2021/12/14 更新

写真a

カワイ ホタカ
河合 穂高
KAWAI Hotaka
所属
医歯薬学域 助教
職名
助教
外部リンク

学位

  • 博士(歯学)

  • 博士(歯学) ( 岡山大学 )

研究分野

  • ライフサイエンス / 腫瘍生物学

経歴

  • 岡山大学大学院 医歯薬学総合研究科   口腔病理学分野   助教

    2017年6月 - 現在

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  • 岡山大学大学院 医歯薬学総合研究科   口腔病理学分野   博士研究員

    2017年4月 - 2017年5月

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論文

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

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

    JCI Insight   2021年12月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Clinical Investigation  

    DOI: 10.1172/jci.insight.148960

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  • Biological Effects of Bioresorbable Materials in Alveolar Ridge Augmentation: Comparison of Early and Slow Resorbing Osteosynthesis Materials. 査読 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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    担当区分:筆頭著者   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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  • Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process. 査読 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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    担当区分:筆頭著者, 責任著者   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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  • Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma. 査読 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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    担当区分:責任著者   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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  • Triple knockdown of CDC37, HSP90-alpha and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer. 査読 国際誌

    Kisho Ono, Chiharu Sogawa, Hotaka Kawai, Manh Tien Tran, Eman A Taha, Yanyin Lu, May Wathone Oo, Yuka Okusha, Hirohiko Okamura, Soichiro Ibaragi, Masaharu Takigawa, Ken-Ichi Kozaki, Hitoshi Nagatsuka, Akira Sasaki, Kuniaki Okamoto, Stuart K Calderwood, Takanori Eguchi

    Journal of extracellular vesicles   9 ( 1 )   1769373 - 1769373   2020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)  

    Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones - CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial-mesenchymal transition (EMT), although their contribution to EVs-mediated cell-cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer-derived EVs (MEV) were enriched with HSP90α HSP90β and cancer-initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV-driven malignancy events. In metastatic oral cancer patient-derived tumours, HSP90β was significantly accumulated in infiltrating tumour-associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90-enriched MEV-induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA-mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV-driven malignancy events in the tumour microenvironment. Abbreviations: CDC37: cell division control 37; EMT: epithelial-mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour-associated macrophage.

    DOI: 10.1080/20013078.2020.1769373

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    DOI: 10.3390/ma12223681

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  • 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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    担当区分:責任著者   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.

    DOI: 10.3390/cells8070761

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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

    Sukegawa S, Kawai Hotaka, Nakano K, Kanno T, Takabatake K, Nagatsuka H, Furuki Y

    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)  

    DOI: 10.7150/ijms.27986

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

    Kawai Hotaka, Tsujigiwa H, Siar CH, Nakano K, Takabatake K, Fujii M, Hamada M, Tamamura R, Nagatsuka H

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

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

    DOI: 10.7150/ijms.24370

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  • Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury. 査読 国際誌

    Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki

    Biochimica et biophysica acta. Molecular basis of disease   1867 ( 11 )   166236 - 166236   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)  

    Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such as Porphyromonas gingivalis (Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term "periodontal medicine" is used to describe how periodontal infection/inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived from Pg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected with Pg. We observed that EVs from Pg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice. Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. The Pg-inf EVs or the recombinant histone H3 activated the NF-κB pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.

    DOI: 10.1016/j.bbadis.2021.166236

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  • Dynamic contrast-enhanced MRI as a predictor of programmed death ligand-1 expression in patients with oral squamous cell carcinoma 査読

    Nouha Tekiki, Mariko Fujita, Tatsuo Okui, Hotaka Kawai, May Oo, Toshiyuki Kawazu, Miki Hisatomi, Shunsuke Okada, Yohei Takeshita, Majd Barham, Hitoshi Nagatsuka, Yoshinobu Yanagi, Jun-Ichi Asaumi

    ONCOLOGY LETTERS   22 ( 5 )   2021年11月

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

    Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) are highly promising therapies for oral squamous cell carcinoma (OSCC). The assessment of PD-L1 expression may help predicting the therapeutic effect of ICIs and, thus, benefit patient selection. Contrast index (CI) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been proven as efficient to assess microvessel density (MVD) in OSCC. The present study aimed to determine the correlation between DCE-MRI parameters and MVD and between DCE-MRI parameters and PD-L1 expression to determine whether DCE-MRI could be used non-invasively to evaluate PD-L1 expression in patients with OSCC. A total of 21 patients with primary OSCC who had undergone a 3T MRI scan, including DCE-MRI, were included in the present study, and CI curve-derived parameters were examined. The MVD and PD-L1 expression in the surgically resected specimens were analyzed using immunohistochemistry (IHC) staining for CD31 and IHC staining for PD-L1, respectively. The results demonstrated that the expression levels of these markers were correlated with DCE-MRI parameters. PD-L1 expression levels were found to be significantly correlated with the maximum CI (CI-max; P=0.007), peak CI (CI-peak; P=0.007), maximum CI gain (CI-gain; P=0.006) and MVD (P=0.001) values. The mean CI-max, CI-peak, CI-gain and MVD values were significantly higher in tumors with high PD-L1 expression (P<0.05). MVD levels were also significantly correlated with the time of CI-max (T-max; P=0.003) and CI-gain (P=0.037). The mean CI-gain was significantly increased, and the mean T-max was significantly shorter in high MVD tumors (P<0.05 and P<0.01, respectively). In summary, the findings from the present study confirmed the correlation between CI parameters, derived from DCE-MRI, and MVD, and suggested that these parameters may be correlated with PD-L1 expression in OSCC tumor cells.

    DOI: 10.3892/ol.2021.13039

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  • Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma. 査読 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. 査読 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 (Kaunas, Lithuania)   57 ( 8 )   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)  

    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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  • The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma. 査読 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. 査読 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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  • Multi-Task Deep Learning Model for Classification of Dental Implant Brand and Treatment Stage Using Dental Panoramic Radiograph Images. 査読 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.

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  • Factors of Successful Treatment Using the Bone Lid Technique in Maxillofacial Surgery: A Pilot Study(和訳中) 査読

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

    Journal of Hard Tissue Biology   30 ( 2 )   193 - 198   2021年4月

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    記述言語:英語   出版者・発行元:硬組織再生生物学会  

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  • A case of oral cancer with delayed occipital lymph node metastasis: Case report. 査読 国際誌

    Kisho Ono, Norie Yoshioka, Masanori Masui, Kyoichi Obata, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Hitoshi Nagatsuka, Akira Sasaki

    Clinical case reports   8 ( 12 )   2469 - 2475   2020年12月

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    記述言語:英語  

    Consideration of unexpected metastasis in patients who have undergone neck dissection with advanced tumors must be anticipated with careful follow-up.

    DOI: 10.1002/ccr3.3086

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  • Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation. 査読 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. 査読 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? 査読

    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.

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

    Yumi Sakamoto, Tatsuo Okui, Toshiyuki Yoneda, Shoji Ryumon, Tomoya Nakamura, Hotaka Kawai, Yuki Kunisada, Soichiro Ibaragi, Masanori Masui, Kisho Ono, Kyoichi Obata, Tsuyoshi Shimo, Akira Sasaki

    Biochemical and biophysical research communications   531 ( 3 )   422 - 430   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

    DOI: 10.1016/j.bbrc.2020.07.120

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  • Clinical study on primary screening of oral cancer and precancerous lesions by oral cytology. 査読 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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  • ニコチンが口腔癌細胞に与える影響の検討 査読

    伊原木 聰一郎, 清水 理恵子, 奥井 達雄, 高畠 清文, 河合 穂高, 小野 喜章, 長塚 仁, 佐々木 朗

    日本口腔科学会雑誌   69 ( 3 )   235 - 235   2020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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  • ニコチンが口腔癌細胞に与える影響の検討 査読

    伊原木 聰一郎, 清水 理恵子, 奥井 達雄, 高畠 清文, 河合 穂高, 小野 喜章, 長塚 仁, 佐々木 朗

    日本口腔科学会雑誌   69 ( 3 )   235 - 235   2020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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  • Biomechanical Loading Comparison between Titanium and Bioactive Resorbable Screw Systems for Fixation of Intracapsular Condylar Head Fractures. 査読 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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  • Maxillofacial Trauma Surgery Patients With Titanium Osteosynthesis Miniplates: Remove or Not? 査読

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

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

    DOI: 10.1097/SCS.0000000000006352

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  • 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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  • 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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  • 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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  • Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver. 査読 国際誌

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

    Biochimica et biophysica acta. Molecular basis of disease   1866 ( 6 )   165731 - 165731   2020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)  

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

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  • Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles. 査読 国際誌

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

    Cancers   12 ( 5 )   2020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)  

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

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

    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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  • 口腔癌間質細胞が骨髄由来細胞の動員に与える影響

    河合 穂高, メイワト・ウ, 辻極 秀次, 高畠 清文, 大森 悠加, 藤井 昌江, 中野 敬介, 長塚 仁

    日本病理学会会誌   109 ( 1 )   315 - 315   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • エナメル上皮腫開窓術の適応に関する組織学的検討

    大森 悠加, 高畠 清文, 河合 穂高, 吉田 沙織, メイワト・ウ, 浜田 芽衣, 中野 敬介, 長塚 仁

    日本病理学会会誌   109 ( 1 )   316 - 316   2020年3月

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  • Antiparkinson Drug Benztropine Suppresses Tumor Growth, Circulating Tumor Cells, and Metastasis by Acting on SLC6A3/DAT and Reducing STAT3. 査読 国際誌

    Chiharu Sogawa, Takanori Eguchi, Manh Tien Tran, Masayuki Ishige, Kilian Trin, Yuka Okusha, Eman Ahmed Taha, Yanyin Lu, Hotaka Kawai, Norio Sogawa, Masaharu Takigawa, Stuart K Calderwood, Kuniaki Okamoto, Ken-Ichi Kozaki

    Cancers   12 ( 2 )   2020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)  

    Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-κB, and β-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors.

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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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  • Morphological characteristics of radicular cysts using computed tomography. 査読

    Shintaro Sukegawa, Hidenobu Matsuzaki, Naoki Katase, Hotaka Kawai, Takahiro Kanno, Jun-Ichi Asaumi, Yoshihiko Furuki

    Odontology   108 ( 1 )   74 - 83   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The purpose of this study was to evaluate computed tomography (CT) findings of radicular cysts with a focus on location, size, and condition of the surrounding bone. Subjects comprised 60 men and 86 women (mean age 47.2 years) with histopathologically confirmed radicular cysts who underwent CT examination between 2012 and 2014. Mesiodistal and buccolingual diameters were measured at the location where the lesion appeared to be largest on CT axial images. Of the 146 cases, 103 lesions were in the maxilla and 43 were in the mandible. Mesiodistal diameter of the maxillary lesions was significantly larger than that of the mandibular lesions. However, the ratio of mesiodistal diameter to buccolingual diameter in the mandible was significantly larger than that in the maxilla. Bone expansion was more significant in the maxilla than in the mandible. Mesiodistal and buccolingual diameters in only the maxilla and perilesional sclerotic radiolucency in images of both jaws were significantly associated with the severity of clinical symptoms. The findings suggest that radicular cysts in the maxilla are accompanied by bone expansion in the mesiodistal and buccolingual directions and those in the mandible progress in the mesiodistal direction without bone expansion. Clinical acute symptoms (pain and swelling) are correlated with lesion size in the maxilla; such a correlation is not clear for mandibular lesions, and discovery of mandibular lesions may, therefore, be delayed.

    DOI: 10.1007/s10266-019-00443-5

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    DOI: 10.3892/ol.2019.11045

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  • 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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  • 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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  • 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.

    DOI: 10.3390/ijms20225779

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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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  • Oropharyngeal adenoid cystic carcinoma invading the mandibular bone through the mandibular foramen 査読

    Yohei Takeshita, Shunsuke Okada, Miki Hisatomi, Hidenobu Matsuzaki, Hotaka Kawai, Yohei Noda, Jun Murakami, Mariko Fujita, Hitoshi Nagatsuka, Yoshinobu Yanagi, Junichi Asaumi

    ORAL RADIOLOGY   35 ( 3 )   335 - 340   2019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)   出版者・発行元:SPRINGER  

    Adenoid cystic carcinoma (ACC) is a rare epithelial tumor of the head and neck region, and one of the most common malignant tumors of the salivary glands. ACC is a slow-growing tumor characterized by perineural invasion and often has a high-recurrence rate. We describe a case of oropharyngeal ACC invading the mandibular bone through the mandibular foramen that showed a rare pattern of origin and invasion. A 70-year-old woman complained of noise and pain around the right temporomandibular joint. Osteomyelitis was suspected on the initial imaging examinations, although the findings were slightly atypical. However, a mass was observed in the right oropharyngeal wall on subsequent imaging examinations, and mandibular bone invasion, rather than osteomyelitis, was additionally suspected. The mass in the right oropharyngeal wall and right mandible was surgically excised. On postoperative histopathological examination, the mass was finally diagnosed as ACC. As tumor cells were also observed around the inferior alveolar nerve, mandibular bone invasion through the mandibular foramen was suspected. An oropharyngeal ACC invading the mandibular bone through the mandibular foramen is extremely rare. The present case suggests that bone invasion should be considered carefully with several imaging examinations when a malignant tumor such as ACC is observed around the jaw bone.

    DOI: 10.1007/s11282-018-0359-3

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  • A case of intraoral plasmablastic lymphoma spontaneously regressed after biopsy in HIV-negative patient 査読

    Ono Kisho, Okui Tatsuo, Ibaragi Soichiro, Kawai Hotaka, Obata Kyoichi, Fujita Mariko, Sasaki Akira

    JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY   31 ( 4 )   280 - 283   2019年7月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ajoms.2019.03.012

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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

    Sukegawa S, Kanno T, Yamamoto N, Nakano K, Takabatake K, Kawai Hotaka, Nagatsuka H, Furuki Y

    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)  

    DOI: 10.3390/ma12091557

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

    Nakano K, Takabatake K, Kawai Hotaka, Yoshida S, Maeda H, Kawakami T, Nagatsuka H

    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)  

    DOI: 10.3390/ijms20081973

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  • Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma. 査読 国際誌

    Rieko Shimizu, Soichiro Ibaragi, Takanori Eguchi, Daisuke Kuwajima, Shinichi Kodama, Takashi Nishioka, Tatsuo Okui, Kyoichi Obata, Kiyofumi Takabatake, Hotaka Kawai, Kisho Ono, Kuniaki Okamoto, Hitoshi Nagatsuka, Akira Sasaki

    International journal of oncology   54 ( 1 )   283 - 294   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)  

    Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance.

    DOI: 10.3892/ijo.2018.4631

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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.

    DOI: 10.7150/ijms.29995

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  • Locally injected ivabradine inhibits carrageenan-induced pain and inflammatory responses via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. 査読

    Miyake S, Higuchi H, Honda-Wakasugi Y, Fujimoto M, Kawai Hotaka, Nagatsuka H, Maeda S, Miyawaki T

    PloS one   14 ( 5 )   e0217209   2019年

  • Solitary Fibrous Tumor Arising in the Buccal Space. 査読 国際誌

    Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Akira Sasaki

    Case reports in medicine   2019   9459837 - 9459837   2019年

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    記述言語:英語  

    A 39-year-old Japanese woman presented to the Department of Oral and Maxillofacial Surgery, Okayama University Hospital, with the complaint of a slowly growing buccal mass. The mass was well defined, had rounded margins, and was free from skin and muscles. A color Doppler echographic examination indicated high flow velocity of the blood surrounding the mass. Contrast-enhanced images on CT and contrast-enhanced T1-weighted images on MRI displayed a homogeneous enhanced mass with a well-defined margin. A fine-needle aspiration biopsy and histological examination were performed. On immunohistochemistry, spindle cells were strongly positive for CD34, STAT6, and vimentin and negative for EMA, S100, and α-SMA. The tumor was removed with extracapsular dissection. The tumor was composed of bland spindle cells proliferating in a patternless arrangement with a collagenous background. Most of the tumor mass consisted of hypocellular areas including ectatic blood vessels. A prominent branching vascular pattern was observed. Immunohistochemistry demonstrated that the tumor cells were positive for CD34, STAT6, vimentin, and Bcl-2, and negative for α-SMA, S100, and EMA. Three mitotic cells were observed per 10 high-power fields, and the Ki-67 index was 5.7%. The morphological and immunohistochemical features were consistent with a diagnosis of solitary fibrous tumor.

    DOI: 10.1155/2019/9459837

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2485/jhtb.28.377

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  • Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma. 査読 国際誌

    Kazuaki Hasegawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Hotaka Kawai, Shoji Ryumon, Koji Kishimoto, Yuka Okusha, Nur Mohammad Monsur Hassan, Akira Sasaki

    International journal of molecular sciences   19 ( 11 )   2018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)  

    Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

    DOI: 10.3390/ijms19113317

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

    Matsuda H, Takabatake K, Tsujigiwa H, Watanabe S, Ito S, Kawai Hotaka, Hamada M, Yoshida S, Nakano K, Nagatsuka H

    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)  

    DOI: 10.7150/ijms.28452

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  • Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells. 査読 国際誌

    Namba Y, Sogawa C, Okusha Y, Kawai Hotaka, Itagaki M, Ono K, Murakami J, Aoyama E, Ohyama K, Asaumi JI, Takigawa M, Okamoto K, Calderwood SK, Kozaki KI, Eguchi T

    Frontiers in oncology   8   376 - 376   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fonc.2018.00376

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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

    Takabatake K, Tsujigiwa H, Song Y, Matsuda H, Kawai Hotaka, Fujii M, Hamada M, Nakano K, Kawakami T, Nagatsuka H

    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)  

    DOI: 10.7150/ijms.24605

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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

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

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

    JOURNAL OF HARD TISSUE BIOLOGY   26 ( 4 )   425 - 430   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  

    Ameloblastic fibro-odontoma (AFO) is defined as a tumor with general characteristics of an ameloblastic fibroma along with the presence of enamel and dentine. AFO is a well-encapsulated, painless, slow-growing, and expanding tumor in young patients. Histologically, it has been classified as an ameloblastic fibroma or odontoma. In the 2017 new WHO classification of odontogenic tumor, AFO is described that they in most cases represent developmental stages of either complex or compound odontoma and that retaining them as separate entities would therefore be illogical. However, there is still considerable confusion concerning the nature and histology of AFO and the surgical therapy for this lesion. Here we present a case of maxillary AFO and review the relevant literature regarding the clinical and surgical features of this lesion.

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  • Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma 査読

    Hiroyuki Takada, Soichiro Ibaragi, Takanori Eguchi, Tatsuo Okui, Kyoichi Obata, Masanori Masui, Ayaka Morisawa, Kiyofumi Takabatake, Hotaka Kawai, Norie Yoshioka, Nur Mohammad Monsur Hassan, Tsuyoshi Shimo, Guo-Fu Hu, Hitoshi Nagatsuka, Akira Sasaki

    INTERNATIONAL JOURNAL OF ONCOLOGY   51 ( 2 )   625 - 632   2017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:SPANDIDOS PUBL LTD  

    Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor kappa beta ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.

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  • Surgical Treatment and Dental Implant Rehabilitation after the Resection of an Osseous Dysplasia 査読

    Shintaro Sukegawa, Takahiro Kanno, Hotaka Kawai, Akane Shibata, Kenichi Matsumoto, Yuka Sukegawa-Takahashi, Kyosuke Sakaida, Hitoshi Nagatsuka, Yoshihiko Furuki

    JOURNAL OF HARD TISSUE BIOLOGY   25 ( 4 )   437 - 441   2016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  

    Osseous dysplasia (OD), which is subdivided into four subtypes (focal cement-osseous dysplasia, florid osseous dysplasia, periapical cemental dysplasia, and familial gigantiform cementoma), is an idiopathic process located in the periapical region of the tooth-bearing jaw areas, characterized by a replacement of normal bone by fibrous tissue and metaplastic bone. Unless accompanied by bulging or secondary infection of the jawbone, treatment is not necessary. However, treatment for extirpation is required when a secondary infection is present. Consequently, occlusion reconstruction becomes difficult because of large bone defect. Herein, we report the surgical technique to maintain the alveolar ridge form after resecting the lesion and for the case of an infected alveolar bone in a patient with OD. The loss of the buccal cortical bone was inevitable after removal of the infected area. For postoperative occlusal reconstruction, we performed a bone graft to maintain the alveolar ridge form at the same time as the tumor extirpation. Deficient buccal cortical bone was rebuilt with bone taken from the mandibular ramus and a bioactive resorbable plate. We describe the management of OD and the surgical technique for alveolar ridge form management by resecting the lesion and infected alveolar bone.

    DOI: 10.2485/jhtb.25.437

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  • A Clinical Retrospective Study of Surgical Treatment for Medication-Related Osteonecrosis of the Jaw 査読

    Shintaro Sukegawa, Takahiro Kanno, Hotaka Kawai, Satoko Nakamura, Akane Shibata, Yuka Sukegawa-Takahashi, Hitoshi Nagatsuka, Yoshihiko Furuki

    JOURNAL OF HARD TISSUE BIOLOGY   25 ( 4 )   447 - 454   2016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  

    In 2014, the American Association of Oral and Maxillofacial Surgery recommended surgical treatment for medication-related osteonecrosis of the jaw (MRONJ) patients classified as stage 3 or those with mobile segments of bony sequestrum. However, there is limited information regarding the healing mechanism in MRONJ surgical treatments. This study aimed to retrospectively elucidate clinical outcomes of the surgical treatment of MRONJ patients. This study included 26 patients (7 men, 19 women; age: 42-92 years; mean standard deviation, 75.3 +/- 11.7 years) who were classified as stage 3 or had mobile segments of bony sequestrum, and intake of the offending drug was ceased. The sequestrum was removed with surrounding vital bone, and segmental resection was performed in one patient with a pathological mandibular fracture. The outcome was classified into one of the following three categories: "Healing," "Improvement," "Unchanged." and "Exacerbation." The mean postoperative follow-up period was 16.6 months (3.0-57.9 months), and complete healing was observed in 21 patients (80.8%), improvement of the lesion was observed in four patients (15.4%), and the outcome of one patient was unchanged (3.8%). The procedure described here may be recommended with relatively high clinical success rate for the patients with MRONJ requiring surgical treatment.

    DOI: 10.2485/jhtb.25.447

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  • Postoperative Infection Caused by a Resorbable Plate Used to Treat a Zygomatic Fracture 査読

    Shintaro Sukegawa, Takahiro Kanno, Hotaka Kawai, Akane Shibata, Yuka Sukegawa-Takahashi, Yoshihiko Furuki

    Clinics in Surgery   1 ( 1 )   2016年

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    記述言語:英語  

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  • Spontaneous regression of plasmablastic lymphoma in an elderly human immunodeficiency virus (HIV)-negative patient 査読

    Takuro Igawa, Yasuharu Sato, Hotaka Kawai, Eisei Kondo, Mai Takeuchi, Tomoko Miyata-Takata, Katsuyoshi Takata, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   10   183   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:BIOMED CENTRAL LTD  

    Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with human immunodeficiency virus (HIV) infection. Herein we describe a rare case of PBL that spontaneously regressed. An 80-year-old man was referred to our hospital owing to an exophytic gingival tumor in the right maxillary second molar region. He had no significant past medical history, and a screening test for HIV was negative. Imaging showed that the tumor measured 26 x 23 x 16 mm and was confined in the alveolar bone. The tumor was histologically comprised of highly proliferative immunoblastic cells positive for CD138 and Epstein-Barr virus (EBV)-encoded RNA. Monoclonal IgH chain gene rearrangement was detected via polymerase chain reaction. After biopsy and diagnosis of PBL, the tumor began to decrease in size and had apparently disappeared at the time of surgery. There was no histological evidence of a residual lesion in the surgical specimen. In conclusion, a minority of immunosenescence-associated PBLs in the elderly should be recognized as a unique clinicopathological entity distinct from common aggressive PBL.

    DOI: 10.1186/s13000-015-0421-y

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  • Nasopalatine duct cyst associated with dental implant treatment: A case report 査読

    Shintaro Sukegawa, Takahiro Kanno, Hotaka Kawai, Yuichiro Takebe, Akane Shibata, Yuka Takahashi, Hitoshi Nagatsuka, Yoshihiko Furuki

    Oral and Maxillofacial Surgery Cases   1 ( 3 )   38 - 41   2015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)   出版者・発行元:Elsevier Inc  

    Maxillary anterior implants are associated with the risk of nasopalatine canal damage. Here we present the case of a 37-year-old man who developed a nasopalatine duct cyst after maxillary implant placement. The patient received an implant 3 months after the extraction of a fractured maxillary right central incisor. At a maintenance visit 9 years after the procedure, he complained of swelling and mild pain in the palatal region of the implant. A panoramic radiograph and computed tomography (CT) scan revealed a large, well-circumscribed, periapical radiolucency surrounding the apical portion of the implant and extending to the nasopalatine duct. We removed the entire lesion without removing the implant. Histopathologic examination of the resected specimen revealed a nasopalatine duct cyst. Accidental contact with the nasopalatine canal during implant surgery may have led to the development of the nasopalatine duct cyst. Careful planning using a preoperative CT scan prior to implant placement may prevent such complications.

    DOI: 10.1016/j.omsc.2015.06.003

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  • Long-Term Bioresorption of Bone Fixation Devices Made from Composites of Unsintered Hydroxyapatite Particles and Poly-L-Lactide 査読

    Shintaro Sukegawa, Takahiro Kanno, Hotaka Kawai, Akane Shibata, Yuka Takahashi, Hitoshi Nagatsuka, Yoshihiko Furuki

    JOURNAL OF HARD TISSUE BIOLOGY   24 ( 2 )   219 - 224   2015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  

    Osteosynthetic bone fixation devices made from composites of uncalcined and unsintered hydroxyapatite (u-HA) particles and poly-L-lactide (PLLA) are widely adopted for clinical use because of their bioresorbability and osteoconductive properties. However, how the plate systems constituting these devices change during long-term use in vivo is unknown. In this study, we present cases of two patients fitted with u-HA/PLLA devices for &gt;5 years after surgery and evaluate the resorption process on the basis of the residual versus the resorbed material. In both cases, the majority of the degraded plates and screws had been replaced by bone. In post-operative three-dimensional (3D) CT imaging, plate and screws were maintained until two years after surgery, and then they were degraded and replaced to bone in 4-6 years after surgery. Examination of the aggregation of hydroxyapatite and decrease in molecular weight suggested that the residual material was in the final stages of resorption. The plate system examined demonstrated stable degradation without foreign body reactions in vivo. Although complete resorption is a lengthy process, it is possible to follow its progress using CT.

    DOI: 10.2485/jhtb.24.219

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▼全件表示

MISC

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

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

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

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • Porphyromonas gingivalisはマクロファージの細胞外小胞を介して胎盤・胎児の成長発育を阻害する(Porphyromonas gingivalis impairs placental and fetal development through macrophage-derived extracellular vesicles)

    棚井 あいり, 福原 瑶子, 江口 傑徳, 河合 穂高, 池亀 美華, 岡村 裕彦, 植田 幸嗣

    Journal of Oral Biosciences Supplement   2021   205 - 205   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ハニカムTCPを用いた細胞外微小環境制御による象牙質再生

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

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

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 口腔扁平上皮癌におけるシスプラチン-CXCR4阻害剤併用療法の有効性

    吉田 沙織, 河合 穂高, 長塚 仁, 竹下 洋平, 岡田 俊輔, 藤倉 満美子, 久富 美紀, 河津 俊幸, 浅海 淳一, 柳 文修

    日本病理学会会誌   110 ( 1 )   275 - 275   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 手術室における褥瘡発生予防を継続するための多職種連携による効果

    山室 穂高, 本城 友子, 中川 千春, 小松 和也, 清水 健太, 二宮 知子, 大音 博美, 河合 勝也

    日本褥瘡学会誌   22 ( 3 )   302 - 302   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本褥瘡学会  

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  • 口腔癌間質細胞が骨髄由来細胞の動員に与える影響

    河合 穂高, メイワト・ウ, 辻極 秀次, 高畠 清文, 大森 悠加, 藤井 昌江, 中野 敬介, 長塚 仁

    日本病理学会会誌   109 ( 1 )   315 - 315   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • エナメル上皮腫開窓術の適応に関する組織学的検討

    大森 悠加, 高畠 清文, 河合 穂高, 吉田 沙織, メイワト・ウ, 浜田 芽衣, 中野 敬介, 長塚 仁

    日本病理学会会誌   109 ( 1 )   316 - 316   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • CXCR4の阻害が口腔扁平上皮癌の腫瘍血管に与える影響

    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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  • 頬粘膜に発生した腺房細胞癌の1例 -本邦における小唾液腺腺房細胞癌に関する文献的検討-

    小畑協一, 小畑協一, 岸本晃治, 岸本晃治, 小野喜章, 河合穂高, 柴田茜, 奥井達雄, 矢尾真弓, 伊原木聰一郎, 佐々木朗

    日本口腔腫瘍学会誌   32 ( 3 )   77 - 82   2020年

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    記述言語:日本語   出版者・発行元:(一社)日本口腔腫瘍学会  

    小唾液腺由来の腺房細胞癌は非常にまれな唾液腺悪性腫瘍である。今回われわれは69歳女性に発生した小唾液腺腺房細胞癌を経験したので、文献的考察を加えて報告する。患者は右側頬粘膜下に腫瘤を触知したため受診、MRIにて25×20mm大の腫瘤を認め、全身麻酔下で腫瘍切除術を施行した。病理組織学的に腫瘍は小唾液腺に連続し、漿液腺房細胞様の細胞が大部分を占めていた。術後1年8ヵ月経過したが、再発や転移を認めていない。(著者抄録)

    J-GLOBAL

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02382&link_issn=&doc_id=20200925280003&doc_link_id=10.5843%2Fjsot.32.77&url=https%3A%2F%2Fdoi.org%2F10.5843%2Fjsot.32.77&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • オルガノイドを応用したドラッグリポジショニング開発

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

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

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • CXCR4の阻害が口腔扁平上皮癌の腫瘍血管に与える影響

    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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  • エナメル上皮腫における細胞診の有用性

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

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

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    記述言語:日本語   出版者・発行元:(公社)日本臨床細胞学会  

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  • 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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  • 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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  • 動物モデルを用いた高転移臓器における転移促進的微小環境の検討

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌におけるCXCR4の腫瘍血管新生への関与

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 動物モデルを用いた高転移臓器における転移促進的微小環境の検討

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌におけるCXCR4の腫瘍血管新生への関与

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 生体活性/吸収性骨接合材料SuperFIXSORB MXを科学する 口腔病理医の立場から

    河合 穂高

    日本口腔科学会雑誌   68 ( 1 )   47 - 47   2019年3月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • ハニカムTCP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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    記述言語:日本語  

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  • 口腔扁平上皮癌におけるPD-L1発現傾向の臨床病理学的解析

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

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

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • ニコチンは口腔扁平上皮癌細胞のセツキシマブ耐性を促進する

    清水 理恵子, 伊原木 聰一郎, 江口 傑徳, 奥井 達雄, 高畠 清文, 河合 穂高, 小野 喜章, 岡元 邦彰, 長塚 仁, 佐々木 朗

    岡山歯学会雑誌   37 ( 2 )   80 - 81   2018年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • 口腔扁平上皮癌におけるPD-L1発現傾向の臨床病理学的解析

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

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

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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

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

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

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ハニカムTCPを用いた硬組織形成制御における血管新生について

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

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

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

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

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • 肺癌移植マウス高転移臓器における骨髄由来細胞の局在と役割の検討

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 肺癌移植マウス高転移臓器における骨髄由来細胞の局在と役割の検討

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

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

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 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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  • 癌切除症例の病理組織診断報告に要する日数の検討と改善について

    堀田 真智子, 牛丸 牧子, 河合 穂高, 伏見 聡一郎, 和仁 洋治

    姫路赤十字病院誌   ( 41 )   38 - 41   2017年7月

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    記述言語:日本語   出版者・発行元:姫路赤十字病院  

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    その他リンク: http://search.jamas.or.jp/link/ui/2017355324

  • 胃癌切除症例の病理組織診断報告に要する日数の検討と改善について

    堀田 真智子, 牛丸 牧子, 河合 穂高, 伏見 聡一郎, 和仁 洋治

    姫路赤十字病院誌   41   38 - 41   2017年7月

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    記述言語:日本語   出版者・発行元:姫路赤十字病院図書学術委員会  

    当院では、胃癌の手術後に追加化学療法が不要な病期I期の患者には、がん地域連携クリティカルパスを利用し、地域の医療機関への逆紹介が行われている。今回、2015年1月〜12月の胃癌切除110例を対象とし、「手術から病理組織診断報告までの所要日数」「退院までに報告できなかった遅延症例の数」「病期」「遅延の要因」などについて検討した。結果、手術から病理診断報告までの所要日数は平均12.1日、遅延症例は18例(16%)であった。病期はIA期45例、IB期13例、II期以上52例で、遅延18例のうちIA期は10例、IB期4例、II期以上4例であった。遅延症例のうち14例(78%)は遅延の理由として追加検索が行われており、追加検索されなかった4例の遅延要因は、他の症例や他の業務が優先されていたことや、病理診断は週1回勤務の非常勤医が担当するため数日のロスが生じたことであった。これらの結果を受け、遅延を減らすために以下の改善策を講じ、効果が認められた。1)病理診断医が患者の退院予定日を把握できるよう、診断依頼伝票に退院予定日を記載する。2)病理診断医が他の症例より優先的に早期胃癌症例に取り組むようにする。3)追加検索が必要な症例は、検索によって深達度・病期が変更されうる可能性について了承を得たうえで中間報告を行う。

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  • 胃癌切除症例の組織診報告所要日数の検討

    堀田 真智子, 牛丸 牧子, 河合 穂高, 伏見 聡一郎, 和仁 洋治

    姫路赤十字病院誌   41   62 - 62   2017年7月

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    記述言語:日本語   出版者・発行元:姫路赤十字病院図書学術委員会  

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  • ヴァーチャルスライドサーバーの活用について(続報)

    伏見 聡一郎, 堀田 真智子, 河合 穂高, 牛丸 牧子, 和仁 洋治

    姫路赤十字病院誌   41   61 - 62   2017年7月

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    記述言語:日本語   出版者・発行元:姫路赤十字病院図書学術委員会  

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  • GFP骨髄移植マウスを用いた腫瘍間質における骨髄由来細胞の動態と役割

    河合 穂高

    岡山歯学会雑誌   36 ( 1 )   1 - 13   2017年6月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

    腫瘍の浸潤部組織や転移巣における骨髄由来細胞(BMDC)の局在や性質を調べ、BMDCが腫瘍の浸潤性や転移についてどのような影響を与えているか検討した。実験動物には7週齢の雌性GFPトランスジェニックマウス8匹および7週齢の雌性同系野生型マウス15匹の計23匹を使用した。本実験により、多数のBMDCが腫瘍組織内に存在しており、部位により局在が異なることが明らかとなった。BMDCは特に腫瘍が周囲組織に浸潤している腫瘍辺縁部や転移巣で著明に集簇し、腫瘍の浸潤性や転移能に積極的に関与している可能性が示唆された。さらに、腫瘍内に存在する腫瘍血管は非骨髄由来であり、組織から動員されていると考えられたが、腫瘍血管が多く存在する腫瘍辺縁部や転移巣で、CD31陽性BMDCの集簇がみられ、これらの細胞が血管新生を促進して、腫瘍の浸潤性や転移能に関与している可能性が示唆された。

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  • 診断に苦慮した卵巣腫瘍の一例

    堀田 真智子, 太田 陽子, 河合 穂高, 伏見 聡一郎, 和仁 洋治

    日本婦人科腫瘍学会雑誌   35 ( 3 )   689 - 689   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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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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    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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  • 術後、未治療で緩徐な経過を示した紡錘形細胞癌の一例

    堀田 真智子, 伏見 聡一郎, 河合 穂高, 和仁 洋治

    日本病理学会会誌   106 ( 1 )   447 - 447   2017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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  • 穿刺吸引細胞診で甲状腺癌の転移との鑑別を要した成人型顆粒膜細胞腫の転移例

    伏見 聡一郎, 堀田 真智子, 河合 穂高, 藤澤 真義, 牛丸 牧子, 廣尾 嘉樹, 井上 瞳, 永谷 たみ, 春名 勝也, 山本 繁秀, 和仁 洋治

    日本臨床細胞学会雑誌   55 ( Suppl.2 )   512 - 512   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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  • 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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  • 胃癌切除症例におけるturn around time(TAT)の検討

    堀田 真智子, 牛丸 牧子, 河合 穂高, 伏見 聡一郎, 和仁 洋治

    日赤医学   68 ( 1 )   148 - 148   2016年9月

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    記述言語:日本語   出版者・発行元:日本赤十字社医学会  

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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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  • 薬剤関連性顎骨壊死(MRONJ)に対する外科的治療法の検討

    助川 信太郎, 管野 貴浩, 河合 穂高, 柴田 茜, 助川 由佳, 古木 良彦

    日本口腔科学会雑誌   65 ( 2 )   158 - 158   2016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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  • 下顎骨内へ広範に浸潤した中咽頭腺様嚢胞癌の一例

    松崎 秀信, 河合 穂高, 野田 洋平, 松本 洋, 水川 展吉, 柳井 広之, 小野田 友男, 浅海 淳一, 木股 敬裕

    頭頸部癌   42 ( 2 )   230 - 230   2016年5月

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    記述言語:日本語   出版者・発行元:(一社)日本頭頸部癌学会  

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  • エナメル上皮癌-二次型(脱分化型)、周辺性の1例

    河合 穂高, 伏見 聡一郎, 堀田 真智子, 河田 卓也, 和仁 洋治

    日本病理学会会誌   105 ( 1 )   506 - 506   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌における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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    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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  • 超音波内視鏡下穿刺吸引術 (EUS-FNA) で得られた gangliocytic paraganglioma の細胞像の検討

    河合 穂高, 伏見 聡一郎, 板倉 淳哉, 井上 博文, 藤井 昌江, 武部 祐一郎, 松川 昭博

    日本臨床細胞学会雑誌   55 ( 6 )   376 - 381   2016年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本臨床細胞学会  

    <p><b>背景</b> : Gangliocytic paraganglioma (GP) は, 十二指腸乳頭部に好発するまれな腫瘍で, 主として粘膜下に存在するため, 生検による確定診断は困難なことが多い. EUS-FNA は術前診断の有効な方法として期待されるが, その報告は少ない.</p><p><b>症例</b> : 60 歳代, 男性. タール便を主訴に上部消化管内視鏡が施行された. 生検では十二指腸粘膜のみしか得られなかった.</p><p>EUS-FNA 検体では, 細顆粒状クロマチンを有する短紡錘形~類円形の核をもつ紡錘形細胞に加え, 少数ながら核小体の目立つ大型細胞も認められた. 多彩な細胞像を呈し, 核所見などから神経内分泌系の腫瘍が疑われた.</p><p>膵十二指腸切除検体では十二指腸乳頭部の近傍に粘膜下腫瘍が認められた. 組織学的に腫瘍は, Zellballen 配列をとる上皮様細胞, 明瞭な核小体をもつ神経節細胞様細胞, 束状の紡錘形細胞 (支持細胞) の 3 成分から構成されていた. 最終的に GP と病理診断された.</p><p><b>結論</b> : EUS-FNA 検体では必ずしも 3 成分の細胞が採取されない可能性がある. しかし, 3 成分の細胞が正しく採取され, さらにセルブロックの免疫組織化学的検討を加えれば, 診断は可能と思われた.</p>

    DOI: 10.5795/jjscc.55.376

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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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    記述言語:日本語   出版者・発行元:岡山歯学会  

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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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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • ハニカムβ-TCPを用いた象牙芽細胞様細胞の誘導

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

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

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ハニカムβ‐TCPを用いた象牙芽細胞様細胞の誘導

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

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

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 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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  • ハニカムβ-TCPを用いた幾何学構造による骨・軟骨組織再生制御

    高畠 清文, 辻極 秀次, 于 淞, 武部 祐一郎, 伊藤 聡, 藤井 昌江, 松田 寛之, 河合 穂高, 長塚 仁

    日本口腔科学会雑誌   64 ( 2 )   199 - 199   2015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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  • 腫瘍の微小環境形成における骨髄由来細胞の動態

    河合 穂高, 玉村 亮, 藤井 昌江, 武部 祐一郎, 高畠 清文, 松田 寛之, 浜田 芽衣, 辻極 秀次, 長塚 仁

    日本病理学会会誌   104 ( 1 )   383 - 383   2015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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  • 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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    記述言語:日本語  

    J-GLOBAL

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  • エナメル上皮腫におけるCCN2およびYAPの局在とその役割

    武部 祐一郎, 河合 穂高, 藤井 昌江, 高畠 清文, 辻極 秀次, 長塚 仁

    岡山歯学会雑誌   33 ( 2 )   45 - 46   2014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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  • ハニカムβ-TCPを用いた細胞外微小環境再現による硬組織再生

    高畠 清文, 辻極 秀次, 武部 祐一郎, 藤井 昌江, 河合 穂高, 于 淞, 長塚 仁

    Journal of Oral Biosciences Supplement   2014   121 - 121   2014年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 口腔扁平上皮癌における1p36領域のLOH解析およびRIZ1発現の検討

    玉村 亮, 岡田 裕之, 武部 祐一郎, 河合 穂高, 辻極 秀次, 長塚 仁

    日本病理学会会誌   103 ( 1 )   282 - 282   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • エナメル上皮腫におけるCCN2の発現解析

    河合 穂高, 武部 祐一郎, 片瀬 直樹, 于 淞, 藤井 昌江, 高畠 清文, 辻極 秀次, 長塚 仁

    日本病理学会会誌   103 ( 1 )   308 - 308   2014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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  • 硬組織形成過程における細胞外微小環境としてのハニカムβ-TCP

    辻極 秀次, 伊藤 聡, 片瀬 直樹, 玉村 亮, 于 淞, 李 海テイ, 武部 祐一郎, 河合 穂高, 長塚 仁

    日本口腔科学会雑誌   63 ( 1 )   100 - 100   2014年1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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  • DKK3の頭頸部扁平上皮癌における発現の検討

    藤井昌江, 片瀬直樹, 高畠清文, 武部祐一郎, YU Song, 河合穂高, 辻極秀次, 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   25th   122   2014年

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    記述言語:日本語  

    J-GLOBAL

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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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    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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  • 頭頸部扁平上皮癌におけるDkk-3の免疫組織化学的検討

    藤井 昌江, 伊藤 聡, 于 淞, 武部 祐一郎, 河合 穂高, 辻極 秀次, 長塚 仁

    Journal of Oral Biosciences Supplement   2013   115 - 115   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • エナメル上皮腫におけるCCN2の発現と間質線維芽細胞への作用について

    武部 祐一郎, 辻極 秀次, 于 淞, 藤井 昌江, 河合 穂高, 玉村 亮, 佐々木 朗, 長塚 仁

    Journal of Oral Biosciences Supplement   2013   165 - 165   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 腫瘍の微小環境形成に関与する骨髄由来細胞の動態について

    玉村 亮, 武部 祐一郎, 片瀬 直樹, 河合 穂高, 辻極 秀次, 長塚 仁

    日本病理学会会誌   102 ( 1 )   437 - 437   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter retrospective analysis in Japan.

    Takata K, Okada H, Ohmiya N, Nakamura S, Kitadai Y, Tari A, Akamatsu T, Kawai H, Tanaka S, Araki H, Yoshida T, Okumura H, Nishisaki H, Sagawa T, Watanabe N, Arima N, Takatsu N, Nakamura M, Yanai S, Kaya H, Morito T, Sato Y, Moriwaki H, Sakamoto C, Niwa Y, Goto H, Chiba T, Matsumoto T, Ennishi D, Kinoshita T, Yoshino T

    Cancer Sci   102 ( 8 )   1532 - 1536   2011年

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  • Promotion of Bone Regeneration by CCN2 Incorporated into Gelatin Hydrogel .

    Kikuchi T, Kubota S, Asaumi K, Kawai Hotaka, Nishida T, Kawata K, Mitani S, Tabata Y, Ozaki T, Takigawa M

    Tissue Engineering : Part A   14 ( 6 )   1089 - 1098   2008年

  • Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy

    Hotaka Kawai, K Kiura, M Tabata, T Yoshino, Takata, I, A Hiraki, K Chikamori, H Ueoka, M Tanimoto, M Harada

    LUNG CANCER   35 ( 3 )   305 - 314   2002年3月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We established several in vitro drug-resistant cell lines after continuous, long-term exposure of each drug to elucidate mechanisms of drug resistance. Whether drug resistance in these in vitro resistant cell lines reflects clinical drug resistance still remains unanswered. In this study, a pair of lung cancer cell lines was established from one patient with squamous cell carcinoma of the lung, with one line being established before and one line after combination chemotherapy (cisplatin/ifosfamide/vindesine). Combination chemotherapy selected resistant EBC-2/R cells, which showed cross-resistance to 4-hydroxyifosfamide (3.2-fold), cisplatin (2.3-fold), and methotrexate (3.7-fold) and collateral sensitivity to vindesine (0.77-fold) compared with parent EBC-2 cells. EBC-2/R cells showed decrease in intracellular accumulation of cisplatin, increase in intracellular concentration of glutathione (GSH), and overexpression of multidrug resistance-associated protein (MRP) 3 when compared with EBC-2 cells. A single cycle of chemotherapy was not sufficient to select other mechanisms of drug resistance, such as multidrug resistance-1/P-glycoprotein, MRPs 1, 2, 4, and 5, lung resistance-related protein, metallothionein IIa, glutathione S-transferase pi, gamma-glutamyleysteine synthetase (light and heavy chain), and excision repair cross complementing 1. Sequentially we established two cell lines, which cell lines showed the differences of the cisplatin resistance, expression level of MRP3, intracellular GSH level and intracellular accumulation of cisplatin. A pair of cell lines will be useful to elucidate resistant mechanisms of cisplatin in heterogeneous lung cancer cells. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0169-5002(01)00430-5

    Web of Science

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講演・口頭発表等

  • Distribution of bone marrow-derived cells in highly metastatic organs. 招待

    Hotaka Kawai

    The first international symposium of Intercellular communication and extracellular vesicles (ICEV-1)  2019年10月 

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    記述言語:英語   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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  • 生体活性/吸収性骨接合材料Super FIXSORB MX®️を科学する〜口腔病理医の立場から〜 招待

    河合穂高

    第66回日本口腔科学会 中国・四国地方部会  2018年11月 

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    記述言語:日本語   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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産業財産権

  • 組織再生材料及びその製造方法

    河合穂高, 宝田剛, 長塚仁

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    出願番号:特願2020-168891 

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受賞

  • 教育研究助成

    2021年5月   公益財団法人 川崎医学・医療福祉学振興会  

    河合穂高

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  • 優秀発表賞

    2020年10月   第31回 日本臨床口腔病理学会  

    河合穂高

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  • 研究活動費助成事業

    2020年10月   公益財団法人 寺岡記念育英会  

    河合穂高

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  • ブレインストーミング ポスター賞

    2020年9月   岡山大学  

    河合穂高

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  • 優秀ポスター賞

    2020年1月   日本口腔腫瘍学会  

    河合 穂高

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  • Poster Competition Award

    2019年12月   he 4th International symposium of medical and dental education in Okayama (ISMDEO)  

    河合 穂高

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  • Young Investigator Award

    2019年11月   The first international symposium of Intercellular communication and extracellular vesicles (ICEV-1)  

    河合 穂高

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  • 研究活動費助成事業 (基礎:癌領域)

    2019年6月   公益財団法人ウエスコ学術振興財団  

    河合 穂高

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  • 生物学研究奨励賞

    2018年9月   両備檉園記念財団  

    河合 穂高

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共同研究・競争的資金等の研究

  • 口腔扁平上皮癌における胎児期卵黄嚢由来組織マクロファージの役割と動態の検討

    研究課題/領域番号:21K17089  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    河合 穂高

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 高転移臓器における前転移nicheの性質の検討

    2020年10月 - 2021年10月

    公益財団法人 寺岡記念育英会  研究活動費助成事業 

    河合穂高

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    担当区分:研究代表者 

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  • CXCR4をターゲットとした新たな抗腫瘍血管治療の開発

    2019年10月 - 2020年10月

    公益財団法人ウエスコ学術振興財団  研究活動費助成事業 

    河合穂高

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    担当区分:研究代表者 

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  • 口腔扁平上皮癌の前転移niche形成における、骨髄由来細胞の役割の解明

    研究課題/領域番号:18K17224  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    河合 穂高

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    腫瘍が遠隔臓器に転移する際に重要な役割を果たす「前転移niche」の形成には、骨髄由来細胞が重要な役割を果たすことが報告されている。しかし、口腔癌に おける前転移nicheと骨髄由来細胞の関係は未だ明らかとなっていない。申請者は、放射線照射を行なったヌードマウスに、GFPヌードマウスより採取した骨髄細 胞を移植することで、骨髄細胞のみGFPでラベルされたGFP陽性骨髄移植ヌードマウスを作製し、同マウスにヒト由来口腔癌細胞を移植し高転移臓器を検索するこ とで、口腔癌における前転移nicheと骨髄由来細胞の関係、および前転移niche形成に関与する骨髄由来細胞を特定することが可能と考えた。 令和元年度は、転移モデルの作成を行った。尾静脈よりHSC2, HSC3を注射し、遠隔臓器への転移の有無を調べた。リンパ節転移モデルの作成は苦慮している。

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  • 細胞競合による癌の生物学的性格および癌化の制御

    研究課題/領域番号:21K10043  2021年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中野 敬介, 河合 穂高, 志茂 剛, 長塚 仁, 辻極 秀次, 高畠 清文

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 口腔扁平上皮癌における新規遠隔転移抑制治療の開発

    研究課題/領域番号:20H03888  2020年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    長塚 仁, 山近 英樹, 中野 敬介, 河合 穂高, 江口 傑徳, 辻極 秀次, 高畠 清文

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

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  • エナメル上皮腫の生物学的性格制御による腫瘍実質ー間質相互作用破綻の誘導

    研究課題/領域番号:20K10094  2020年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    藤井 昌江, 長塚 仁, 中野 敬介, 高畠 清文, 河合 穂高

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • miRNAが支配する骨・軟骨分化方向決定メカニズムの解明

    研究課題/領域番号:20K10178  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    伏見 滋子, 中野 敬介, 河合 穂高, 長塚 仁, 辻極 秀次, 高畠 清文

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 三次元腫瘍オルガノイド評価系により見出された新規癌転移抑制化合物の創薬展開

    研究課題/領域番号:20K09904  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    十川 千春, 岡元 邦彰, 江口 傑徳, 河合 穂高, 青山 絵理子

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • 口腔癌分泌エクソソームを用いた分子標的抗癌剤感受性試験の開発

    研究課題/領域番号:19K10288  2019年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    村上 純, 長塚 仁, 河合 穂高, 高畠 清文

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    近年、癌細胞が分泌するエクソソーム顆粒が、癌の転移に重要な役割を果たすことが報告 された。癌細胞から分泌されたエクソソームは、様々な癌関連マイクロRNA等を内包し、細 胞間の情報伝達に関与する。また、エクソソームは血液等の体液にも含まれ、低侵襲な体液 診断の切り札として、大きな注目を浴びつつある。2018年、申請者らは口腔癌においてエク ソソームが分子標的抗癌剤動態へ関与する可能性を報告している。
    当該研究の目的は、口腔癌が分泌するエクソソームによるセツキシマブ動態への影響を明ら かにし、エクソソームを利用した簡便かつ低侵襲性の体液診断型分子標的抗癌剤セツキシマブ感受性予測法を開発することである。
    本年は、ヒト口腔扁平上皮癌細胞株(HSC4、3、2、SAS、Hep2、Ca9-22株)培養上清からPureExo&#174; エクソソーム単離キット(コスモ・バイオ株式会社)にてエクソソームを回収する。マイクロRNA回収にはExoMirTMエキソソームRNA抽出キット(コスモ・バイオ株式会社)を用い、 DNA Chip法(3D-Gene&#174;、東レ株式会社)を用いて口腔癌細胞株特異的マイクロRNAの存在 を網羅的に検討した。

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  • 癌間質による癌の生物学的性格の制御および癌誘発の検討

    研究課題/領域番号:18K09789  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中野 敬介, 長塚 仁, 高畠 清文, 河合 穂高, 江口 傑徳, 辻極 秀次, 志茂 剛

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究の目的は、口腔癌の間質が癌細胞に作用して、癌の生物学的性質を変化させることの検証、および、癌間質が癌の周囲の正常細胞に働きかけて癌化を引き起こす可能性を検証することである。平成30年度では口腔扁平上皮癌細胞株と間質細胞の組合せによる培養、腫瘍間質の違いによる腫瘍細胞の生物学的性格(増殖能、浸潤能、遊走能、形態)に与える影響を検討した。腫瘍細胞株は高浸潤癌:HSC-2、低浸潤癌:SAS、対照細胞: HaCaT細胞を用いた。間質組織は岡山大学病院手術摘出材料から高浸潤癌症例、低浸潤癌症例を選定して用いた。由来の異なる癌間質を癌細胞株と共培養し、また同複合体をマウス皮下に移植した。その結果、腫瘍組織は癌の間質の違いによって大きくその性状を変化させることが示された。培養系を用いた検討では共培養する間質細胞の違いにより癌細胞に対する遊走、増殖能が変化することが明らかになった。癌細胞と間質複合体の移植実験では組織学的および免疫組織化学的検討を行い、癌細胞の増殖と分化の様相が間質細胞によって影響されることが明らかになった。また、移植実験系では当初予想していなかった非常に特殊な間質細胞の動態が明らかになった。この点については今後さらに追及していく予定である。本年度の研究結果は、癌間質が直接的に癌の生物学的性格を調節していることを強く裏付けるものである。この研究結果は癌間質に注目した癌の治療戦略に結び付く非常に重要な成果である。

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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

  • チュートリアル (2020年度) 第1学期  - 火4,火5,火6,火7

  • 人体病理学 (2020年度) 第1学期  - 火5,火6,火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

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

 

メディア報道

  • ガンを兵糧攻め? 新たな抗腫瘍治療の開発 テレビ・ラジオ番組

    NHK岡山放送局  おはよう岡山  2019年10月

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