Faculty Profiles - TANUMA Junichi

Papers - TANUMA Junichi

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Quantitative and longitudinal monitoring of cancer cell invasion in a three-dimensional in vitro model of oral cancer using optical coherence tomography Reviewed

Kenta Haga, Yoshifumi Kamimura, Manabu Yamazaki, Akinori Funayama, Yuko Saito, Masako Kida, Jun-ichi Tanuma, Kenji Izumi

Scientific Reports 2025.11

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

Abstract

We previously developed a three-dimensional (3D) organotypic culture model of oral squamous cell carcinoma (OSCC) by incorporating cancer-associated fibroblasts to replicate oral tissue architecture and the tumor microenvironment (TME). This model provides a relevant platform for investigating cancer cell invasion. Optical coherence tomography (OCT), a noninvasive, high-resolution imaging technique, enables both real-time and longitudinal observations. This study assessed the applicability and feasibility of combining OCT with deep learning for the quantitative, longitudinal monitoring of cancer cell invasion in our 3D model. OCT effectively captured cross-sectional images and identified three regions—original cancer cell region, invasive cancer cell region, and stromal layer—based on scattering intensity and optical density, demonstrating nondestructive visualization of tissue microarchitecture. Sequential OCT imaging facilitated 3D image reconstruction and repeated monitoring. Planimetric and volumetric analyses of 3D OCT images revealed internal structural alterations and enabled comparative evaluation of invasion behaviors across OSCC cell types, TME conditions, and culture durations. Moreover, the invasiveness parameter obtained from 3D OCT images strongly correlated with histomorphometric-based data, confirming its reliability. These findings support the use of OCT imaging as a promising tool for noninvasive, quantitative assessment of invasiveness in organotypic cancer models.

DOI： 10.1038/s41598-025-28471-y

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Other Link： https://www.nature.com/articles/s41598-025-28471-y

Effects of Adipose-Derived Stem Cell Extract on Peripheral Nerve Cells Reviewed

Yuzo Imai, Naotaka Kishimoto, Yuhei Koyama, Kazunori Sango, Kosei Takeuchi, Manabu Yamazaki, Jun-ichi Tanuma, Simon D Tran, Kenji Seo

Cureus 2025.10

口腔粘膜病変の病理診断:現状と課題，生検検体で考慮すべき鑑別疾患 Invited Reviewed

阿部達也, 丸山智, 山﨑学, 田沼順一

診断病理 42 ( 4 ) 263 - 271 2025.10

Evaluation of factors affecting depth of invasion measurement in tongue squamous cell carcinoma using intraoral ultrasonography Reviewed

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

Dentomaxillofacial Radiology 2025.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

Objective

Intraoral ultrasonography (US) is known for its high accuracy in evaluating the depth of invasion (DOI) in tongue squamous cell carcinoma (SCC). However, measurement discrepancies, such as overestimation or underestimation, can occur in certain cases. This study aimed to identify factors affecting the measurement accuracy of intraoral US.

Methods

A total of 96 cases were included in this study. Patients who underwent imaging diagnosis for primary tongue SCC by oral and maxillofacial radiologists, followed by surgical resection by oral surgeons at our institution between April 2014 and March 2022, were included in the study. Cases were classified according to their clinical and histopathological characteristics, including clinical growth pattern, maximum pathological tumour diameter, pathological T classification, and pattern of invasion (Yamamoto-Kohama classification). Measurement accuracy was evaluated using Spearman’s rank correlation coefficient and Bland-Altman analysis.

Results

A total of 76 cases were analysed. Intraoral US demonstrated high diagnostic accuracy across various tumour characteristics. However, greater DOI and larger maximum tumour diameter were associated with increased variability in measurements. Exophytic lesions were more likely to be overestimated, whereas lesions with diffuse infiltration tended to be underestimated.

Conclusion

Although intraoral US provides high accuracy in the preoperative evaluation of tongue SCC, clinicians should be aware of specific tumour characteristics that may influence measurement precision, leading to potential overestimation or underestimation.

File： twaf062.pdf

DOI： 10.1093/dmfr/twaf062

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Does chemotherapy improve the prognosis in patients with jaw osteosarcoma? A systematic review and meta-analysis Reviewed

L. Zhang, Y. Guo, Y. Sumita, H. Hirai, M. Yamazaki, T. Hayashi, J.-i. Tanuma, K. Tomihara

International Journal of Oral and Maxillofacial Surgery 2025.9

下顎歯肉への転移を契機に診断に至った膵癌の1例

須田大亮, 船山昭典, 新美奏恵, 佐久間英伸, 齋藤大輔, 林孝文, 丸山智, 田沼順一, 小林正治

日本口腔腫瘍学会誌 36 ( 4 ) 89 - 95 2024.12

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

Authorship：Corresponding author Language：English 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.

File： biomedicines-12-02373-v2.pdf

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

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

Kawasaki M, Kawasaki K, Sari FT, Kudo T, Nihara J, Kitamura M, Nagai T, Utama V, Ishida Y, Meguro F, Kesuma A, Fujita A, Nishimura T, Kogure Y, Maruyama S, Tanuma J, Kakihara Y, Maeda T, Ghafoor S, Khonsari RH, Corre P, Sharpe PT, Cobourne M, Franco B, Ohazama A

eLife 13 e85042 2024.10

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

Authorship：Corresponding author Language：English 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.

File： ijms-25-09438.pdf

DOI： 10.3390/ijms25179438

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

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

Cureus 16 ( 8 ) 2024.8

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

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

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.

File： s41598-024-64126-0.pdf

DOI： 10.1038/s41598-024-64126-0

PubMed

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Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses Invited Reviewed

Amirmoezz yonesi, Kei Tomihara, Danki Takatsuka, Hidetake Tachinami, Manabu Yamazaki, Amir Reza Younesi Jadidi, Mayu Takaichi, Shuichi Imaue, Kumiko Fujiwara, Shin-ichi Yamada, Jun-ichi Tanuma, Makoto Noguchi

Biomedicines 2024.5

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

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

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

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 36 ( 4 ) 624 - 631 2024.4

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

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

Pathology - Research and Practice 254 155148 - 155148 2024.1

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

Authorship：Last author,　Corresponding author Language：English 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.

File： biomedicines-11-03119-v2.pdf

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

Authorship：Corresponding author Language：English 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.

File： biomedicines-11-02981.pdf

DOI： 10.3390/biomedicines11112981

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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 ( 20 ) 132 - 138 2023.7

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Papers - TANUMA Junichi