Updated on 2026/04/01

写真a

 
MARUYAMA Satoshi
 
Organization
University Medical and Dental Hospital Oral Surgery,Radiology and Anesthesia Oral and Maxillofacial Surgery Lecturer
Graduate School of Medical and Dental Sciences Oral Life Science Lecturer
Title
Lecturer
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Degree

  • 歯学博士「歯学」 ( 2004.3   新潟大学 )

Research Interests

  • Oral Pathology

  • salivary gland tumor

  • Hypoxia

  • Oral Cancer

Research Areas

  • Life Science / Oral pathobiological science

Research History (researchmap)

  • Niigata University   Medical and Dental Hospital

    2009.2

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  • Niigata University   Graduate School of Medical and Dental Sciences

    2005.5 - 2009.1

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  • Niigata University   Graduate School of Medical and Dental Sciences

    2004.5 - 2005.4

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  • Hamamatsu University School of Medicine

    1999.5 - 2000.3

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Research History

  • Niigata University   University Medical and Dental Hospital Oral Surgery,Radiology and Anesthesia   Lecturer

    2012.11

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science   Lecturer

    2009.2

  • Niigata University   University Medical and Dental Hospital Surgical Care   Lecturer

    2009.2 - 2012.11

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science   Assistant Professor

    2005.5 - 2009.1

  • Niigata University   Graduate School of Medical and Dental Sciences   Researcher

    2004.5 - 2005.4

Education

  • Niigata University   大学院歯学研究科博士課程   （口腔病理学講座）

    2000.4 - 2004.3

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    Country： Japan

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  • Niigata University   Faculty of Dentistry   歯

    1993.4 - 1999.3

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    Country： Japan

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Professional Memberships

 

Papers

  • Development of a surgical ciliated cyst after maxillary sinus floor augmentation for dental implants: A case report and review of the literature

    Hiroyuki Kano, Yusuke Kato, Satoko Fukui, Satoshi Maruyama, Tadaharu Kobayashi

    JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY   37 ( 5 )   1018 - 1021   2025.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.ajoms.2025.04.002

    Web of Science

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  • Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts Reviewed

    Yuka Aizawa, Kenta Haga, Nagako Yoshiba, Witsanu Yortchan, Sho Takada, Rintaro Tanaka, Eriko Naito, Tatsuya Abé, Satoshi Maruyama, Manabu Yamazaki, Jun-ichi Tanuma, Kazuyo Igawa, Kei Tomihara, Shinsaku Togo, Kenji Izumi

    Biomedicines   12 ( 10 )   2373 - 2373   2024.10

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME.

    DOI： 10.3390/biomedicines12102373

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  • Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling Reviewed

    Maiko Kawasaki, Katsushige Kawasaki, Finsa Tisna Sari, Takehisa Kudo, Jun Nihara, Madoka Kitamura, Takahiro Nagai, Vanessa Utama, Yoko Ishida, Fumiya Meguro, Alex Kesuma, Akira Fujita, Takayuki Nishimura, Yuan Kogure, Satoshi Maruyama, Jun-ichi Tanuma, Yoshito Kakihara, Takeyasu Maeda, Sarah Ghafoor, Roman H Khonsari, Pierre Corre, Paul T Sharpe, Martyn Cobourne, Brunella Franco, Atsushi Ohazama

    eLife   13   2024.10

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    Publishing type：Research paper (scientific journal)   Publisher：eLife Sciences Publications, Ltd  

    Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma, and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested tongue swelling formation. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies.

    DOI： 10.7554/elife.85042

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    Other Link： https://cdn.elifesciences.org/articles/85042/elife-85042-v1.xml

  • Ladinin-1 in actin arcs of oral squamous cell carcinoma is involved in cell migration and epithelial phenotype Reviewed

    Tatsuya Abé, Manabu Yamazaki, Motohiro Nozumi, Satoshi Maruyama, Kaori Takamura, Riuko Ohashi, Yoichi Ajioka, Jun-ichi Tanuma

    Scientific Reports   14   22778   2024.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41598-024-74041-z

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  • 広範な骨膜反応を呈した非細菌性下顎骨骨髄炎の1例

    須田 大亮, 船山 昭典, 佐久間 英伸, 齋藤 大輔, 羽賀 健太, 林 孝文, 丸山 智, 田沼 順一, 小林 正治

    日本口腔科学会雑誌   73 ( 3 )   272 - 273   2024.9

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    Language：Japanese   Publisher：(NPO)日本口腔科学会  

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  • Oral Focal Mucinosis of the Tongue: Case Report and Review of the Literature

    Ryota Kobayashi, Hideaki Hirai, Satoshi Maruyama, Jun-ichi Tanuma, Kei Tomihara

    Cureus   2024.8

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.7759/cureus.67882

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  • Extensive ameloblastic fibroma of the mandible in an elderly woman: A case report and review of the literature

    Kenta Haga, Akinori Funayama, Manabu Yamazaki, Satoshi Maruyama, Taichi Hara, Naoaki Saito, Daisuke Saito, Yohei Sotsuka, Takafumi Hayashi, Jun-ichi Tanuma, Tadaharu Kobayashi

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   36 ( 3 )   333 - 340   2024.5

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.ajoms.2023.08.003

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  • Wnt/β-catenin-C-kit axis may play a role in adenoid cystic carcinoma prognostication Reviewed

    Shinsuke Fujii, Kana Hasegawa, Takashi Maehara, Kari J Kurppa, Kristiina Heikinheimo, Kristy A. Warner, Satoshi Maruyama, Yudai Tajiri, Jacques E. Nör, Jun-ichi Tanuma, Shintaro Kawano, Tamotsu Kiyoshima

    Pathology - Research and Practice   155148 - 155148   2024.1

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.prp.2024.155148

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  • Comparing the Diagnostic Accuracy of Ultrasonography, CT, MRI, and PET/CT in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma Reviewed

    Masaki Takamura, Yutaka Nikkuni, Takafumi Hayashi, Kouji Katsura, Hideyoshi Nishiyama, Manabu Yamazaki, Satoshi Maruyama, Jun-ichi Tanuma

    Biomedicines   11 ( 12 )   3119 - 3119   2023.11

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    (1) Background: In oral cancer staging, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) are routinely used in clinical practice. The present study is a retrospective examination of the diagnostic accuracy of cervical lymph node metastasis using US, CT, MRI, and PET/CT, with histopathological diagnosis as a reference, to compare the different diagnostic imaging modalities. (2) Methods: The participants included 16 patients with oral squamous cell carcinoma who underwent US-, CT-, MRI-, and PET/CT-based preoperative diagnostic imaging and simultaneous primary lesion resection and neck dissection, including 82 level regions and 424 lymph nodes. We compared the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of each imaging modality based on the imaging results and the pathology results of metastasis. (3) Results: Of the four diagnostic imaging modalities, PET/CT exhibited the highest sensitivity but the lowest specificity and accuracy. US, CT, and MRI had high specificities. Comparing each level region and lymph node showed that differences were observed in PET/CT. (4) Conclusions: PET/CT to diagnose lymph node metastasis requires a comprehensive evaluation because it produces more false positives than other diagnostic imaging modalities. Using US, CT, and MRI, which have excellent spatial resolution, improves diagnostic accuracy at the lymph node level.

    DOI： 10.3390/biomedicines11123119

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  • Hypoxia-Induced Biosynthesis of the Extracellular Matrix Molecules, Perlecan and Fibronectin, Promotes the Growth of Pleomorphic Adenoma Cells In Vitro Models Reviewed

    Satoshi Maruyama, Manabu Yamazaki, Tatsuya Abé, Jun Cheng, Takashi Saku, Jun-ichi Tanuma

    Biomedicines   11 ( 11 )   2981 - 2981   2023.11

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    Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Salivary pleomorphic adenoma is histopathologically characterized by its colorful stroma with myxoid, chondroid, and hyaline appearances, due to enhanced biosynthesis of extracellular matrix (ECM) molecules and poor vascularity. Thus, pleomorphic adenoma cells embedded in the stroma typically survive under hypoxic conditions. We determined the expression kinetics of ECM molecules, such as perlecan and fibronectin (FN), under hypoxia in SM-AP1 cells which are duct epithelial differentiated cells, and in SM-AP4 cells, which are myoepithelial differentiated cells, cloned from pleomorphic adenoma of the parotid gland. We investigated hypoxia-inducible factor-1α (HIF-1α)-inducing pathways through a variety of ECM molecules in association with their cellular proliferation and migration. We observed that hypoxic conditions with elevated HIF-1α protein levels induced increased expression of perlecan and FN in SM-AP cells than in controls. Moreover, perlecan and FN knockdown reduced the proliferation of SM-AP1 and SM-AP4 cells under hypoxia. Further, SM-AP1 cell migration was enhanced by both perlecan and FN knockdown, whereas SM-AP4 cell migration was increased by perlecan knockdown and inhibited by fibronectin knockdown. The results indicated that pleomorphic adenoma cells can survive under hypoxic conditions by promoting cell proliferation via enhanced synthesis of ECM molecules. Overall, ECM molecules may be a new anti-tumor target under hypoxic conditions.

    DOI： 10.3390/biomedicines11112981

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  • Searching for new early detection markers of oral epithelial dysplasia and oral squamous cell carcinoma using oral liquid-based cytology

    Toshiyuki Akimori, Manabu Yamazaki, Tatsuya Abé, Satoshi Maruyama, Kei Tomihara, Takeyasu Maeda, Jun-ichi Tanuma

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   2023.11

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.ajoms.2023.11.007

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  • 光干渉断層撮影を用いた3次元口腔癌モデルにおける癌浸潤の定量解析(Quantitative analysis of cancer cell invasion on 3D in vitro oral cancer models using optical coherence tomography)

    羽賀 健太, 山崎 学, 丸山 智, 阿部 達也, 小林 正治, 田沼 順一

    日本癌学会総会記事   82回   970 - 970   2023.9

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    Language：English   Publisher：(一社)日本癌学会  

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  • Masticatory muscle tendon-aponeurosis hyperplasia that was initially misdiagnosed for polymyositis: a case report and review of the literature

    Wataru Katagiri, Daisuke Saito, Satoshi Maruyama, Makiko Ike, Hideyoshi Nisiyama, Takafumi Hayashi, Jun-ichi Tanuma, Tadaharu Kobayashi

    Maxillofacial Plastic and Reconstructive Surgery   45 ( 1 )   2023.5

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Background

    Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review.

    Case presentation

    A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction.

    Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 μm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively.

    Conclusions

    Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

    DOI： 10.1186/s40902-023-00386-6

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    Other Link： https://link.springer.com/article/10.1186/s40902-023-00386-6/fulltext.html

  • Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma Invited Reviewed

    Nyein Nyein Chan, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Kenta Haga, Masami Kawaharada, Kenji Izumi, Tadaharu Kobayashi, Jun-ichi Tanuma

    International Journal of Molecular Sciences   24 ( 7 )   6035   2023.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3390/ijms24076035

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  • Liquid‐based cytology for differentiating two cases of pemphigus vulgaris from oral squamous cell carcinoma Reviewed International journal

    Maruyama S, Yamazaki M, Abé T, Kato Y, Kano H, Sumita Y, Tomihara K, Tanuma J

    Diagnostic Cytopathology   51 ( 5 )   1 - 6   2023.2

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by blisters on the skin and mucous membrane. Since it often appears in the oral mucosa first, it may be diagnosed by oral mucosal cytology. Although the cytologic finding is characterized by acantholytic cells, that is, Tzanck cells, it is important to distinguish PV from neoplastic lesions of the oral mucosal epithelium, including differentiation from atypical parabasal/basal cells, which appear in squamous cell carcinoma (SCC). In this study, we examined the cellular findings in two cases of PV and a case of well-differentiated SCC with loss of epithelial cell cohesion. The samples were prepared using liquid-based cytology, which showed small round-shaped and deeply stained atypical, orangeophilic keratinocytes not only in SCC but also in PV, which made differentiation between the two difficult. However, Tzanck cells found in PV differ from the deep atypical parabasal/basal cells of SCC, suggesting that the cell outline is indistinct and small protrusions and brush-like structures are observed. This feature of Tzanck cells may be useful in cytological judgment.

    DOI： 10.1002/dc.25117

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  • 口底部に生じた異所性胃腸管嚢胞の1例

    齋藤 直朗, 丸山 智, 加藤 祐介, 竹内 涼子, 田沼 順一, 小林 正治

    日本口腔外科学会雑誌   69 ( 1 )   27 - 31   2023.1

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    Language：Japanese   Publisher：(公社)日本口腔外科学会  

    4歳5ヵ月女児。既往として出生前診断で指摘されていた口底部の嚢胞様病変に対し、生後3日に開窓術が施行され、病理組織学的に類表皮嚢胞と診断された。今回、3歳9ヵ月時に開窓部からの出血を主訴に当科へ受診となった。数日後に出血が治まったため、いったん終診となったが、4歳2ヵ月頃より唾仙痛様症状が出現したため再診した。口腔内所見および画像所見を踏まえて、開窓術後の変化を伴う口底部類表皮嚢胞と診断され、5歳時に全身麻酔下で嚢胞摘出術が行われた。その結果、病理組織学的に異所性胃腸管嚢胞と確定診断された。術後3年経過現在、再発なく、経過良好である。

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    Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01073&link_issn=&doc_id=20230201450005&doc_link_id=10.5794%2Fjjoms.69.27&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.69.27&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Adenosquamous Carcinoma with the Acantholytic Feature in the Oral Cavity: A Case Report and Comprehensive Literature Review

    Tatsuya Abé, Manabu Yamazaki, Satoshi Maruyama, Nobuyuki Ikeda, Yoshimasa Sumita, Kei Tomihara, Jun-ichi Tanuma

    Diagnostics   12 ( 10 )   2398 - 2398   2022.10

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Adenosquamous carcinoma (ASC) is an aggressive subtype of squamous cell carcinoma (SCC). Due to its poor prognosis, a precise pathological diagnosis of ASC is essential but challenging because its pathological criteria are still unclear. Here, we present a rare case of oral ASC accompanied by acantholytic features. The tumor was raised in the mandibular gingiva and recurred locally approximately 13 months after the initial surgery with cervical lymph node metastasis. Pathological specimens of the primary lesion showed acantholysis in a large area of the SCC. Mucous cells, the characteristic finding indicating glandular differentiation, were imperceptible in the initial surgical specimen but increased in the locally recurrent and metastatic lymph node specimens. In a comprehensive literature review of oral ASC cases, the present case was the only case of ASC with acantholytic features. We reconfirmed that ASC has poor prognoses, such as low 5-year overall survival and disease-free survival, high locoregional recurrence, and high distant metastasis rates. A precise diagnosis of ASC is required for estimating prognosis and undergoing close follow-up, even if the adenocarcinomatous component is limited to a small area in the lesion.

    DOI： 10.3390/diagnostics12102398

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  • Clinicopathologic factors influencing the screening accuracy of oral cytology: A retrospective cohort study Reviewed International journal

    MASAMI KAWAHARADA, SATOSHI MARUYAMA, MANABU YAMAZAKI, TATSUYA ABÉ, NYEIN NYEIN CHAN, AKINORI FUNAYAMA, ATSUSHI UENOYAMA, TOSHIYUKI AKIMORI, KEI TOMIHARA, JUN-ICHI TANUMA

    Oncology letters   24 ( 385 )   385 - 385   2022.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    Cytology is a simple and non-invasive screening method for oral cancer. However, this method is not yet routinely used by clinicians because of its high false negative rate (FNR) and due to lack of sufficient studies examining the factors for high FNRs. The present retrospective study aimed to compare the screening performance of conventional cytology (CC) and liquid-based cytology (LBC) through histological validation, and to elucidate factors inducing false negative screening in oral cytology. Cytological specimens with histological examination and intraoral digital images of the lesion were retrospectively collected between January 2017 and December 2018 for CC and between October 2019 and September 2021 for LBC. Oral cytological screening was conducted based on the oral Bethesda system for oral cytology. Clinical subtypes were re-evaluated using intraoral digital images. The screening accuracy of oral cytology was calculated considering the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting the malignant transformation of oral lesions. No statistically significant difference was noted in the inadequate rate between CC and LBC groups. For CC and LBC, the sensitivities were 60.9 and 59.2%, the specificities were 87.3 and 79.1%, the PPVs were 85.8 and 76.2%, and the NPVs were 63.9 and 63.2%, respectively. Thus, the screening accuracy was similar between methodologies. Among the clinicopathological factors investigated, histological diagnosis and cellularity contributed to false negative results. Homogeneous findings of oral epithelial dysplasia and the superficial growth of carcinoma in situ/squamous cell carcinoma resulted in false negative findings for CC and LBC. Furthermore, LBC samples with a lower cell number (<2,000 squamous cells) exhibited statistically significantly increased FNRs. The present study found that the cytological methods did not affect the inadequate rate and screening accuracy, whereas clinical subtype and cellularity decreased screening accuracy. Therefore, cytological screening and subsequent follow-up should be performed while considering clinical findings and the cellularity of cytology smears.

    DOI： 10.3892/ol.2022.13505

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  • 下顎歯肉部転移性腫瘍を契機に診断に至った膵癌の1例

    須田 大亮, 船山 昭典, 齋藤 大輔, 新國 農, 丸山 智, 林 孝文, 田沼 順一, 小林 正治

    日本口腔科学会雑誌   71 ( 2 )   159 - 159   2022.7

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    Language：Japanese   Publisher：(NPO)日本口腔科学会  

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  • Novel cytological model for the identification of early oral cancer diagnostic markers: The carcinoma sequence model. International journal

    Masami Kawaharada, Manabu Yamazaki, Satoshi Maruyama, Tatsuya AbÉ, Nyein Nyein Chan, Taiichi Kitano, Tadaharu Kobayashi, Takeyasu Maeda, Jun-Ichi Tanuma

    Oncology letters   23 ( 3 )   76 - 76   2022.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    Most oral squamous cell carcinomas (OSCCs) arise from a premalignant lesion, oral epithelial dysplasia; however, useful markers for the early detection of OSCC are lacking. The present study aimed to establish a novel experimental model to observe changes in the sequential expression patterns of mRNAs and proteins in a rat model of tongue cancer using liquid-based cytology techniques. Cytology specimens were collected at 2, 5, 8, 11, 14, 17 and 21 weeks from rats treated with 4-nitroquinoline 1-oxide to induce tongue cancer. The expression of candidate biomarkers was examined by performing immunocytochemistry and reverse transcription-quantitative PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats developed OSCC of the tongue at 21 weeks. The mRNA expression levels of bromodomain protein 4 (Brd4), c-Myc and Tp53 were upregulated during the progression from negative for intraepithelial lesion or malignancy to squamous cell carcinoma (SCC). Brd4- and c-Myc-LI increased in low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion and SCC specimens. p53-LI was significantly increased in SCC specimens. This novel experimental model allowed the observation of sequential morphological changes and the expression patterns of mRNAs and proteins during carcinogenesis. Combining immunocytochemistry with cytology-based diagnoses may potentially improve the diagnostic accuracy of OSCC.

    DOI： 10.3892/ol.2022.13196

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  • コレステロールは口腔扁平上皮癌細胞の極性を制御し遊走を促進する(Cholesterol assists migration of oral squamous cell carcinoma by regulating front-rear cell polarity)

    チャン・ニェインニェイン, 山崎 学, 丸山 智, 阿部 達也, 河原田 壮史, 小林 正治, 田沼 順一

    日本病理学会会誌   111 ( 1 )   278 - 278   2022.3

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    Language：English   Publisher：(一社)日本病理学会  

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  • Metastasis of pulmonary adenocarcinoma to the oral cavity: A case report and literatures review of the last 30 years

    Masami Kawaharada, Satoshi Maruyama, Tatsuya Abé, Takafumi Hayashi, Tadaharu Kobayashi, Jun‐ichi Tanuma

    Oral Science International   2022.1

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/osi2.1130

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1130

  • 広範な口腔潰瘍を契機に診断に至った多発血管炎性肉芽腫症の1例

    須田 大亮, 竹内 玄太郎, 丸山 智, 小林 正治, 加納 浩之

    日本口腔外科学会雑誌   68 ( 1 )   8 - 14   2022.1

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    Language：Japanese   Publisher：(公社)日本口腔外科学会  

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  • 広範な口腔潰瘍を契機に診断に至った多発血管炎性肉芽腫症の1例

    須田 大亮, 竹内 玄太郎, 丸山 智, 小林 正治, 加納 浩之

    日本口腔外科学会雑誌   68 ( 1 )   8 - 14   2022.1

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    Language：Japanese   Publisher：(公社)日本口腔外科学会  

    症例は64歳男性。右側下顎大臼歯が自然脱落し脱落部の潰瘍が増大したため、精査加療目的で当院を紹介受診した。右側頬粘膜、歯槽堤粘膜、口底、舌に及ぶ40×30mm大の比較的境界明瞭な潰瘍と右下4～7番相当部の歯槽堤に骨露出を認めた。造影CTでは潰瘍に一致して表層から3～4mmの深さで均一な造影所見を認めた。右側下顎歯肉癌疑いで2度の生検を行い、病理組織学的に肉芽腫性血管炎と診断された。血管炎症候群の診療指針より、多発血管炎性肉芽腫症(GPA)が疑われ、腎臓内科で全身検索するも口腔潰瘍以外に壊死性病変は認められず、限局型GPAと確定診断された。プレドニゾロン40mg/日の高用量ステロイド療法を開始し、治療開始より45日後に退院した。退院後、潰瘍が及んでいた部位の瘢痕拘縮が強くなり、口唇閉鎖不全と舌の運動障害を呈し、口腔前庭形成術ならびに口唇形成術を施行した。潰瘍治癒後3年現在、GPAの再発はみられない。

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    Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01073&link_issn=&doc_id=20220131380002&doc_link_id=10.5794%2Fjjoms.68.8&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.68.8&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Melanotic neuroectodermal tumor of infancy in the mandible: A case report. International journal

    Ryoko Takeuchi, Akinori Funayama, Yohei Oda, Tatsuya Abé, Manabu Yamazaki, Satoshi Maruyama, Takafumi Hayashi, Jun-Ichi Tanuma, Tadaharu Kobayashi

    Medicine   100 ( 50 )   e28001   2021.12

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    RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

    DOI： 10.1097/MD.0000000000028001

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  • Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-β/SOX9 axis in cancer progression

    Kenta Haga, Manabu Yamazaki, Satoshi Maruyama, Masami Kawaharada, Ayako Suzuki, Emi Hoshikawa, Nyein Nyein Chan, Akinori Funayama, Toshihiko Mikami, Tadaharu Kobayashi, Kenji Izumi, Jun-ichi Tanuma

    Translational Oncology   14 ( 12 )   101236 - 101236   2021.12

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    DOI： 10.1016/j.tranon.2021.101236

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  • 口腔領域に発症したOI-LPD4例の臨床病理学的検討と最近15年間の文献的考察

    河原田 壮史, 丸山 智, 山崎 学, 阿部 達也, 黒川 亮, 片桐 渉, 林 孝文, 高木 律男, 小林 正治, 田沼 順一

    新潟歯学会雑誌   51 ( 2 )   114 - 115   2021.12

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  • 口腔がん早期診断用マーカーの同定に向けた新規発がんモデルの作製

    河原田 壮史, 山崎 学, 丸山 智, 阿部 達也, 北野 太一, Chan Nyein Nyein, 小林 正治, 田沼 順一

    新潟歯学会雑誌   51 ( 2 )   124 - 124   2021.12

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  • Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report. International journal

    Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Yoshimasa Sumita, Yuji Katsumi, Yutaka Nikkuni, Takafumi Hayashi, Jun-Ichi Tanuma

    Journal of medical case reports   15 ( 1 )   438 - 438   2021.8

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    BACKGROUND: Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. CASE PRESENTATION: A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. CONCLUSION: The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

    DOI： 10.1186/s13256-021-03066-z

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  • Central mucoepidermoid carcinoma arising directly from a glandular odontogenic cyst of the mandible: a case report. Reviewed International journal

    Satoshi Maruyama, Taisuke Mori, Manabu Yamazaki, Tatsuya Abé, Eijitsu Ryo, Hiroyuki Kano, Go Hasegawa, Jun-Ichi Tanuma

    Diagnostic pathology   16 ( 1 )   61 - 61   2021.7

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    BACKGROUND: Central mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor that affects the jawbone. Glandular odontogenic cyst (GOC) is also a rare odontogenic developmental cyst with glandular differentiation. GOC shares some histological features with central MEC, and a pre-existing GOC can develop into central MEC. Here, we present a rare case of central MEC developed directly from a pre-existing GOC of the mandible. CASE PRESENTATION: A 67-year-old Japanese man presented with a cystic lesion in the right third molar region. Histologically, the biopsy specimen demonstrated both typical findings of a GOC component lined with non-keratinized squamous epithelium and a recognizable component of central MEC consisting of polycystic nests with mucous cells, intermediate cells, and epidermoid cells in the cyst wall. The results from the immunohistochemistry for cytokeratin (CK) profiling demonstrated that, while both central MEC and GOC expressed CKs 7, 14, 18, and 19, CK13 was interestingly exclusively expressed in GOC. Fluorescence in-situ hybridization (FISH) revealed the rearrangement of the Mastermind like (MAML)-2 gene in both the MEC and GOC components. CONCLUSIONS: Our case suggests that central MEC and GOC may be in the same spectrum of diseases caused by the rearrangement of the MAML-2 gene. However, given that the expression profile of CK13 was completely different between central MEC and GOC, they can be considered as separate tumors. Overall, we demonstrated a rare case in which central MEC may have originated directly from the GOC.

    DOI： 10.1186/s13000-021-01124-0

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  • 口腔領域に発症したOI-LPDの臨床病理学的解析

    河原田 壮史, 丸山 智, 山崎 学, 阿部 達也, 黒川 亮, 片桐 渉, 林 孝文, 高木 律男, 小林 正治, 田沼 順一

    日本口腔科学会雑誌   70 ( 2 )   147 - 147   2021.7

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  • Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in the oral cavity: a clinicopathologic study of 4 cases and literature review. International journal

    Masami Kawaharada, Satoshi Maruyama, Tatsuya Abé, Manabu Yamazaki, Akira Kurokawa, Wataru Katagiri, Ritsuo Takagi, Takafumi Hayashi, Tadaharu Kobayashi, Jun-Ichi Tanuma

    Oral surgery, oral medicine, oral pathology and oral radiology   132 ( 6 )   687 - 697   2021.6

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    OBJECTIVES: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OI-LPD) have been reported as one of the adverse effects of immunosuppressive therapy. The aim of this study was to describe the clinicopathologic and immunohistochemical features of OI-LPD in the oral cavity. STUDY DESIGN: Immunohistochemistry was performed to describe the immunohistochemical features in our 4 cases. The results were analyzed along with 62 cases of oral OI-LPD in the English and Japanese literature to define clinical and pathologic characteristic features. RESULTS: In our immunohistochemical analysis, Epstein-Barr virus (EBV)-positive OI-LPD showed a higher percentage of mouse double minute 2-positive cells than EBV-negative samples. A literature survey revealed that OI-LPD (including the present cases) arises primarily in the gingiva, followed by the tongue, and usually occurs with a male-to-female ratio of 1:1.9. The rate of EBV positivity was 93.8%. Further, 31 of 66 patients had osteonecrosis of the jaw and 24 of 31 patients had taken multiple immunosuppressive drugs in combination. CONCLUSIONS: We can therefore conclude that the overexpression of mouse double minute 2 in OI-LPD is associated with EBV infection, and the combination of multiple immunosuppressive drugs may be a risk factor for osteonecrosis of the jaw.

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  • A comparative study between CT, MRI, and intraoral US for the evaluation of the depth of invasion in early stage (T1/T2) tongue squamous cell carcinoma

    Masaki Takamura, Taichi Kobayashi, Yutaka Nikkuni, Kouji Katsura, Manabu Yamazaki, Satoshi Maruyama, Jun-ichi Tanuma, Takafumi Hayashi

    Oral Radiology   38 ( 1 )   114 - 125   2021.5

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    <title>Abstract</title><sec>
    <title>Objectives</title>
    This study aimed to clarify the accuracy of intraoral ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) in preoperative image depth of invasion (DOI) measurement of T1/T2 tongue cancer through comparison with histopathological measurements.


    </sec><sec>
    <title>Methods</title>
    Imaging of the primary lesions was performed at our hospital; the lesions were classified into T1 and T2 based on the 8th edition of the AJCC/UICC, and surgery performed. There was histopathological confirmation of lesions as squamous cell carcinoma in 48 patients with tongue cancer. T3 and T4 cases, cases in which preoperative chemotherapy and radiation therapy were performed, and cases where biopsy was performed before imaging were excluded. The radiological DOI in US, CT, and MRI and the histopathological DOI as base were comparatively investigated and statistical analyses were performed by Bland–Altman analysis and Spearman's rank correlation coefficient.


    </sec><sec>
    <title>Results</title>
    Bland–Altman analysis showed that the US radiological DOI was overestimated by an average of 0.2 mm compared to the histopathological DOI, while CT and MRI radiological DOI were overestimated by an average of 2–3 mm. The comparison of CT and MRI revealed that the difference between the MRI and histopathological DOI, as well as the 95% limit of agreement, were smaller than those of the CT radiological DOI.


    </sec><sec>
    <title>Conclusions</title>
    US is the most accurate preoperative diagnostic tool for T1 and T2 squamous cell carcinoma; CT and MRI tend to have an overestimation of about 2–3 mm and so caution is required.


    </sec>

    DOI： 10.1007/s11282-021-00533-7

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    Other Link： https://link.springer.com/article/10.1007/s11282-021-00533-7/fulltext.html

  • Keratin 17-positive Civatte bodies in oral lichen planus—distribution variety, diagnostic significance and histopathogenesis

    Tatsuya Abé, Norio Kitagawa, Shohei Yoshimoto, Satoshi Maruyama, Manabu Yamazaki, Tetsuichiro Inai, Shuichi Hashimoto, Takashi Saku

    Scientific Reports   10 ( 1 )   2020.12

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1038/s41598-020-71496-8

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    Other Link： http://www.nature.com/articles/s41598-020-71496-8

  • 下顎埋伏智歯に関連した原発性骨内癌の1例

    小林 亮太, 高木 律男, 新國 農, 丸山 智, 山崎 学, 上野山 敦士, 田沼 順一, 林 孝文, 児玉 泰光

    日本口腔腫瘍学会誌   32 ( 4 )   243 - 250   2020.12

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  • 早期舌癌の術前DOI計測におけるCT、MRI、口腔内USの比較

    高村 真貴, 小林 太一, 新國 農, 勝良 剛詞, 山崎 学, 丸山 智, 田沼 順一, 林 孝文

    新潟歯学会雑誌   50 ( 2 )   107 - 107   2020.12

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  • 癌関連線維芽細胞と口腔扁平上皮癌細胞の相互作用におけるTGF-β/SOX9経路の役割

    羽賀 健太, 山崎 学, 丸山 智, 船山 昭典, 小林 正治, 田沼 順一

    Journal of Oral Biosciences Supplement   2020   329 - 329   2020.9

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  • Kissing molars Class IIIの2例

    内藤 絵里子, 池田 順行, 勝見 祐二, 小山 貴寛, 高木 律男, 西山 秀昌, 林 孝文, 丸山 智, 山崎 学, 田沼 順一

    日本口腔科学会雑誌   69 ( 2 )   115 - 115   2020.7

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  • Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: A possible driving force for tumor progression. Reviewed International journal

    Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Masayuki Tsuneki, Hiroko Kato, Kenji Izumi, Jun-Ichi Tanuma, Jun Cheng, Takashi Saku

    Experimental cell research   112013 - 112013   2020.4

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    Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.

    DOI： 10.1016/j.yexcr.2020.112013

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  • がん細胞による死細胞貪食は細胞遊走とDKK1発現を促進する

    山崎 学, 丸山 智, 阿部 達也, 朔 敬, 田沼 順一

    日本病理学会会誌   109 ( 1 )   396 - 396   2020.3

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  • 舌上皮性異形成および上皮内癌と診断された病変の診断および治療の検討 Reviewed

    新美 奏恵, 船山 昭典, 丸山 智, 勝良 剛詞, 新國 農, 田沼 順一, 林 孝文, 小林 正治

    日本口腔診断学会雑誌   33 ( 1 )   126 - 126   2020.2

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  • 下顎骨内に発生した類皮嚢胞の1例 Reviewed

    笠原 映, 山崎 学, 丸山 智, 勝良 剛詞, 黒川 亮, 河原田 壮史, 林 孝文, 高木 律男, 田沼 順一

    日本口腔診断学会雑誌   33 ( 1 )   139 - 139   2020.2

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  • 舌腫瘍 Reviewed

    河原田 壮史, 丸山 智, 笠原 映, 山崎 学, 林 孝文, 片桐 渉, 小林 正治, 田沼 順一

    日本口腔診断学会雑誌   33 ( 1 )   81 - 81   2020.2

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  • Low-grade myofibroblastic sarcoma of the tongue with difficulty of diagnosis: A case report and review of the literature Reviewed

    Masami Kawaharada, Wataru Katagiri, Satoshi Maruyama, Hideyoshi Nishiyama, Takafumi Hayashi, Tadaharu Kobayashi, Jun ichi Tanuma

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   33 ( 1 )   93 - 97   2020

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    DOI： 10.1016/j.ajoms.2020.07.011

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  • 舌腫瘍 Reviewed

    河原田 壮史, 丸山 智, 笠原 映, 山崎 学, 林 孝文, 片桐 渉, 小林 正治, 田沼 順一

    日本口腔内科学会雑誌   25 ( 2 )   71 - 71   2019.12

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  • PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment. Reviewed International journal

    Ken Saito, Hidekazu Iioka, Satoshi Maruyama, I Wayan Sumardika, Masakiyo Sakaguchi, Eisaku Kondo

    Neoplasia (New York, N.Y.)   21 ( 12 )   1121 - 1132   2019.12

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    Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attention, as their expression was reported to correlate with poor prognosis for patients with diverse origins including PDAC; however, previous studies reported independently on their respective biological significance. Here we demonstrate that PODXL1 is essential for metastasis of PDAC cells through its specific interaction with C5aR. In vitro assay demonstrated that PODXL1 bound to C5aR, which stabilized C5aR protein and recruited it to cancer cell plasma membranes to receive C5a, an inflammatory chemoattractant factor. PODXL1 knockout in PDAC cells abrogated their metastatic property in vivo, emulating the liver metastatic mouse model treated with anti-C5a neutralizing antibody. In molecular studies, PODXL1 triggered EMT on PDAC cells in response to stimulation by C5a, corroborating PODXL1 involvement in PDAC cellular invasive properties via specific interaction with the C5aR/C5a axis. Confirming the molecular assays, histological examination showed coexpression of PODXL1 and C5aR at the invasive front of primary cancer nests as well as in liver metastatic foci of PDAC both in the mouse metastasis model and patient tissues. Hence, the novel direct interaction between PODXL1 and the C5aR/C5a axis may provide a better integrated understanding of PDAC biological characteristics including its tumor microenvironment factors.

    DOI： 10.1016/j.neo.2019.09.003

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  • 舌上皮性異形成および上皮内癌と診断された病変の診断および治療の検討

    新美 奏恵, 船山 昭典, 丸山 智, 勝良 剛詞, 新國 農, 田沼 順一, 林 孝文, 小林 正治

    日本口腔内科学会雑誌   25 ( 2 )   116 - 116   2019.12

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  • がん関連線維芽細胞は口腔扁平上皮癌においてSOX9発現を増強させ浸潤を促進する

    羽賀 健太, 山崎 学, 丸山 智, 鈴木 絢子, 干川 絵美, 船山 昭典, 三上 俊彦, 小林 正治, 泉 健次, 田沼 順一

    新潟歯学会雑誌   49 ( 2 )   86 - 86   2019.12

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  • 下顎第一大臼歯にみられたsubmerged toothの1例 対合歯である上顎第一大臼歯は低位を呈した1例

    鶴巻 浩, 渡部 桃子, 結城 龍太郎, 隅田 賢正, 山崎 学, 丸山 智

    新潟歯学会雑誌   49 ( 2 )   55 - 60   2019.12

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  • Masseter muscle hypertrophy: A case report

    Masayuki Tsuneki, Satoshi Maruyama, Manabu Yamazaki, Kanae Niimi, Tadaharu Kobayashi, Hideyoshi Nishiyama, Takafumi Hayshi, Jun ichi Tanuma

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   31 ( 6 )   428 - 431   2019.11

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    DOI： 10.1016/j.ajoms.2019.08.005

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  • 癌関連線維芽細胞はSOX9を高発現させ口腔癌細胞の遊走および浸潤を促進する(Cancer-associated fibroblasts promote the migration and invasion of oral cancer cells via enhancing SOX9 expression)

    羽賀 健太, 山崎 学, 丸山 智, 小林 正治, 田沼 順一

    日本癌学会総会記事   78回   P - 1258   2019.9

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  • Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma. Reviewed International journal

    Yoshimasa Sumita, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Jun Cheng, Ritsuo Takagi, Jun-Ichi Tanuma

    Oncology reports   40 ( 5 )   2487 - 2496   2018.11

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    Transcription factor SRY‑box 9 (SOX9) is a key regulator of chondrocyte differentiation and sex determination, and it is also involved in the progression of various types of human cancer. However, its putative association with oral squamous cell carcinoma (OSCC) remains elusive. The aim of the present study was to investigate the expression profiles of SOX9 in various oral epithelial lesions, including OSCC. We performed immunohistochemical analysis of SOX9 expression in surgical specimens of OSCC, which simultaneously exhibited different grades of epithelial lesions, and analyzed the correlation between SOX9 expression and several clinicopathological factors. Moreover, we performed immunofluorescent staining, western blot analysis and real‑time reverse transcription‑polymerase chain reaction to assess SOX9 expression in OSCC HSC‑3 (a metastatic cell line) and HSC‑4 (a non‑metastatic cell line) cell lines. In surgical specimens, SOX9 expression was detected in the nuclei of proliferating cells in areas with epithelial dysplasia and carcinoma in situ, but not in areas with normal epithelia. Nuclear SOX9 expression was observed in most SCC cells. Notably, cytoplasmic SOX9 expression was confirmed only in some SCC cells; however, cytoplasmic SOX9 expression was significantly and positively correlated with poor clinical outcomes. Both protein and mRNA expression of SOX9 were significantly higher in the HSC‑3 cell line than that in the HSC‑4 line. Notably, however, only HSC‑3 cells exhibited cytoplasmic localization of SOX9 expression. Our findings indicate that SOX9 may be involved in the tumorigenesis and progression of OSCC. Furthermore, its cytoplasmic expression represents a potential predictive biomarker for tumor aggressiveness and OSCC prognosis.

    DOI： 10.3892/or.2018.6665

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  • Identification of TRA-1-60-positive cells as a potent refractory population in follicular lymphomas. Reviewed

    Takata K, Saito K, Maruyama S, Miyata-Takata T, Iioka H, Okuda S, Ling Y, Karube K, Miki Y, Maeda Y, Yoshino T, Steidl C, Kondo E

    Cancer science   110 ( 1 )   443 - 457   2018.11

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  • An unusual and difficult diagnosis of synovial chondromatosis: A case report. Reviewed

    Toshihiko Mikami, Yusuke Kato, Taku Kojima, Tatsuya Abe, Satoshi Maruyama, Hideyoshi Nishiyama, Takafumi Hayashi, Tadaharu Kobayashi

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   30 ( 5 )   422 - 427   2018.9

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  • 骨粗鬆症治療薬を中心とした薬剤関連顎骨壊死：病理診断の要点とその発生機序 Reviewed

    丸山 智, 塚田真弓, 朔 敬

    病理と臨床   36 ( S )   134 - 138   2018.4

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  • Oral and maxillofacial manifestations of methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis: Report of a case Reviewed

    Kanae Niimi, Susumu Shingaki, Akinori Funayama, Toshihiko Mikami, Hideyoshi Nishiyama, Takafumi Hayashi, Manabu Yamazaki, Satoshi Maruyama, Takashi Saku, Takashi Saku, Tadaharu Kobayashi

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   31 ( 2 )   86 - 93   2018.1

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    DOI： 10.1016/j.ajoms.2018.07.010

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  • Stromal mesenchymal stem cells facilitate pancreatic cancer progression by regulating specific secretory molecules through mutual cellular interaction. Reviewed International journal

    Ken Saito, Masakiyo Sakaguchi, Satoshi Maruyama, Hidekazu Iioka, Endy Widya Putranto, I Wayan Sumardika, Nahoko Tomonobu, Takashi Kawasaki, Keiichi Homma, Eisaku Kondo

    Journal of Cancer   9 ( 16 )   2916 - 2929   2018

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    Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most intractable malignancies with a typical scirrhous pattern in histology. Due to its abundant tumor stroma and scant vascularization, chemotherapeutic agents are considered inefficiently permeable to cancer nests, making it highly difficult to cure the patients with PDAC. However, PDAC is also considered to owe its intractability to other critical factors such as cellular interaction between tumor cells and tumor microenvironment as well as architectural barriers, which increases in therapeutic resistance. Here, we report a specific cellular interaction between PDAC cells and mesenchymal stem cells (MSCs) intermingled in PDAC stroma, which facilitates cancer invasion. Secretory phenotype profiling revealed that production of Amphiregulin (AREG) and MMP-3 were specifically upregulated under the coexistence of BxPC3 cells with human MSCs (approximately four to ten folds in AREG, and twenty to sixty-folds in MMP-3 compared to that of BxPC3 cells alone), whereas MMP-9 expression was decreased (less than one-tenth comparing with that of BxPC3 cells alone). Blockage of AREG production by its specific siRNA removed MSC-mediated driving force of BxPC3 invasiveness. Immunohistochemical analysis of tissue samples obtained both from PDAC patients and PDAC imitating mouse xenografted models revealed that significant coexpression of AREG and its receptor EGFR were detected on the cancer cells at invasive front. These results strongly suggested that cellular interaction between cancer cells and MSCs in the PDAC stroma might be critical to cancer progression, especially in the process of local invasion and the early stage development of metastasis.

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  • Clinical significance of intraoral strain elastography for diagnosing early stage tongue carcinoma: a preliminary study Reviewed

    Motoki Shingaki, Yutaka Nikkuni, Kouji Katsura, Nobuyuki Ikeda, Satoshi Maruyama, Ritsuo Takagi, Takafumi Hayashi

    ORAL RADIOLOGY   33 ( 3 )   204 - 211   2017.9

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  • A case of small cell carcinoma arising in the palatine gland Reviewed

    小島 拓, 三上俊彦, 林 孝文, 丸山 智, 山崎 学, 小林正治

    日口腔外会誌   63 ( 7 )   358 - 363   2017.7

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    <p>Small cell carcinoma (SmCC) arising in salivary gland is extremely rare, and most of the primary lesions occur in the parotid glands. We report a case of SmCC arising in the palatine gland in a 64-year-old man. The patient had an ulcerated tumor, measuring 35 × 20 mm, in the left side of the palate. A number of enlarged lymph nodes were recognized in the left cervical region. No distant metastases or other tumors were detected on <sup>18</sup>F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A biopsy was performed from the palatal lesion, and the histopathological diagnosis was SmCC. The patient received radiotherapy alone, because chemotherapy had an increased risk of severe adverse events due to the presence of chronic kidney failure. Radiotherapy was administered to the left palatal and cervical regions in a total dose of 60 Gy. The tumor and the metastatic lymph nodes markedly shrank after the radiotherapy. However, 3 months later, metastatic cervical lymph nodes appeared in the right cervical region. Bony metastases to the right ilium and the left pubis were also detected on FDG-PET/CT. Additional radiotherapy was administered (60 Gy to the right cervical lymph nodes and 40 Gy to the metastatic bone lesions), but was not effective. Regrowth of the primary tumor and bilateral metastatic cervical lymph nodes appeared, and skin, lung, and liver metastases were identified. Finally, the patient died of multiple organ failure 12 months after the initial diagnosis.</p>

    DOI： 10.5794/jjoms.63.358

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  • Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia Reviewed

    Tatsuya Abe, Satoshi Maruyama, Manabu Yamazaki, Bo Xu, Hamzah Babkair, Yoshimasa Sumita, Jun Cheng, Tadashi Yamamoto, Takashi Saku

    EXPERIMENTAL AND MOLECULAR PATHOLOGY   102 ( 2 )   327 - 336   2017.4

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  • Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma Reviewed

    Hamzah Babkair, Manabu Yamazaki, Md. Shihab Uddin, Satoshi Maruyama, Tatsuya Abe, Ahmed Essa, Yoshimasa Sumita, Md. Shahidul Ahsan, Wael Swelam, Jun Cheng, Takashi Saku

    HUMAN PATHOLOGY   57   51 - 60   2016.11

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  • Tumour-associated macrophages are recruited and differentiated in the neoplastic stroma of oral squamous cell carcinoma Reviewed

    Ahmed Abdelaziz Mohamed Essa, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abe, Hamzah Babkair, Adel Mohamed Raghib, Eman Money El-Din Megahed, Jun Cheng, Takashi Sakui

    PATHOLOGY   48 ( 3 )   219 - 227   2016.4

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  • Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa Reviewed

    Mayumi Hasegawa, Jun Cheng, Satoshi Maruyama, Manabu Yamazaki, Tatsuya Abe, Hamzah Babkair, Chikara Saito, Takashi Saku

    PATHOLOGY RESEARCH AND PRACTICE   212 ( 5 )   426 - 436   2016

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  • Simultaneous immunolocalization of desmoglein 3 and IgG4 in oral pemphigus vulgaris: IgG4 predominant autoantibodies in its pathogenesis Reviewed

    Tatsuya Abe, Satoshi Maruyama, Hamzah Babkair, Manabu Yamazaki, Jun Cheng, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   44 ( 10 )   850 - 856   2015.11

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  • Paradental cyst is an inclusion cyst of the junctional/sulcular epithelium of the gingiva: histopathologic and immunohistochemical confirmation for its pathogenesis Reviewed

    Satoshi Maruyama, Manabu Yamazaki, Tatsuya Abe, Hamzah Babkair, Jun Cheng, Takashi Saku

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY   120 ( 2 )   227 - 237   2015.8

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  • 歯周炎罹患歯肉組織におけるNeprilysin(Alzheimer病関連遺伝子)の発現

    根津 新, 久保田 健彦, 丸山 智, 水田 昌毅, 堀水 慎, 濃野 要, 保苅 崇大, 両角 俊哉, 朔 敬, 吉江 弘正

    日本歯周病学会会誌   57 ( 秋季特別 )   131 - 131   2015.8

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  • Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells Reviewed

    Kamal Al-Eryani, Jun Cheng, Tatsuya Abe, Satoshi Maruyama, Manabu Yamazaki, Hamzah Babkair, Ahmed Essa, Takashi Saku

    HUMAN PATHOLOGY   46 ( 7 )   991 - 999   2015.7

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  • Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration Reviewed

    Toshihiko Mikami, Satoshi Maruyama, Tatsuya Abe, Takanori Kobayashi, Manabu Yamazaki, Akinori Funayama, Susumu Shingaki, Tadaharu Kobayashi, Cheng Jun, Takashi Saku

    VIRCHOWS ARCHIV   466 ( 5 )   559 - 569   2015.5

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  • Keratin pearl degradation in oral squamous cell carcinoma: reciprocal roles of neutrophils and macrophages Reviewed

    Ahmed A. M. Essa, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abe, Hamzah Babkair, Jun Cheng, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   43 ( 10 )   778 - 784   2014.11

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  • MFG-E8 expression for progression of oral squamous cell carcinoma and for self-clearance of apoptotic cells Reviewed

    Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abe, Ahmed Essa, Hamzah Babkair, Jun Cheng, Takashi Saku

    LABORATORY INVESTIGATION   94 ( 11 )   1260 - 1272   2014.11

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  • Perlecan-enriched intercellular space of junctional epithelium provides primary infrastructure for leukocyte migration through squamous epithelial cells Reviewed

    Satoshi Maruyama, Manami Itagaki, Hiroko Ida-Yonemochi, Takehiko Kubota, Manabu Yamazaki, Tatsuya Abe, Hiromasa Yoshie, Jun Cheng, Takashi Saku

    HISTOCHEMISTRY AND CELL BIOLOGY   142 ( 3 )   297 - 305   2014.9

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  • Three-dimensional visualization of perlecan-rich neoplastic stroma induced concurrently with the invasion of oral squamous cell carcinoma Reviewed

    Satoshi Maruyama, Yoshihito Shimazu, Tomoo Kudo, Kaori Sato, Manabu Yamazaki, Tatsuya Abe, Hamzah Babkair, Jun Cheng, Takaaki Aoba, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   43 ( 8 )   627 - 636   2014.9

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  • 口腔扁平上皮癌とその境界病変における術中迅速病理診断の意義 局所再発に関する臨床病理学的検討

    御代田 駿, 小林 孝憲, 宮島 久, 永田 昌毅, 星名 秀行, 小林 正治, 高木 律男, 丸山 智, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   447 - 447   2014.9

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  • Hybrid ameloblastoma and adenomatoid odontogenic tumor: report of a case and review of hybrid variations in the literature Reviewed

    Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abe, Hamzah Babkair, Hajime Fujita, Ritsuo Takagi, Jun-ichi Koyama, Takafumi Hayashi, Jun Cheng, Takashi Saku

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY   118 ( 1 )   E12 - E18   2014.7

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    DOI： 10.1016/j.oooo.2013.08.032

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  • 口腔扁平上皮癌とその境界病変における術中迅速病理診断の意義 再発に関する臨床病理学的検討

    御代田 駿, 小林 孝憲, 宮島 久, 小林 正治, 高木 律男, 丸山 智, 朔 敬

    新潟医学会雑誌   128 ( 3 )   143 - 143   2014.3

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  • 悪性腫瘍 口腔粘膜扁平上皮癌および悪性境界病変の再発に関する臨床病理学的検討

    御代田 駿, 小林 孝憲, 宮島 久, 星名 秀行, 小林 正治, 高木 律男, 丸山 智, 朔 敬

    日本口腔診断学会雑誌   27 ( 1 )   122 - 122   2014.2

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  • Intramuscular keratocyst as a soft tissue counterpart of keratocystic odontogenic tumor: differential diagnosis by immunohistochemistry Reviewed

    Tatsuya Abe, Satoshi Maruyama, Manabu Yamazaki, Ahmed Essa, Hamzah Babkair, Toshihiko Mikami, Susumu Shingaki, Tadaharu Kobayashi, Takafumi Hayashi, Jun Cheng, Takashi Saku

    HUMAN PATHOLOGY   45 ( 1 )   110 - 118   2014.1

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  • Radiation-induced undifferentiated high-grade pleomorphic sarcoma (malignant fibrous histiocytoma) of the mandible: Report of a case arising in the background of long-standing osteomyelitis with a review of the literature Reviewed

    Takahiro Koyama, Takanori Kobayashi, Satoshi Maruyama, Tatsuya Abe, Wael Mohamed Swelam, Yasumitu Kodama, Hideyuki Hoshina, Ritsuo Takagi, Takafumi Hayashi, Takashi Saku

    PATHOLOGY RESEARCH AND PRACTICE   210 ( 12 )   1123 - 1129   2014

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    御代田 駿, 小林 孝憲, 宮島 久, 星名 秀行, 小林 正治, 高木 律男, 丸山 智, 朔 敬

    日本口腔内科学会雑誌   19 ( 2 )   121 - 121   2013.12

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  • Hemophagocytosis-mediated keratinization in oral carcinoma in situ and squamous cell carcinoma: A possible histopathogenesis of keratin pearls Reviewed

    Kamal Al-Eryani, Jun Cheng, Tatsuya Abe, Manabu Yamazaki, Satoshi Maruyama, Masayuki Tsuneki, Ahmed Essa, Hamzah Babkair, Takashi Saku

    JOURNAL OF CELLULAR PHYSIOLOGY   228 ( 10 )   1977 - 1988   2013.10

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  • Identification of the actinomycete 16S ribosomal RNA gene by polymerase chain reaction in oral inflammatory lesions Reviewed

    Kayo Kuyama, Kenji Fukui, Eriko Ochiai, Satoshi Maruyama, Kimiharu Iwadate, Takashi Saku, Hirotsugu Yamamoto

    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology   116 ( 4 )   485 - 491   2013.10

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  • Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma Reviewed

    Masayuki Tsuneki, Manabu Yamazaki, Satoshi Maruyama, Jun Cheng, Takashi Saku

    LABORATORY INVESTIGATION   93 ( 8 )   921 - 932   2013.8

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  • Gene and protein localisation of tumour necrosis factor (TNF)-alpha converting enzyme in gingival tissues from periodontitis patients with drug-induced gingival overgrowth Reviewed

    Takayuki Tomita, Takehiko Kubota, Naohiro Nakasone, Toshiya Morozumi, Daisuke Abe, Satoshi Maruyama, Taro Shimizu, Makoto Horirilizu, Takashi Saku, Hiromasa Yoshie

    ARCHIVES OF ORAL BIOLOGY   58 ( 8 )   1014 - 1020   2013.8

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  • Central neurofibroma of the mandible: Report of a case and review of the literature Reviewed

    Hamdy Metwaly, Jun Cheng, Satoshi Maruyama, Manabu Yamazaki, Ahmed Essa, Tatsuya Abé, Hamzah Babkair, Hideyuki Hoshina, Ritsuo Takagi, Takafumi Hayashi, Takashi Saku

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   25 ( 3 )   294 - 298   2013.7

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    DOI： 10.1016/j.ajoms.2012.12.002

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  • Extracellular heat shock protein A9 is a novel interaction partner of podoplanin in oral squamous cell carcinoma cells Reviewed

    Masayuki Tsuneki, Satoshi Maruyama, Manabu Yamazaki, Bo Xu, Ahmed Essa, Tatsuya Abé, Hamzah Babkair, Jun Cheng, Tadashi Yamamoto, Takashi Saku

    Biochemical and Biophysical Research Communications   434 ( 1 )   124 - 130   2013.4

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  • Podoplanin is a novel myoepithelial cell marker in pleomorphic adenoma and other salivary gland tumors with myoepithelial differentiation Reviewed

    Masayuki Tsuneki, Satoshi Maruyama, Manabu Yamazaki, Ahmed Essa, Tatsuya Abe, Hamzah Ali Babkair, Md Shahidul Ahsan, Jun Cheng, Takashi Saku

    VIRCHOWS ARCHIV   462 ( 3 )   297 - 305   2013.3

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  • Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa Reviewed

    Takanori Kobayashi, Satoshi Maruyama, Tatsuya Abe, Jun Cheng, Ritsuo Takagi, Chikara Saito, Takashi Saku

    HISTOPATHOLOGY   61 ( 5 )   910 - 920   2012.11

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    DOI： 10.1111/j.1365-2559.2012.04283.x

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  • Parenchymal-stromal switching for extracellular matrix production on invasion of oral squamous cell carcinoma Reviewed

    Hamdy Metwaly, Satoshi Maruyama, Manabu Yamazaki, Masayuki Tsuneki, Tatsuya Abe, Kai Yu Jen, Jun Cheng, Takashi Saku

    HUMAN PATHOLOGY   43 ( 11 )   1973 - 1981   2012.11

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  • Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections Reviewed

    Hiroko Ida-Yonemochi, Satoshi Maruyama, Takanori Kobayashi, Manabu Yamazaki, Jun Cheng, Takashi Saku

    MODERN PATHOLOGY   25 ( 6 )   784 - 794   2012.6

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  • Short telomeres in an oral precancerous lesion: Q-FISH analysis of leukoplakia Reviewed

    Junko Aida, Takanori Kobayashi, Takashi Saku, Masatsune Yamaguchi, Naotaka Shimomura, Ken-Ichi Nakamura, Naoshi Ishikawa, Satoshi Maruyama, Jun Cheng, Steven S. S. Poon, Motoji Sawabe, Tomio Arai, Kaiyo Takubo

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   41 ( 5 )   372 - 378   2012.5

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    DOI： 10.1111/j.1600-0714.2011.01120.x

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  • Intraepithelially entrapped blood vessels in oral carcinoma in-situ Reviewed

    Akinori Funayama, Satoshi Maruyama, Manabu Yamazaki, Kamal Al-Eryani, Susumu Shingaki, Chikara Saito, Jun Cheng, Takashi Saku

    VIRCHOWS ARCHIV   460 ( 5 )   473 - 480   2012.5

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    DOI： 10.1007/s00428-012-1224-0

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  • Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study. Reviewed

    Tsuneki M, Maruyama S, Yamazaki M, Abe T, Adeola HA, Cheng J, Nishiyama H, Hayashi T, Kobayashi T, Takagi R, Funayama A, Saito C, Saku T

    Oral Diseases   19 ( 4 )   415 - 424   2012.5

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  • Podoplanin expression profiles characteristic of odontogenic tumor-specific tissue architectures Reviewed

    Masayuki Tsuneki, Satoshi Maruyama, Manabu Yamazaki, Jun Cheng, Takashi Saku

    PATHOLOGY RESEARCH AND PRACTICE   208 ( 3 )   140 - 146   2012

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  • Differential expression of perlecan receptors, alpha-dystroglycan and integrin beta 1, before and after invasion of oral squamous cell carcinoma Reviewed

    Md Shahidul Ahsan, Manabu Yamazaki, Satoshi Maruyama, Takanori Kobayashi, Hiroko Ida-Yonemochi, Mayumi Hasegawa, Adeola Henry Ademola, Jun Cheng, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   40 ( 7 )   552 - 559   2011.8

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  • Nuclear translocation of beta-catenin synchronized with loss of E-cadherin in oral epithelial dysplasia with a characteristic two-phase appearance Reviewed

    Carlos G. Alvarado, Satoshi Maruyama, Jun Cheng, Hiroko Ida-Yonemochi, Takanori Kobayashi, Manabu Yamazaki, Ritsuo Takagi, Takashi Saku

    HISTOPATHOLOGY   59 ( 2 )   283 - 291   2011.8

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    DOI： 10.1111/j.1365-2559.2011.03929.x

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  • Emergence of keratin 17 vs. loss of keratin 13: Their reciprocal immunohistochemical profiles in oral carcinoma in situ Reviewed

    Toshihiko Mikami, Jun Cheng, Satoshi Maruyama, Takanori Kobayashi, Akinori Funayama, Manabu Yamazaki, Henry A. Adeola, Lanyan Wu, Susumu Shingaki, Chikara Saito, Takashi Saku

    ORAL ONCOLOGY   47 ( 6 )   497 - 503   2011.6

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    DOI： 10.1016/j.oraloncology.2011.03.015

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  • Complication of adenoid cystic carcinoma and sialolithiasis in the submandibular gland: report of a case and its etiological background Reviewed

    M. Hasegawa, J. Cheng, S. Maruyama, M. Yamazaki, A. Iida, R. Takagi, R. Tanaka, T. Hayashi, C. Saito, T. Saku

    INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   40 ( 6 )   647 - 650   2011.6

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    DOI： 10.1016/j.ijom.2010.11.009

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  • Acetic Acid Treatment for Wrinkle-Free Oral Mucosal Epithelia in Paraffin Section Preparation Reviewed

    Md. Shahidul Ahsan, Satoshi Maruyama, Jun Cheng, Kamal Al-Eryani, Manabu Yamazaki, Mayumi Hasegawa, Masayuki Tsuneki, Takashi Saku

    MICROSCOPY RESEARCH AND TECHNIQUE   74 ( 3 )   264 - 268   2011.3

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  • A case of desmoplastic ameloblastoma arising in the maxillary alveolus: the origin and time-course changes in the early stage of tumour development observed on dental radiographs Reviewed

    K. Katsura, S. Maruyama, M. Suzuki, T. Saku, R. Takagi, T. Hayashi

    DENTOMAXILLOFACIAL RADIOLOGY   40 ( 2 )   126 - 129   2011.2

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    DOI： 10.1259/dmfr/55423624

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  • Oral cancer in Myanmar: a preliminary survey based on hospital-based cancer registries Reviewed

    Htun Naing Oo, Yi Yi Myint, Chan Nyein Maung, Phyu Sin Oo, Jun Cheng, Satoshi Maruyama, Manabu Yamazaki, Minoru Yagi, Faleh A. Sawair, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   40 ( 1 )   20 - 26   2011.1

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    DOI： 10.1111/j.1600-0714.2010.00938.x

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  • Enhanced Expression of Podoplanin in Oral Carcinomas in situ and Squamous Cell Carcinomas Reviewed

    Akinori Funayama, Jun Cheng, Satoshi Maruyama, Manabu Yamazaki, Takanori Kobayashi, Mei Syafriadi, Sukalyan Kundu, Susumu Shingaki, Chikara Saito, Takashi Saku

    PATHOBIOLOGY   78 ( 3 )   171 - 180   2011

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    DOI： 10.1159/000324926

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  • Tumor mimicking actiomycosis of the upper lip: report of two cases Reviewed

    Kayo Kuyama, Yan Sun, Kenji Fukui, Satoshi Maruyama, Eriko Ochiai, Masahiko Fukumoto, Nobuyuki Ikeda, Toshihiro Kondoh, Kimiharu Iwadate, Ritsuo Takagi, Takashi Saku, Hirotsugu Yamamoto

    Oral Med Pathol   15   95 - 99   2011

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    DOI： 10.3353/omp.15.95

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  • Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology Reviewed

    Masayuki Tsuneki, Manabu Yamazaki, Jun Cheng, Satoshi Maruyama, Takanori Kobayashi, Takashi Saku

    HISTOPATHOLOGY   57 ( 6 )   806 - 813   2010.12

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    DOI： 10.1111/j.1365-2559.2010.03712.x

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  • Histopathological varieties of oral carcinoma in situ: Diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia Reviewed

    Takanori Kobayashi, Satoshi Maruyama, Jun Cheng, Hiroko Ida-Yonemochi, Minoru Yagi, Ritsuo Takagi, Takashi Saku

    PATHOLOGY INTERNATIONAL   60 ( 3 )   156 - 166   2010.3

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    DOI： 10.1111/j.1440-1827.2009.02499.x

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  • Metastasis-associated genes in oral squamous cell carcinoma and salivary adenoid cystic carcinoma: a differential DNA chip analysis between metastatic and nonmetastatic cell systems Reviewed

    Satoshi Maruyama, Jun Cheng, Manabu Yamazaki, Xiao-jian Zhou, Zhi-yuan Zhang, Rong-gen He, Takashi Saku

    CANCER GENETICS AND CYTOGENETICS   196 ( 1 )   14 - 22   2010.1

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    DOI： 10.1016/j.cancergencyto.2009.08.002

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  • Oral solitary fibrous tumor: a cytogenetic analysis of tumor cells in culture with literature review Reviewed

    Wael M. Swelam, Jun Cheng, Hiroko Ida-Yonemochi, Satoshi Maruyama, Takashi Saku

    CANCER GENETICS AND CYTOGENETICS   194 ( 2 )   75 - 81   2009.10

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    DOI： 10.1016/j.cancergencyto.2009.05.003

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  • Establishment and characterization of pleomorphic adenoma cell systems: an in-vitro demonstration of carcinomas arising secondarily from adenomas in the salivary gland Reviewed

    Satoshi Maruyama, Jun Cheng, Susumu Shingaki, Takashi Tamura, Shuichi Asakawa, Shinsei Minoshima, Yoshiko Shimizu, Nobuyoshi Shimizu, Takashi Saku

    BMC CANCER   9   247   2009.7

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    DOI： 10.1186/1471-2407-9-247

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  • Lymphoepithelial cyst of the parotid gland: its possible histopathogenesis based on clinicopathologic analysis of 64 cases Reviewed

    Lanyan Wu, Jun Cheng, Satoshi Maruyama, Manabu Yamazaki, Masayuki Tsuneki, Yong Lu, Zhixiu He, Yage Zheng, Zhiyu Zhou, Takashi Saku

    HUMAN PATHOLOGY   40 ( 5 )   683 - 692   2009.5

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    DOI： 10.1016/j.humpath.2008.10.012

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  • Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas Reviewed

    Satoshi Maruyama, Jun Cheng, Manabu Yamazaki, Airu Liu, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   38 ( 4 )   377 - 385   2009.4

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    DOI： 10.1111/j.1600-0714.2008.00742.x

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  • Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ: An aid for histopathologic recognition of their cell proliferation centers Reviewed

    W. M. Tilakaratne, W. M. Tilakaratne, T. Kobayashi, H. Ida-Yonemochi, W. Swelam, M. Yamazaki, T. Mikami, C. G. Alvarado, A. Md Shahidul, S. Maruyama, J. Cheng, T. Saku, T. Saku

    J Oral Pathol Med   38   348 - 355   2009.4

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  • Adenoid cystic carcinoma of sublingual gland involving the submandibular duct Reviewed

    Saito M, Nishiyama H, Maruyama S, Oda Y, Saku T, Hayashi T

    Dentomaxillofac Radiol   37 ( 7 )   421 - 424   2008.10

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    DOI： 10.1259/dmfr/31299961

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  • Perlecan-rich epithelial linings as a background of proliferative potentials of keratocystic odontogenic tumor Reviewed

    Masayuki Tsuneki, Jun Cheng, Satoshi Maruyama, Hiroko Ida-Yonemochi, Motowo Nakajima, Takashi Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   37 ( 5 )   287 - 293   2008.5

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    DOI： 10.1111/j.1600-0714.2007.00620.x

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  • A case report of multiple-drug-induced gingival overgrowth with TIMP-3 over-expression Reviewed

    KUBOTA T

    Oral Med Pathol   12 ( 4 )   141 - 148   2008

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    DOI： 10.3353/omp.12.141

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  • High relative frequency of oral squamous cell carcinoma in Yemen: Qat and tobacco chewing as its aetiological background

    Faleh A. Sawair, Ammar Al-Mutwakel, Kamal Al-Eryani, Ameera Al-Surhy, Satoshi Maruyama, Jun Cheng, Ali Al-Sharabi, Takashi Saku

    INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH   17 ( 3 )   185 - 195   2007.6

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    DOI： 10.1080/09603120701254813

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  • Lymphatic involvement in the histopathogenesis of mucous retention cyst

    Sukalyan Kundu, Jun Cheng, Satoshi Maruyama, Makoto Suzuki, Hiroyuki Kawashima, Takashi Saku

    PATHOLOGY RESEARCH AND PRACTICE   203 ( 2 )   89 - 97   2007

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    DOI： 10.1016/j.prp.2006.11.003

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  • Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

    H Utsunomiya, WM Tilakaratne, K Oshiro, S Maruyama, M Suzuki, H Ida-Yonemochi, J Cheng, T Saku

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   34 ( 8 )   498 - 507   2005.9

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    DOI： 10.1111/j.1600-0714.2005.00339.x

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  • Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible

    H Metwaly, J Cheng, S Maruyama, K Ohshiro, Suzuki, I, Y Hoshina, T Saku

    PATHOLOGY INTERNATIONAL   55 ( 6 )   331 - 342   2005.6

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    DOI： 10.1111/j.1440-1827.2005.01833.x

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  • Vascular endothelial growth factor in salivary pleomorphic adenomas: one of the reasons for their poorly vascularized stroma

    W Swelam, H Ida-Yonemochi, S Maruyama, K Ohshiro, J Cheng, T Saku

    VIRCHOWS ARCHIV   446 ( 6 )   653 - 662   2005.6

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    DOI： 10.1007/s00428-005-1219-1

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  • Solitary fibrous tumor of the lower lip involving minor salivary gland components: Report of a case and review of the literature of salivary gland cases

    Wael Swelam, Hiroko Ida-Yonemochi, Satoshi Maruyama, Terué Ikarashi, Junichi Fukuda, Ritsuo Takagi, Takafumi Hayashi, Takashi Saku

    Oral Oncology Extra   40 ( 10 )   107 - 112   2004

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    DOI： 10.1016/j.ooe.2004.06.002

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  • Castleman's disease of the buccal mucosa: Report of a case and review of the literature of head and neck cases

    S Maruyama, N Hao, J Cheng, K Horino, M Ohnishi, M Fukushi, M Fujii, T Saku

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS   93 ( 3 )   305 - 310   2002.3

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    DOI： 10.1067/moe.2002.120026

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  • Sebaceous lymphadenoma of the lip: Report of a case of minor salivary gland origin

    Satoshi Maruyama, Jun Cheng, Tatsuo Inoue, Ritsuo Takagi, Takashi Saku

    Journal of Oral Pathology and Medicine   31 ( 4 )   242 - 243   2002

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    DOI： 10.1034/j.1600-0714.2002.310409.x

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MISC

  • 下顎歯肉への転移を契機に診断に至った膵癌の1例

    須田 大亮, 船山 昭典, 新美 奏恵, 佐久間 英伸, 齋藤 大輔, 林 孝文, 丸山 智, 田沼 順一, 小林 正治

    日本口腔腫瘍学会誌   36 ( 4 )   89 - 95   2024.12

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  • 頭頸部扁平上皮癌におけるmRNAスプライシングシグネチャーと病理学的意義の探索(Alternative splicing signatures of mRNA in head and neck squamous cell carcinoma and pathological significance)

    阿部 達也, 凌 一葦, 奥田 修二郎, 山崎 学, 丸山 智, 田沼 順一

    日本癌学会総会記事   83回   P - 2222   2024.9

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  • 広範な骨膜反応を呈した非細菌性下顎骨骨髄炎の1例

    須田 大亮, 船山 昭典, 佐久間 英伸, 齋藤 大輔, 羽賀 健太, 林 孝文, 丸山 智, 田沼 順一, 小林 正治

    日本口腔科学会雑誌   73 ( 3 )   272 - 273   2024.9

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  • 口腔扁平上皮癌における異所性核酸受容分子の発現解析(Expression of heterotopic nucleic acid-sensing molecules in oral squamous cell carcinoma)

    山崎 学, 阿部 達也, 丸山 智, 田沼 順一

    日本病理学会会誌   113 ( 1 )   351 - 351   2024.2

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  • 良性および悪性唾液腺腫瘍の診断におけるCD73免疫組織化学的検索(CD73 immunohistochemical analysis for the diagnosis of benign and malignant salivary gland tumors)

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    日本病理学会会誌   113 ( 1 )   351 - 351   2024.2

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  • 頭頸部扁平上皮癌における選択的スプライシングシグネチャーによる予後予測(Prediction of prognosis by alternative splicing signature in head and neck squamous cell carcinoma)

    阿部 達也, 凌 一葦, 奥田 修二郎, 山崎 学, 丸山 智, 田沼 順一

    日本病理学会会誌   113 ( 1 )   296 - 296   2024.2

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  • 患者由来がん関連線維芽細胞を含む3次元口腔がんモデルの開発とその特徴解析

    相澤有香, 相澤有香, 羽賀健太, 吉羽永子, WITSANU Yortchan, 高田翔, 田中凛太郎, 内藤絵里子, 阿部達也, 丸山智, 山崎学, 田沼順一, 冨原圭, 泉健次

    新潟歯学会雑誌   54 ( 2 )   2024

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  • メトトレキサート関連リンパ増殖性疾患により顎骨壊死をきたした関節リウマチ患者の1例

    加納浩之, 加藤祐介, 小林正治, 丸山智

    新潟歯学会雑誌   54 ( 2 )   2024

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  • 歯科インプラント治療のための上顎洞底挙上術術後に発症したsurgical ciliated cystの1例

    福井智子, 加藤祐介, 小林正治, 丸山智, 加納浩之

    新潟歯学会雑誌   54 ( 2 )   2024

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  • 同種死細胞により誘導される口腔扁平上皮癌細胞の活性化メカニズム(Dead cancer cell-induced activation mechanisms of oral squamous cell carcinoma cells)

    山崎 学, 阿部 達也, 丸山 智, 田沼 順一

    日本癌学会総会記事   82回   233 - 233   2023.9

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  • 頭頸部扁平上皮癌における特異的選択的スプライシングの探索 データベース解析とロングリード-ケンシング(Alternative splicing in head and neck squamous cell carcinoma: public database exploration and long-read sequencing)

    阿部 達也, 凌 一葦, 奥田 修二郎, 山崎 学, 丸山 智, 田沼 順一

    日本癌学会総会記事   82回   1083 - 1083   2023.9

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  • 唾液腺多形腺腫由来細胞は低酸素環境下にてCD73による増殖及び遊走能を亢進する

    丸山 智, 山崎 学, 阿部 達也, Chan Nyein Nyein, 田沼 順一

    日本病理学会会誌   112 ( 1 )   292 - 292   2023.3

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  • 口腔扁平上皮癌におけるladinin-1と細胞極性・上皮性格制御

    阿部 達也, 山崎 学, 丸山 智, Chan Nyein Nyein, 田沼 順一

    日本病理学会会誌   112 ( 1 )   289 - 289   2023.3

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  • 頭頸部癌特異的スプライシングイベントの探索

    阿部 達也, 山崎 学, 丸山 智, Chan Nyein Nyein, 田沼 順一

    日本病理学会会誌   112 ( 1 )   291 - 291   2023.3

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  • 天疱瘡2例のLBC法における細胞像の検討

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    新潟県臨床細胞学会会報   ( 37 )   54 - 54   2022.12

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  • 口腔細胞診の従来法とLBC法において判定精度に影響を与える臨床病理学的因子の検討

    河原田壮史, 河原田壮史, 丸山智, 山崎学, 阿部達也, 上野山敦士, 秋森俊行, 秋森俊行, 小島拓, 小島拓, 冨原圭, 小林正治, 田沼順一

    日本口腔診断学会総会プログラム・抄録集   35th   2022

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  • 舌上皮性異形成および上皮内癌と診断された病変の診断および治療の検討

    新美 奏恵, 船山 昭典, 丸山 智, 勝良 剛詞, 新國 農, 田沼 順一, 林 孝文, 小林 正治

    日本口腔診断学会雑誌   33 ( 1 )   126 - 126   2020.2

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  • 下顎骨内に発生した類皮嚢胞の1例

    笠原 映, 山崎 学, 丸山 智, 勝良 剛詞, 黒川 亮, 河原田 壮史, 林 孝文, 高木 律男, 田沼 順一

    日本口腔診断学会雑誌   33 ( 1 )   139 - 139   2020.2

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  • 舌腫瘍

    河原田 壮史, 丸山 智, 笠原 映, 山崎 学, 林 孝文, 片桐 渉, 小林 正治, 田沼 順一

    日本口腔診断学会雑誌   33 ( 1 )   81 - 81   2020.2

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  • 舌縁に生じたectomesenchymal chondromyxoid tumorの1例

    櫻井航太郎, 仲盛健治, 山崎学, 丸山智, 田沼順一

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

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  • 唾液腺多形腺腫における低酸素応答性増殖機構(Hypoxia-induced proliferation in salivary pleomorphic adenoma cells)

    丸山 智, 山崎 学, 田沼 順一

    日本癌学会総会記事   78回   P - 2282   2019.9

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  • 癌関連線維芽細胞はSOX9を高発現させ口腔癌細胞の遊走および浸潤を促進する(Cancer-associated fibroblasts promote the migration and invasion of oral cancer cells via enhancing SOX9 expression)

    羽賀 健太, 山崎 学, 丸山 智, 小林 正治, 田沼 順一

    日本癌学会総会記事   78回   P - 1258   2019.9

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  • PET-CT検査における口腔癌の頸部リンパ節転移の診断精度に関する検討

    新垣 元基, 勝見 祐二, 小山 貴寛, 永田 昌毅, 星名 秀行, 高村 真貴, 林 孝文, 丸山 智, 田沼 順一, 高木 律男

    日本口腔科学会雑誌   68 ( 2 )   111 - 111   2019.7

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  • 下顎角部に発生した奇形様嚢胞の1例

    齋藤 大輔, 原 太一, 丸山 智, 西山 秀昌, 林 孝文, 小林 正治

    日本口腔外科学会雑誌   65 ( 7 )   479 - 483   2019.7

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    症例は17歳女性で、8歳頃に発熱した際に左側下顎角部の腫脹を認め、解熱後も残存していたが放置していた。14歳ごろから徐々に増大を自覚しており当科を紹介受診した。画像所見から脂肪腫または類皮嚢胞と診断し、全身麻酔下で経皮的に病変の摘出術を施行した。病変は耳下腺下極の内側に入り込んでおり、周囲耳下腺組織からの剥離は一部でやや困難であったが一塊として摘出した。術後6年6ヵ月間経過観察を行っていたが、再発所見を認めないため経過観察を終了とした。病理組織学的所見では大小2個の嚢胞腔を認め、いずれの嚢胞も内腔面は皮膚表皮様の基底線の平坦な重層扁平上皮で被覆されており、線維性組織から成る難胞壁はおおむね薄く、二つの嚢胞間部は肥厚していた。奇形様嚢胞との病理組織学的診断を下した。

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  • 放射線誘発が疑われた口腔内多発癌の1例

    三上 俊彦, 船山 昭典, 金丸 祥平, 新美 奏恵, 丸山 智, 小林 正治

    日本口腔内科学会雑誌   25 ( 1 )   10 - 15   2019.6

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  • 高分子ゲル音響カップリング材を併用した舌癌の口腔内超音波検査による深達度計測

    林孝文, 曽我麻里恵, 小林太一, 高村真貴, 新國農, 勝良剛詞, 丸山智, 田沼順一

    超音波医学   46 ( Suppl. )   S788 - S788   2019.4

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  • 口腔上皮性腫瘍の病理学的考察:口腔の前癌病変と早期癌に関する問題点

    田沼順一, 山崎学, 丸山智

    日本病理学会会誌   108 ( 1 )   226 - 226   2019.4

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  • PET‐CT検査における口腔癌の頸部リンパ節転移の診断精度に関する検討

    新垣元基, 勝見祐二, 小山貴寛, 永田昌毅, 星名秀行, 高村真貴, 林孝文, 丸山智, 田沼順一, 高木律男

    日本口腔科学会学術集会プログラム・抄録集   73rd   157   2019

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  • 舌扁平上皮癌cN0症例の頸部後発転移に関する検討

    小玉直樹, 永田昌毅, 小山貴寛, 勝見祐二, 新垣元基, 木口哲郎, 原夕子, 池田順行, 児玉泰光, 星名秀行, 西山秀昌, 林孝文, 丸山智, 田沼順一, 高木律男

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   37th   185   2019

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  • Ladinin-1 regulating proliferation and migration of oral squamous cell carcinoma via actin molecules

    Tatsuya Abe, Yoichi Ajioka, Manabu Yamazaki, Satoshi Maruyama

    108 ( 1 )   323 - 323   2019

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  • LADININ-1 IS INVOLVED IN CELL MOTILITY AND PROLIFERATION OF ORAL SQUAMOUS CELL CARCINOMA CELLS (proceeding)

    Tatsuya Abe, Manabu Yamazaki, Satoshi Maruyama, Yoichi Ajioka

    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology   128 ( 1 )   e81 - e82   2019

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  • 口蓋に生じた唾液腺導管癌の一例

    山崎学, 丸山智, 常木雅之, 田沼順一, 田沼順一

    日本臨床細胞学会雑誌(Web)   57   647   2018.10

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  • 口蓋に生じた唾液腺導管癌の一例

    山崎 学, 丸山 智, 常木 雅之, 田沼 順一

    日本臨床細胞学会雑誌   57 ( Suppl.2 )   647 - 647   2018.10

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  • 口腔粘膜悪性境界病変におけるp53免疫組織化学的検索の取り組み

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   459 - 459   2018.4

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  • 口腔扁平上皮癌における死細胞誘導性細胞増殖機構の解明

    山崎 学, 丸山 智, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   346 - 346   2018.4

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  • 口腔扁平上皮癌細胞におけるladinin-1の機能解析

    阿部 達也, 丸山 智, 山崎 学, 味岡 洋一

    日本病理学会会誌   107 ( 1 )   458 - 458   2018.4

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  • 口腔粘膜悪性境界病変におけるp53免疫組織化学的検索の取り組み

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   459 - 459   2018.4

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  • 口腔扁平上皮癌における死細胞誘導性細胞増殖機構の解明

    山崎 学, 丸山 智, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   346 - 346   2018.4

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  • 舌扁平上皮癌における「厚み」の臨床病理学的検討

    三上俊彦, 金丸祥平, 千田正, 船山昭典, 小田陽平, 新美奏恵, 丸山智, 林孝文, 小林正治

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   36th   204   2018

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  • Ladinin-1 regulates proliferation and migration of oral squamous cell carcinoma cells via mediation of actin dynamics

    Abe Tatsuya, Yamazaki Manabu, Maruyama Satoshi, Ajioka Yoichi

    86 - 86   2018

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  • 当科における口腔粘膜細胞診と組織診の臨床病理学的検討

    船山昭典, 千田正, 三上俊彦, 金丸祥平, 新美奏恵, 小田陽平, 丸山智, 芳澤享子, 小林正治

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   36th   2018

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  • 下顎骨辺縁切除を行った乳児黒色神経外胚葉性腫瘍の1例

    小田陽平, 千田正, 竹内涼子, 三上俊彦, 金丸祥平, 船山昭典, 山崎学, 丸山智, 新國農, 林孝文, 小林正治

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   36th   2018

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  • 口腔扁平上皮癌におけるSOX 9細胞質発現は予後不良と関連する

    隅田 賢正, 山崎 学, 阿部 達也, 高木 律男, 丸山 智

    新潟歯学会雑誌   47 ( 2 )   120 - 121   2017.12

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  • 下顎部に発生したInfantile Fibromatosisの1例

    小玉 直樹, 高山 裕司, 永田 昌毅, 小山 貴寛, 勝見 祐二, 新垣 元基, 隅田 賢正, 池田 順行, 大貫 尚志, 齋藤 太郎, 山田 瑛子, 西山 秀昌, 林 孝文, 丸山 智, 高木 律男

    小児口腔外科   27 ( 2 )   68 - 68   2017.10

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  • 感染性リンパ節腫脹との鑑別に苦慮した悪性リンパ腫の1例

    三上 俊彦, 原 太一, 加藤 祐介, 船山 昭典, 金丸 祥平, 小田 陽平, 新美 奏恵, 阿部 達也, 丸山 智, 西山 秀昌, 林 孝文, 小林 正治

    日本口腔科学会雑誌   66 ( 2 )   182 - 182   2017.7

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  • Expression of neprilysin in periodontitis-affected gingival tissues

    A. Nezu, T. Kubota, S. Maruyama, M. Nagata, K. Nohno, T. Morozumi, H. Yoshie

    ARCHIVES OF ORAL BIOLOGY   79   35 - 41   2017.7

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  • 低酸素環境下でMYCは唾液腺多形性腺腫由来細胞の生存・増殖を亢進する

    丸山 智, 山崎 学, 阿部 達也, 隅田 賢正, 程 クン, 朔 敬

    日本病理学会会誌   106 ( 1 )   295 - 295   2017.3

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  • 口腔扁平上皮癌におけるSOX9の発現様式

    隅田 賢正, 丸山 智, 山崎 学, 阿部 達也, 高木 律男, 程 クン

    日本病理学会会誌   106 ( 1 )   364 - 364   2017.3

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  • 口腔表在性癌と非癌部粘膜上皮との界面におけるタンパク質動態解析

    阿部 達也, 丸山 智, 山崎 学, 許 波, 隅田 賢正, 程 クン, 山本 格, 朔 敬

    日本病理学会会誌   106 ( 1 )   408 - 408   2017.3

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  • 口腔癌治療後に生じたbizarre stromal reactionの2例

    山崎 学, 隅田 賢正, 丸山 智, 阿部 達也, 程 くん, 朔 敬

    日本病理学会会誌   106 ( 1 )   424 - 424   2017.3

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  • 前舌腺に発生した腺癌NOSの1例

    三上俊彦, 船山昭典, 金丸祥平, 小田陽平, 山崎学, 丸山智, 西山秀昌, 林孝文, 小林正治

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集   35th   174   2017

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  • 歯周炎罹患歯肉組織におけるネプリライシンの遺伝子発現レベルと免疫組織局在の解析

    根津新, 久保田健彦, 丸山智, 永田昌毅, 堀水慎, 濃野要, 保苅崇大, 両角俊哉, 朔敬, 吉江弘正

    新潟歯学会雑誌   46 ( 2 )   115   2016.12

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  • 新潟大学医歯学総合病院顎顔面口腔外科における口腔扁平苔癬患者の臨床統計的検討

    齋藤 太郎, 小山 貴寛, 黒川 亮, 西川 敦, 原 夕子, 清水 志保, 丸山 智, 程 君, 高木 律男

    新潟歯学会雑誌   46 ( 2 )   119 - 120   2016.12

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  • 口腔表在性癌と非癌部粘膜上皮との界面における細胞競合現象の解析

    阿部 達也, 丸山 智, 山崎 学, 許 波, Babkair Hamzah, 隅田 賢正, 程 君, 山本 格, 朔 敬

    日本病理学会会誌   105 ( 1 )   421 - 421   2016.4

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  • 口腔粘膜乳頭腫は粘液腺導管開口部に発生する

    朔 敬, 丸山 智, 山崎 学, 阿部 達也, バブカイール・ハムザ, 隅田 賢正, 程 君

    日本病理学会会誌   105 ( 1 )   419 - 419   2016.4

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  • 唾液腺多形性腺腫細胞は低酸素環境下でHIF-1α-MYC相互作用によってエネルギー代謝を制御している

    丸山 智, 山崎 学, 阿部 達也, バブカイール・ハムザ, 隅田 賢正, 程 君, 朔 敬

    日本病理学会会誌   105 ( 1 )   468 - 468   2016.4

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  • 発生学的組織病理形成ではなく炎症により生じた口腔内リンパ管上皮嚢胞(Inflammatory but not developmental histopathogenesis of intraoral lymphoepithelial cyst)

    山崎 学, 丸山 智, 阿部 達也, バブカイール・ハムザ, 隅田 賢正, 程 君, 朔 敬

    日本病理学会会誌   105 ( 1 )   424 - 424   2016.4

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  • 口腔扁平上皮癌における皮膚型角化の分化誘導と細胞増殖の調整機構

    阿部 達也, 丸山 智, 山崎 学, Babkair Hamzah, 隅田 賢正, 程 くん, 朔 敬

    新潟歯学会雑誌   45 ( 2 )   103 - 103   2015.12

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  • 口腔表在性癌と非癌部粘膜上皮との界面における細胞競合現象

    阿部 達也, 丸山 智, 山崎 学, Babkair Hamzah, 隅田 賢正, 程 くん, 朔 敬

    新潟歯学会雑誌   45 ( 2 )   105 - 106   2015.12

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  • 歯周炎罹患歯肉組織におけるNeprilysin(Alzheimer病関連遺伝子)の発現

    根津新, 久保田健彦, 丸山智, 永田昌毅, 堀水慎, 濃野要, 保苅崇大, 両角俊哉, 朔敬, 吉江弘正

    日本歯周病学会会誌(Web)   57   131   2015.8

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  • PROTEASE-ACTIVATED RECEPTOR-2 IN REGULATION OF PROLIFERATION AND INVASION OF ORAL SQUAMOUS CELL CARCINOMA CELLS

    J. Cheng, K. Al-Eryani, T. Abe, S. Maruyama, M. Yamazaki, H. Babkair, T. Saku

    EUROPEAN JOURNAL OF CANCER   51   E12 - E13   2015.7

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    DOI： 10.1016/j.ejca.2015.06.039

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  • 角化嚢胞性歯原性腫瘍の組織学的バリエーションの検討 炎症性修飾を中心に

    山崎 学, 丸山 智, 阿部 達也, 程 くん, 酒井 剛, 朔 敬

    日本病理学会会誌   104 ( 1 )   469 - 469   2015.3

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  • 低酸素応答性ファイブロネクチン生合成が唾液腺多形性腺腫由来SM-AP細胞の増殖を促進する

    丸山 智, 山崎 学, 阿部 達也, バブカイル・ハムザ, 程 くん, 朔 敬

    日本病理学会会誌   104 ( 1 )   449 - 449   2015.3

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  • 口腔扁平上皮癌および正角化型異型上皮における正角化関連分子の動態

    阿部 達也, 丸山 智, 山崎 学, バブカイル・ハムザ, 程 くん, 朔 敬

    日本病理学会会誌   104 ( 1 )   467 - 467   2015.3

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  • 腺様嚢胞癌細胞の転移 KGFシグナルによる細胞増殖性と遊走性の相反的制御機構

    丸山 智, 山崎 学, 阿部 達也, 程 クン, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   435 - 436   2014.9

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  • 口腔扁平上皮癌においてMFG-E8は同種死細胞処理だけでなく腫瘍進展にも関与している

    山崎 学, 程 クン, 丸山 智, 阿部 達也, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   387 - 387   2014.9

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  • 角化嚢胞性歯原性腫瘍は咀嚼筋内にも発生する 角化性嚢胞の免疫組織化学的鑑別法

    阿部 達也, 丸山 智, 山崎 学, ハムザ・バブカイル, 三上 俊彦, 新垣 晋, 小林 正治, 林 孝文, 程 クン, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   414 - 415   2014.9

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  • 口腔異型上皮-扁平上皮癌シーケンスにおける正角化関連分子の発現動態

    阿部 達也, 丸山 智, Ahmed Essa, Hamzah Babkair, 山崎 学, 程 くん, 朔 敬

    日本病理学会会誌   103 ( 1 )   281 - 281   2014.3

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  • 口腔扁平上皮癌における接着結合分子のclaudin 1とzonula occludens 1(Tight junction molecules, claudin 1 and zonula occludens 1, in oral squamous cell carcinoma)

    Hamzah Babkair, 山崎 学, 阿部 達也, Ahmed Essa, 丸山 智, 程 くん, 朔 敬

    日本病理学会会誌   103 ( 1 )   281 - 281   2014.3

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  • 口腔扁平上皮癌細胞におけるMFG-E8発現の意義 過剰発現細胞系による解析

    山崎 学, 程 くん, 丸山 智, 阿部 達也, 朔 敬

    日本病理学会会誌   103 ( 1 )   295 - 295   2014.3

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  • 唾液腺多形性腺腫由来SM-AP細胞の増殖は低酸素応答性パールカン生合成に依存している

    丸山 智, 山崎 学, 阿部 達也, Babkair Hamzah, 程 くん, 朔 敬

    日本病理学会会誌   103 ( 1 )   296 - 296   2014.3

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  • 唾液腺腫瘍の新規筋上皮細胞マーカとしてのコネキシン43とpodoplanin(Connexin 43 and podoplanin as novel myoepithelial cell markers in salivary gland tumors)

    Ahmed Essa, 常木 雅之, 山崎 学, 丸山 智, 阿部 達也, Hamzah Babkair, 程 くん, 朔 敬

    日本病理学会会誌   103 ( 1 )   273 - 273   2014.3

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  • Amyloid beta (A4) precursor protein expression in human periodontitis-affected gingival tissues

    T. Kubota, T. Kubota, S. Maruyama, D. Abe, T. Tomita, T. Morozumi, N. Nakasone, T. Saku, T. Saku, H. Yoshie

    Archives of Oral Biology   59   586 - 594   2014.1

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  • 当科における過去10年間の口腔がん患者の臨床的検討

    三上俊彦, 船山昭典, 芳澤享子, 新垣晋, 林孝文, 丸山智, 朔敬, 小林正治

    新潟歯学会雑誌   43 ( 2 )   163 - 164   2013.12

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  • 口腔扁平上皮癌とその境界病変における術中迅速病理診断の意義 局所再発に関する臨床病理学的検討

    御代田 駿, 小林 孝憲, 宮島 久, 永田 昌毅, 星名 秀行, 小林 正治, 高木 律男, 丸山 智, 朔 敬

    新潟歯学会雑誌   43 ( 2 )   163 - 163   2013.12

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  • MFG-E8は口腔扁平上皮癌の進展と死細胞貪食を促進する

    山崎 学, 程 くん, 丸山 智, 阿部 達也, 朔 敬

    日本病理学会会誌   102 ( 1 )   360 - 360   2013.4

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  • 口腔扁平上皮癌の側方進展界面における細胞死

    阿部 達也, 丸山 智, Ahmed Essa, Hamzah Babkair, 山崎 学, 程 くん, 朔 敬

    日本病理学会会誌   102 ( 1 )   319 - 319   2013.4

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  • 口腔扁平上皮癌における間質性マクロファージ(Stromal macrophages in oral squamous cell carcinoma)

    Ahmed Essa, 山崎 学, 丸山 智, 阿部 達也, Hamzah Babkair, 程 くん, 朔 敬

    日本病理学会会誌   102 ( 1 )   361 - 361   2013.4

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  • 唾液腺多形性腺腫細胞における低酸素応答性の細胞外基質合成

    丸山 智, 山崎 学, 阿部 達也, 程 くん, 朔 敬

    日本病理学会会誌   102 ( 1 )   364 - 364   2013.4

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  • 口腔扁平上皮癌・上皮内癌の側方進展界面の病理組織学的解析(Histopathological varieties of lateral invasion fronts in oral squamous cell carcinoma and carcinoma in-situ)

    阿部 達也, 丸山 智, 山崎 学, アーメッド・イーサー, 程 ジュン, 朔 敬

    日本癌学会総会記事   71回   144 - 145   2012.8

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  • 口腔扁平上皮癌の浸潤を契機とした細胞外基質産生の実質細胞から間質細胞へのスイッチング機構(Parenchymal-stromal switching for extracellular matrix production before/after invasion of oral squamous cell carcinoma)

    丸山 智, 山崎 学, 阿部 達也, 程 ジュン, 朔 敬

    日本癌学会総会記事   71回   144 - 144   2012.8

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  • Sialadenitis as a possible risk factor for salivary gland cancer

    M. Hasegawa, J. Cheng, S. Maruyama, M. Yamazaki, T. Saku

    INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   40 ( 12 )   1449 - 1450   2011.12

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    DOI： 10.1016/j.ijom.2011.06.022

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  • Podoplanin Regulates the Proliferation of Oral Squamous Cell Carcinoma Cells via Its Binding to Extracellular Matrix

    M. Tsuneki, S. Maruyama, M. Yamazaki, J. Cheng, T. Saku

    EUROPEAN JOURNAL OF CANCER   47   S550 - S550   2011.9

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  • 口腔扁平上皮癌の浸潤性評価:パールカン免疫陽性間質の立体構築

    丸山智, 島津徳人, 工藤朝雄, 青葉孝昭, 朔敬

    日本病理学会会誌   100 ( 1 )   2011

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  • 顎下腺内側のリンパ節【傍顎下腺リンパ節】転移と考えられる舌癌4症例の画像診断学的検討

    星名 由紀子, 林 孝文, 新垣 晋, 齊藤 力, 星名 秀行, 高木 律男, 丸山 智

    頭頸部癌   36 ( 2 )   186 - 186   2010.5

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  • ビスフォスフォネート製剤による顎骨壊死の病理組織学的検討

    長谷川 真弓, 程 くん, 丸山 智, 小林 孝憲, 又賀 泉, 田中 彰, 岡田 康男, 田上 正, 小松 繁樹, 泉 直也, 齊藤 力, 高木 律男, 田中 礼, 林 孝文, 朔 敬

    日本口腔科学会雑誌   58 ( 4 )   199 - 199   2009.9

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  • Hemophagocytosis-related keratinization in squamous cell carcinoma and carcinoma in-situ of the oral mucosa

    K. Al-Eryani, J. Cheng, S. Maruyama, M. Yamazaki, T. Kobayashi, T. Saku

    EJC SUPPLEMENTS   7 ( 2 )   481 - 481   2009.9

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  • 脈管分布様式からみたワルチン腫瘍のリンパ性間質

    阿部 達也, 程 くん, 丸山 智, 朔 敬

    日本病理学会会誌   98 ( 1 )   398 - 398   2009.3

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  • CK17と14‐3‐3σの共発現が口腔粘膜扁平上皮癌で強調される

    三上俊彦, CHENG Jun, 丸山智, 小林孝憲, 依田浩子, 新垣晋, 齊藤力, 朔敬

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集   19th   69   2008.8

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  • 口腔粘膜扁平上皮癌・上皮内癌の再発に関する臨床病理学的検討

    小林 孝憲, 依田 浩子, 丸山 智, 程 くん, 齊藤 力, 高木 律男, 朔 敬

    日本病理学会会誌   97 ( 1 )   320 - 320   2008.3

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  • 口腔粘膜悪性境界病変におけるケラチン分子とその関連因子

    三上俊彦, 程くん, 丸山智, 新垣晋, 齊藤力, 朔敬

    新潟歯学会雑誌   37 ( 2 )   257 - 257   2007.12

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  • 口腔扁平上皮癌のいわゆる癌真珠の免疫組織学的検討

    三上俊彦, CHENG J, 丸山智, AL‐ERYANI K, 新垣晋, 齊藤力, 朔敬

    J Oral Biosci   49 ( Supplement )   132 - 132   2007.8

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  • 第三大臼歯に関連した下顎第二大臼歯の重篤な歯根吸収

    飯田 明彦, 高木 律男, 丸山 智, 朔 敬, ホワイト・レイモンド

    日本口腔外科学会雑誌   53 ( Suppl. )   181 - 181   2007.8

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  • 口腔粘膜上皮内癌の鑑別診断にはCK17の免疫組織化学が有用である

    三上俊彦, 程くん, 船山昭典, 丸山智, スカリアン クンドゥ, スカリアン クンドゥ, 新垣晋, 齊藤力, 朔敬

    日本病理学会会誌   96 ( 1 )   291 - 291   2007.2

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  • Periosteal osteosarcoma of the jawbones: a clinicopathological review

    Sawair FA, Cheng J, Hao N, Maruyama S, Hoshina H, Takagi R, Koyama J, Hayashi T, Saku T

    Oral Med Pathol   12 ( 1 )   3 - 10   2007

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  • 第三大臼歯に関連した歯根吸収により抜歯にいたった下顎第二大臼歯の2症例

    飯田明彦, 高木律男, 丸山智, 朔敬, 齋藤功

    新潟歯学会雑誌   36 ( 2 )   303   2006.12

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  • [No.29] Malignant schwannoma of maxilla

    Maruyama Satoshi, Nakazato Takayuki, Koyama Junichi, Suzuki Makoto

    Niigata dental journal   36 ( 2 )   31 - 34   2006.12

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    Other Link： http://hdl.handle.net/10191/1343

  • 口腔粘膜上皮悪性境界病変におけるいわゆる幹細胞マーカ分子の発現様式

    小林 孝憲, 依田 浩子, 船山 昭典, 丸山 智, 程 君, 高木 律男, 朔 敬

    日本病理学会会誌   95 ( 1 )   288 - 288   2006.4

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  • 口腔粘膜悪性境界病変の病理組織学的診断根拠としての機能性分子発現様式の解析

    小林 孝憲, 依田 浩子, 丸山 智, 程 くん, 高木 律男, 朔 敬

    新潟歯学会雑誌   35 ( 2 )   247 - 247   2006.1

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  • 上顎悪性神経鞘腫

    丸山 智, 中里隆之, 小山純市, 鈴木 誠

    新潟歯学会雑誌   36 ( 2 )   239 - 42   2006

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  • 歯原性角化嚢胞モデルとしてのMsx2ノックアウトマウス顎骨嚢胞

    朔 敬, 板垣 真奈美, 依田 浩子, 丸山 智, 程 君, 大島 勇人, 里方 一郎

    Journal of Oral Biosciences   47 ( Suppl. )   96 - 96   2005.9

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  • Integrin alpha is indispensable for ligaments to resist mechanical stress-induced mineralization.

    F Takizawa, T Yoshizawa, S Maruyama, F Iizawa, A Matsuda, O Ishibashi, T Saku, H Yoshie, U Mayer, H Kawashima

    JOURNAL OF BONE AND MINERAL RESEARCH   20 ( 9 )   S109 - S110   2005.9

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  • Establishment and characterization of pleomorphic adenoma cell systems: an in-vitro demonstration of adenoma-carcinoma sequence in the salivary gland

    Maruyama Satoshi, Cheng Jun, Shingaki Susumu

    Niigata dental journal   35 ( 1 )   73 - 74   2005.7

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  • 石灰化歯原性嚢胞上皮細胞の幻影細胞化と石灰化機序の検討

    程 君, 丸山 智, 鈴木 誠, 藤田 一, 高木 律男, 草間 薫, 朔 敬

    日本病理学会会誌   94 ( 1 )   252 - 252   2005.3

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  • 石灰化歯原性嚢胞上皮細胞 : 染色体解析と移植腫瘍石灰化機序の検討

    程 王君., 丸山 智, 鈴木 誠, 下川 仁弥太, 朔 敬.

    歯科基礎医学会雑誌   45 ( 5 )   317 - 317   2003.9

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  • 唾液腺多形性腺腫腫由来細胞PMA1-PMA6による細胞外基質生合成

    丸山 智, 程 君, 朔 敬

    歯科基礎医学会雑誌   45 ( 5 )   359 - 359   2003.9

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  • Carcinoma in-situ of the Oral Mucosa has a Definite Tendency towards Keratinization

    Syafriadi Mei, Ida-Yanemochi Hiroko, Ikarashi Terue, Maruyama Satoshi, Jen Kai Yu, Cheng Jun, Hoshina Hideyuki, Takagi Ritsuo, Saku Takashi

    Oral medicine & pathology   8 ( 2 )   43 - 44   2003

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    A 81-year-old female had suffered from a white lesion in the right lateral margin of the tongue for 10 years. The lesions was surgically removed and examined histopathologically. The surgical specimen showed small foci of squamous cell carcinoma invading up to 4 mm in the muscle layer with a diameter of less than 7 mm in the central portion. The carcinomatous foci were surrounded by epithelial dysplasia in various degrees with a dense lymphocytic infiltration in the lamina propriae. Some of the dysplasia parts just next to the carcinomatous foci contained obviously atypical cells without basal cell alignment but with an apparent keratinizing tendency, which could not be otherwise diagnosed as carcinoma in-situ. Based on this case report, a new concept of carcinoma in-situ of the oral mucosa was proposed, because the histology was different in terms of keratinization degree from so-called carcinoma in-situ as frequently seen in the cervix uteri, which were mainly composed of proliferation of basaloid cells.

    DOI： 10.3353/omp.8.43

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    Other Link： http://search.jamas.or.jp/link/ui/2004123235

  • 40. Tumor of the upper lip

    Maruyama S, Cheng J, Ikarashi T, Hoshina H, Takagi R, Saku T

    Oral medicine & pathology   7 ( 2 )   98 - 98   2002.12

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  • 20. White lesion of the oral mucosa

    Syafriadi M, Ida H, Ikarashi I, Maruyama S, Jen KY, Cheng J, Hoshina H, Takagi R, Saku T

    Oral medicine & pathology   7 ( 2 )   94 - 94   2002.12

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  • 石灰化歯原性嚢胞5例の臨床病理学的検討

    奈良井 省太, 福田 純一, 高木 律男, 小野 和宏, 星名 秀行, 藤田 一, 長島 克弘, 平 周三, 丸山 智, 朔 敬

    新潟歯学会雑誌   32 ( 2 )   355 - 356   2002.12

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  • 石灰化歯原性嚢胞上皮細胞の試験管内石灰化と幻影細胞化

    程 くん, 丸山 智, 鈴木 誠, 藤田 一, 高木 律男, 朔 敬

    歯科基礎医学会雑誌   44 ( 5 )   480 - 480   2002.9

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  • Mucoepidermoid Carcinoma in Children : Report of a case and review of literature

    Jen Kai Yu, Cheng Jun, Maruyama Satoshi, Hayashi Takafumi, Suzuki Ichiro, Shingaki Susumu, Saku Takashi

    Oral medicine & pathology   7 ( 1 )   27 - 31   2002.6

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    A rare case of mucoepidermoid carcinoma arising in a 15-year-old boy is reported. The patient had palatal swelling with tenderness for two years. After a diagnosis of mucoepidermoid carcinoma was obtained by biopsy and CT scan examinations, the patient underwent a partial maxillectomy. Histopathologically, the tumor arising in the palatal mucosa involved the maxillary bone and the base of the right maxillary sinus. The tumor consisted not only of predominantly clear cells and squamous cells in solid nests but also of mucous cells forming various sized cystic cavities. From a review of the literature, mucoepidermoid carcinoma was shown to be the most frequent salivary tumor in children, comprising 3% to 8% of the total numbers of patients with mucoepidermoid carcinoma. When compared with adult cases, childhood cases more frequently involve the parotid gland and less frequently the minor salivary glands.

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  • 舌癌—舌癌と胃癌が重複した１例—

    丸山 智, 林 孝文, 川上美貴

    新潟歯学会雑誌   32 ( 1 )   79 - 82   2002

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  • 11.Mucoepidermoid carcinoma of children : report of a case and literature review

    Jen KY, Cheng J, Maruyama S, Suzuki I, Shingaki S, Saku T

    Oral medicine & pathology   6 ( 2 )   111 - 111   2001.12

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  • 24.Tumor of the maxilla

    Maruyama S, Cheng J, Suzuki M, Sohma Y, Takagi R, Saku T

    Oral medicine & pathology   6 ( 2 )   114 - 114   2001.12

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  • 23.Tumor of the mandible

    Igarashi T, Maruyama S, Hoshina H, Takagi R, Saku T

    Oral medicine & pathology   6 ( 2 )   113 - 114   2001.12

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  • 疣贅型黄色腫10例の検討

    加納 浩之, 小林 正治, 新垣 晋, 飯田 明彦, 高木 律男, 丸山 智, 朔 敬

    日本口腔外科学会雑誌   47 ( 13 )   1060 - 1060   2001.12

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  • 23:Submucosal tumor of the buccal mucosa

    Maruyama S, Hao N, Cheng J, Horino K, Saku T

    Oral medicine & pathology   5 ( 2 )   122 - 122   2000.12

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  • 唾液腺多形性腺腫の被膜浸潤

    丸山 智, 朔 敬, 程 君, 鈴木 誠

    歯科基礎医学会雑誌   42 ( 5 )   436 - 436   2000.8

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Research Projects

  • Immune escape mechanisms induced by dead cell-derived ectopic nucleic acids in oral cancer

    Grant number：24K13126

    2024.4 - 2027.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Pathological significance of mRNA alternative splicing in oral/head and neck squamous cell carcinoma

    Grant number：24K12895

    2024.4 - 2027.3

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    Awarding organization：Japan Society for the Promotion of Science

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  • Role of the CD73-CXCL10 signaling pathway in tumor self-regulating mechanisms in the extracellular matrix

    Grant number：24K13110

    2024.4 - 2027.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • Elucidation of the molecular mechanisms in the microenvironment of oral cancer using single-cell RNA sequence analysis

    Grant number：23K09150

    2023.4 - 2026.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

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  • 細胞外基質環境下における腫瘍特異的なCD73誘導低酸素応答性増殖機構の解明

    Grant number：21K10109

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    丸山 智, 阿部 達也, 山崎 学, 田沼 順一

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    1) CD73発現抑制によるECMの発現動態の検証: 低酸素環境下におけるCD73発現とECM合成能との関係を解析するために、siRNA法によるCD73発現抑制下でのECM分子である、perlecanやfibronectinの発現を検討したところ、SM-AP1/4ともに発現抑制はみられなかった。よってCD73発現はECM合成能に影響を及ぼしていない可能性が示唆された。
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    2) 細胞増殖関連液性因子の網羅的解析: SM-AP細胞を低酸素培養条件下と通常培養条件下及びsiRNA法によるCD73発現抑制下で培養した後、各培養上清を回収し、Proteome ProfilerTM 抗体アレイキット(R&D systems)を用いて細胞増殖関連液性因子の網羅的解析を行った。その結果、IP-10やAngiogeninなどCD73発現抑制下で同様に発現が抑制されるいくつかの候補分子を見出した。さらにこれまでの研究で、これらの候補分子は低酸素培養条件（1％O２/5％CO２/94％N２）及び通常培養条件下でのSM-AP細胞系における各培養上清において発現が亢進していることもわかっており、低酸素下において、HIF-1αを介したCD73発現上昇との関連も確認されている。
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    3) CD73発現動態におけるSTAT3の影響についての検討: 昨年度に続いて、siRNA法によるCD73及びHIF-1α発現抑制下でのSTAT3の発現を比較してみると、SM-AP1/4ともにCD73抑制下では、STAT3の発現抑制傾向が見られたものの、HIF-1α発現抑制下ではSTAT3の発現抑制はみられなかった。以上の結果からは、低酸素下において、HIF-1αを介さない別の経路でSTAT3の発現上昇をきたしている可能性が示唆された。

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  • 死細胞貪食による口腔がん細胞活性化：脂質クオリティが果たす役割を探る

    Grant number：21K09856

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    山崎 学, 阿部 達也, 丸山 智, 冨原 圭, 泉 健次, 田沼 順一

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    がん細胞は正常細胞とは異なる脂質代謝を有し、近年、がんにおける脂質クオリティ（脂質組成）の重要性が明らかになりつつある。本研究課題では、「死細胞貪食を起点としたがん細胞活性化の機序に、死細胞由来脂質によってもたらされる脂質クオリティ変化が関与する」という仮説のもと、(1)がん細胞のおける死細胞由来脂質の局在変化を追跡し、(2)貪食後に生じるがん細胞の脂質クオリティを解析することで、(3)細胞増殖・遊走・浸潤能に関わる分子機構との接点を明らかにすることを目的としている。今年度は、以下の疑問を解決すべく検討をおこなった。
    1) ネクローシス細胞は生活がん細胞に貪食されるのか？: 口腔扁平上皮癌由来培養細胞株を脂質親和性色素PKH26にて標識後、凍結融解によって誘導したネクローシス細胞を、同種の生活がん細胞と共培養した。共焦点レーザー顕微鏡解析の結果、PKH26陽性を示す死細胞断片は生活がん細胞の細胞質内に認められた。これより、ネクローシス細胞は生活がん細胞によって貪食されることが示された。
    2) 細胞内コレステロール変化は細胞機能を変化させるのか？: これまでの検討により、ネクローシス細胞と共培養した際、生活がん細胞内にコレステロールが蓄積される可能性が推測された。そこでまず、細胞内コレステロールレベル変化による細胞の機能変化を検索した。コレステロール-MCD複合体の添加により、細胞内コレステロールを上昇させると、細胞形態は多辺形から扇状へと変化し、細胞遊走能が亢進することが示された。

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  • 口腔扁平上皮癌の間質浸潤と側方上皮内進展：その相反的制御と分子基盤

    Grant number：21K09841

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    阿部 達也, 山崎 学, 田沼 順一, 丸山 智

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    これまでに, 口腔扁平上皮癌の癌-非癌界面における蛋白質網羅的解析により, 癌界面部組織に特異的に増加した蛋白質である ladinin-1 (LAD1) が癌細胞の平面遊走と垂直遊走に相反的な制御を行っている可能性が見出されていることに加え, 免疫蛍光染色を用いた解析から, LAD1 抑制細胞における細胞形態変化と, vimentin 陽性細胞の有意な増加, E-cadherin の細胞膜上からの有意な減少および細胞質内陽性像の有意な増加を認めたことから, 上皮間葉転換 (EMT) 様表現型の表出に関わっている可能性が考えられていた.
    また, EMT 関連遺伝子の発現変動を LAD1 発現抑制下で検討すると, LAD1 発現を抑制した口腔扁平上皮癌培養細胞株 HSC-2 および HSC-4 で, WNT5A 遺伝子の有意な発現増加が認められたことから, WNT pathway のなかでも, 特に EMT と細胞平面極性への関連が知られる膜貫通タンパクである ROR2 の関連性を検討した. LAD1 の発現抑制下での ROR2 遺伝子発現は, 特に HSC-4 で WNT5A 発現と連動性がみられたことから, LAD1 の発現変動に伴う細胞遊走極性と, EMT 様表現型の発現に, ROR2 の関連性が示唆され, 現在, 同じく siRNA 法での ROR2 発現抑制下での LAD1 および EMT に関連した vimentin・E-cadherin の発現変動, また LAD1・ROR2 の共発現抑制の系を検討中である.

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  • Basic research on multi-step tongue carcinogenesis model for realizing clinical sequence

    Grant number：19K10069

    2019.4 - 2022.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Tanuma Junichi

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    OSCC arises from oral epithelial dysplasia; however, there is no useful marker for early OSCC detection, likely owing to the inability to continuously observe the carcinoma sequence. We aimed to establish an experimental model to observe changes in the sequential expression patterns of mRNAs and proteins in the same rat using liquid-based cytology techniques. Cytology specimens were collected from a 4NQO-induced rat tongue cancer model at every 3 weeks. We examined candidate biomarker expression using immunocytochemistry and qRT-PCR. The labeling index (LI) was calculated as the percentage of positively stained nuclei. Brd4 and c-Myc mRNA levels were upregulated during progression from NILM to OSCC. BRD4- and c-Myc-LI were increased in LSIL, HSIL, and OSCC.
    BRD4 and c-Myc are effective in classifying lesions of NILM and LSIL or higher, and could be useful diagnostic markers for the early detection of oral cancer.

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  • Hypoxia-responsive CD73 promotes the growth and migration of pleomorphic adenoma cells

    Grant number：18K09740

    2018.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Maruyama Satoshi

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    In this study, we investigated the role of CD73, one of the target molecules of the hypoxia inducible factors (HIF) activation mechanism, in cell function under hypoxia. We cultured SM-AP cells, which were established from a human pleomorphic adenoma, under normal or hypoxic conditions, and examined the expression of HIF-1α and CD73, as well as cell migration and proliferation when the level of CD73 synthesis was controlled by siRNA. The HIF-1α gene and protein were highly expressed in the nucleus under hypoxic conditions for 48 hours, and CD73 expression was also highly expressed. Under hypoxic conditions, the cell migration ability was enhanced compared to normal culture conditions. On the other hand, when CD73 expression was suppressed, cell proliferation was inhibited. These results suggest that activation of HIF-1α under hypoxic conditions promotes cell proliferation and migration of pleomorphic adenoma cells through their own high expression of CD73.

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  • Molecular regulation of actin polymerization and arrangement in the lateral front between oral squamous cell carcinoma and non-cancerous epithelium

    Grant number：18K09550

    2018.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Abe Tatsuya

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    We have reported that ladinin-1 (LAD1) was highly expressed in cancer tissues adjacent to non-cancerous tissues by proteomic analysis of histopathological specimens of oral squamous cell carcinoma (OSCC). In a present study, we investigated the role of LAD1 in cancer development. LAD1-knockdown OSCC cells by siRNA method showed decreased cell proliferation, decreased planar cell migration, and enhanced three-dimensional cell migration. LAD1 localized to actin fibers in intracellular actin arcs, and inhibition of LAD1 expression resulted in decreased expansion of lamella and loss of epithelial-like cell morphology. These results suggested that LAD1 involved in cell migration through regulation of actin molecule and related to the expression of epithelial morphology and properties.

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  • Cell death-driven mechanisms for cancer progression: targeting the dying codes

    Grant number：18K09533

    2018.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Yamazaki Manabu

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    Cell death through apoptosis and/or necrosis is frequently observed in malignant tumor tissues, including oral squamous cell carcinoma (OSCC). However, a significance of dead tumor cells has not been fully understood. On a hypothesis that dead tumor cells activate neighboring tumor cells and promote tumor progression, we performed the experiments using OSCC-derived cultured cells. Consequently, necrotic OSCC cells robustly activated proliferation, migration and invasion of living OSCC cells. Moreover, necrotic OSCC cells induced activation of NF-kB pathway and increased production of inflammatory cytokines. Our study demonstrated dead tumor cell-induced cellular activation mechanisms in OSCC.

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  • Gene network analyses of AD in periodontitis-affected gingival tissue

    Grant number：15K11382

    2015.4 - 2020.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    KUBOTA Takehiko

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    We have first reported that the significantly elevated expression of Amyloid beta (A4) precursor protein (APP) and Neprilysin (NEP) transcript levels in human periodontitis-affected gingival tissues. The APP-expressing cells in inflamed gingival tissues were mainly macrophages, whereas NEP were expressed in neutrophils and fibroblasts (Archs Oral Biol 2017). The series of our research on inflammatory tissue metabolisms in periodontitis-affected gingival tissues including MMP/TIMP balance and Alzheimer’s disease(AD)-related gene networks won the 2018 senior investigator award from Japanese Society of Periodontology. The review paper was published in Journal of JSP 2018.

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  • Hypoxia-responsive MYC promotes the survival and growth of pleomorphic adenoma cells in hypoxic conditions.

    Grant number：15K11069

    2015.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Maruyama Satoshi

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    On the basis of hypovasucularity of the salivary pleomorphic adenoma, we had a hypothesis that pleomorphic adenoma cells are able to survive in hypoxic conditions. To understand the hypoxia-dependent manner of energy metabolism in this particular tumor, we analyzed function of MYC, which are the most important factor of metabolic regulation, in cell proliferation and migration in hypoxic-conditioned pleomorphic adenoma cells. In hypoxic condition, SM-AP cells, human pleomorphic adenoma cell systems, showed higher gene expression levels of HIF-1α and MYC in hypoxia. HIF-1α protein was also kept in higher levels and localized more significantly in nuclei. The proliferation and migration of SM-AP cells were reduced under the lack of MYC expression. These results indicated that hypoxic conditions induced pleomorphic adenoma cells to produce MYC, which was maintained by high HIF-1α protein levels.

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  • Phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: a possible driving force for cancer progression

    Grant number：15K11006

    2015.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Yamazaki Manabu

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    Apoptotic cancer cells are cleaned by macrophages and also by the neighboring cancer cells. Based on a hypothesis that apoptotic cell clearance by living carcinoma cells could contribute to cancer cell activities and tumor progression, we investigated a biological significance of this phenomenon using cultured cell lines derived from oral squamous cell carcinoma. When co-cultured with UV-induced apoptotic cells, the most of living cells engulfed apoptotic cells, and this engulfment was inhibited by Rac1 inhibitor. Electron microscopy demonstrated the engulfed cells localized within the phagosomes, with which the lysosomes seem to fuse. Furthermore, co-culture with apoptotic cells enhanced migration and invasion. These results suggested that self-clearance may upregulate cancer cell activities. Control of self-clearance in cancer would open up a new direction for therapeutic intervention.

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  • Molecular pathways and functional varieties of hemophagocytosis-induced keratinization in oral squamous cell carcinoma cells: from cell death to proliferation and invasion

    Grant number：15K15693

    2015.4 - 2017.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Challenging Exploratory Research

    Awarding organization：Japan Society for the Promotion of Science

    SAKU Takashi

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    Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）

    We have defined the keratinization of oral squamous cell carcinoma as skin-type orthokeratinization due to keratin 17 expression which never occurs in normal oral mucosa. Such an expression of dyskeratotic keratin 17 was shown to be induced by hemophagacytosis-derived hemoglobin released from erythrocytes and to mediate expressions of OH-1, PAR-2, 14-3-3σ, and YAP. These functional factors contributed to molecular pathways not only for cell death but for cellular proliferation and invasion in oral squamous cell carcinoma. In addition, cell death in oral lichen planus was explained by similar mechanisms starting from hemophagacytosis because hemorrhage often occurred along the epithelial interface, and keratinization-based cellular evaluation was confirmed to be useful in oral cytology to diagnose malignancy. This much functional varieties of phagocytosis-mediated keratinization were never expected, when we formulated our hypothesis that keratinization is initiated by hemophagocytosis.

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  • Pathogenesis of chewing-related oral cancer in Myanmar: a molecular pathoepidemiological study

    Grant number：26305032

    2014.4 - 2019.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Saku Takashi

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    Grant amount：\15990000 （ Direct Cost: \12300000 、 Indirect Cost：\3690000 ）

    Based on our international collection of oral cancer cases including precancerous lesions and our newly developed virtual microscopy network, we listed up new and important histopathological findings of oral carcinoma in-situ. Then, we explained the significance of those histopathological features by various experiments by using oral squamous cell carcinoma cells in culture. As a result, we were successful in proposing science-based diagnostic criteria of oral carcinoma in-situ. In Myanmar, we carried out cohort study series in areas where betel chewing habits were highly prevalent. Frequencies of oral cancer and mucosal lesions were more frequent among chewers, while control residents who took beta-carotene containing fruits and vegetables with their high beta-carotene blood levels had less mucosal troubles. The present micro-level and macro-level approaches have achieved valuable future prospects for more accurate diagnostic methodology and more efficient prevention for oral cancer.

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  • Molecular patho-epidemiological study on the etiological background for oral superficial carcinoma among Asian ethnic groups

    Grant number：25305035

    2013.4 - 2017.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun

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    Grant amount：\18200000 （ Direct Cost: \14000000 、 Indirect Cost：\4200000 ）

    To investigate the epidemiological and biological backgrounds for the occurrence of oral superficial carcinomas, which are recently increasing in number in Japan with an aging population, we collected those cases from several Asian countries as controls. We firstly established a science/evidence-based standard for histopathological diagnosis of oral superficial carcinomas, with which we eliminated diagnostic disparities among hospitals from those countries. As a result, we confirmed that our new diagnostic standard based on combined expressions of some particular molecules was useful for any cases whose ethnic and etiological backgrounds were obviously different from each other. Hence, we were successful in demonstrating the diagnostic standard certainly worked in any occasions. Among the expressions of the particular molecules, those of keratin 17 were shown by our cell machinery investigations to characterize dyskeratotic carcinoma cells, which mimicked epidermal orthokeratosis.

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  • Proteome analysis of invasion starter molecules in oral squamous cell carcinoma

    Grant number：25462849

    2013.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Cheng Jun, MARUYAMA Satoshi, YAMAZAKI Manabu, ABE Tatsuya, SAKU Takashi

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    Grant amount：\5070000 （ Direct Cost: \3900000 、 Indirect Cost：\1170000 ）

    The molecular mechanism of invasion of oral squamous cell carcinoma still remains unknown. To understand what sort of crosstalk between cancer cells and surrounding non-cancerous epithelial cells or stromal cells, we performed proteome analyses of laser-capture microdissected samples obtained from the interfaces between cancer cell nests and their surrounding non-cancerous epithelium of the oral mucosa or stromal tissues, which were objectively visualized by the aid of immunohistochemistry. As a result, we have determined proteins which were specifically expressed at both cancer and non-cancer sides of the interface zone. They were immunohistochemically identified to be expressed more in cancer or non-cancer sides. Thus, these newly identified molecules are considered to function in regulating squamous cell carcinoma cells to start to invade. It is expected to understand the machinery of cancer invasion when these molecules are investigated more in detail.

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  • Elevated expression of Alzheimer disease related genes in periodontiti-affected gingival tissues

    Grant number：24593119

    2012.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Kubota Takehiko, MARIYAMA SATOSHI, NOUNO KANAME

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    Grant amount：\5330000 （ Direct Cost: \4100000 、 Indirect Cost：\1230000 ）

    We have first reported that the significantly elevated expression of Amyloid beta (A4) precursor protein (APP) transcript levels in human periodontitis-affected gingival tissues. It was also identified that the APP-expressing cells in inflamed gingival tissues were mainly macrophages (Archs Oral Biol 2014). Secondary, significantly upregulated genes including MD-2, CD14, IL-1beta, IL-8 and CXCL-9, which belongs to toll-like receptor (TLR) signaling pathway were also found in periodontitis-affected gingival tissues. It was reported and published in Opn J Stomatol 2014.

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  • Survival of salivary pleomorphic adenoma cells under the hypoxia-responsive extracellular matrix biosynthesis

    Grant number：24592829

    2012.4 - 2015.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    MARUYAMA Satoshi, ABE Tatsuya, YAMAZAKI Manabu, CHENG Jun, SAKU Takashi

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    Grant amount：\5330000 （ Direct Cost: \4100000 、 Indirect Cost：\1230000 ）

    Salivary pleomorphic adenoma is histopathologically characterized by its colorful stroma with myxoid, chondroid, and hyaline appearances, which is realized by its enhanced biosynthesis of extracellular matrix (ECM) molecules as well as by poor vascularity. Thus, pleomorphic adenoma cells embedded in such stromata are supposed to be able to survive in hypoxic conditions. To understand the hypoxia-dependent manner of cellular proliferation in this particular tumor, we analyzed function of perlecan and fibronectin, which are the most abundant ECM molecules, in cell proliferation in hypoxic-conditioned pleomorphic adenoma cells. Hypoxic conditions induce pleomorphic adenoma cells to produce perlecan and fibronectin, which is maintained by high HIF-1α protein levels, which is further realized by perlecan and fibronectin-rich circumstance of the stroma. The results indicate that pleomorphic adenoma cells have to go round in hypoxic circles to survive.

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  • A molecular pathoepidemiological study on tobacco chewing-related oral cancer in Asian and African areas

    Grant number：23406038

    2011.4 - 2015.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    SAKU, Takashi, CHENG Jun, MARUYAMA Satoshi, YAMAZAKI Manabu, ABE Tatsuya

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    Grant amount：\14820000 （ Direct Cost: \11400000 、 Indirect Cost：\3420000 ）

    Betel quid chewing has been regarded as one of the most representative causative factor of oral squamous cell carcinoma (SCC) in the south Asian area. Taking these chewing-related oral SCC samples, we investigated them in comparison with non-chewers’ SCC samples from many aspects. Epidemiologically, we have carried out a cohort study in Myanmar to analyze oral and nutritional conditions among chewers and non-chewers and confirmed that chewing habits affected the oral mucosa to generate malignant lesions. Oral submucous fibrosis was closely related to epithelial alterations leading to such precancerous lesions as epithelial dysplasia and carcinoma in-situ. Investigating those samples, we have found several specific subtypes of precancerous lesions, and their biological significances were demonstrated in vivo. Those research efforts have been applied to our diagnostic services, and they were shown to be useful in objective histopathological diagnosis of oral mucosal malignancies.

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  • Imaging of the microvascular distribution in the mandibular bone marrow using Dual Energy Computed Tomography Imaging; a trial run

    Grant number：23592760

    2011 - 2013

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    TANAKA Ray, HAYASHI Takafumi, IDA Hiroko, IKE Makiko, OHSHIMA Hayato, MARUYAMA Satoshi

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    The aim was imaging of the microvascular distribution in the mandibular bone marrow using Dual Energy CT Imaging (DEI). Histopathological specimens of the mandibular bone and pre-operative CT images from the patients who underwent the resection of the mandibular disease were used. The extent of the microvascular distribution within the bone marrow on the histological specimen was subjectively assessed. Multi-Planar Reconstruction Images generated from the pre-operative CT images were compared with the histological findings. Creation of optimal CT images for analysis of the microvascularization in the bone marrow of the mandible was unsatisfactory. The bone marrow area was extremely small to visualize on CT images even with DEI. The area of adipose tissue was predominantly larger than that of microvessels distribution on histological images. It was conceivable that such microvascularization could not make the clear density variations on CT images.

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  • Molecular mechanisms of ghost cell formation and calcification in calcifying cystic odontogenic tumor (CCOT) cell lines

    Grant number：22592033

    2010 - 2012

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun, MARUYAMA Satoshi, YAMAZAKI Manabu, SAKU Takashi, ABE Tatsuya

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    Calcifying cystic odontogenic tumor (CCOT) is histopathologically characterized by the emergence of ghost cells. However, their histopathogenesis has been poorly understood. To understand the cellular mechanism towards ghost cell formation, we have successfully established of cell lines from a CCOT surgical specimen. Using these CCOT cells, we successfully demonstrated that ghost cells were generated due to intracellular deposits of extracellular matrix molecules including perlecan, and that their calcification was started in those matrices and completed by proteolysis of deposited matrices towards their denucleated forms.

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  • Survival of salivary pleomorphic adenoma cells in hypoxic condition

    Grant number：22791810

    2010 - 2011

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    MARUYAMA Satoshi

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    Salivary pleomorphic adenoma(PA) is histopathologically characaterized by its colorful stroma with myxoid appearances, which are poorly vascularized, and PA cells are supposed to be able to survive in hypoxic conditions. To understand the hypoxia-dependent manner of cellular proliferation, we determined both protein and gene expression levels of hypoxia-inducible factor 1α(HIF-1α), vascular endothelial growth factor(VEGF), and von Hippel-Lindau(vHL), which degrades HIF-1α. SM-AP cells, which I established from a human parotid pleomorphic adenoma, showed more enhanced levels of HIF-1α, and their VEGF protein levels were kept higher in hypoxic conditions than in aerobic ones. SM-AP cells showed lower expression levels for the vHL gene. Likewise, tumor tissue masses of transplanted SM-AP cells were lower in O_2 concentration than normal subcutanous tissue. The results indicate that pleomorphic adenoma cells can proliferate in the hypoxic condition in which HIF-1αprotein levels were maintained in higher levels because the degradation of HIF-1αwas inhibited due to the lower vHL protein levels. It is thus concluded that hypoxia is more beneficial for PA cell proliferation.

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  • Pathological roles of tissue inhibitors of metalloproteinases in the tissues of drug-induced fibrous gingival over growth.

    Grant number：21592622

    2009 - 2011

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    KUBOTA Takehiko, NAKASONE Naohiro, MARUYAMA Satoshi, NOUNO Kaname

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    We have reported the 1^<st> report "Gene expression and immunohistochemical protein localization of TIMP-3 and TIMP-in gingival overgrowth and periodontitis-affected gingival tissues" Archs Oral Biology(2009). Then I have received the Academic Senior Investigator's Award for this series of studies in 2009 from Japanese Society of Conservative Dentistry(Review 2010)。The 2^<nd> and 3^<rd> reports :"Microarray and data-mining analyses for specific gene expression in drug-induced gingival overgrowth tissues. Archs Oral Biology(2011)", and "Altered gene expression pattern and specific biological pathways in periodontitis-affected gingival tissues." J Periodont Res(2011) have published in international scientific peer review journals.

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  • Molecular patho-epidemiological study on oral superficial carcinoma in East Asia regions

    Grant number：20406029

    2008 - 2011

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun, MARUYAMA Satoshi, SAKU Takashi, IDA Hiroko, YAMAZAKI Manabu

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    Grant amount：\16770000 （ Direct Cost: \12900000 、 Indirect Cost：\3870000 ）

    Oral cancers, especially superficial carcinomas, are increasing in number not only in Japan but also Asian countries, which seems to be in parallel to changing of those countries into aging societies. Epidemiologically and molecular pathologically comparing Japanese cases and East Asian cases, we have shown that oral superficial carcinoma is a lesional complex of borderline malignancies including from epithelial dysplasia to micro-invasive carcinoma by establishing pathological diagnostic criteria for carcinoma in-situ, which were biological evidence-based.

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  • Survival of salivary pleomorphic adenoma cells in hypoxic condition

    Grant number：20791331

    2008 - 2009

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    MARUYAMA Satoshi

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    Salivary pleomorphic adenoma is histopathologically characaterized by its colorful stroma including myxoid one which is poorly vascularized. Pleomorphic adenoma (PA) cells embedded in such poorly-vasculaized stromata are supposed to have their own device to survive in hypoxic conditions. To understand the hypoxia-dependent manner of cellular proliferation, we determined both protein and gene expression levels of hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and von Hippel-Lindau (vHL) protein which degrades HIF-1α in SM-AP cells originated from a pleomorphic adenoma. They showed more enhanced gene expression levels for VEGF but not for those for HIF-1α under hypoxic conditions. In contrast, HIF-1α and VEGF protein levels were kept higher in hypoxic conditions than in aerobic ones. SM-AP cells had lower expression levels for the vHL gene. On the one hand, their VEGF protein levels were kept lower in hypoxic conditions than in aerobic ones. The results indicate that PA cells are able to proliferate in the hypoxic condition because of the accumulation of HIF-1α probably due to repressed levels of vHL.

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  • Pathogenesis of oral cancer due to chewing habits spread in Asia to East Africa

    Grant number：19406030

    2007 - 2010

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    SAKU Takashi, CHENG Jun, MARUYAMA Satoshi, IDA Hiroko, YAMAZAKI Manabu

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    Grant amount：\16640000 （ Direct Cost: \12800000 、 Indirect Cost：\3840000 ）

    Since betel quid chewing in the south Asian area is the most representative causative factor of oral cancer, we surveyed oral cancer cases in Yemen, Jordan, Egypt, Sudan, Morocco, and Myanmar, where different sorts of chewing habits are performed. In those areas, chewing-related oral cancer was shown to be one of the most frequent cancers. Analyzing tissue specimens collected from there, we have established important histopathological diagnostic criteria for carcinoma in-situ and epithelial dysplasia both of which superficial carcinoma is comprised of. Their criteria were scientifically supported in multiple aspects by cell biology-based evidence.

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  • The role of perlecan in the oral mucosa and the skin appendage-Transgenic mice overexpression of perlecan-

    Grant number：19592105

    2007 - 2008

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    IDA Hiroko

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • Molecular and pathology analyses for switching mechanism of stromal inducement in invasive oral carcinoma

    Grant number：18390486

    2006 - 2008

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    SAKU Takashi, CHENG Jun, MARUYAMA Satoshi, SUZUKI Makoto, IDA Hiroko

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    Grant amount：\18450000 （ Direct Cost: \15300000 、 Indirect Cost：\3150000 ）

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  • 歯原性角化嚢胞モデルとしてのMsx2ノックアウトマウスの顎骨嚢胞

    Grant number：18659554

    2006 - 2007

    System name：科学研究費助成事業

    Research category：萌芽研究

    Awarding organization：日本学術振興会

    里方 一郎, 鈴木 誠, 朔 敬, 程 ゆん, 丸山 智, 里方 一郎, 伊東 達雄

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    Grant amount：\3300000 （ Direct Cost: \3300000 ）

    1.ヒト歯原性角化嚢胞患者におけるのMSX2遺伝子異常解析
    ヒトの歯原性角化嚢胞患者からDNAを抽出し、PCRによってMSX2遺伝子のexonlおよびexon2を増幅し、直接シークエンス法によってそれらの塩基配列を決定し、変異状況を検索した。30例の非症候群性歯原性角化嚢胞患者では、MSX2遺伝子の変異は認められなかった。症候群性歯原性角化嚢胞(母斑基底細胞癌症候群)9家系について解析を行ったところ、1家系にintronlのsplice donor siteの点変異が発見された。この変異によりMSX2 haploinsufficiencyが生じることがin vitroの実験により示された。さらに、症候群性歯原性角化嚢胞の原因遺伝子とされるPTCH1の変異は検出されなかったことより、この家系ではMSX2が症候群性歯原性角化嚢胞の原因遺伝子であると結論した。
    2.Msx2ノックアウトマウスにおけるBMP4の部位特異的強制発現によるレスキュー実験
    Msx2ノックアウトマウスのエナメル上皮細胞におけるBMP4の部位特異的強制発現を行い、BMP4の発現低下を補った場合に歯原性角化嚢胞の形成を阻止できるか調べた。Msx2遺伝子の発現部位に特異的にBMP4を発現するトランスジェニックマウスとMsx2ノックアウトマウスの交配により、エナメル上皮由来細胞に特異的にBMP4を発現するMsx2ノックアウトマウスの作成を行った。歯原性角化嚢胞の発生頻度は、Tg/+;Msx2-/-マウスでは歯原性角化嚢胞の発生頻度がMsx2-/-マウスと比較して差はなかったが、Tg/Tg;Msx2-/-マウスでは、歯原性角化嚢胞の発生頻度がMsx2-/-マウスと比較して有意に低下した。この結果は、BMP4遺伝子の発現低下が歯原性角化嚢胞の形成に重要な役割を果たしていることが考えられた。

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  • 唾液腺多形性腺腫の乏血性環境における増殖機構

    Grant number：18791345

    2006 - 2007

    System name：科学研究費助成事業

    Research category：若手研究(B)

    Awarding organization：日本学術振興会

    丸山 智

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    Grant amount：\3500000 （ Direct Cost: \3500000 ）

    (1)免疫細胞化学的検索
    ヒト唾液腺多形性腺腫より樹立したSMAP1/4細胞株を用いて、1.2x10^4細胞をチャンバースライドに植え込み、経時的に4%パラフォルムアルデヒドで固定後、低酸素応答性の転写因子であるHIF-1aおよびHIF-1aにより増幅されるといわれている血管内皮増殖因子であるVEGF、かつHIF-1aとJab-1を介して関連があることがすでにわかっているがん抑制遺伝子であるp53に対する各抗体をもちいて、これらの発現を蛍光抗体法にて検討した。その結果、低酸素下で、HIF-1aおよびVEGFの発現レベルが高い傾向がみられた。さらにHIF-1aについては、しばしは核に移行している像がしばしばみとめられ、degradationを受けずに核に移行したHIF-1aにより、VEGFの発現が促進された可能性が示唆された。また変異のみられたp53の発現はみとめられなかった。
    (2)実験結果の評価と研究の総括
    以上の実験結果より、多形性腺腫由来細胞では、pVHLの低発現およびp53の変異によりHIF-1aのdegradationの抑制機構がはたらいており、低酸素状態で核に移行したHIF-1aによりVEGFの高い発現レベルを維持することで、低酸素環境で増殖さらには転移形質を誘導しているのではないかと考えられた。今後はより詳細にHIF-1a蛋白質の低酸素培養条件下での分解挿制機構を明らかにしていく予定である。

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  • Molecular pathological study of mechanism in malignant changes of benign odontogenic tumors

    Grant number：18591999

    2006 - 2007

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun, SATOSHI Maruyama, TAKASHI Saku

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    Grant amount：\3830000 （ Direct Cost: \3500000 、 Indirect Cost：\330000 ）

    This research project was carried out in order to study a possible molecular pathway of secondary malignant transformation from oral benign tumors. We mainly focused on calcifying cystic odontogenic tumor (COT), because we had already proposed a possible of malignant changes within calcifying odontogenic cyst. To this end, we have isolated six cell systems (designated COT1 to COT6) from a calcifying odontogenic cyst arising in the maxilla of a 54 year-old male. COT1-COT6 showed odontogenic epithelial characteristics with polygonal cell shapes: they were immunopositive for keratin and expressed distinct mRNA levels for keratin 16, amelogenin, tuftelin, BSP, MMP-20, and ALP. In co-cultures with fibroblasts, COT6 cells grew to form nestic structures, in which ghost cells and calcified materials appeared in the later stage. Finally, they developed into calcified nodules within the COT6 cell nests. Chromosome analyses showed the cells had not only numeral abnormalities such as 3n ploidies with average numbers of 59 chromosomes but also various kinds of structural abnormalities. Among them, der(9)t(9; 13)(p13.3;q12.3) was shared by all of the six cell systems. COT cells formed tumors with a squamous cell carcinoma-like appearance in nude mice. Keratinization in transplanted tumor cell foci was closely associated with ghost cell differentiation and calcification. Also in surgical specimens of COC, ghost cells were positive for extracellular matrix (ECM) molecules including perlecan as well as MMP7 or β-catenin. The results indicated that ghost cells were generated by cytoplasmic retention of ECM molecules, which were related to Wnt signaling pathways.
    These results show that COT is potentially neoplastic, and that the six COT cell systems are useful models for investigating the molecular mechanisms of ghost cell differentiation and epithelial calcification. In addition, the findings suggest that COT contains precancerous tumor cells which are able to transform into malignant with above mentioned gene alterations. The present study is the first in-vitro demonstration of secondary malignant transformation from a benign odontogenic tumor.

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  • 口腔粘膜上皮<胚細胞>の同定とその二方向性分化経路概念の確立

    Grant number：17659576

    2005 - 2006

    System name：科学研究費助成事業

    Research category：萌芽研究

    Awarding organization：日本学術振興会

    朔 敬, 程 〓, 丸山 智

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    Grant amount：\3300000 （ Direct Cost: \3300000 ）

    マウス口腔粘膜扁平上皮増殖中心細胞の同定とその発現遺伝子の特定:4週齢ICR系マウス腹腔にBrdUを投与して、パラフィン切片を作製し、BrdU取り込み細胞を同定した。その結果、マウス口腔粘膜では、BrdU陽性細胞は上皮基底層第一・二層に分布し、ヒト粘膜とは必ずしも対応しない分布であることが判明した。
    (1)マウス口腔粘膜上皮胚細胞の試験管内分化誘導:前項までに確立したマウス口腔粘膜より扁平上皮胚細胞集団を分離し、試験管内にそれらの胚細胞を単層培養して、分化誘導実験の条件検討を試みたが、細胞維持が困難なために実験系のデザインを検討中である。
    (2)ヒト口腔粘膜異型上皮と上皮内癌における基底細胞分化抗原の免疫組織学的確認:前年度までに確定された増殖細胞抗原として有用なマーカKi-67のほかに、ケラチン分子種のうち、CK13,17,10,16,19、さらに角質分化関連分子のうち、インヴォルクリン、フィラグリン、機能は不明ながらポドプラニンの有用性をヒト口腔粘膜境界病変で免疫組織学的に確認した。とくにCK13消失とCK17出現の対応はもっとも重要な所見と評価された。
    (3)総括:以上より、扁平上皮杯細胞の所在は基底部であることは想定されるが、第一層であるのか第二層であるのかを特定することはなお困難である。しかし、異型細胞が生じて上皮内癌に向かう過程では、基底第二層に増殖中心があることは判明し、角化あるいは基底細胞分化経路に未だ入らない細胞群の存在は確認できた。したがって、少なくともがん幹細胞は上皮基底第二層に存在するという概念を固めることができた。

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  • The role of basement membrane type heparan sulfate proteoglycan, perlecan, in epithelial morphogenesis -transgenic mice overexpressing perlecan in the epithelial cells-

    Grant number：17591902

    2005 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    IDA Hiroko, MARUYAMA Satoshi, SATOH Toshiya, CHENG Jun, SAKU Takashi, SUZUKI Makoto

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    Grant amount：\3600000 （ Direct Cost: \3600000 ）

    Perlecan, a basement membrane-type heparan sulfate proteoglycan, is localized in the intercellular space of the enamel organ. Hence, it has been suggested to play an important role in tooth morphogenesis. To elucidate the function of perlecan in odontogenesis, we generated transgenic mice overexpressing perlecan in the epithelial cells using a keratin 5 promoter, and examined the effect of perlecan overexpression on enamel organ formation. Transgenic mice were generated by pronuclear microinjection of fertilized C57BL/C3H F1 oocytes with the DNA construct, and they express the entire perlecan core protein under the control of a bovine keratin 5 promoter. Their molar tooth germs were studied by EM, immunohistochemistry, and RT-PCR for perlecan and tooth germ-related molecules.
    Perlecan was immunohistochemically confirmed to be expressed strongly in epithelial tissues, including the enamel organ of Tg mice. Morphologically, the stellate reticulum of the Tg molars showed widened intercellular spaces and thick, irregularly shaped dental laminae at the embryonic stage (E13-E18). In postnatal day 1 (P1) Tg mice, the enamel organ was obviously lacking cell density and was less vascularized. Finally, the crown shape of Tg molars became dull-ended, with incomplete crystallization and divergent tooth roots in mandibular molars. mRNA expression levels for FGF-2, TGF-β1, and PKC-a were elevated in Tg tooth germs at P1.
    From these results, it was suggested that perlecan may control the space arrangement of stromata by binding and releasing of growth factors, and it may act as a carrier for nutrient transport by diffusion within the epithelial milieu. Also in the process of odontogenesis, perlecan might contribute in forming highly hydrated circumstances to realize cell growth and differentiation in the enamel organ. However, the time schedule of the intraepithelial expression of perlecan seems to be critically controlled, because a constant overexpression perlecan has interfered normal tooth morphogenesis.

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  • Molecular biologic and pathologic analysis of Epstein-Barr virus infection related salivary lymphoepithelial carcinoma

    Grant number：16406033

    2004 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun, MARUYAMA Satoshi, SAKU Takashi

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    Grant amount：\11300000 （ Direct Cost: \11300000 ）

    We have collected the total 180 cases of lymphoepithelial carcinoma (LEC) of salivary gland, which were confirmed as EBV-infected tumors by various molecular biological.
    A complete sequence for the LMP1 gene, one of the EBV gene and has been regarded as an oncogene, was obtained from patients' tissue samples. It was cloned into an expression vector and the constructs were transfected into 293T cells. The transfected cells showed significant elevation of NFkB activities and suppressed cell growth, which were also seen in cells transfected with vectors with different LMP1 genes such as CAO, which has been isolated from a nasopharyngeal carcinoma, and B95-8, a prototype EBV. The results indicated that the expression of LMP1 affects transcription activities in LEC cells but that the overall mutations found in the present study were not always reasons for the tumorigenesis. The promoter region of the LMP1 gene was also analyzed from 20 cases of them, and all of the cases shared common mutational events in regions that were expected to be associated with transcription factors.
    We tried primary cultures for salivary LECs for many times. Unfortunately, however, it was hard to establish cell lines from the cells in culture. In one of the primary cultures, we were successful in maintaining cells, which were confirmed to be their salivary duct epithelial and myoepithelial characteristics as well as EBV infected.
    As a background disease, lymphoepithelial cyst was studied based on clinicopathological analyses of sixty-four cases of the parotid gland. The lymphoid stroma of the cyst seemed to be resulted from granulation tissue reaction of focal sialadenitis but not induced by EBV infection.
    Our functional study shows a new insight for EBV roles in the pathogenesis of salivary LEC, although it is still necessary to carry out further investigations for the whole mechanisms of EBV oncogenesis.

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  • Molecular pathological study of mechanism in malignant changes of oral benign tumors

    Grant number：16591821

    2004 - 2005

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    CHENG Jun, MARUYAMA Satoshi, SAKU Takeshi

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    Grant amount：\3600000 （ Direct Cost: \3600000 ）

    This research project was carried out in order to study a possible molecular pathway of malignant transformation of oral benign tumors. We mainly focus on salivary pleomorphic adenoma, because we had already proposed a possibility of malignant changes of atypical tumor cells or focal carcinomas within pleomorphic adenomas. To this end, we have isolated six cell systems (designated SMAP1 to SMAP6) from a benign pleomorphic adenoma of the parotid gland of a 61 year-old female. SMAP1/3 showed duct epithelial characteristics with polygonal cell shapes, while SMAP4/6 were spindle-shaped with some myoepithelial cell differentiation. Chromosome analyses showed the cells had not only numeral abnormalities such as 5n ploidies with average numbers of 107 chromosomes but also various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9; 13)(p13.3;q12.3) was shared by all of the six cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which would result in generation of its nonsense gene product. The findings suggest that pleomorphic adenoma contains tumor cells which are precancerous and are able to transform into malignant with above mentioned gene alterations, and the present study is the first in-vitro demonstration that carcinomas can arise secondarily from adenomas in the salivary gland.
    In addition to such gene alterations, there were some other biological characteristics to pleomorphic adenomas. They were capsular and vascular invasions. Their frequency was 100% (extracapular 20%) and 15%, respectively, when examined histopathologically in 104 surgical specimens. In the sites with capsular or vascular invasions, the stroma was myxoid and poorly vascularized. This histology was explained by VEGF and HIF-1a expression modes, which were hypoxia-related. In cells established from a melanotic neuroectodermal tumor of infancy, there was the same chromosome alteration found in SMAP cells, and this translocation will be worthwhile to be investigated further for the molecular mechanism of secondary malignant changes of benign tumors.

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  • Molecular pathological analysis of oral carcinoma caused by chewing habits in Asia

    Grant number：15256005

    2003 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (A)

    Awarding organization：Japan Society for the Promotion of Science

    SAKU Takashi, CHENG Jun, MARUYAMA Satoshi, IDA Hiroko, MIYAZAKI Hideo, NAGAO Toru

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    Grant amount：\34060000 （ Direct Cost: \26200000 、 Indirect Cost：\7860000 ）

    Oral cancers and its precancerous lesions were collected from Taiwan, India, Sri-Lanka, Bangladesh, Yemen, Madagascar, and Myanmar. Through the present collection of oral cancers and precancerous lesions, we have found lesions referred to as superficial carcinoma with or without the custom of chewing tobacco. The frequencies of oral carcinoma were shown to be related to chewing habits. The clinicopathological summary of superficial carcinoma in Japan was characterized by elder female patients, more commonly occurring in the tongue and gingival, less consumptions of tobacco for smoking and alcohol, but association with prosthetic treatments. In contrast, the lesion from Asian countries was found exclusively in the buccal mucosa and gingival, and the patients were mainly males with chewing habits. Histopathology of the superficial carcinoma of the Japanese and Asian patients resembled each other. They were commonly composed of carcinoma in-situ, which could be divided into three types, such as basaloid, verrucous, and acanthotic, and of surrounding epithelial dysplasia with the characteristic two-phase appearances. In addition, intraepithelial deposition of perlecan was demonstrated in epithelial dysplasia and carcinoma in-situ. This finding has been developed into a new concept of intraepithelial stroma. These two findings had greatly contributed to an objective histopathlogical diagnosis for oral borderline malignancies.
    Using paraffin-embedded specimens collected from Asian countries, oral submucous fibrosis and superficial carcinomas were investigated in by immunohistochemistry and in-situ hybridization, PCR, and DNA sequencing techniques. Histopathologically, oral submucous fibrosis was graded with immunohistochemical patterns of extracellular matrix remodeling. The final status of oral submucous fibrosis was also shown to be poorly vascularized or hypoxic, which were important background for oral carcinogenesis. DNA samples obtained by microdissection were analyzed for mutational events in cancer-related genes. Among them, there were several characteristic mutations in the p53 gene which were shared by the collected cases, although samples from Asian countries were not always appropriate for DNA extraction and following experiments.
    Samples of chewing staffs, such as betel, areca nuts, or qat, were organic-chemically demonstrated to have basically the same ingredients from area to area.
    The data obtained in this study showed that oral carcinomas caused by different environmental factors shared similar genetic alterations and histopathological characteristics.

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Teaching Experience

  • 臨床口腔細胞診断学演習IB

    2022
    Institution name：新潟大学

  • 臨床口腔細胞診断学演習IIA

    2022
    Institution name：新潟大学

  • 臨床口腔細胞診断学演習IA

    2022
    Institution name：新潟大学

  • 臨床口腔細胞診断学演習IIB

    2022
    Institution name：新潟大学

  • 臨床口腔病理学演習IB

    2021
    Institution name：新潟大学

  • 臨床口腔病理学演習IA

    2021
    Institution name：新潟大学

  • 臨床口腔病理学演習IIB

    2021
    Institution name：新潟大学

  • 臨床口腔病理学演習IIA

    2021
    Institution name：新潟大学

  • 齲蝕学

    2020
    Institution name：新潟大学

  • 臨床実習Ⅰ

    2020
    -
    2021
    Institution name：新潟大学

  • 臨床実習Ⅲ

    2020
    Institution name：新潟大学

  • 臨床実習Ⅱ

    2019
    -
    2021
    Institution name：新潟大学

  • 臨床口腔病理学演習ⅠA

    2018
    Institution name：新潟大学

  • う蝕学

    2015
    -
    2018
    Institution name：新潟大学

  • 臨床予備実習

    2010
    -
    2021
    Institution name：新潟大学

  • 病理学総論

    2007
    Institution name：新潟大学

  • 口腔病理学

    2007
    Institution name：新潟大学

  • 基礎科学演習

    2007
    -
    2015
    Institution name：新潟大学

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