研究者詳細 - 河合　穂高

論文 - 河合　穂高

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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

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

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

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

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

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

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）

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

DOI： 10.3390/ijms20225779

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

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）

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

DOI： 10.3390/ma12223681

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高転移臓器における転移促進的微小環境の性質の検討

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

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

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

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

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

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

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

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

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

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

Web of Science

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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

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

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

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

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

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. 査読国際誌

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

PloS one 14 ( 5 ) e0217209 2019年

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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