, H, Tsujigiwa, H, Nakano, K, Nagai, N

    PROCEEDINGS of Asian Science Seminar in Okayama 2000   2000年

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  • Immunohistochemistry in hard tissue research

    Nagatsuka, H, Ishiwari,Y, Nakano, K, Tsujigiwa, H

    PROCEEDINGS of Asian Science Seminar in Okayama 2000   2000年

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  • 14. Distribution pattern of αl(IV)- α6(IV)chains of type IV collagen in tooth germ morphogenesis(8th Annual Meeting of the Society of Hard Tissue Biology July 24, 1999 in Asahikawa)

    Noriyuki Nagai, Keisuke Nakano, Yuzo Ishiwari, Hitoshi Nagatsuka, Yoshiko Kitamura, Tohru Takagi, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Biochemistry Faculty of Dentistry of Tokyo Medical and Dental University

    Journal of hard tissue biology = Journal of hard tissue biology   9 ( 1 )   27 - 28   2000年

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  • IV型コラーゲンα3鎖欠損マウスの歯胚形成におけるα鎖の消長

    井上 正久, 中野 敬介, 藤井 英貴, 玉村 亮, 永井 教之

    歯科基礎医学会雑誌   41 ( 5 )   404 - 404   1999年8月

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    記述言語:日本語   出版者・発行元:歯科基礎医学会  

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  • 15. Natural bovine bone morphogenetic protein (BMP) induces cytological and functional differentiation of preodontoblasts in vitro. :

    Murata Masaru, Tsujigiwa Hidetsugu, Liu Gui-ru, Nakano Keisuke, Akagi Takumi, Ruch Jean Victor, Nagai Noriyuki

    日本硬組織研究技術学会雑誌 = Journal of hard tissue biology   7 ( 2 )   68 - 68   1998年

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    記述言語:英語   出版者・発行元:日本硬組織研究技術学会  

    First lower molar dental papillae, isolated from day-17 mouse embryos, were embedded in 10 E l of BGJ-b medium including fetal calf serum and 0.5% agar. Two E1 of BMP solution at the different dose of BMP were added to the medium before getting. The papillae embedded in the semi-solidmedium were deposited on Millipore filters, and cultured for 6 days. This BMP fraction promoted functional differentiatioun of odontoblast-like cells and stimtulated the matrix secretion, dependent on the concentration of BMP.

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    その他リンク: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=306655

  • 12. Gene expressions of bone and cartilage matrix proteins during ectopic hard tissue formation induced by BMP. :

    Takagi Hiroshi, Ishiwari Yuzo, Tsujigiwa Hidetsugu, Tan Jun, Nakano Keisuke, Nosaka Yukio, Nagathuka Hitoshi, Nagai Noriyuki

    日本硬組織研究技術学会雑誌 = Journal of hard tissue biology   7 ( 2 )   72 - 72   1998年

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    記述言語:英語   出版者・発行元:日本硬組織研究技術学会  

    Gene expressions of bone and cartilage matrix protein during the ectopic hard tissue formation induced by BMP were investigated using in situ hybridization method. The gene expressions of type I and II as well as type X and osteocalcin, which is not able to be seen in normal chondral ossification, were observed in chondrocyte-like cells. The results indicate that chondrocyte-like cells in ectopic bone formation may have both characters of chondrocytes and osteoblasts.

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    その他リンク: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=306672

  • 4. Gene expression of amelogenin in odontogenic tumors :

    Nakano Keisuke, Nagatsuka Hitoshi, Inoue Masahisa, Takagi Tohru, Nagai Noriyuki

    日本硬組織研究技術学会雑誌 = Journal of hard tissue biology   7 ( 2 )   62 - 62   1998年

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    記述言語:英語   出版者・発行元:日本硬組織研究技術学会  

    The distribtution of amelogenin mRNA was investigated in ameloblastoma and adenomatoid odontogeznic tumor (AOT). Digoxygenin(DIG) labeled RNA probe was prepared from human plexiform type amelobastoma. Sections of rat incisors human ameloblastoma and ACT were hybridized with the above-mentioned probe, and immuno-detection of the hybridized probe was performed with the DIG Ntucleic Acid Detection Kit. In the rat incisor, amelogenin mRNA was detected in the preameloblast and ameloblast. Amelogeuuin mRNA was detected mainly in the high columutar cells of the amelobastoma. Amelogenin mRNA was also detected in many duct-like and solid strtuctture tumor cells of AOT.

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    その他リンク: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=306625

  • 13. Bone Augmentation by BMP-Collagen composite in calvarial subperiosteum of matured rats. :

    Huang Bingzhen, Inoue Masahisa, Nakano Keisuke, Hoh Chouhuku, Nojima Tetsundo, Murata Masaru, Tsigono Yoshiho, Nagai Noriyuki

    日本硬組織研究技術学会雑誌 = Journal of hard tissue biology   7 ( 2 )   72 - 72   1998年

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    記述言語:英語   出版者・発行元:日本硬組織研究技術学会  

    The composite of recombinant bone morphogenetic protein 2 (rhBMP-2) and type I atelocollagen fibers was implanted under the calvarial periosteum of wistar rats of 8 months old. Each composite was removed at 2, 4, 6, and 8 weeks after implantation, and evaluated histologically as an onlay bone graft substitute in a calvarial model. The results demonstrated that the composite of BMP and collagen was an effective material with osteoindtnctivity as an onlay bone graft substitute even in matured rats.

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  • Aging and Ectopic Bone Formation Induced by Partially Purified Bone Morphogenetic Protein : Blood Vessel Ingrowth and Localization of Type I Collagen and Osteocalcin Assessed by Immunohistochemistry

    Chun-Lin QIN, Keisuke NAKANO, Yuzo ISHIWARI, Kazuteru HIBI, Katsuhiro KURODA, Yukio NOSAKA, Nobuyuki IIDA, Noriyuki NAGAI, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University

    Journal of hard tissue biology   6 ( 3 )   95 - 104   1997年10月

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    記述言語:英語  

    A mixture of heparin-Sepharose-purified bovine bone morphogenetic protein (BMP) and type I atellocollagen as the carrier was implanted in the subcutaneous tissues of 4-week, 10-month and 18-month old rats. The explants were evaluated usilrg H&E staining, morphometric analysis, as well as immunohistochemical staining of type IV collagen for blood vessel distribution, type I collagen and ostcocalcin for bone matrix proteins. Ectopic bone formation was reduced and the rate of blood vessel ingrowth was delayed and hindered in aged rats. The difference in blood vessel distribution might be one reason for the reductlon in ectopic bone formation in aged rats. The localization of type I collagen and osteocalcin was consistent with the bone formation observed histologically, L e., more extensive areas positive to type I collagen and osteocalcin in 4-week old rats than in 10-month and 18-month old rats.

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    その他リンク: http://search.jamas.or.jp/link/ui/1998111752

  • Immunohistochemical Study of Cytokeratin Patterns in Follicular and Plexiform Ameloblastoma

    Hitoshi NAGATSUKA, Hong-In SHIN, Hee-Kyung PARK, Yuzo ISHIWARI, Katsuhiro KURODA, Yukio NOSAKA, Han SONG, Chun-Lin QIN, Shao-Quan ZHANG, Keisuke NAKANO, Yoshiho CHIGONO, Hidetsugu TSUJIGIWA, Tohru TAKAGI, Noriyuki NAGAI, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Kyungpook National University, Department of Oral Pathology School of Dentistry Kyungpook National University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, Department of Oral Pathology School of Dentistry Okayama University, First Department of Oral Surgery Faculty of Medicine Teikyo University, Department of Oral Pathology School of Dentistry Okayama University, Department of Biochemistry Tokyo Medical and Dental University Faculty of Dentistry Yushima, Department of Oral Pathology School of Dentistry Okayama University

    Journal of hard tissue biology   4 ( 2 )   50 - 56   1995年11月

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    記述言語:英語  

    The distribution of cytokeratin was investigated in follicular and plexiform ameloblastomas using immunohistochemical methods. The findings were compared with that of human fetal oral mucosa, developing tooth germ and adult gingiva. The following cytokeratin antibodies were used:CK-1,SE-K,NSE-K and 19-K. In the follicular ameloblastoma, the cytokeratin pattern of nest's structure was not comparable to that of the enamel organ at the bell stage. The peripheral columnar cells reacted positively for NES-K and 19-K and negatively for SE-K. The central stellate reticulum-like cells showed an immunoreactivity with all used markers of cytokeratins, as well as the outer enamel epithelium. In the plexiform ameloblastoma, the immunoreaction pattern was like that of the oral mucosal epithelium of the fetus. Both the central and peripheral cells demonstrated positive reactions with SE-K and 19-K but not with NSE-K. In the developing teeth, SE-K, NES-K and 1999-K were well demonstrated in the dental lamina, and each layer of the enamel organ. In the adult gingiva, contrary to the fetal oral mucosa, the basal cells did not show an immunoreactivity with 19-K except for Merkel cells. A clear difference in cytokeratin pattern was noted between ameloblastoma and tooth germs. Especially, the reactive pattern of NSE-K and 19-K showed differences between the peripheral columnar cells of ameloblastoma and the inner enamel epithelium. These findings support the concept that the columnar cells of follicular ameloblastomas have little resemblance to the pre-ameloblast like cells in the cytokeratin distribution.

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  • Gene Expression of Bone Matrix Protein mRNA during BMP Induced Chondrogenesis and Osteogenesis by in situ Hybridization

    Noriyuki NAGAI, Hitoshi NAGATSUKA, Masaru MURATA, Masahisa INOUE, Takumi AKAGI, Chun-Lin QIN, Keisuke NAKANO, Yuzo ISIWARI, Hironobu KONOUCHI, Hidetsugu TSUJIGIWA, Yoshiho CHIGONO, Tohru TAKAGI, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Pathology Okayama University Dental School, Department of Oral Surgery Faculty of Medicine Teikyo University, Department of Biochemistry Tokyo Medical and Dental University Faculty of Dentistry

    Journal of hard tissue biology   4 ( 1 )   15 - 23   1995年3月

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    記述言語:英語  

    A sensitive in situ hybridization method with high resolution has been developed usin digoxigenin-II VTP labeled cRNA as a probe. The system was applied to a heterotopic induced bone with crude BMP. The localization of mRNA of the bone matrix proteins, osteopontin (OSP) and osteocalcin (OSC), was examined in the BMP-induced cartilage and bone in comparison with the endochondral ossification. In the heterotopic bone, OSP mRNA were detected in the osteoblast, young osteocyte and chondrocyte-like cells. In fatal endochondral ossification OSP mRNA was detected in the hypertrophic chondrocyte, osteoblast and young osteocyte, while OSC mRNA was detected in the osteoblast and young osteocyte, but hypertrophic chondrocyte was not detected. These results suggest that the chondrocyte-like cells in the BMP induced bone demonstrate the ambifunctions of the chondrocyte and osteoblast. Our results indicate that in situ hybridization immunohistochemistry is useful in identifying the cell phenotypes and their function.

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    その他リンク: http://search.jamas.or.jp/link/ui/1997001332

  • 顎骨のセメント質-骨形成性線維腫と化骨性線維腫の発生母組織に関する一考察

    井上 正久, 秦 春林, 中野 敬介, 辻極 秀次, 此内 浩信, 永井 教之

    Journal of hard tissue biology = 日本硬組織研究技術学会雑誌   4 ( 3 )   9 - 14   1995年

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    記述言語:日本語   出版者・発行元:日本硬組織研究技術学会  

    The histological differential diagnosis between cemento-ossifying fibroma and ossifying fibroma is still controversial since distingushing bone from cementum and non-specific calcification tissue by routine methods shows little reliabi11ty. Here we studied one case of each lesion by CPC treatment, immunohistochemical detection of collagen type I and III, and electron microscopy. We round that the distinction among bone, cementum and non-specific calcirication tissues might be greatly improved by these means, leading, therefore,to a more accurate differential diagnosis between cemento-ossirying and ossifying fibroma. The tissue origin in both cases is also discussed.

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▼全件表示

講演・口頭発表等

  • 口腔扁平上皮癌腫瘍間質が腫瘍関連マクロファージの集族・分化に与える影響について

    Piao Tianyan, 高畠 清文, Chan Anqi, 河合 穂高, 中野 敬介, 長塚 仁

    第44回岡山歯学会総会・学術大会  2023年12月10日 

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    開催年月日: 2023年12月10日

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  • 口腔細胞診におけるNILM症例についての再検討 招待

    中野敬介

    第62回日本臨床細胞学会秋期大会  2023年11月4日 

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    開催年月日: 2023年11月4日 - 2023年11月5日

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 口腔扁平上皮癌における骨髄由来間葉系幹細胞の動態の検討

    佐能 彰, 河合穂高, May Wathone Oo, Htoo, Shwe Eain, 藤井昌江, 高畠清文, 中野敬介, 伊原木聰一郎, 長塚 仁

    第31回硬組織再生生物学会学術大会・総会  2023年9月8日 

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    開催年月日: 2023年9月8日

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  • 口腔扁平上皮癌の腫瘍血管形成におけるCXCR4の役割の検討

    Yamin Soe, 河合 穂高, Htoo Shwe Eain, 高畠 清文, 吉田 沙織, 佐能 彰, 森松 歩, 中野 敬介

    第34回日本臨床口腔病理学会 学術大会  2023年8月25日 

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    開催年月日: 2023年8月24日 - 2023年8月26日

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  • ハニカム構造を有するTCPを応用した 骨髄組織誘導

    稲田 靖則, 高畠 清文, 辻極 秀次, 河合 穂高, 中野 敬介, 長塚 仁

    第77回NPO法人日本口腔科学会学術集会  2023年5月13日 

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    開催年月日: 2023年5月11日 - 2023年5月13日

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  • 口腔扁平上皮癌の病理組織学的診断におけるAI深層学習補助診断の効果検討

    助川 信太郎, 中野 敬介, 小野 佐和子, 嶋田 勝光, 高畠 清文, 河合 穂高, 村上 聡, 長塚 仁, 三宅 実

    第77回NPO法人日本口腔科学会学術集会  2023年5月12日 

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    開催年月日: 2023年5月11日 - 2023年5月13日

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  • CX3CL1 の口腔癌リンパ節転移における役割の検討

    河合 穂高, トゥシュエイン, 高畠 清文, 中野 敬介, 長塚 仁

    第112回日本病理学会総会  2023年4月14日 

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    開催年月日: 2023年4月13日 - 2023年4月15日

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  • 浸潤癌由来癌間質細胞は、MMP2 陽性骨髄由来細胞の浸潤に関与する

    May Wathone Oo, 河合 穂高, Htoo Shwe Eain, Yamin Soe, 高畠 清文, 中野 敬介, 中山 雅敬, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月28日

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  • 口腔扁平上皮癌の進展における骨髄由来細胞の役割

    Chang Anqi, 高畠 清文, 河合 穂高, May, Wathone Oo, Shan Qiusheng, Piao Tianyan, 中野敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月26日 - 2023年1月28日

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  • リンパ節転移における CX3CL1 の役割の検討

    Htoo Shwe Eain, 河合 穂高, May, Wathone Oo, Yamin Soe, 佐能 彰, 高畠 清文, 中野 敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月26日 - 2023年1月28日

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  • AI 診断支援は病理医にとって有用か? 招待

    助川 信太郎, 中野 敬介, 原 武史, 長塚 仁, 三宅 実

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月26日 - 2023年1月28日

    記述言語:日本語  

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  • 若年者口腔扁平上皮癌の臨床病理学的特徴について

    小野 早和子, 河合 穂高, 高畠 清文, 中野 敬介, 長塚 仁, 助川 信太郎, 古木 良彦

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月26日 - 2023年1月28日

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  • 動物モデルを用いた、骨髄由来間葉系幹細胞の転移に対するメカニズム

    佐能 彰, 河合 穂高, Htoo Shwe Eain、May, Wathone Oo, Yamin Soe, 高畠 清文, 中野 敬介, 伊原木 聰一郎, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年1月26日 

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    開催年月日: 2023年1月26日 - 2023年1月28日

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  • HIF-1αを介したエナメル上皮腫開窓術 作用機序の解明

    高畠 清文, 稲田 靖則, 藤井 昌江, 河合 穂高, 中野 敬介

    第77回NPO法人日本口腔科学会学術集会  2023年 

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    開催年月日: 2023年

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  • エナメル上皮腫における HIF-1 を介した開窓術作用機序の解明

    稲田 靖則, 高畠 清文, 藤井 昌江, 伏見 滋子, 中野 敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年 

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    開催年月日: 2023年

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  • エナメル上皮腫が分泌する CCN2 による腫瘍間質を介した骨吸収に及ぼす影響

    武部 祐一郎, 辻極 秀次, 高畠 清文, 稲田 靖則, 藤井 昌江, 河合 穂高, 中野 敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年 

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    開催年月日: 2023年

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  • Patient-derived xenograft モデルを用いた口腔癌の骨浸潤メカニズムの再考

    Shan Qiusheng, 高畠 清文, Piao Tianyan, Chang Anqi, 河合 穂高, 中野 敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年 

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    開催年月日: 2023年

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  • 口腔扁平上皮癌腫瘍間質が腫瘍関連マクロファージ浸潤に与える影響について

    Piao Tianyan, Shan Qiusheng, 高畠 清文, Chan Anqi, 河合 穂高, 中野 敬介, 長塚 仁

    第41回日本口腔腫瘍学会総会・学術大会  2023年 

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    開催年月日: 2023年

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  • ハニカムTCPを用いた骨髄組織再生

    稲田靖則, 高畠清文, 辻極秀次, 河合穂高, 伏見滋子, 中野敬介, 長塚 仁

    第31回硬組織再生生物学会学術大会・総会  2023年 

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    開催年月日: 2023年

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  • 骨髄由来間葉系幹細胞の新規採取技術および骨髄由来間葉系幹細胞移植法の確立

    河合 穂高, メイ ワト ウ, 高畠 清文, 佐能 彰, 中野 敬介, 宝田 剛, 長塚 仁

    第77回NPO法人日本口腔科学会学術集会  2023年 

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    開催年月日: 2023年

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  • 癌の骨破壊病変に対する銅のキレートを応用した治療に関する基礎的検討

    佐々木 朗, 坂本 裕美, 中野 敬介, 金本 栄華, 吉岡 德枝, 竜門 省二, 西山 明慶, 志茂 剛, 伊原木 聰一郎

    第33回日本臨床口腔病理学会 学術大会  2022年9月23日 

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    開催年月日: 2022年9月23日 - 2022年9月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma

    Qiusheng Shan, 高畠 清文, 河合 穂高, Wathone Oo May, 稲田 靖則, 中野 敬介, 長塚 仁

    第33回日本臨床口腔病理学会 学術大会  2022年9月23日 

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    開催年月日: 2022年9月23日 - 2022年9月24日

    記述言語:日本語   会議種別:ポスター発表  

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  • エナメル上皮腫が分泌するCCN2による腫瘍間質を介した顎骨吸収メカニズムの検討

    稲田靖則, 武部祐一郎, 高畠清文, 河合穂高, 中野敬介, 長塚 仁

    第13回日本 CCN ファミリー研究会  2022年9月3日 

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    開催年月日: 2022年9月3日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 動物モデルを用いた、骨髄由来間葉系幹細胞の他臓器転移に対する役割

    佐能 彰, 河合穂高, MayWathoneOo, HtooShweEain, YaminSoe, 高畠清文, 中野敬介, 伊原木聰一郎, 長塚 仁

    第30回硬組織再生生物学会学術大会・総会  2022年8月27日 

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    開催年月日: 2022年8月26日 - 2022年8月27日

    記述言語:日本語  

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  • エナメル上皮腫開窓術における HIF-1α を介した腫瘍縮小メカニズムの解明

    稲田靖則, 高畠清文, 藤井昌江, PiaoTianyan, ChangAngi, 河合穂高, 中野敬介, 長塚 仁

    第30回硬組織再生生物学会学術大会・総会  2022年8月27日 

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    開催年月日: 2022年8月26日 - 2022年8月27日

    記述言語:日本語   会議種別:ポスター発表  

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  • 口腔癌間質由来のCCL2はCCR2陽性骨髄由来免疫抑制細胞の腫瘍間質への動員に関与する

    河合 穂高, メイ・ワトウ, 高畠 清文, 冨田 秀太, 小野 喜章, 江口 傑徳, 大原 利章, 中野 敬介, 長塚 仁

    第26回日本がん免疫学会総会  2022年7月21日 

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    開催年月日: 2022年7月20日 - 2022年7月22日

    記述言語:日本語   会議種別:ポスター発表  

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  • 正常間質組織による口腔扁平上皮癌の生物学的性格制御の可能性

    髙畠 清文, 大森 悠加, Shan Qiusheng, 河合 穂高, May, Wathone Oo, 稲田 靖則, 中野 敬介, 長塚 仁

    第76回NPO法人日本口腔科学会学術集会  2022年4月21日 

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    開催年月日: 2022年4月21日 - 2022年4月23日

    会議種別:ポスター発表  

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  • 口腔癌間質由来の CCL2 は CCR2 陽性骨髄由来免疫抑制細胞の遊走に 関与する

    メイワトウ, 河合 穂高, 高畠 清文, 藤井 昌江, 稲田 靖則, 大森 悠加, 中野 敬介, 長塚 仁

    第111回日本病理学会総会  2022年4月15日 

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    開催年月日: 2022年4月14日 - 2022年4月16日

    記述言語:日本語  

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  • 口腔癌における CX3CL1 の影響

    トゥシュエイン, 河合 穂高, 中山 真彰, メイワトウ, 伏見 滋子, 中野 敬介, 飯田 征二, 長塚 仁

    第111回日本病理学会総会  2022年4月14日 

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    開催年月日: 2022年4月14日 - 2022年4月16日

    記述言語:日本語  

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  • 異型上皮を伴う口腔粘膜疾患の細胞像 招待

    中野敬介

    第171回日本臨床細胞学会東海連合会例会  2021年12月2日 

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    開催年月日: 2021年12月2日

    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • Stromal cell in the tumor microenvironment promote the progression of oral squamous cell carcinoma

    Shan Qiusheng, 高畠清文, 大森悠加, 河合穂高, May Wathone Oo, 中野敬介, 伊原木聰一郎, 佐々木 朗, 長塚 仁

    第42回岡山歯学会総会・学術大会  2021年11月28日 

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    開催年月日: 2021年11月28日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • 新規生体材料の幾何学的構造制御による象牙質再生

    稲田靖則, 高畠清文, 辻極秀次, 河合穂高, 中野敬介, 長塚仁

    第42回岡山歯学会総会・学術大会  2021年11月28日 

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    開催年月日: 2021年11月28日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 口腔領域の組織像 招待

    中野 敬介

    第60回日本臨床細胞学会秋期大会  2021年11月20日 

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    開催年月日: 2021年11月20日 - 2021年11月21日

    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 癌微小環境における口腔癌間質細胞と骨髄由来細胞の 関係性について

    河合 穂高, メイ ワト ウ, 高畠 清文, 中野 敬介, 長塚 仁

    第67回日本病理学会秋期特別総会  2021年11月4日 

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    開催年月日: 2021年11月4日 - 2021年11月5日

    記述言語:日本語   会議種別:ポスター発表  

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  • 3 次元培養システムを用いた口腔癌の薬剤応答性に対する新規 in vitro モデルの検証

    佐藤 晃平, 小野 喜章, 河合 穂高, 中野 敬介, 長塚 仁, 佐々木 朗

    第63回歯科基礎医学会学術大会・総会  2021年10月9日 

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    開催年月日: 2021年10月9日 - 2021年10月17日

    記述言語:日本語  

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  • 新規生体材料ハニカム TCP を用いた細胞外微小環境再現による象牙質再生

    稲田靖則, 高畠清文, 辻極秀次, 河合穂高, 中野敬介, 長塚 仁

    第29回硬組織再生生物学会学術大会・総会  2021年8月28日 

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    開催年月日: 2021年8月28日

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  • 口腔癌間質による実質の生物学的性格制御について

    高畠清文, Shan Qiusheng, 大森悠加, 河合穂高, May Wathone Oo, 中野敬介, 長塚 仁

    第29回硬組織再生生物学会学術大会・総会  2021年8月28日 

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    開催年月日: 2021年8月28日

    記述言語:日本語  

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  • Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

    第32回日本臨床口腔病理学会 学術大会  2021年8月14日 

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    開催年月日: 2021年8月12日 - 2021年8月14日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • 口腔細胞診による口腔癌および前癌病変の一次スクリーニングの有用性 招待

    助川信太郎, 小野早和子, 中野敬介, 長塚 仁, 古木良彦

    第62回日本臨床細胞学会春期大会  2021年6月4日 

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    開催年月日: 2021年6月4日 - 2021年6月6日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • ハニカムTCPを用いた細胞外微小環境制御による象牙質再生

    髙畠 清文, 辻極 秀次, 吉田 沙織, 稲田 靖則, 河合 穂高, 中野 敬介, 長塚 仁

    第75回NPO法人日本口腔科学会学術集会  2021年5月12日 

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    開催年月日: 2021年5月12日 - 2021年5月14日

    記述言語:日本語   会議種別:ポスター発表  

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  • CCL2-CCR2 axisを介した癌関連線維芽細胞による骨髄由来細胞の動員

    河合 穂高, メイワトウ, 高畠 清文, 大森 悠加, 中野 敬介, 長塚 仁

    第110回日本病理学会総会  2021年4月23日 

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    開催年月日: 2021年4月22日 - 2021年4月24日

    会議種別:口頭発表(一般)  

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  • 口腔扁平上皮癌微小環境が腫瘍関連マクロファージ浸潤に与える影響 について

    Tianyan Piao, 高畠 清文, Chang Anqi, 河合 穂高, 大森 悠加, 荒島 拓馬, 中野 敬介, 長塚 仁

    第34回日本臨床口腔病理学会 学術大会  2023年8月25日 

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  • Hypoxia Inducible Factor-1α(HIF-1α)を介したエナメル上皮腫開 窓術作用機序の解明

    Chang Anqi, 高畠 清文, 藤井 昌江, 稲田 靖則, 河合 穂高, 伏見 滋子, 中野 敬介, 長塚 仁

    第34回日本臨床口腔病理学会 学術大会  2023年 

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  • 口腔扁平上皮癌のDisseminated Tumor Cells(DTCs)形成に関与する骨髄由来細胞

    廣田 知佳, 長井 涼香, 河合 穂高, 高畠 清文, 中野 敬介, 長塚 仁

    第34回日本臨床口腔病理学会 学術大会  2023年 

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  • 口腔扁平上皮癌リンパ節転移におけるCX3CL1の役割の検討

    Htoo Shwe Eain, 河合 穂高, Oo May Wathone, Yamin Soe, 高畠 清文, 向仲 佑美香, 中野 敬介, 長塚 仁

    第34回日本臨床口腔病理学会 学術大会 

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▼全件表示

共同研究・競争的資金等の研究

  • 腫瘍間質リモデリングによる新規転移抑制治療の開発

    研究課題/領域番号:24K02644  2024年04月 - 2029年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    長塚 仁, 中野 敬介, 河合 穂高, 志茂 剛, 高畠 清文, 伊原木 聰一郎

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    配分額:18590000円 ( 直接経費:14300000円 、 間接経費:4290000円 )

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  • 骨髄由来間葉系幹細胞を起点とした新たな口腔癌転移メカニズムの解明

    研究課題/領域番号:24K13130  2024年04月 - 2028年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    河合 穂高, 中野 敬介, 大野 充昭, 長塚 仁, 高畠 清文

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • Runx2を軸とする細胞競合を用いた口腔癌の進展制御

    研究課題/領域番号:24K13088  2024年04月 - 2028年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 河合 穂高, 長塚 仁, 高畠 清文, 伊原木 聰一郎

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

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  • 病理画像診断の言語モデルをもった口腔がんの新たな診断法の基盤構築

    研究課題/領域番号:24K13114  2024年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    助川 信太郎, 原 武史, 中野 敬介

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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  • miRNAとTCPハイブリッド生体材料用いた選択的骨・軟骨分化誘導と下顎頭再建法の開発

    研究課題/領域番号:23K09080  2023年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    伏見 滋子, 中野 敬介, 河合 穂高, 助川 信太郎, 長塚 仁, 高畠 清文

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

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  • 癌骨破壊病変において新規破骨細胞形成促進因子Angiogeninが果たす役割の解明

    研究課題/領域番号:23H03100  2023年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    伊原木 聰一郎, 長塚 仁, 中野 敬介, 岡村 裕彦

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    配分額:18720000円 ( 直接経費:14400000円 、 間接経費:4320000円 )

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  • 癌骨破壊病変において新規破骨細胞形成促進因子Angiogeninが果たす役割の解明

    研究課題/領域番号:23K27790  2023年04月 - 2027年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    伊原木 聰一郎, 長塚 仁, 岡村 裕彦, 中野 敬介

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    配分額:18720000円 ( 直接経費:14400000円 、 間接経費:4320000円 )

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  • バイオマテリアルin vitro安全性評価のためのgPAD-オルガノイドシステムの開発

    研究課題/領域番号:23K11926  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    十川 千春, 十川 紀夫, 宮崎 育子, 中野 敬介, 塚本 壮輔

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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  • CCN2を基軸とした腫瘍間質改変による新規エナメル上皮腫治療法開発

    研究課題/領域番号:23K09332  2023年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤井 昌江, 高畠 清文, 長塚 仁, 中野 敬介, 河合 穂高

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 口腔癌間質が主導する実質進展制御メカニズム解明と新規治療法開発

    研究課題/領域番号:22K10170  2022年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高畠 清文, 長塚 仁, 中野 敬介, 辻極 秀次, 河合 穂高

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 細胞競合による癌の生物学的性格および癌化の制御 国際共著

    研究課題/領域番号: 21K10043  2021年04月 - 現在

    日本学術振興会  科研費  基盤研究(C)

    中野敬介

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

  • 細胞競合による癌の生物学的性格および癌化の制御

    研究課題/領域番号:21K10043  2021年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 河合 穂高, 志茂 剛, 長塚 仁, 辻極 秀次, 高畠 清文

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    2021年は腫瘍の生物学的な特性と関連因子の発現を確認するために、移植腫瘍を用いた組織学的な検討をおこなった。臨床的に内向型の発育様式を示す口腔扁平上皮癌は上皮下結合組織へ浸潤増殖していくが、口腔扁平上皮癌の亜型の疣贅癌は体表外へ向かって外向性に増殖し、結合組織への浸潤性に乏しい。通常型の口腔扁平上皮癌(高浸潤型癌)、およびその亜型である疣贅癌(低浸潤型癌)について、これら性格の異なる2つの癌の間質細胞を互いに入れ替えてマウスに移植した。その結果、低浸潤型癌の間質細胞は、高浸潤型癌を低浸潤型に変化させ、高浸潤型癌の間質は低浸潤型癌を高浸潤癌に変化させた。移植癌組織を組織学的に検討し、低浸潤型癌組織では、間質細胞にYAP, Notch をはじめとして、細胞競合で勝者に発現する細胞競合勝者因子が強く発現し、高浸潤型癌組織では、癌細胞に細胞競合勝者因子が強く発現していることを確認した。癌の間質は従属的組織として癌の制御下におかれているのではなく、細胞競合の働きによって癌細胞へ働きかけて癌細胞の性格そのものを変化させている可能性示唆する結果を得られた。また癌細胞と間質細胞を共培養し、癌と間質細胞の相互作用を検討できる実験モデルの作製を行った。

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  • miRNAが支配する骨・軟骨分化方向決定メカニズムの解明

    研究課題/領域番号:20K10178  2020年04月 - 現在

    日本学術振興会  科研費  基盤研究(C)

    伏見 滋子

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    担当区分:研究分担者  資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

  • 口腔扁平上皮癌における新規遠隔転移抑制治療の開発 国際共著

    研究課題/領域番号: 20H03888  2020年04月 - 現在

    日本学術振興会  科研費  基盤研究(B)

    長塚 仁

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    担当区分:研究分担者  資金種別:競争的資金

    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

  • エナメル上皮腫の生物学的性格制御による腫瘍実質ー間質相互作用破綻の誘導 国際共著

    研究課題/領域番号:20K10094  2020年04月 - 現在

    日本学術振興会  科研費  基盤研究(C)

    藤井 昌江

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    担当区分:研究分担者  資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

  • 口腔扁平上皮癌における新規遠隔転移抑制治療の開発

    研究課題/領域番号:20H03888  2020年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    長塚 仁, 山近 英樹, 中野 敬介, 河合 穂高, 江口 傑徳, 辻極 秀次, 高畠 清文

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    本年度は、リンパ節における転移niche形成の検討を行うために、GFP骨髄移植を行なったマウスにヒト好転移ヒト扁平上皮癌細胞株を頬粘膜に移植して、リンパ節転移モデルの作成を行なった。腫瘍組織は、通報に従い標本を作成し、免疫組織化学染色、蛍光免疫二重染色、蛍光免疫多重染色を行い検討を行なった。
    ●蛍光免疫多重染色(Opal 7 color manual IHC)による目的細胞の組織内での局在の検討
    転移に関与するBMDCのプロファイルがある程度特定されれば、次に蛍光免疫多重染色(Opal 7 color manual IHC)を用いることにより、目的BMDCの組織での局在を明らかとする。Opal 7 color manual IHCは、同一切片内で最大7色までの多重染色を行うことが可能な染色手法で、FACSで得られた情報をそのまま切片内に再現することが可能である。これにより、組織内での目的BMDCの局在や動態の詳細を継時的に観察した。

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  • エナメル上皮腫の生物学的性格制御による腫瘍実質ー間質相互作用破綻の誘導

    研究課題/領域番号:20K10094  2020年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤井 昌江, 長塚 仁, 中野 敬介, 高畠 清文, 河合 穂高

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    エナメル上皮腫は若年層に発症し、顎骨切除術を行うと著しくQOLが低下する。現在では顎骨保存外科的療法(開窓術)が適応されることが多い。しかし、開窓術においても、複数回の手術が必要であり、再発率も高いため、全く新しい視点からアプローチする新規治療法の確立が望まれている。申請者らはこれまでに歯原性腫瘍の腫瘍実質と腫瘍間質の相互作用に着目した研究を行ってきた。その結果、腫瘍間質には未分化で骨芽細胞に分化しうる細胞 が存在することを発見している。この未分化な細胞に対して腫瘍実質が産生する因子が分化抑制を行い、細胞浸潤や骨吸収に影響を与える研究成果を得ている。 さらに、開窓術の科学的根拠の検索のために、エナメル上皮腫における開窓術前後の組織学的変化を検討してきた。その結果、開窓術によりエナメル上皮腫が正常口腔粘膜上皮と連続することで、腫瘍実質が抑制的に制御されるとの研究成果を得ている。 そこで本申請課題では、正常粘膜上皮との連続による腫瘍実質の生物学的性格の変化を利用し、腫瘍実質と腫瘍間質の相互作用機構を破綻させ、外科的手法を 用いないエナメル上皮腫の新規治療法の開発に向けた基礎的研究を行う。 2021年度は、樹立したエナメル上皮腫間質細胞とエナメル上皮腫腫瘍細胞(AM-1)の共培養実験を行い、エナメル上皮腫の腫瘍微小環境を再現した。具体的には、エナメル上皮腫間質細胞とAM-1をシャーレ上(2D共培養)とコラーゲンゲル上(3D共培養)で培養し、腫瘍微小環境を再現した。

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  • miRNAが支配する骨・軟骨分化方向決定メカニズムの解明

    研究課題/領域番号:20K10178  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    伏見 滋子, 中野 敬介, 河合 穂高, 長塚 仁, 辻極 秀次, 高畠 清文

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    申請者らはすでにウサギ組織内にBMPとハニカムTCPで作成した特殊な環境下において骨組織と軟骨組織をシームレスに連続した状態で誘導することに成功している(シームレス骨・軟骨分化誘導モデル)。令和3年度はマウスを用いたシームレスな骨・軟骨モデルの作製を行い良好な再現性を実現できることを確認している。マウスを使用して、安定的にシームレス骨・軟骨分化誘導モデルを作製することが可能となった。これまでに明らかになっているウサギの実験条件を流用しマウス組織内にも同様な骨・軟骨シームレス組織が形成されることを確認した。ハニカムCTPは孔径の異なる種類を用い、濃度の異なるBMP-2を含侵させ同所性および異所性に結合組織内へ埋入し、骨・軟骨誘導をおこなった。今回の研究で使用しているスカフォールドの形態が細胞分化に影響を及ぼし特定の細胞分化に関連する遺伝子発現を誘導することを見出した。これらの結果は学術誌上で報告した。

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  • 癌間質による癌の生物学的性格の制御および癌誘発の検討

    研究課題/領域番号:18K09789  2018年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 長塚 仁, 高畠 清文, 河合 穂高, 江口 傑徳, 辻極 秀次, 志茂 剛

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究の目的は、口腔癌の間質が癌細胞に作用して、癌の生物学的性質を変化させることの検証、および癌間質が癌の周囲の正常細胞に働きかけて癌化を引き起こす可能性を検証することである。口腔扁平上皮癌細胞株と間質細胞の組合せによる培養、腫瘍間質の違いによる腫瘍細胞の生物学的性格(増殖能、浸潤能、遊走能、形態)に与える影響を病理組織学的に検討した。その結果、腫瘍組織は癌の間質の違いによって大きくその性状を変化させることが示された。本研究結果は、癌間質が直接的に癌の生物学的性格を調節していることを強く裏付けるものである。

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  • 癌遺伝子プロモーター活性を指標とした新規スクリーニング系による既存薬再開発

    研究課題/領域番号:17K11643  2017年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    十川 千春, 江口 傑徳, 奥舎 有加, 大山 和美, 中野 敬介, 岡元 邦彰, 十川 紀夫

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究は、癌の転移および治療抵抗性を統合的に評価できる薬剤スクリーニングシステムの開発とそれを応用した既存薬再開発を目的とした。癌の浸潤・転移過程において高発現するMMP9遺伝子プロモーター活性を指標とし、転移性マウス大腸癌細胞を用いて、MMP9のプロモーター誘導性蛍光レポーター細胞を構築した。さらに生体内の腫瘍特性により近づけるために,三次元腫瘍オルガノイド(tumoroid)モニタリングを応用し、癌幹細胞性とMMP9レポーター活性とが同時に評価可能な薬物評価系を確立した。既存薬スクリーニングの結果、パーキンソン病治療薬であるベンツトロピンの抗腫瘍効果を見出した。

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  • 腫瘍転移モデルマウスを用いた前転移niche形成メカニズムの解明

    研究課題/領域番号:16K11441  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    長塚 仁, 中野 敬介, 辻極 秀次, 山近 英樹, 高畠 清文

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    CD31は血管内皮細胞に発現する代表的な膜接着因子である。しかし、腫瘍間質に浸潤する骨髄由来細胞の一部はCD31を発現しており、腫瘍の転移巣や浸潤部に特異的に観察された。これらの細胞は、腫瘍の浸潤や転移に関与している可能性が示唆された。また、一部は前転移niche形成への関与も考えられた。
    CD11b, Gr-1 double positiveを示す骨髄由来細胞は、免疫抑制性骨髄由来細胞 (Myeloid derived suppressor cells: MDSC)と考えられ、MDSCが前転移nicheの形成に関与している可能性が考えられた。

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  • 象牙質・歯髄複合体の修復反応における骨髄間葉系細胞の関与

    研究課題/領域番号:16K11817  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    正村 正仁, 大須賀 直人, 川上 敏行, 辻極 秀次, 中野 敬介, 松田 紗衣佳, 森山 敬太, 西川 祐一朗

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    ヨードホルム加水酸化カルシウム糊材を象牙質・歯髄複合体に貼付したラットの観察を病理組織学的に行う事により、糊材応用部周囲に形成された修復象牙質が第三象牙質に分類されるものであると明らかになった。
    また、GFP骨髄細胞移植マウスを用いた実験より、人為的髄床底穿孔部に生じた歯根膜ポリープの構成細胞には骨髄由来のものが含まれるであろう事が示唆された。

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  • 歯周組織リモデリングの分子調節機構解明と再生修復促進

    研究課題/領域番号:26463104  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 長塚 仁, 村岡 理奈, 辻極 秀次, 川上 敏行

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    本研究課題で以下の結果を得た。
    1.骨髄幹細胞が歯根膜構成細胞および歯髄細胞に分化することを確認した。2.骨髄由来幹細胞はリモデリングの盛んな部位に生着することを示した。3.傷害性刺激を加えた歯根膜組織では骨髄由来細胞とHSPや神経内分泌関連因子とが密接に関連していた。4.歯科矯正治療法の改良や新手法の開発、外傷の効果的な治療法につながる結果を得た。

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  • 顎骨部腫瘍の形質発現に関わる分子病理

    研究課題/領域番号:26463054  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    長谷川 博雅, 辻極 秀次, 嶋田 勝光, 中野 敬介, 落合 隆永

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    歯原性腫瘍は様々な形態変化を伴う形質変化を示す細胞が出現するが知られている。本研究は、これら歯原性病変での神経内分泌細胞への分化制御機構と歯原性上皮の角化機序を検討した。エナメル上皮腫において神経内分泌細胞の特徴であるCD56とSynaptophysin (SYP)の局在と遺伝子発現を認めた。さらに分化制御因子であるNotchがSYP発現部位に一致して局在した。角化関連因子の発現は歯原性疾患により架橋酵素や構成タンパク質が疾患により構成が異なった。歯原性上皮の形質変化の制御機構や歯原性上皮の角化機序の制御機構は、病態の形成や形態的な変化を誘導し、歯原性疾患の鑑別に応用される可能性が示唆された。

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  • 顎口腔における増殖性病変の病理発生に関する研究

    研究課題/領域番号:26463031  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    川上 敏行, 富田 美穂子, 中野 敬介, 辻極 秀次

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    本研究の特色・独創的な成果は,口腔腫瘍(エナメル上皮腫と唾液腺多形腺腫),その他の慢性炎症性病変である細胞の増殖性病変における細胞分化と言う視点から捉え,追究したものである。これらの成果は新規治療法の開発につながるであろう。概略は以下の通りである。
    歯原性腫瘍と唾液腺腫瘍の増殖・分化について,腫瘍細胞の分化の観点から追究し,WntシグナルやHSPが密接に関与している事を明らかにした。さらに,歯科矯正学的なメカニカルストレスや外傷性咬合にる歯根膜組織の傷害の修復には骨髄間葉系細胞が多数移動してきており,本来中胚葉性の骨髄間葉系細胞が,神経堤由来の外胚葉性間葉細胞に分化する事を明らかに出来た。

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  • 音楽が疼痛閾値に及ぼす影響と自律神経のバランスとの関係

    研究課題/領域番号:25463158  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    富田 美穂子, 寺田 知新, 川上 敏行, 中野 敬介

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    痛みは身体の障害を知らせる重要な感覚であるが継続するとストレスとなる。この痛みの感覚を軽減させる環境を見つけるために音楽の効果を調べた。45名の被験者に対して、3種類の音楽を聞かせた時と無音時の前腕と口腔粘膜4箇所の痛覚閾値を測定した結果、スローテンポの曲は痛覚閾値を有意に上昇させた。また被験者10名に対して自律神経活動を調べた結果、音楽を聞かせると副交感神経優位になる傾向があった。さらに侵害刺激に対して反応を示した帯状回の神経活動は、音楽を聞くことで減弱する傾向にあった。これらの結果より、音楽を聞くことは疼痛認知の軽減に有効であることが示唆された。

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  • 歯周組織リモデリングにおける細胞の供給と移動そして分化の分子調節機構

    研究課題/領域番号:25463204  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岡藤 範正, 富田 美穂子, 中野 敬介, 川上 敏行, 辻極 秀次

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    外傷性咬合による歯周組織の改造について,主としてGFP骨髄移植マウスを用いた動物実験モデルによって検討したところ,当該の歯根分岐部歯根膜には,その部位の細胞および骨髄由来細胞によりなされ,同部の修復過程にHSPの関与がある事を明らかに出来た。
    歯科矯正学的実験で,牽引側,圧迫側ともに細胞の増殖を促す事が示唆され,これらの細胞増殖は未分化間葉系細胞が骨髄から移動して増加したと推測される。さらに,蛍光免疫二重染色により歯周組織に移動した骨髄由来の未分化間葉系細胞は、血管内皮細胞,マクロファージ,破骨細胞,歯根膜線維芽細胞等の歯周組織を構成する細胞へ分化したものと考えられた。

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  • 骨髄幹細胞を用いた組織修復およびリモデリングの促進とその分子調節機構の解明

    研究課題/領域番号:23593075  2011年 - 2013年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 川上 敏行, 辻極 秀次, 富田 美穂子, 村岡 理奈

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    配分額:5200000円 ( 直接経費:4000000円 、 間接経費:1200000円 )

    本研究課題で以下の結果を得た。
    1.骨髄幹細胞が歯根膜構成細胞および歯髄細胞に分化することを確認した。2.骨髄由来幹細胞はリモデリングの盛んな部位に生着することを示した。3.傷害性刺激を加えた歯根膜組織ではRunx2、Msx2、ALPの発現に加え、HSPや神経内分泌関連因子の発現増強があった。4.歯科矯正治療法の改良や新手法の開発、外傷の効果的な治療法につながる結果を得た。

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  • 骨髄幹細胞移植を用いた口腔の増殖性病変における細胞分化の分子調節機構の解明

    研究課題/領域番号:23592951  2011年 - 2013年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    川上 敏行, 中野 敬介, 富田 美穂子, 辻極 秀次

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    配分額:5200000円 ( 直接経費:4000000円 、 間接経費:1200000円 )

    GFP骨髄移植マウスを用いて骨髄幹細胞の動態を検討し以下の結果を得た。
    1)傷害性刺激を加えた歯根膜組織ではRunx2、Msx2、ALPの発現に加え、HSPや神経内分泌関連因子の発現増強があった。2)Runx2をはじめとするこれらの因子が歯周組織の恒常性維持と組織修復に重要な役割を持っていることを示した。3)歯周組織では細胞増殖が活発な場所に骨髄幹細胞が集中的に生着することを明らかにした。4)骨髄幹細胞の動態に神経系の細胞が関与していることを示した。5)増殖性病変の生物学的性格の確立への骨髄幹細胞の関与を示唆した。6)骨髄幹細胞を用いた組織修復促進や増殖性疾患の制御を可能とする学術的根拠を得た。

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  • 骨髄幹細胞を用いた歯科矯正学的リモデリングの促進とその分子調節機構の解明

    研究課題/領域番号:22592303  2010年 - 2012年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岡藤 範正, 中野 敬介, 富田 美穂子, 川上 敏行, 辻極 秀次

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    1.骨髄幹細胞が歯根膜構成細胞および歯髄細胞に分化することを確認した。2.骨髄由来幹細胞はリモデリングの盛んな部位に生着することを示した。3.骨髄幹細胞の誘導に神経が関与していることを示唆した。4.歯科矯正治療法の改良や新手法の開発、外傷の効果的な治療法につながる結果を得た。

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  • 薬物誘発性歯肉増殖症の発症メカニズムの解明および治療薬の探索

    研究課題/領域番号:22592321  2010年 - 2012年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    服部 敏己, 荒 敏昭, 川上 敏行, 中野 敬介

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    歯肉増殖症を引き起こすニフェジピン(高血圧治療薬)およびフェニトイン(抗てんかん薬)は歯肉線維芽細胞のカルシウム(Ca2+)感知受容体に直接作用する.そこからのシグナル伝達により細胞内Ca2+ストアからのCa2+遊離および細胞膜上のTRPV1チャネルからのCa2+流入により細胞内Ca2+濃度が上昇する.そのことが引き金となって細胞増殖およびコラーゲン生成が促進され最終的に歯肉増殖症を惹起することが判明した(修正Ca2+トリガー説).

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  • 骨吸収を惹起する増殖性病変における細胞分化の分子調節機構

    研究課題/領域番号:20592349  2008年 - 2010年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    川上 敏行, 中野 敬介, 長塚 仁

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    顎骨の骨吸収を惹起する増殖性病変の代表的なものとして,種々の歯原性腫瘍型を取り上げ研究してきた。その結果,顎骨の骨吸収を惹起する増殖性病変の代表的なものとしての歯原性腫瘍やその他の腫瘍型においても,その発生母細胞,母組織の発生時における発現状況と若干異なる事がわかり,腫瘍性を獲得した後においてもNotchシグナルは細胞分化時,腫瘍組織内においてもその細胞性格の相違する部位に良く発現しており,腫瘍細胞の細胞分化に強く働いている事が明らかになった。

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  • メカニカルストレスが惹起する細胞分化の分子調節機構

    研究課題/領域番号:20592419  2008年 - 2010年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中野 敬介, 川上 敏行, 岡藤 範正

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    マウス歯根膜におけるメカニカルストレスが引き起こすRunx2とMsx2の発現状況の初期変化を免疫組織化学的に検討した. 結果として,実験群では,Runx2とMsx2は20分で牽引側の歯根膜線維芽細胞に強い免疫陽性反応がみられた.さらにALPも同様の反応を示した.BMPやHSPの発現も上昇していた。これらの実験結果はRunx2が骨芽細胞分化の初期では分化を促進し,Msx2はRunx2の作用を活性化する方向に働いていること,またHSPが分子シャペロンとして働いている可能生を強く示唆した.

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  • 歯科矯正学的観点からの顎骨・歯周組織の改造現象における細胞分化の分子調節機構

    研究課題/領域番号:19592374  2007年 - 2008年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岡藤 範正, 川上 敏行, 中野 敬介, 栗原 三郎

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    主たる研究成果は以下の通りである。
    実験的歯の矯正治療時における歯周組織等における種々の細胞の反応牽引側歯根膜線維芽細胞には刺激を受けた直後から細胞反応が起こる事が明らかになり,またRunx2の促進因子としてMsx2が働いている事が明らかになった。
    下顎頭軟骨の初期発生の調節機構マウスの下顎頭軟骨の初期発生にはNotchシグナルが重要な役割を果たしていることを明らかにした。これらの内容は数回の学会発表を行うとともに,論文として印刷公表した。

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  • 歯胚の誘導制御における基底膜VI型コラーゲンα鎖の役割

    研究課題/領域番号:13771073  2001年

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    中野 敬介

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    配分額:1100000円 ( 直接経費:1100000円 )

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  • 歯胚と歯原性腫瘍の分子病理学的研究

    研究課題/領域番号:12470385  2000年 - 2002年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    永井 教之, MEHMET Gunduz, 辻極 秀次, 長塚 仁, 小守 壽文, 長岡 紀幸, 中野 敬介, 石割 裕三

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    配分額:13600000円 ( 直接経費:13600000円 )

    歯胚分化過程における上皮間葉相互作用を明らかにする為,BMP family遺伝子発現,基底膜の主要構成成分であるIV型コラーゲンの各α鎖の局在および消長を観察した。胎生11日歯胚ですでにBMP-4,7の発現が認められ胎生12日でBMP-2の発現も認められた。IV型コラーゲン各α鎖は,歯胚上皮基底膜に部位および時期特異的な局在と組み合わせが存在することが明らかになった。
    また,Cbfa1ノックアウトマウスを用いて詳細な検討を行った結果。歯牙形態形成と基質蛋白遺伝子発現にCbfa1の関与が認められた。Cbfa1ノックアウトマウスにおける臼歯の歯胚発育は,帽状期で停止しており,α5鎖が特異的な染色性を示す所見が得られた。一方,切歯では基質蛋白遺伝子発現から象牙芽細胞およびエナメル芽細胞にまで分化しており,臼歯および骨芽細胞とは異なるCbfa1による分化機構や転写調節機構が存在する可能性が示唆された。
    歯原性腫瘍の細胞分化および機能分化を明らかにする為、IV型コラーゲン各α鎖,BMP familyの関与について検討した。IV型コラーゲンはエナメル上皮腫ではα1,2,5,6鎖から構成されていたが,腺様歯原性腫瘍,線維形成性エナメル上皮腫ではα4の特異的な局在が認められた。BMP familyは線維形成性エナメル上皮腫では,間質は歯周組織への分化を示し,これらの分化にBMP familyが関与している可能性が示唆された。腺様歯原性腫瘍では,BMP familyの局在および機能分化から,歯胚の基質形成期に類似していた。以上より歯原性腫瘍においても歯胚と同様にIV型コラーゲンα鎖の局在が腫瘍細胞の分化と関与しており,各組織型の腫瘍実質と間質の分化・誘導にBMP familyが特異的に関与している可能性が示唆された。

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  • 歯の発生におけるBMPファミリーおよびそのレセプターの遺伝子発現と機能解析

    研究課題/領域番号:11470377  1999年 - 2001年

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    長塚 仁, GUNDUZ Mehmet, 辻極 秀次, 永井 教之, 長岡 紀幸, 中野 敬介, 石割 裕三, 井上 正久

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    配分額:10400000円 ( 直接経費:10400000円 )

    歯胚発育における基質蛋白遺伝子の発現を胎生17.5日,生後0日,生後2.5日生後8日マウスにおいて経時的に観察した結果,I型コラーゲンmRNAのシグナルは、胎生17.5日から、成長端differentiating papilla cellから切端部osteodentinまで、odontoblastの細胞分化のすべてのステージにおいて認められた。オステオネクチンmRNAのシグナルも、胎生17.5日から、同様に認められた。オステオポンチンmRNAのシグナルは、胎生17.5日下顎切歯において、pre-odontoblastやyoung odontoblastに周期的に認められ、osteodentinのodontoblastにも認められたが、生後0日、生後2.5日では減少し、舌側の一部odontoblastとosteodentinに弱く認められるのみとなった。オステオカルシンmRNAのシグナルは、観察したすべての日齢において、pre-odontoblastから切端部osteodentinまでの細胞分化のすべてのステージにおいて認められた。DSPPmRNAのシグナルは、観察したすべての日齢において、pre-odontoblastから切端部osteodentinまでの細胞分化のすべてのステージにおいて認められた。また、pre-ameloblastにも限局的に認められた。アメロゲニンmRNAのシグナルは、観察したすべての日齢において、pre-ameloblastからsecretory ameloblastに連続して認められた。次に器官形成の上皮間葉相互作用に関わる因子として注目されているBMPファミリーが,歯胚分化過程のいかなる時期で発現しているかをin situ hybridizadon法を用いて検索した。BMP-2,3,4,5,6,7のそれぞれに特異的なディゴキシゲニン標識cRNAプローブを作製し,胎生11日から生後1日までのマウス歯胚に対して非放射性in situ hybridization法を行った。胎生11日にすでに発現が見られたのはBMP-4および7であり,胎生12日になるとBMP-2の発現も見られた。これらの蛋白を免疫組織化学的に検索した結果ほほ遺伝子発現領域に一致した分布を示した。BMP-2,4,7は歯牙発生の初期から上皮間葉相互作用による形態形成および細胞分化に関与すると考えられた。BMP-5は胎生17日の帽状期後期の内エナメル上皮でその発現が観察され,エナメル質あるいは象牙質形成に重要な役割を果たしている可能性が考えられた。一方,歯胚基底膜の主要構成成分であるIV型コラーゲンのα1からα6までの6種類のα鎖の歯牙発生過程での局在と消長を免疫組織学的に観察した結果、歯胚上皮基底膜にα鎖の部位および時期特異的な局在と組み合わせが存在することが明らかになった。これらの結果は基底膜と成長因子の共同作用が初期歯胚形態形成、細胞分化に関与している可能性を示唆している。歯胚発育過程において,BMPと密接な関連を有するcbfa1の関与について検索を行った。その結果,Cbfa1ノックアウトマウスにおける臼歯の歯胚発育は、組織学的には帽状期で停止していたが,切歯では基質蛋白の遺伝子発現の面からは象牙芽細胞およびエナメル芽細胞にまで分化しており,臼歯とは異なるシグナル伝達系が存在する可能性が考えられた。

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  • 病理解剖学・外科病理学演習 (2018年度) 第2学期  - 水4,水5,水6,水7

  • 病理解剖学・外科病理学演習 (2018年度) 第2学期  - 水4,水5,水6,水7

  • 発病と治癒の病理組織学実習 (2018年度) 第1学期  - 水4,水5,水6,水7

  • 発病と治癒の病理組織学実習 (2018年度) 第1学期  - 水4,水5,水6,水7

  • 発病と治癒の病理組織学実習 (2018年度) 第1学期  - 水4,水5,水6,水7

  • 発病と治癒の病理組織学実習 (2018年度) 第1学期  - 水4,水5,水6,水7

  • 発病の病理・病態学 (2018年度) 第1学期  - 火5,火6,火7

  • 発病の病理・病態学 (2018年度) 第1学期  - 火5,火6,火7

  • 統合病理学実習 (2018年度) 第4学期  - 水4,水5,水6,水7,水8

  • 統合病理学実習 (2018年度) 第4学期  - 水4,水5,水6,水7,水8

  • 臨床病理学実習 (2018年度) 第4学期  - 火4,火5,火6,火7,火8

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