2021/12/26 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

  • 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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  • 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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  • 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   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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  • 【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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  • 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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  • Factors of Successful Treatment Using the Bone Lid Technique in Maxillofacial Surgery: A Pilot Study

    Shintaro Sukegawa, Norio Yamamoto, Tamamo Matsuyama, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

    Journal of Hard Tissue Biology   30 ( 2 )   193 - 198   2021年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Society for Hard Tissue Regenerative Biology  

    DOI: 10.2485/jhtb.30.193

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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.

    DOI: 10.3390/biom10111534

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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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  • 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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  • 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.

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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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  • 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.

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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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  • 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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  • 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.

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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.

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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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  • 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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  • 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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  • 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.

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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.

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  • Comparing the Osteogenic Potentials and Bone Regeneration Capacities of Bone Marrow and Dental Pulp Mesenchymal Stem Cells in a Rabbit Calvarial Bone Defect Model

    Yu-Chieh Lee, Ya-Hui Chan, Sung-Chih Hsieh, Wei-Zhen Lew, Sheng-Wei Feng

    International Journal of Molecular Sciences   20 ( 20 )   5015 - 5015   2019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:MDPI AG  

    The bone regeneration efficiency of bone marrow mesenchymal stem cells (BMSCs) and dental pulp mesenchymal stem cells (DPSCs) combined with xenografts in the craniofacial region remains unclear. Accordingly, this study commenced by comparing the cell morphology, cell proliferation, trilineage differentiation, mineral synthesis, and osteogenic gene expression of BMSCs and DPSCs in vitro. Four experimental groups (empty control, Bio-Oss only, Bio-Oss+BMSCs, and Bio-Oss+DPSCs) were then designed and implanted in rabbit calvarial defects. The BMSCs and DPSCs showed a similar morphology, proliferative ability, surface marker profile, and trilineage-differentiation potential in vitro. However, the BMSCs exhibited a higher mineral deposition and expression levels of osteogenic marker genes, including alkaline phosphatase (ALP), runt related transcription factor 2 (RUNX2), and osteocalcin (OCN). In the in vivo studies, the bone volume density in both MSC groups was significantly greater than that in the empty control or Bio-Oss only group. Moreover, the new bone formation and Collagen I / osteoprotegerin protein expressions of the scaffold+MSC groups were higher than those of the Bio-Oss only group. Finally, the Bio-Oss+BMSC and Bio-Oss+DPSC groups had a similar bone mineral density, new bone formation, and osteogenesis-related protein expression. Overall, the DPSCs seeded on Bio-Oss matched the bone regeneration efficacy of BMSCs in vivo and hence appear to be a promising strategy for craniofacial defect repair in future clinical applications.

    DOI: 10.3390/ijms20205015

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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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  • 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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  • 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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  • 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)  

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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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  • 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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  • 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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  • 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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  • 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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  • 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

  • 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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  • 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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  • 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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  • 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

  • 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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  • 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 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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  • 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.

    DOI: 10.7150/ijms.12217

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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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  • 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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  • 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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  • 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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  • 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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  • 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.

    DOI: 10.2485/jhtb.20.53

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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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  • 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.

    DOI: 10.7150/ijms.4.264

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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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  • 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

  • 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

  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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

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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

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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   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   2010年

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  • 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   2010年

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  • 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   2009年

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  • 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   2009年

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  • 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

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  • 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

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  • 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

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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

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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

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  • 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   2005年

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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.

    PubMed

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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

    PubMed

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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   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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  • 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   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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▼全件表示

講演・口頭発表等

  • 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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共同研究・競争的資金等の研究

  • 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

      詳細を見る

    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 )

  • 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 )

 

担当授業科目

  • 人体病理学 (2021年度) 第1学期  - 火5,火6,火7

  • 口腔病理学 (2021年度) 第2学期  - 火5,火6,火7

  • 口腔病理学実習 (2021年度) 第2学期  - 水4,水5,水6,水7

  • 口腔病理学I(演習・実習) (2021年度) 特別  - その他

  • 口腔病理学I(講義・演習) (2021年度) 特別  - その他

  • 口腔病理学II(演習・実習) (2021年度) 特別  - その他

  • 口腔病理学II(講義・演習) (2021年度) 特別  - その他

  • 病理学総論実習 (2021年度) 第1学期  - 水4,水5,水6,水7

  • 統合病理学実習 (2021年度) 第4学期  - 木4,木5,木6,木7,木8

  • 臨床病理学実習 (2021年度) 第4学期  - 火4,火5,火6,火7,火8

  • 人体病理学 (2020年度) 第1学期  - 火5,火6,火7

  • 再生歯学の基礎的演習 (2020年度) 第4学期  - 水4,水5,水6,水7,水8

  • 再生歯学の生物学的解析実習 (2020年度) 特別  - その他

  • 再生歯学の生物学的解析実習 (2020年度) 第4学期  - 水4,水5,水6,水7,水8

  • 口腔疾患の病理・病態学 (2020年度) 第2学期  - 火5,火6,火7

  • 口腔疾患,腫瘍の病理組織学実習 (2020年度) 第2学期  - 水4,水5,水6,水7

  • 口腔疾患,腫瘍の病理組織学実習 (2020年度) 第2学期  - 水4,水5,水6,水7

  • 口腔病理学 (2020年度) 第2学期  - 火5,火6,火7

  • 口腔病理学実習 (2020年度) 第2学期  - 水4,水5,水6,水7

  • 口腔病理学I(演習・実習) (2020年度) 特別  - その他

  • 口腔病理学I(講義・演習) (2020年度) 特別  - その他

  • 口腔病理学II(演習・実習) (2020年度) 特別  - その他

  • 口腔病理学II(講義・演習) (2020年度) 特別  - その他

  • 口腔腫瘍の病理・病態学 (2020年度) 第2学期  - 火5,火6,火7

  • 外科病理診断基礎実習 (2020年度) 特別  - その他

  • 外科病理診断基礎実習 (2020年度) 第4学期  - 火4,火5,火6,火7,火8

  • 治癒の病理・病態学 (2020年度) 第1学期  - 火5,火6,火7

  • 病理学総論実習 (2020年度) 第1学期  - 水4,水5,水6,水7

  • 病理解剖学・外科病理学演習 (2020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 (2020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 (2020年度) 第1学期  - 水4,水5,水6,水7

  • 発病の病理・病態学 (2020年度) 第1学期  - 火5,火6,火7

  • 統合病理学実習 (2020年度) 第4学期  - 水4,水5,水6,水7,水8

  • 臨床病理学実習 (2020年度) 第4学期  - 火4,火5,火6,火7,火8

▼全件表示