研究者詳細 - 河合　穂高

脂質・コレステロール排出ポンプABCG1標的による腫瘍内エクソソーム蓄積および腫瘍縮小

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

江口傑徳, 十川千春, 難波友里, 奥舎有加, 河合穂高, 小野喜章, 板垣まみ, 村上純, 大山和美, 浅海淳一, 岡元邦彰

日本薬理学会年会要旨集 92 2-YIA-26 2019年

記述言語：日本語出版者・発行元：公益社団法人日本薬理学会

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10% to 35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs, their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

DOI： 10.1254/jpssuppl.92.0_2-yia-26

CiNii Article

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

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

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

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

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

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

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

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

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

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

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

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

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.

DOI： 10.2485/jhtb.26.425

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

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

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

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

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.

DOI： 10.3892/ijo.2017.4050

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

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

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

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

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

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

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

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

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

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

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

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

Scopus

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

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 >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