Updated on 2026/03/05

写真a

 
YAMAZAKI Manabu
 
Organization
Academic Assembly Institute of Medicine and Dentistry SHIGAKU KEIRETU Associate Professor
Faculty of Dentistry Department of Dentistry Associate Professor
Graduate School of Medical and Dental Sciences Oral Life Science Tissue Regeneration and Reconstruction Associate Professor
Title
Associate Professor
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Degree

  • 博士（歯学） ( 2006.3   新潟大学 )

Research Interests

  • oral cancer

  • cell death

  • apoptosis

  • heterotopic nucleic acid

Research Areas

  • Life Science / Oral pathobiological science

Research History (researchmap)

  • Niigata University   Graduate School of Medical and Dental Sciences   Associate Professor

    2023.4

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  • 新潟大学大学院   医歯学総合研究科 口腔病理学分野   講師

    2021.4

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

    2009.7

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  • Niigata University   Graduate School of Medical and Dental Sciences   Researcher

    2009.4 - 2009.6

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  • 国立がん研究センター東病院   がん研究振興財団リサーチ・レジデント

    2006.4 - 2009.3

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Research History

  • Niigata University   Tissue Regeneration and Reconstruction, Oral Life Science, Graduate School of Medical and Dental Sciences   Associate Professor

    2023.4

  • Niigata University   School of Dentistry, Faculty of Dentistry   Associate Professor

    2023.4

  • Niigata University   Institute of Medicine and Dentistry, Academic Assembly   Associate Professor

    2023.4

  • Niigata University   Institute of Medicine and Dentistry, Academic Assembly   Lecturer

    2021.4 - 2023.3

  • Niigata University   School of Dentistry, Faculty of Dentistry   Lecturer

    2021.4 - 2023.3

  • Niigata University   Tissue Regeneration and Reconstruction, Oral Life Science, Graduate School of Medical and Dental Sciences   Lecturer

    2021.4 - 2023.3

  • Niigata University   Faculty of Dentistry School of Dentistry   Assistant Professor

    2009.7 - 2021.3

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

    2009.7 - 2021.3

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Education

  • 新潟大学大学院医歯学総合研究科 口腔病理学分野 大学院博士課程

    2002.4 - 2006.3

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  • Niigata University   歯学部

    1995.4 - 2001.3

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Qualification acquired

  • 死体解剖資格

  • Dentist

 

Papers

  • Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma 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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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3390/ijms24076035

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

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

    DOI： 10.1016/j.tranon.2021.101236

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

    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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  • 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   392 ( 1 )   112013 - 112013   2020.4

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

    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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  • CD36 expression on oral squamous cell carcinoma cells correlates with enhanced proliferation and migratory activity. Reviewed International journal

    Sakurai K, Tomihara K, Yamazaki M, Heshiki W, Moniruzzaman R, Sekido K, Tachinami H, Ikeda A, Imaue S, Fujiwara K, Noguchi M

    Oral Dis.   26 ( 4 )   745 - 755   2019.10

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

    OBJECTIVE: Recent studies have demonstrated the pro-tumour role of CD36 in multiple cancer types. However, its role has not been well elucidated in oral squamous cell carcinoma (OSCC). Here, we aimed to evaluate the role of CD36 in proliferation and migration of OSCC cells. METHODS: Human OSCC cell lines HSC-2, HSC-3, HSC-4 and Ca9-22 were assessed for proliferation by staining with the cell proliferation marker Ki-67. We also assessed migration activity, and the expression of cell adhesion molecules such as E-cadherin and β-catenin and platelet-derived growth factor receptors (PDGFRs) of CD36-positive cells. RESULTS: CD36-positive cells showed increased expression of Ki-67 and migration activity compared with CD36-negative cells. Moreover, CD36-positive cells showed reduced expression of E-cadherin and β-catenin, whereas the expression of PDGFRs increased compared with that in CD36-negative cells. CONCLUSIONS: Our results strongly suggest that CD36 has an important role in facilitating the proliferation and migration activity of OSCC cells, indicating its usefulness in the diagnosis of high-grade tumour and targeted therapy of oral cancer.

    DOI： 10.1111/odi.13210

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

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

    DOI： 10.1016/j.humpath.2016.07.001

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

    DOI： 10.1016/j.pathol.2016.02.006

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

    DOI： 10.1111/jop.12197

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

    DOI： 10.1038/labinvest.2014.108

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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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  • 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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  • 下顎歯肉癌を発症したBloom症候群の1例 Reviewed

    船山 昭典, 竹内 涼子, 齋藤 大輔, 須田 大亮, 羽賀 健太, 西山 秀昌, 林 孝文, 山崎 学, 田沼 順一, 小林 正治

    日本口腔科学会雑誌   73 ( 2 )   207 - 207   2024.9

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

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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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  • Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer Reviewed

    Mayu Takaichi, Hidetake Tachinami, Danki Takatsuka, Amirmoezz Yonesi, Kotaro Sakurai, Muhammad Irfan Rasul, Shuichi Imaue, Shin-Ichi Yamada, Muhammad Ruslin, Manabu Yamazaki, Jun-Ichi Tanuma, Makoto Noguchi, Kei Tomihara

    International Journal of Molecular Sciences   25 ( 17 )   9438 - 9438   2024.8

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

    The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.

    DOI： 10.3390/ijms25179438

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  • The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy Reviewed

    Eriko Naito, Kazuyo Igawa, Sho Takada, Kenta Haga, Witsanu Yortchan, Orakarn Suebsamarn, Ryota Kobayashi, Manabu Yamazaki, Jun-ichi Tanuma, Tsuyoshi Hamano, Takashi Shimokawa, Kei Tomihara, Kenji Izumi

    In Vitro Cellular & Developmental Biology - Animal   2024.8

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

    DOI： 10.1007/s11626-024-00958-4

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    Other Link： https://link.springer.com/article/10.1007/s11626-024-00958-4/fulltext.html

  • PAK4 inhibition augments anti-tumour effect by immunomodulation in oral squamous cell carcinoma. Reviewed International journal

    Danki Takatsuka, Hidetake Tachinami, Nihei Suzuki, Manabu Yamazaki, Amirmoezz Yonesi, Mayu Takaichi, Shuichi Imaue, Shin-Ichi Yamada, Jun-Ichi Tanuma, Makoto Noguchi, Kei Tomihara

    Scientific reports   14 ( 1 )   14092 - 14092   2024.6

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

    Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours, warranting novel treatments. Here, we examined the therapeutic efficacy of inhibiting p21 activated kinase 4 (PAK4) in OSCC and determined its immunomodulatory effect by focusing on the enhancement of anti-tumour effects. We examined PAK4 expression in OSCC cells and human clinical samples and analysed the proliferation and apoptosis of OSCC cells following PAK4 inhibition in vitro. We also investigated the effects of in vivo administration of a PAK4 inhibitor on immune cell distribution and T-cell immune responses in OSCC tumour-bearing mice. PAK4 was detected in all OSCC cells and OSCC tissue samples. PAK4 inhibitor reduced the proliferation of OSCC cells and induced apoptosis. PAK4 inhibitor significantly attenuated tumour growth in mouse and was associated with increased proportions of IFN-γ-producing CD8+ T-cells. Furthermore, PAK4 inhibitor increased the number of dendritic cells (DCs) and up-regulated the surface expression of various lymphocyte co-stimulatory molecules, including MHC-class I molecules, CD80, CD83, CD86, and CD40. These DCs augmented CD8+ T-cell activation upon co-culture. Our results suggest that PAK4 inhibition in OSCC can have direct anti-tumour and immunomodulatory effects, which might benefit the treatment of this malignancy.

    DOI： 10.1038/s41598-024-64126-0

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

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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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  • 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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  • 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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    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 Reviewed

    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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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    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.

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

    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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    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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    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.

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  • Rosai-Dorfman disease of the maxilla: A rare case report and literature review Reviewed

    Takahiro Nagai, Manabu Yamazaki, Atsushi Nishikawa, Yasumitsu Kodama, Hideyoshi Nishiyama, Takafumi Hayashi, Jun-ichi Tanuma, Ritsuo Takagi, Kei Tomihara

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   34 ( 5 )   665 - 671   2022.9

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    DOI： 10.1016/j.ajoms.2022.02.007

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  • Solitary central osteoma of the mandible with unusual clinicoradiological presentations: A case report and literature review Reviewed

    Nyein Nyein Chan, Manabu Yamazaki, Hidenobu Sakuma, Takafumi Hayashi, Tadaharu Kobayashi, Jun‐ichi Tanuma

    Oral Science International   2022.7

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    Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/osi2.1155

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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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    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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  • 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.

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

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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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    OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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  • Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells. International journal

    Rie Akyu Takei, Kei Tomihara, Manabu Yamazaki, Rohan Moniruzzaman, Wataru Heshiki, Katsuhisa Sekido, Hidetake Tachinami, Kotaro Sakurai, Amirmoezz Yonesi, Shuichi Imaue, Kumiko Fujiwara, Makoto Noguchi

    Oral surgery, oral medicine, oral pathology and oral radiology   132 ( 5 )   549 - 565   2021.4

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    OBJECTIVE: Accumulating evidence has demonstrated the protumor role of estrogen receptor (ER)-mediated signaling in multiple cancer types, which is distinct from this signaling in sex steroid-dependent organs. However, its role in oral squamous cell carcinoma (OSCC) remains unclear. STUDY DESIGN: We assessed the expression of ERα and ERβ in human OSCC tissues by immunohistochemistry and evaluated the expression of both receptors in OSCC cell lines by immunoblotting and flow cytometry. To further assess the contribution of ER-mediated signals to oral cancer progression, proliferation, invasion, and chemosensitivity, cell lines were stimulated with the ER agonist β-estradiol. RESULTS: Immunohistochemical analysis of OSCC tissues showed that ERβ was present in the cytoplasm and nuclei of OSCC cells. In contrast, ERα was not detected in any of the cases analyzed. Additionally, the proliferation and invasiveness of OSCC cells were significantly elevated following stimulation with β-estradiol. Chemotherapeutic agent-induced apoptosis of cancer cells was attenuated by pretreatment with β-estradiol. CONCLUSIONS: ER-mediated signaling plays a crucial role in oral cancer progression by facilitating the proliferation, invasion, and chemoresistance of OSCC cells, indicating its potential for developing novel targeted therapies for this type of cancer.

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  • Identification and characterization of R2TP in the development of oral squamous cell carcinoma. International journal

    Tetsuo Kiguchi, Yoshito Kakihara, Manabu Yamazaki, Kouji Katsura, Kenji Izumi, Jun-Ichi Tanuma, Takashi Saku, Ritsuo Takagi, Makio Saeki

    Biochemical and biophysical research communications   548   161 - 166   2021.4

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    R2TP is a well-conserved molecular chaperone complex, composed of Pontin, Reptin, RPAP3, and PIH1D, in eukaryotes. Recent studies have suggested an involvement of R2TP in cancer development. However, it remains unclear if it is related to the development of oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer. Here, we identify and investigate the function of R2TP in OSCC development. Immunohistochemical analysis reveals that all of the R2TP components are strongly expressed in normal oral epithelia and OSCC tissues, where actively proliferating cells are abundant. Co-immunoprecipitation assay identifies that R2TP components form a protein complex in OSCC-derived HSC4-cells. Knockdown experiments show that all R2TP components, except for RPAP3, are required for the cell proliferation and migration of HSC-4 cells. Furthermore, we reveal that Pontin contributes to a gain-of-function (GOF) activity of mutp53-R248Q in HSC-4 cells by regulating phosphorylation levels of mutp53 at Ser15 and Ser46. To our knowledge, this study is the first to report the functional involvement of R2TP and its components in the malignant characteristics of OSCC cells.

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  • A case of anti-laminin 332 mucous membrane pemphigoid manifesting as desquamative gingivitis

    Sahoko Imai Maeda, Kumiko Fujiwara, Kei Tomihara, Manabu Yamazaki, Shuichi Imaue, Makoto Noguchi

    ORAL SCIENCE INTERNATIONAL   18 ( 1 )   73 - 77   2021.1

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    DOI： 10.1002/osi2.1073

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  • Corrigendum to “An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue” [Int J Oral Maxillofac Surg 49 (2020) 1290–1203] (International Journal of Oral … Maxillofacial Surgery (2020) 49(10) (1290–1293), (S0901502720301399), (10.1016/j.ijom.2020.04.010))

    K. Sakurai, K. Nakamori, M. Yamazaki, J. I. Tanuma

    International Journal of Oral and Maxillofacial Surgery   2021

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    DOI： 10.1016/j.ijom.2021.05.021

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  • 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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  • 前舌腺に発生した腺癌NOSの1例

    三上 俊彦, 船山 昭典, 西山 秀昌, 山崎 学, 田沼 順一, 小林 正治

    日本口腔外科学会雑誌   66 ( 11 )   553 - 558   2020.11

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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, 西山 秀昌, 山崎 学, 田沼 順一, 小林 正治

    日本口腔外科学会雑誌   66 ( 11 )   553 - 558   2020.11

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    52歳女。舌の違和感を主訴に近医を受診し、右側舌腫瘍を指摘された。他院のMRIで腫瘍性病変を認められ、当科での加療を勧められて来院した。右側舌下面粘膜下に15×15×15mm大の比較的境界明瞭な弾性硬の腫瘤を認めた。画像所見からは腺系腫瘍が示唆され、良悪性を含めた病理組織学的診断目的に生検を行ったが、組織型の確定には至らず、舌癌の診断のもと全身麻酔下に舌部分切除術を施行した。切除標本の病理組織所見は、淡明細胞の胞巣状増殖が主体ながら、粘液産生を示す二相性腺管がわずかに混在していたことから、鑑別疾患として筋上皮癌、上皮筋上皮癌、多型腺癌、明細胞癌が挙げられた。免疫染色によって筋上皮癌、上皮筋上皮癌、多型腺癌は否定され、EWSR1遺伝子のFISH解析によって明細胞癌も否定されたため腺癌NOS(not otherwise specified)と診断した。術後4年の現在まで再発・転移は認めていない。

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  • Keratin 17-positive Civatte bodies in oral lichen planus-distribution variety, diagnostic significance and histopathogenesis. Reviewed International journal

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

    Scientific reports   10 ( 1 )   14586 - 14586   2020.9

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    Although emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+ speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+ epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.

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  • An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue. Reviewed International journal

    K Sakurai, K Nakamori, M Yamazaki, J-I Tanuma

    International journal of oral and maxillofacial surgery   2020.5

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    Ectomesenchymal chondromyxoid tumour (ECT) is an extremely rare intraoral mesenchymal tumour. Most of these tumours have been identified on the anterior aspect of the dorsal surface of the tongue. ECT is difficult to diagnose because of its rarity. We report a case of ECT arising on the lateral border of the tongue in a 67-year-old woman. The tumour, measuring 20 × 10 mm in size, was surgically removed. Histopathologically, the tumour was composed of small polygonal cells arranged in sheets, with a myxoid or hyalinized stroma. The tumour boundary was clear; however, the tumour showed a multinodular structure expanding along the tongue surface without obvious capsule. Careful examination revealed the tumour nodule to be spreading in a skip lesion-like fashion away from the main part of the tumour in the striated muscle layer. Although there was no evidence of recurrence at 18 months after the surgery, our observations suggest that surgery for ECT resection with a safety margin is more appropriate than enucleation.

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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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  • 下顎骨に発生した象牙質形成性幻影細胞腫の1例 Reviewed

    船山 昭典, 三上 俊彦, 新美 奏恵, 片桐 渉, 金丸 祥平, 西山 秀昌, 林 孝文, 阿部 達也, 山崎 学, 小林 正治

    日本口腔科学会雑誌   68 ( 2 )   188 - 188   2019.7

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  • Severe stomatitis caused by misuse of methotrexate in an elderly patient with chronic rheumatoid arthritis

    Kohta Yamada, Kei Tomihara, Manabu Yamazaki, Makoto Noguchi

    JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY   31 ( 4 )   284 - 287   2019.7

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    DOI： 10.1016/j.ajoms.2018.06.009

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

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

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   31 ( 2 )   86 - 93   2019.3

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    DOI： 10.1016/j.ajoms.2018.07.010

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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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  • Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas Reviewed

    Kazuki Hashimoto, Ryuichi Hayashi, Takashi Mukaigawa, Manabu Yamazaki, Satoshi Fujii

    HUMAN PATHOLOGY   63   110 - 119   2017.5

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    DOI： 10.1016/j.humpath.2017.02.017

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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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    DOI： 10.1016/j.yexmp.2017.02.018

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  • Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b(+)Gr-1(+) cells and its contribution to immunosuppressive activity Reviewed

    Hiroki Fuse, Kei Tomihara, Wataru Heshiki, Manabu Yamazaki, Rie Akyu-Takei, Hidetake Tachinami, Ken-ichiro Furukawa, Kotaro Sakurai, Moniruzzaman Rouwan, Makoto Noguchi

    ORAL ONCOLOGY   59   20 - 29   2016.8

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    DOI： 10.1016/j.oraloncology.2016.05.012

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  • Electron Probe Microanalysis of Exogenous Pigmentation of Oral Mucosa Originating from Dental Alloy: Two Case Reports Reviewed

    Funayama A, Mikami T, Niimi1 K, Kano H, Nikkuni Y, Yamazaki M, Kobayashi T

    Open Journal of Stomatology   2016 ( 6 )   120 - 126   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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  • 放射線性骨髄炎後に発生し生検で肉腫が疑われた扁平上皮癌の1例

    隅田 賢正, 勝見 祐二, 小玉 直樹, 小山 貴寛, 安島 久雄, 星名 秀行, 程 くん, 山崎 学, 林 孝文, 高木 律男

    日本口腔科学会雑誌   64 ( 4 )   348 - 348   2015.12

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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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    DOI： 10.1111/jop.12290

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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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    DOI： 10.1016/j.oooo.2015.04.001

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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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    DOI： 10.1016/j.humpath.2015.03.003

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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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    DOI： 10.1007/s00428-015-1735-6

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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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    DOI： 10.1007/s00418-014-1198-x

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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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    DOI： 10.1111/jop.12184

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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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  • Detection of subsequent cervical lymph node metastasis in a patient with gingival carcinoma using computed tomography perfusion with a single-compartment kinetic model Reviewed

    Takafumi Hayashi, Ray Tanaka, Manabu Yamazaki, Jun Cheng, Yohei Oda, Harumi Hayashi, Etsuro Takeishi, Katsuhiko Honma, Hideyoshi Nishiyama

    ORAL RADIOLOGY   30 ( 2 )   186 - 191   2014.5

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    DOI： 10.1007/s11282-013-0153-1

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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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    DOI： 10.1016/j.humpath.2013.08.011

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  • Identification of a soluble isoform of human IL-17RA generated by alternative splicing Reviewed

    Miwa Sohda, Yoshio Misumi, Kosuke Tashiro, Manabu Yamazaki, Takashi Saku, Kimimitsu Oda

    CYTOKINE   64 ( 3 )   642 - 645   2013.12

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    DOI： 10.1016/j.cyto.2013.09.012

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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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  • 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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    DOI： 10.1038/labinvest.2013.86

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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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  • Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx Reviewed

    Satoshi Fujii, Hideoki Uryu, Ken Akashi, Kensuke Suzuki, Manabu Yamazaki, Makoto Tahara, Ryuichi Hayashi, Atsushi Ochiai

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   18 ( 3 )   454 - 463   2013.6

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    DOI： 10.1007/s10147-012-0402-z

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  • Inflammatory histopathogenesis of nasopalatine duct cyst: A clinicopathological study of 41 cases Reviewed

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

    Oral Diseases   19 ( 4 )   415 - 424   2013.5

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    DOI： 10.1111/odi.12022

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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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    DOI： 10.1016/j.bbrc.2013.03.057

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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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    DOI： 10.1007/s00428-012-1359-z

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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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    DOI： 10.1016/j.humpath.2012.02.006

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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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    DOI： 10.1038/modpathol.2011.218

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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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  • 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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    DOI： 10.1016/j.prp.2011.12.016

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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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  • 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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    DOI： 10.1111/j.1600-0714.2010.00990.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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  • 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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  • Morphologic evaluation of the inferior alveolar nerve in patients with sensory disorders by high-resolution 3D volume rendering magnetic resonance neurography on a 3.0-T system Reviewed

    Makoto Terumitsu, Kenji Seo, Hitoshi Matsuzawa, Manabu Yamazaki, Ingrid L. Kwee, Tsutomu Nakada

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY   111 ( 1 )   95 - 102   2011.1

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    DOI： 10.1016/j.tripleo.2010.09.002

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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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  • 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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  • High expression level of geminin predicts a poor clinical outcome in salivary gland carcinomas Reviewed

    Manabu Yamazaki, Satoshi Fujii, Yukinori Murata, Ryuichi Hayashi, Atsushi Ochiai

    HISTOPATHOLOGY   56 ( 7 )   883 - 892   2010.6

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    DOI： 10.1111/j.1365-2559.2010.03561.x

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  • Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinoma Reviewed

    Satoshi Fujii, Manabu Yamazaki, Manabu Muto, Atsushi Ochiai

    HISTOPATHOLOGY   56 ( 4 )   510 - 522   2010.3

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  • Targeting of Bone-Derived Insulin-Like Growth Factor-II by a Human Neutralizing Antibody Suppresses the Growth of Prostate Cancer Cells in a Human Bone Environment Reviewed

    Taichi Kimura, Takeshi Kuwata, Satoshi Ashimine, Manabu Yamazaki, Chisako Yamauchi, Kanji Nagai, Akashi Ikehara, Yang Feng, Dimiter S. Dimitrov, Seiichi Saito, Atsushi Ochiai

    CLINICAL CANCER RESEARCH   16 ( 1 )   121 - 129   2010.1

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    DOI： 10.1158/1078-0432.CCR-09-0982

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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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  • 唾液腺癌におけるGemininの発現レベルと予後との関連(High expression level of geminin predicts a poor clinical outcome in salivary gland carcinomas)

    山崎 学, 藤井 誠志, 林 隆一, 落合 淳志

    日本癌学会総会記事   68回   349 - 350   2009.8

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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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  • Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy Reviewed

    Shuji Ota, Genichiro Ishii, Koichi Goto, Kaoru Kubota, Young Hak Kim, Masakazu Kojika, Yukinori Murata, Manabu Yamazaki, Yutaka Nishiwaki, Kenji Eguchi, Atsushi Ochiai

    LUNG CANCER   64 ( 1 )   98 - 104   2009.4

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    DOI： 10.1016/j.lungcan.2008.07.014

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

    Journal of Oral Pathology and Medicine   38 ( 4 )   348 - 355   2009.4

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    DOI： 10.1111/j.1600-0714.2009.00750.x

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  • Carcinoma showing thymus-like differentiation (CASTLE) with neuroendocrine differentiation Reviewed

    Manabu Yamazaki, Satoshi Fujii, Hiroyuki Daiko, Ryuichi Hayashi, Atsushi Ochiai

    PATHOLOGY INTERNATIONAL   58 ( 12 )   775 - 779   2008.12

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    DOI： 10.1111/j.1440-1827.2008.02310.x

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  • 下顎骨粘液腫

    山崎学, 船山昭典, 林孝文, 鈴木誠

    新潟歯学会雑誌   34 ( 1 )   41 - 44   2004.8

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  • A case of isolated osteoma in the maxillary sinus of a patient with jaw deformity

    OKUBO Hiroki, FUKUDA Jun-ichi, HOSHINA Hideyuki, YAMAZAKI Manabu, SAKU Takashi, HAYASHI Takafumi

    Journal of Oral Surgery Society of Japan   50 ( 3 )   193 - 196   2004.3

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    Osteoma in the maxillary sinus, especially isolated osteoma, is very rare in Japan. We present a case of isolated osteoma in the maxillary sinus that was detected by chance on cephalograms obtained before surgical orthodontic treatment to correct facial asymmetry. There were no signs or symptoms caused by the osteoma. After orthodontic treatment for 3 years, the tumor was removed simultaneously with Le Fort I osteotomy under general anesthesia. The tumor was encapsulated by fibrous tissue and was isolated from the maxillary sinus wall. It measured 28×14×12 mm. Histopathologically, the lesion was diagnosed as an osteoma. There has been no sign of recurrence for 3 years after surgery. Reports of Japanese cases of osteomas of the maxillary sinus are clinicopathologically reviewed.

    DOI： 10.5794/jjoms.50.193

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    Other Link： http://search.jamas.or.jp/link/ui/2004189735

  • Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: A possible pathogenesis of cholesterol granulomas in jaw cysts Reviewed

    Manabu Yamazaki, Jun Cheng, Natsuko Hao, Ritsuo Takagi, Shiro Jimi, Hiroyuki Itabe, Takashi Saku

    Journal of Oral Pathology and Medicine   33 ( 3 )   177 - 184   2004.3

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    DOI： 10.1111/j.0904-2512.2004.00087.x

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  • Maxillary odontogenic keratocyst with respiratory epithelium: A case report Reviewed

    Manabu Yamazaki, Jun Cheng, Tsutomu Nomura, Chikara Saito, Takafumi Hayashi, Takashi Saku

    Journal of Oral Pathology and Medicine   32 ( 8 )   496 - 498   2003.9

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    DOI： 10.1034/j.1600-0714.2003.00149.x

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MISC

  • 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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  • Extensive ameloblastic fibroma of the mandible in a middle-aged female

    羽賀健太, 船山昭典, 長谷部大地, 佐久間英伸, 齋藤大輔, 新美奏恵, 曽束洋平, 山崎学, 田沼順一, 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   41st   2023

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  • Rapamycin induces phenotypic alterations of oral cancer cells that facilitate antitumor T cell response

    AMRIMOEZZ Yonesi, 冨原圭, 高塚団貴, 立浪秀剛, 山崎学, 高市真由, AMIRREZA Younesi, 山田慎一, 田沼順一, 野口誠

    日本口腔科学会学術集会プログラム・抄録集   77th   2023

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  • 口腔癌と口腔粘膜に対する重粒子線照射の影響に関する3次元in vitroモデルを用いた研究

    泉健次, 内藤絵里子, 内藤絵里子, 井川和代, 羽賀健太, 小林亮太, 小林亮太, 齋藤夕子, 山崎学, 田沼順一, 冨原圭

    日本口腔科学会学術集会プログラム・抄録集   77th   2023

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  • 口腔癌および口腔粘膜3次元in vitroモデルに対する重粒子線照射の影響に関する研究 異種放射線治療評価の標準化システムの構築

    内藤 絵里子, 高田 翔, 羽賀 健太, Suebsamarn Orakarn, Witsanu Yortchan, 小林 亮太, 鈴木 絢子, 山崎 学, 田沼 順一, 冨原 圭, 泉 健次

    新潟歯学会雑誌   52 ( 2 )   97 - 98   2022.12

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  • 正常口腔粘膜細胞と口腔癌細胞を用いた3次元in vitroモデル作製法とその応用

    内藤 絵里子, 小林 亮太, 羽賀 健太, 齊藤 夕子, 山崎 学, 田沼 順一, 井川 和代, 冨原 圭, 泉 健次

    日本口腔科学会雑誌   71 ( 2 )   61 - 61   2022.7

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  • 正常口腔粘膜細胞と口腔癌細胞を用いた3次元in vitroモデル作製法とその応用

    内藤 絵里子, 小林 亮太, 羽賀 健太, 齊藤 夕子, 山崎 学, 田沼 順一, 井川 和代, 冨原 圭, 泉 健次

    日本口腔科学会雑誌   71 ( 2 )   61 - 61   2022.7

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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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  • 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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  • 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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  • Response to Letter to the Editor “Ectomesenchymal chondromyxoid tumour on the lateral border of the tongue: some historical and clinical considerations”

    K. Sakurai, K. Nakamori, M. Yamazaki, J. I. Tanuma

    International Journal of Oral and Maxillofacial Surgery   50 ( 10 )   1401   2021.10

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    Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：Churchill Livingstone  

    DOI： 10.1016/j.ijom.2020.11.026

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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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  • 癌関連線維芽細胞は口腔扁平上皮癌においてTGF-β/SOX9経路を介して遊走および浸潤を促進する

    羽賀 健太, 山崎 学, 船山 昭典, 三上 俊彦, 新美 奏恵, 小林 正治, 田沼 順一

    日本口腔科学会雑誌   69 ( 2 )   131 - 131   2020.7

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  • 癌関連線維芽細胞は口腔扁平上皮癌においてTGF-β/SOX9経路を介して遊走および浸潤を促進する

    羽賀 健太, 山崎 学, 船山 昭典, 三上 俊彦, 新美 奏恵, 小林 正治, 田沼 順一

    日本口腔科学会雑誌   69 ( 2 )   131 - 131   2020.7

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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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  • 下顎水平埋伏智歯の歯冠部に生じた下顎骨中心性癌の1例

    小林 亮太, 児玉 泰光, 新國 農, 山崎 学, 黒川 亮, 上野山 敦士, 笠原 映, 田沼 順一, 林 孝文, 高木 律男

    日本口腔科学会雑誌   69 ( 2 )   99 - 99   2020.7

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 口蓋に発生した唾液腺導管癌の1例

    笠原 映, 勝見 祐二, 大貫 尚志, 永田 昌毅, 山崎 学, 西山 秀昌, 田沼 順一, 林 孝文, 高木 律男

    日本口腔科学会雑誌   68 ( 2 )   114 - 115   2019.7

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  • メトトレキサート投与中止後、顎骨に発生したと考えられたメトトレキサート関連リンパ増殖性疾患の1例

    河原田 壮史, 片桐 渉, 荻野 奈保子, 齋藤 大輔, 三上 俊彦, 船山 昭典, 新美 奏恵, 山崎 学, 田沼 順一, 小林 正治

    日本口腔科学会雑誌   68 ( 2 )   172 - 172   2019.7

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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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  • 口蓋に発生した唾液腺導管癌の1例

    笠原映, 勝見祐二, 大貫尚志, 永田昌毅, 山崎学, 西山秀昌, 田沼順一, 林孝文, 高木律男

    日本口腔科学会学術集会プログラム・抄録集   73rd   162   2019

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  • 下顎骨に発生した歯原性癌腫の1例

    原夕子, 小玉直樹, 池田順行, 小山貴寛, 勝見祐二, 新垣元基, 隅田賢正, 木口哲郎, 西山昌秀, 林孝文, 山崎学, 田沼順一, 永田昌毅, 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   141   2019

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  • メトトレキサート投与中止後,顎骨に発生したと考えられたメトトレキサート関連リンパ増殖性疾患の1例

    河原田壮史, 片桐渉, 荻野奈保子, 齋藤大輔, 三上俊彦, 船山昭典, 新美奏恵, 山崎学, 田沼順一, 小林正治

    日本口腔科学会学術集会プログラム・抄録集   73rd   242   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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  • 末梢神経再生における脂肪組織由来幹細胞,脱分化脂肪細胞由来cell extractの有用性の検討

    岸本直隆, 山崎学, 田沼順一, 瀬尾憲司

    日本再生医療学会総会(Web)   18th   ROMBUNNO.P‐03‐035 (WEB ONLY)   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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  • 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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  • 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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  • 舌下腺に発生した多形腺腫の1例

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

    日本口腔科学会雑誌(Web)   67 ( 2 )   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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  • 分子シャペロンR2TPの口腔扁平上皮癌進展における作用機序の解析

    木口 哲郎, 柿原 嘉人, 山崎 学, 高木 律男, 佐伯 万騎男

    Journal of Oral Biosciences Supplement   2017   256 - 256   2017.9

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 口腔癌の新たな治療戦略のための分子病理 口腔扁平上皮癌細胞による死細胞貪食の分子機構とその意義

    山崎 学

    Journal of Oral Biosciences Supplement   2015   144 - 144   2015.9

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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・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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  • 下顎骨エナメル上皮腫・腺様歯原性腫瘍ハイブリッド腫瘍の1例

    藤田 一, 池田 順行, 齋藤 太郎, 高木 律男, 林 孝文, 山崎 学, 朔 敬

    日本口腔外科学会雑誌   56 ( Suppl. )   247 - 247   2010.9

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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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  • Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome

    Satoshi Fujii, Shuichi Mitsunaga, Manabu Yamazaki, Takahiro Hasebe, Genichiro Ishii, Motohiro Kojima, Taira Kinoshita, Takashi Ueno, Hiroyasu Esumi, Atsushi Ochiai

    CANCER SCIENCE   99 ( 9 )   1813 - 1819   2008.9

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  • 口腔血管平滑筋腫の臨床病理学的検討

    西澤 理史歩, 山崎 学, 星名 秀行, 長島 克弘, 高木 律男, 齊藤 力, 朔 敬, 猪本 正人

    日本口腔外科学会雑誌   49 ( 13 )   750 - 750   2003.12

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Research Projects

  • 嗅覚と唾液は自発性異常味覚の苦味を説明できるか？

    Grant number：24K13258

    2024.4 - 2027.3

    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

    船山 さおり, 伊藤 加代子, 任 智美, 濃野 要, 藤村 忍, 山崎 学, 井上 誠

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

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

    Grant number：24K12895

    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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  • 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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  • 腫瘍関連免疫抑制性細胞を標的とした口腔癌に対する新たな免疫療法の開発研究

    Grant number：22K10214

    2022.4 - 2025.3

    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

    冨原 圭, 山崎 学, 立浪 秀剛, 野口 誠

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

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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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  • 免疫学的アプローチによるびまん性浸潤口腔扁平上皮癌の制御に関する基礎的研究

    Grant number：21K10065

    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

    野口 誠, 山崎 学, 藤原 久美子, 冨原 圭

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

    骨髄由来免疫抑制性細胞（MDSC）は腫瘍局所で破骨細胞分化を促進機序、腫瘍局所におけるMDSCの特異的標的化について、C3H/HeNマウス由来の口腔扁平上皮癌NR-S1K細胞およびSCCVII細胞と同マウスを用いシンジェニック口腔癌モデルを作製し、以下の内容について3年計画で検証を予定している。
    １．口腔扁平上皮癌担癌宿主におけるMDSCの形質や機能の特性とその標的化を検証する。
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    ２．MDSCの標的化戦略に基づいて抗腫瘍効果を、マウスモデルを用いた治療実験で検証する。研究代表者の先行研究で、低用量ゲムシタビン投与が、口腔癌担癌マウスの腫瘍組織から、MDSCを選択的に除去することを明らかとした。また、口腔癌マウス由来のMDSCでは、PD-L1の発現が増強し、免疫抑制機能に重要な役割を果たしていることを明らかとした。そこで、以下のような治療実験を行う。
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    コロナ禍のため動物実験が思うように進ま図にいるが、ここ数年間の感染状況を例に今後は年間に計画的なスケジュールをたて遂行する予定である。しかしながら、ヒト口腔癌患者のMDSCサブセットを同定したことでPD-1免疫チェックポイント阻害剤投与後の２に対するヒトでの検証が可能となり今後も継続予定である。

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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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  • 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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  • 自発性異常味覚の苦味の正体にせまる

    Grant number：20K10264

    2020.4 - 2023.3

    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

    船山 さおり, 井上 誠, 山崎 学, 藤村 忍, 伊藤 加代子, 濃野 要

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

    本年度は，主に自発性異常味覚患者のデータ収集に努めた．また，味覚センサーの測定条件の検証を行った昨年度の結果をもとに，実際のデータ測定を進めている．今年度は，昨年はコロナ禍で他施設の利用ができずに不可能であった，味覚センサーの測定も進められた．苦味の詳細は，唾液の成分分析を行った後，考察を行えるようになる．しかしながら，唾液の成分分析は資金繰りの都合上，全データ収集後に行う予定であり，データ収集が遅れているため，いまだ行えていないのが現状である．

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  • Novel strategy for oral cancer targeting myeloid-derived suppressor cells

    Grant number：19K10262

    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

    Tomihara Kei

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

    We investigated whether aging affected the proportion of these immune regulatory cells in oral cancer-bearing mice. The proportion of MDSCs was significantly increased in tumors but not in other organs of aged mice compared to that in young mice. The proportions of CD44 high and CD62L low CD4 T cells were significantly increased in peripheral blood, cervical lymph nodes, peripheral lymph nodes, spleen, and tumors of aged mice compared to those in young mice. The proportions of CD44 high and CD62L low CD8 T cells were significantly increased in peripheral blood, cervical lymph nodes, peripheral lymph nodes, spleen, but not in tumors of aged mice compared to that in young mice.
    Our results indicate that age-associated alterations in the immune system are directly associated with the impairment of anti-tumor immunity in aged mice bearing oral cancer, and might facilitate the progression of the tumor.

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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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  • Oral squamous cell carcinoma and cetuximab loop theory

    Grant number：18K09504

    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

    Saeki Makio

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

    R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma). Finally, we provide an overview of current anti-cancer drug development efforts targeting R2TP/PAQosome.

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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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  • Novel strategy targeting myeloid cells-mediated invasion of oral cancer

    Grant number：18K09741

    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

    Noguchi Makoto

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

    In this study, we aimed to establish novel strategy to target myeloid derived suppressor cell (MDSC)-mediated invasion of oral cancer. Osteoclast differentiation is crucial for bone invasion of oral cancer and one of the cell surface marker for osteoclast is CD11b which is also the marker of MDSC. Therefore, the similarity of osteoclast and MDSC have been suggested. Moreover, the cancer-associated fibroblasts are also important for tumor invasion in various cell types of cancer. We observed that PDGFR-alpha positive cells were accumulated in oral cancer-bearing mice and these cells also expressed CD11b and Gr-1, suggesting that association between CAF and MDSC. Moreover, we purified these CD11b+, Gr-1+ cells from spleen, peripheral blood, and tumor tissue, and evaluated the capacity for osteoclast differentiation. CD11b+, Gr-1+ cells from tumor tissue exhibited significantly increased capacity for osteoclast differentiation compared to those from other sites.

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  • Identification of novel targets and concepts for cancer therapy

    Grant number：17K19748

    2017.6 - 2019.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

    Terunuma Miho, Amaya Yoshihiro, Harada Fumiko

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

    We examined the anticancer effect of cellular energy sensor AMPK and inhibitory neurotransmitter receptor GABAB receptor and their functional crosstalk in oral cancer cells. We found that the structure of GABAB receptors are different from that of neuronal GABAB receptors and their activation did not induce anti-cancer effect. On the other hand, AMPK activation strongly suppressed the cancer proliferation. Therefore, in oral cancer, AMPK downstream signaling maybe a good target for novel drug development.

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  • Examination of five factors related to the diagnosis of phantogeusia.

    Grant number：17K12043

    2017.4 - 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

    Funayama Saori

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

    “Phantogeusia”is a type of taste disorder that describes the distortion of taste in an individual.We hypothesized that a bitter substance in the oral cavity was represented in the salivary Mg, and that these substances are the components of medication, and psychological stress, and may induce bitter taste phantoms. Therefore, to determine the risk factors related to bitterness of Phantogeusia, we investigated clinical patient data that targeted salivary Mg, hyposalivation, adverse drug reaction, psychological stress, and disease, and compared the results to a control group of healthy adults. Our results show that hyposalivation may be a key factor in influencing the phantom sensation of bitterness. In addition, as other risk factors, the salivary magnesium level, adverse drug reaction, psychological stress were also causal factors.These risk factors may be useful for the diagnosis of phantogeusia.

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  • Targeting strategy against myeloid suppressor cells in mouse model of aged oral cancer

    Grant number：16K11720

    2016.4 - 2019.3

    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

    Tomihara Kei

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

    We showed that myeloid derived suppressor cells (MDSCs) are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. In particular, MDSCs in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, MDSCs from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of MDSCs in mice with oral squamous cell carcinoma. The proportion of MDSCs was significantly increased in aged oral cancer-bearing mice. The data also indicate that PD-L1 expression in MDSCs contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.

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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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  • Upregulation of cancer cell functions by apoptotic cell engulfment

    Grant number：25861740

    2013.4 - 2015.3

    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

    YAMAZAKI Manabu

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

    Apoptotic oral squamous cell carcinoma (SCC) cells are engulfed by macrophages or even by neighboring SCC cells. We hypothesized that engulfment of apoptotic carcinoma cells by living carcinoma cells are promoted via MFG-E8, one of phagocytosis regulating molecules, and this phenomenon could contribute to tumor progression. Transient MFG-E8 overexpression in SCC cell lines increased migration, invasiveness, and engulfment of apoptotic cells. Thus we have demonstrated that MFG-E8 is involved in the clearance of apoptotic carcinoma cells by living carcinoma cells, and it might promote tumor progression in oral SCC.

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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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  • Apoptotic cell engulfment by cancer cells

    Grant number：23792099

    2011 - 2012

    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

    YAMAZAKI Manabu

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

    Apoptotic oral squamous cell carcinoma (SCC) cells are engulfed not only by macrophages but also by neighboring SCC cells, which could be a potential anti-cancer avenue. Since apoptotic SCC cells were immunohistochemically positive for milk fat globule-epidermal growth factor-factor 8 (MFG-E8), one of the phagocytosis regulating molecules, apoptotic SCC cells were suggested to be removed by the MFG-E8-related phagocytotic pathways. In addition, MFG-E8 was simultaneously expressed in SCC cells forming small foci at the invading front, and its expression levels in SCC cells in culture were correlated with cell growth, anti-apoptotic activity and invasion. The results indicated that the apoptotic cell clearance via MFG-E8 produced by cancer cells enhances aggressiveness of cancer cell behaviors.

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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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  • 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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Teaching Experience

  • 臨床実習I

    2022
    Institution name：新潟大学

  • 臨床実習II

    2022
    Institution name：新潟大学

  • 臨床予備実習

    2022
    Institution name：新潟大学

  • 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

  • 基礎歯学ｺｰｽﾜｰｸ(口腔病理学ベーシックコースII)

    2021
    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

  • 基礎歯学ｺｰｽﾜｰｸ(口腔病理学ベーシックコースI)

    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

  • 口腔と全身との関わり

    2020
    Institution name：新潟大学

  • 齲蝕学

    2020
    Institution name：新潟大学

  • 疾病とその病態

    2019
    Institution name：新潟大学

  • 口腔の科学

    2019
    Institution name：新潟大学

  • う蝕学

    2015
    -
    2018
    Institution name：新潟大学

  • 口腔病理学

    2010
    Institution name：新潟大学

  • 病理学総論

    2010
    Institution name：新潟大学

  • 基礎科学演習

    2010
    -
    2015
    Institution name：新潟大学

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