Updated on 2026/03/06

写真a

 
SASAHIRA Tomonori
 
Organization
Research Field in Dentistry, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oncology Professor
Title
Professor
Degree
(2008.7 Nara Medical University)

Research Interests

  • 頭頸部癌

  • 浸潤・転移

  • 分子腫瘍学

  • シグナル伝達

  • Molecular oncology

  • Invasion and Metastasis

  • Head and Neck Cancer

  • Gastroenterological Cancer

  • 新規分子腫瘍マーカー

  • 分子病理学

Research Areas

Surgical dentistry, Human pathology

Education

  • - 2003    Showa University   Faculty of Dentistry

  •    Showa University

Research History

  • 2021.4    Kagoshima University   Research Field in Dentistry, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oncology   Professor

  • 2021.4    鹿児島大学   医歯学総合研究科腫瘍学講座口腔病理解析学分野   教授

  • 2012.4 - 2021.3    Nara Medical University   Medical Faculty   Lecturer

  • 2012.4 - 2021.3    Nara Medical University   Lecturer

  • 2005.4 - 2012.3    Nara Medical University   Assistant Professor

Professional Memberships

  •    日本臨床細胞学会

  •    日本臨床口腔病理学会（理事）

  •    日本癌学会

  •    日本病理学会（学術評議員）

  •    日本口腔腫瘍学会（学術評議員）

  •    日本歯科基礎医学会

  •    日本口腔科学会

▼display all

Committee Memberships

  • 2021.8    日本臨床口腔病理学会   理事  

  • 2021.4    南九州歯学会   理事  

 

Papers

  • Hoang HT, Nguyen PT, Huynh NC, Nguyen TT, Tu TTH, Botelho MG, Van Nguyen L, Shima K, Sasahira T .  Reliability of online dental final exams in the pre and post COVID-19 era: A comparative study .  PLoS One18 ( 5 ) e0286148   2023Reviewed

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  • Kaori Shima, Yudai Shimojukkoku, Hiroshi Hijioka, Kiyohide Ishihata, Tomonori Sasahira .  Spindle cell squamous cell carcinoma of the maxillary sinus as a metachronous head and neck cancer .  Oral Science International22 ( 1 )   2025.1

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    Publishing type：Research paper (scientific journal)  

    Background: Spindle cell squamous cell carcinoma (SpSCC) is a rare subtype of squamous cell carcinoma (SCC) showing an unfavorable prognosis. Histologically, SpSCC shows biphasic proliferation of spindle cells and nests of SCC. Case presentation: An 85-year-old Japanese man with a medical history of oral SCC three years ago had SpSCC of the right maxillary sinus. The tumor showed aggressive proliferation of spindle cells with nests of conventional SCC. Subsequent lymph node metastases revealed findings of conventional SCC. Conclusion: This case report contributes to the accumulation of a rare subtype of SCC and multiple cancers of the head and neck region.

    DOI： 10.1002/osi2.1268

    Scopus

  • Yudai Shimojukkoku, Phuong Thao Nguyen, Kiyohide Ishihata, Takayuki Ishida, Yuka Kajiya, Yasunobu Oku, Koshiro Kawaguchi, Takahiro Tsuchiyama, Hideto Saijo, Kaori Shima, Tomonori Sasahira .  Role of early growth response-1 as a tumor suppressor in oral squamous cell carcinoma. .  Discover oncology15 ( 1 ) 714 - 714   2024.11International journal

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

    BACKGROUND: Oral squamous cell carcinoma (OSCC) exhibits pronounced local invasiveness and a propensity for lymph node metastasis. Given its frequent detection at advanced stages and the consequential postoperative functional impairments, the identification of effective molecular markers for early detection and treatment is imperative. Early growth response-1 (EGR-1) serves as a versatile transcription factor expressed across various cell types. Its role in cancer is contentious, acting as either an oncogene or a tumor suppressor gene. METHODS: This study undertook comprehensive analyses, including big data scrutiny, expression profiling using 50 OSCC samples, and in vitro functional assessments, to elucidate EGR-1's involvement in OSCC. RESULTS: Comparative analysis revealed significantly reduced EGR-1 expression in oral cancer tissues compared to healthy controls or normal oral mucosa. In vitro experimentation with multiple OSCC cell lines demonstrated that EGR-1 curbed cell proliferation, migration, and invasion capabilities. Additionally, it was observed that EGR-1 prompted G0/G1 arrest in OSCC cells by modulating the activity of cell cycle regulators. CONCLUSIONS: These findings strongly support EGR-1's tumor-suppressive role in OSCC and hint at the potential for novel OSCC therapies aimed at restoring aberrant EGR-1 function.

    DOI： 10.1007/s12672-024-01611-y

    Scopus

    PubMed

  • Phuong Thao Nguyen, Yudai Shimojukkoku, Yuka Kajiya, Yasunobu Oku, Ayami Tomishima, Kaori Shima, Tomonori Sasahira .  Gene alterations in the nuclear transport receptor superfamily: A study of head and neck cancer .  PLOS ONE19 ( 5 ) e0300446 - e0300446   2024.5

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    Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    In cancer cells, the nuclear transport system is often disrupted, leading to abnormal localization of nuclear proteins and altered gene expression. This disruption can arise from various mechanisms such as mutations in genes that regulate nuclear transport, altered expression of transport proteins, and changes in nuclear envelope structure. Oncogenic protein build-up in the nucleus due to the disturbance in nuclear transport can also boost tumor growth and cell proliferation. In this study, we performed bioinformatic analyses of 23 key nuclear transport receptors using genomic and transcriptomic data from pancancer and head and neck squamous cell carcinoma (HNSCC) datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia and found that the total alteration frequency of 23 nuclear transport receptors in 2691 samples of the PCAWG Consortium was 42.1% and a high levels of genetic alterations was significantly associated with poor overall survival. Amplification was the most common type of genetic alterations, and results in the overexpression of nuclear transport receptors in HNSCC compared to normal tissues. Furthermore, our study revealed that seven out of eight cell cycle genes (CDK1, CDK2, CDK4, CDK6, CCNA1, CCNB1, and CCNE2) were significantly and positively correlated with nuclear transport receptor genes in TCGA pancancer and CCLE datasets. Additionally, functional enrichment analysis showed that nuclear transport receptor genes were mainly enriched in the adhesion junction, cell cycle, ERBB, MAPK, MTOR and WNT signaling pathways.

    DOI： 10.1371/journal.pone.0300446

  • Kaori Shima, Phuong Thao Nguyen, Yudai Shimojukkoku, Yuka Kajiya, Tomonori Sasahira .  Solitary circumscribed neuroma of the upper lip: A case report .  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.2023.11.009

  • 下拾石 雄大, Nguyen Phuong Thao, 嶋 香織, 石田 喬之, 笹平 智則 .  口腔扁平上皮癌における癌抑制遺伝子としてのEGR-1の機能解析 .  Journal of Oral Biosciences Supplement2023   [P1 - 40]   2023.9

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    Language：Japanese   Publisher：(一社)歯科基礎医学会  

  • 嶋　香織、Nguyen Phuong Thao、下拾石雄大、笹平智則 .  上顎に生じたPrimordial odontogenic tumorの2例 .  診断病理40 ( 3 ) 265 - 271   2023Reviewed

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  • Hung Trong Hoang, Phuong Thao Nguyen, Nam Cong-Nhat Huynh, Tam Thi-Thanh Nguyen, Trang Thi Huyen Tu, Michael George Botelho, Lan Van Nguyen, Kaori Shima, Tomonori Sasahira .  Reliability of online dental final exams in the pre and post COVID-19 era: A comparative study. .  PloS one18 ( 5 ) e0286148   2023International journal

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

    Amidst the fourth COVID-19 wave in Viet Nam, national lockdowns necessitated the closure of numerous dental schools. To assess DDS (Doctor of Dental Surgery) graduation exams, this study analyzed their 2021 implementation in comparison to onsite exams conducted in 2020 and 2022 at the Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam (FOS-UMPH). The final online examination comprises two main sessions: a synchronous online examination using FOS-UMPH e-Learning for theories (consisting of 200 MCQs and 3 written tests with 3 clinical situations needed be solved) and a synchronous online examination using Microsoft Teams for practicum (comprising of 12 online OSCE stations). The final grades were evaluated using the same metrics in face-to-face final examinations in 2022 and 2020. A total of 114, 112 and 95 students were recruited for the first-time exams in 2020, 2021 and 2022, respectively. In order to analyze the reliability, histogram and k-mean clustering were employed. The histograms from 2020, 2021 and 2022 showed a striking similarity. However, fewer students failed in 2021 and 2022 (13% and 12.6%, respectively) compared to 2020 (28%), with clinical problem-solving part grades (belonging to theory session) being notably higher in 2021 and 2022. Intriguingly, the MCQ Score results showed the identical patterns. The courses of orthodontics, dental public health, and pediatrics subjects (in the group of prevention and development dentistry) stood out for their exceptional accuracy across both sessions. After examining data gathered over three years, we identified three distinct clusters: the first comprised of scattered average and low scores, the second characterized by high scores but unstable and scattered and the third cluster boasting consistently high and centered scores. According to our study, online and onsite traditional graduation exam results are relatively equivalent, but additional measures are necessary to standardize the final examination and adapt to the new normal trend in dental education.

    DOI： 10.1371/journal.pone.0286148

    PubMed

  • Tomonori Sasahira, Miyako Kurihara-Shimomura, Yudai Shimojjukoku, Kaori Shima, Tadaaki Kirita .  Searching for New Molecular Targets for Oral Squamous Cell Carcinoma with a View to Clinical Implementation of Precision Medicine. .  Journal of personalized medicine12 ( 3 )   2022.3International journal

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

    Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the eighth most common malignancy globally and is characterized by local invasiveness and high nodal metastatic potential. The OSCC incidence is also increasing, and the number of deaths is also rising steadily in Japan. The development of molecular markers to eradicate OSCC is an urgent issue for humankind. The increase in OSCC despite the declining smoking rate may be due to several viral infections through various sexual activities and the involvement of previously unfocused carcinogens, and genetic alterations in individual patients are considered to be more complicated. Given this situation, it is difficult to combat OSCC with conventional radiotherapy and chemotherapy using cell-killing anticancer drugs alone, and the development of precision medicine, which aims to provide tailor-made medicine based on the genetic background of each patient, is gaining attention. In this review article, the current status of the comprehensive search for driver genes and biomarkers in OSCC will be briefly described, and some of the candidates for novel markers of OSCC that were found will be outlined.

    DOI： 10.3390/jpm12030413

    PubMed

  • 近藤智之、嶋　香織、杉浦　剛、中村典史、笹平智則 .  口腔に発生したアミロイドーシス13例の臨床病理学的検討 .  南九州歯学会雑誌3   18 - 24   2022Reviewed

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  • Tomonori Sasahira, Miyako Kurihara-Shimomura, Hiroyuki Shimomura, Tadaaki Kirita .  SERPINE2 is an oral cancer-promoting factor that induces angiogenesis and lymphangiogenesis. .  International journal of clinical oncology26 ( 10 ) 1831 - 1839   2021.10

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

    BACKGROUND: LEM domain containing 1 (LEMD1) is a novel factor involved in the development of oral squamous cell carcinoma (OSCC). We previously performed a microarray analysis and found that serpin peptidase inhibitor, clade E, member 2 (SERPINE2) is an LEMD1-related signal. SERPINE2 is an extracellular serine proteinase inhibitor with secretory capacity. Although SERPINE2 displays tumor-promoting properties in many cancers, some reports indicate that SRPINE2 also has a tumor-suppressing function. Therefore, there are many unclear points about its role in cancer. In this study, we investigated SERPINE2 expression in OSCC. METHODS: The gene expression and secretion levels of SERPINE2 were examined in 42 frozen specimens of OSCC, and SERPINE2 immunostaining was investigated in 167 cases of OSCC. Furthermore, the effect of SERPINE2 on angiogenesis and lymphangiogenesis was analyzed using OSCC cells and endothelial cells. RESULTS: In the frozen specimens, the gene expression (P < 0.0001) and secretion levels (P < 0.0001) of SERPINE2 were higher in OSCC than in the normal oral mucosa. According to the immunohistochemical analysis, SERPINE2 expression was correlated with the depth of invasion (P = 0.0163), nodal metastasis (P = 0.0085), microvessel density (P < 0.0001), and lymphovessel density (P < 0.0001). Additionally, univariate and multivariate analyses indicated that the SERPINE2 expression level was an independent poor prognostic factor for OSCC. In vitro studies using OSCC cells revealed that SERPINE2 promotes angiogenesis and lymphangiogenesis. CONCLUSION: These results suggest that SRPX2 might be a useful tumor marker for OSCC.

    DOI： 10.1007/s10147-021-01970-4

    PubMed

  • Tomonori Sasahira, Miyako Kurihara-Shimomura, Hiroyuki Shimomura, Anja Katrin Bosserhoff, Tadaaki Kirita .  Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO. .  Journal of cancer research and clinical oncology147 ( 6 ) 1659 - 1672   2021.6International journal

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

    PURPOSE: Transport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC. METHODS: In this study, microarray analysis compared gene expression between control and TANGO-repressed HSC3 cells. Protein expression in 213 OSCC tissue samples was analyzed immunohistochemically. RESULTS: TANGO repression decreased or increased expression of Mucin 20 (MUC20) and small proline-rich protein 1B (SPRR1B), respectively. MUC20 increased the growth and invasiveness of OSCC cells via altered matrix metalloproteinase (MMP)-2 and E-cadherin expression and c-met phosphorylation. MUC20 induced angiogenesis and lymphangiogenesis by activating vascular endothelial growth factors A and C. In well-differentiated OSCC, SPRR1B expression was high (P = 0.0091) and correlated with keratinization markers and promoted proliferation by inducing mitogen-activated protein kinase p38 phosphorylation. MUC20 expression correlated significantly with clinical stage (P = 0.0024), lymph node metastasis (P = 0.0036), and number of blood and lymph vessels (P < 0.0001). MUC20-expressing cases had a significantly worse prognosis than non-expressing cases (P < 0.0001). CONCLUSION: MUC20 and SPRR1B located downstream of TANGO may be useful molecular markers for OSCC.

    DOI： 10.1007/s00432-021-03568-9

    PubMed

  • Tamaki S., Yamanaka Y., Shimomura H., Imai Y., Kawashima W., Yamakawa N., Sasahira T., Kirita T. .  Low grade mucoepidermoid carcinoma of the maxillary tuberosity: A case report .  Asian J Oral Maxillofac Surg23   42 - 45   2021Reviewed

  • Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroyuki Shimomura, Tadaaki Kirita .  Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma. .  International journal of molecular sciences21 ( 15 )   2020.7

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    Despite dramatic progress in cancer diagnosis and treatment, the five-year survival rate of oral squamous cell carcinoma (OSCC) is still only about 50%. Thus, the need for elucidating the molecular mechanisms underlying OSCC is urgent. We previously identified the peroxidasin gene (PXDN) as one of several novel genes associated with OSCC. Although the PXDN protein is known to act as a tumor-promoting factor associated with the Warburg effect, its function and role in OSCC are poorly understood. In this study, we investigated the expression, function, and relationship with the Warburg effect of PXDN in OSCC. In immunohistochemical analysis of OSCC specimens, we observed that elevated PXDN expression correlated with lymph node metastasis and a diffuse invasion pattern. High PXDN expression was confirmed as an independent predictor of poor prognosis by multivariate analysis. The PXDN expression level correlated positively with that of pyruvate kinase (PKM2) and heme oxygenase-1 (HMOX1) and with lactate and ATP production. No relationship between PXDN expression and mitochondrial activation was observed, and PXDN expression correlated inversely with reactive oxygen species (ROS) production. These results suggest that PXDN might be a tumor progression factor causing a Warburg-like effect in OSCC.

    DOI： 10.3390/ijms21155416

    PubMed

  • Tomonori Sasahira, Miyako Kurihara-Shimomura, Yukiko Nishiguchi, Hiroyuki Shimomura, Tadaaki Kirita .  Sushi Repeat Containing Protein X-linked 2 Is a Downstream Signal of LEM Domain Containing 1 and Acts as a Tumor-Promoting Factor in Oral Squamous Cell Carcinoma. .  International journal of molecular sciences21 ( 10 )   2020.5

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    Because oral squamous cell carcinomas (OSCCs) have a high potential for locoregional invasion and nodal metastasis, early detection and treatment are essential. A LAP2, emerin, MAN1 (LEM) domain containing 1 (LEMD1) is associated with local progression, clinical stage, nodal metastasis, poor prognosis, angiogenesis, and lymphangiogenesis in OSCC. Although LEMD is a cancer-testis antigen, the cancer-related signals related to LEMD1 remain unknown. In this study, we used a microarray analysis of OSCC cells to identify sushi repeat containing protein X-linked 2 (SRPX2) as a LEMD1-related downstream signal. LEMD1 expression was correlated with lymph node metastasis of OSCC according to the immunohistochemistry analysis. Furthermore, patients expressing SRPX2 had a significantly worse prognosis than those without SRPX2 expression. The concentration of SRPX2 in OSCC was positively correlated with the concentrations of LEMD1, urokinase plasminogen activator receptor (uPAR), and hepatocyte growth factor (HGF). In OSCC cells, SRPX2 secretion levels were elevated by interactions with uPAR and HGF. We also found that SRPX2 promotes endothelial cell proliferation and adhesion between endothelial cells and OSCC cells. These results suggest that SRPX2 might be a useful tumor marker for OSCC.

    DOI： 10.3390/ijms21103655

    PubMed

  • Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroyuki Shimomura, Anja Katrin Bosserhoff, Tadaaki Kirita .  Mast cell chymase promotes angiogenesis and lymphangiogenesis mediated by activation of melanoma inhibitory activity gene family members in oral squamous cell carcinoma. .  International journal of oncology56 ( 5 ) 1093 - 1100   2020.5

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    Mast cells (MCs) are present in the tumor stroma, and MCs that express the mast cell‑specific proteases tryptase and chymase (MCTC) exhibit several tumor‑related functions. It was previously reported that melanoma inhibitory activity (MIA) gene family members, including MIA, MIA2, and transport and Golgi organization protein 1 (TANGO), possess oncogenic functions in oral squamous cell carcinoma (OSCC). However, the relationships between MCTC, and clinicopathological characteristics and activation of the MIA gene family in OSCC remain unknown. In the present study, the functional roles of MCTC in patients with OSCC were investigated using immunohistochemistry and reverse transcription‑quantitative PCR. In addition, the effects of extracellular chymase on oral cancer cells were examined. In patients with OSCC, MCTC density was significantly affected by tumor progression and nodal metastasis, and was correlated with vessel density. MCTC density was also correlated with MIA and MIA2 expression. In OSCC cells, extracellular chymase promoted the secretion of vascular endothelial growth factor family proteins, and the transmigration and adhesion of HSC3 cells to endothelial cells; knockdown of MIA, MIA2 and TANGO attenuated these effects. The present findings indicated that MCTC act as tumor‑progressive factors in OSCC via the activation and secretion of MIA and MIA2, and the induction of angiogenesis and lymphangiogenesis.

    DOI： 10.3892/ijo.2020.4996

    PubMed

  • Hiroyuki Shimomura, Tomonori Sasahira, Chie Nakashima, Miyako Kurihara-Shimomura, Tadaaki Kirita .  Non-SMC Condensin I Complex Subunit H (NCAPH) Is Associated with Lymphangiogenesis and Drug Resistance in Oral Squamous Cell Carcinoma. .  Journal of clinical medicine9 ( 1 )   2019.12

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    BACKGROUND: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common malignancy. OSCC has strong invasive ability, and its malignant potential is closely associated with local expansion and lymph node metastasis. Furthermore, local or nodal recurrence worsens OSCC prognosis. In our previous cDNA microarray analysis, non-structural maintenance of chromosome (SMC) condensin I complex subunit H (NCAPH) was identified as an upregulated gene in recurrent OSCC. Although NCAPH has several functions in tumors, its role in OSCC is unknown. METHODS: In this study, we examined NCAPH expression in OSCC and performed a functional analysis of human OSCC cells. RESULTS: NCAPH expression was higher in OSCC than in normal oral mucosa. In immunohistochemistry using 142 OSCC specimens, the immunostaining of NCAPH was strongly associated with nodal metastasis and lymphatic infiltration. In multivariate analysis using the Cox proportional hazards model, NCAPH expression was an independent poor prognostic indicator for OSCC. Moreover, NCAPH promoted the migration and adhesion of endothelial cells to OSCC cells and promoted the resistance to platinum anticancer drugs. CONCLUSIONS: Our present findings suggest that NCAPH is a novel diagnostic and therapeutic target in OSCC.

    DOI： 10.3390/jcm9010072

    PubMed

  • Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroyuki Shimomura, Chie Nakashima, Tadaaki Kirita .  The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. .  Journal of clinical medicine8 ( 2 )   2019.2

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    BACKGROUND: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. METHODS: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. RESULTS: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. CONCLUSIONS: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.

    DOI： 10.3390/jcm8020273

    PubMed

  • Hiroyuki Shimomura, Tomonori Sasahira, Chie Nakashima, Miyako Shimomura-Kurihara, Tadaaki Kirita .  Downregulation of DHRS9 is associated with poor prognosis in oral squamous cell carcinoma. .  Pathology50 ( 6 ) 642 - 647   2018.10

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    Oral squamous cell carcinoma (OSCC) has a high potential for local invasion and nodal metastasis. Therefore, early detection and elucidation of the detailed molecular mechanisms underlying OSCC are essential. Dehydrogenase/reductase member 9 (DHRS9) is downregulated in recurrent OSCC. Although DHRS9 is reported to act as a tumour suppressor in several malignancies, its expression in OSCC cells is unknown. In this study, we examined DHRS9 expression immunohistochemically in specimens from a sample of 98 OSCC patients. Reduced DHRS9 expression was observed in 68 of 98 patients (69.4%) with OSCC. A significant association was found between low DHRS9 expression and local progression (T factor) (p = 0.0135). Furthermore, patients with low DHRS9 expression had a significantly poorer prognosis than those with high DHRS9 expression (p = 0.0443). In multivariate analysis using the Cox proportional hazards model, decreased DHRS9 expression strongly correlated with worse prognosis. The study findings suggest that DHRS9 might be a useful diagnostic and prognostic marker for OSCC.

    DOI： 10.1016/j.pathol.2018.06.002

    PubMed

  • Tomonori Sasahira, Tadaaki Kirita .  Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma. .  International journal of molecular sciences19 ( 8 )   2018.8

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    Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC's molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators.

    DOI： 10.3390/ijms19082413

    PubMed

  • Tomonori Sasahira, Yukiko Nishiguchi, Miyako Kurihara-Shimomura, Chie Nakashima, Hiroki Kuniyasu, Tadaaki Kirita .  NIPA-like domain containing 1 is a novel tumor-promoting factor in oral squamous cell carcinoma. .  Journal of cancer research and clinical oncology144 ( 5 ) 875 - 882   2018.5

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    PURPOSE: In our previous global gene expression analysis, we identified NIPA-like domain containing 1 (NIPAL1), which encodes a magnesium transporter, as one of the most overexpressed genes in recurrent oral squamous cell carcinoma (OSCC). Although has been NIPAL1 linked with gout pathogenesis, little is known about its expression and function in human malignancies. METHODS: In this study, we examined NIPAL1 expression in 192 cases of OSCC by immunohistochemistry and performed a functional analysis of human OSCC cells. RESULTS: NIPAL1 immunostaining was observed in 39 of 192 OSCC patients (20.3%). NIPAL1 expression correlated significantly with cancer cell intravsation (P = 0.0062), as well as with poorer disease-free survival in a Kaplan-Meier analysis (P < 0.0001). Moreover, a multivariate Cox proportional hazards model analysis revealed that NIPAL1 expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). In a functional analysis, NIPAL1 regulated the growth and adhesion of OSCC tumor cells and endothelial cells. CONCLUSIONS: Our findings suggest that NIPAL1 might be a novel factor promoting OSCC tumorigenesis, as well as a useful molecular marker of OSCC.

    DOI： 10.1007/s00432-018-2612-x

    PubMed

  • Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroshi Nakamura, Chie Nakashima, Hiroki Kuniyasu, Tadaaki Kirita .  Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma. .  Journal of clinical pathology71 ( 5 ) 436 - 441   2018.5

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    AIMS: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear. METHODS: In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC. RESULTS: High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001). CONCLUSIONS: These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC.

    DOI： 10.1136/jclinpath-2017-204770

    PubMed

  • Tomonori Sasahira, Anja Katrin Bosserhoff, Tadaaki Kirita .  The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer. .  Pathology international68 ( 5 ) 278 - 286   2018.5

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    Oral squamous cell carcinoma has a high potential for locoregional invasion and nodal metastasis. Consequently, early detection of such malignancies is of immense importance. The melanoma inhibitory activity (MIA) gene family comprises MIA, MIA2, transport and Golgi organization protein 1 (TANGO), and otoraplin (OTOR). These members of the MIA gene family have a highly conserved Src homology 3 (SH3)-like structure. Although the molecules of this family share 34-45% amino acid homology and 47-59% cDNA sequence homology, those members, excluding OTOR, play different tumor-associated functions. MIA has a pivotal role in the progression and metastasis of melanoma; MIA2 and TANGO have been suggested to possess tumor-suppressive functions; and OTOR is uniquely expressed in cochlea of the inner ear. Therefore, the definite functions of the MIA gene family in cancer cells remain unclear. Since the members of the MIA gene family are secreted proteins, these molecules might be useful tumor markers that can be detected in the body fluids, including serum and saliva. In this review, we described the molecular biological functions of the MIA gene family in oral cancer.

    DOI： 10.1111/pin.12672

    PubMed

  • Tomonori Sasahira, Miyako Kurihara, Yukiko Nishiguchi, Chie Nakashima, Tadaaki Kirita, Hiroki Kuniyasu .  Pancreatic adenocarcinoma up-regulated factor has oncogenic functions in oral squamous cell carcinoma. .  Histopathology70 ( 4 ) 539 - 548   2017.3

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    Language：English   Publisher：WILEY  

    AIMS: Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel secretory protein which promotes tumour progression, metastasis and poor prognosis in pancreatic, cervical and colorectal carcinoma. It is also associated with gemcitabine resistance in pancreatic cancer cells. However, the expression and function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. METHODS AND RESULTS: We performed an immunohistochemical analysis of PAUF in 222 clinicopathologically characterized cases of OSCC. We also investigated the growth, invasion, apoptosis induction and cisplatin resistance of OSCC cells under PAUF knockdown treatment. PAUF was localized in normal salivary glands. In OSCC, immunostaining for PAUF was found in 52 of 222 patients (23.4%), and correlated with nodal metastasis (P < 0.0001) and poor prognosis (P < 0.0001). Multivariate analysis using the Cox proportional hazards model identified that PAUF expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). The down-regulation of PAUF in OSCC cells suppressed cell growth and invasion and induced apoptosis and cisplatin sensitivity. CONCLUSIONS: Our results suggest that PAUF has tumour-promoting functions in OSCC. It may thus be a useful diagnostic and therapeutic marker for OSCC.

    DOI： 10.1111/his.13097

    Web of Science

    PubMed

  • Sasahira T, Kurihara M, Nishiguchi Y, Fujiwara R, Kirita T, Kuniyasu H .  NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma. .  Virchows Archiv : an international journal of pathology469 ( 2 ) 163 - 72   2016.8

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  • Sasahira T, Kurihara M, Nakashima C, Kirita T, Kuniyasu H .  LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration. .  British journal of cancer115 ( 1 ) 52 - 8   2016.6

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  • Sasahira T, Kirita T, Nishiguchi Y, Kurihara M, Nakashima C, Bosserhoff AK, Kuniyasu H .  A comprehensive expression analysis of the MIA gene family in malignancies: MIA gene family members are novel, useful markers of esophageal, lung, and cervical squamous cell carcinoma. .  Oncotarget7 ( 21 ) 31137 - 52   2016.5

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  • Sasahira T, Nishiguchi Y, Fujiwara R, Kurihara M, Kirita T, Bosserhoff AK, Kuniyasu H .  Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression. .  Oncotarget7 ( 18 ) 26751 - 64   2016.5

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  • Obayashi M, Yoshida M, Tsunematsu T, Ogawa I, Sasahira T, Kuniyasu H, Imoto I, Abiko Y, Xu D, Fukunaga S, Tahara H, Kudo Y, Nagao T, Takata T .  microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer. .  Oncotarget7 ( 7 ) 8223 - 39   2016.2

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  • Luo Y, Tanabe E, Kitayoshi M, Nishiguchi Y, Fujiwara R, Matsushima S, Sasaki T, Sasahira T, Chihara Y, Nakae D, Fujii K, Ohmori H, Kuniyasu H .  Expression of MAS1 in breast cancer. .  Cancer science106 ( 9 ) 1240 - 8   2015.9

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  • Luo Yi, Tanabe Eriko, Kitayoshi Misaho, Nishiguchi Yukiko, Fujiwara Rina, Matsushima Sayako, Sasaki Takamitsu, Sasahira Tomonori, Chihara Yoshitomo, Nakae Dai, Fujii Kiyomu, Ohmori Hitoshi, Kuniyasu Hiroki .  乳癌におけるMAS1の発現(Expression of MAS1 in breast cancer) .  Cancer Science106 ( 9 ) 1240 - 1248   2015.9

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    Publisher：John Wiley & Sons Australia, Ltd  

    切除術を行った浸潤性乳管癌(IDC)患者132名を対象に、免疫組織化学的検査によりMAS1発現と腫瘍阻害効果について検討した。良性乳腺組織のMAS1発現は高かったが、IDC患者全例、特にスキルスIDCでは低下していた。MAS1の発現低下は腫瘍増殖、リンパ節転移、悪性度と関連した。132名中12名はトリプルネガティブ乳癌(TNBC)で、この12名と組織アレイを行ったTNBC36名ではMAS1を発現していた。MAS1を発現するTNBC細胞株のMDA-MB-468と4T1の増殖、抗アポトーシス性生存、浸潤はA1-7処理によるMAS1活性化で抑制され、MAS1ノックダウンで増強された。luminal A乳癌細胞株のMCF-7では、タモキシフェンとA1-7との間に相乗作用が認められた。A転換酵素2アクチベーターのシスプラチンとA-II 1型受容体遮断薬との併用は、同系マウスモデルで4T1腫瘍の増殖を相乗的に抑制した。

  • Shimomura H, Sasahira T, Yamanaka Y, Kurihara M, Imai Y, Tamaki S, Yamakawa N, Shirone N, Hasegawa M, Kuniyasu H, Kirita T .  [18F]fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in advanced oral squamous cell carcinoma. .  International journal of clinical oncology20 ( 2 ) 308 - 16   2015.4

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  • Shimomura Hiroyuki, Sasahira Tomonori, Yamanaka Yasutsugu, Kurihara Miyako, Imai Yuichiro, Tamaki Shigehiro, Yamakawa Nobuhiro, Shirone Norihisa, Hasegawa Masatoshi, Kuniyasu Hiroki, Kirita Tadaaki .  進行口腔扁平上皮癌における術前化学放射線療法後の病理組織学的反応の評価のための[18F]FDG-PET([18F]fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in advanced oral squamous cell carcinoma) .  International Journal of Clinical Oncology20 ( 2 ) 308 - 316   2015.4

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    Publisher：シュプリンガー・ジャパン(株)  

    術前同時化学放射線療法(CRT)後に腫瘍切除術が施行された切除可能進行口腔扁平上皮癌(OSCC)45例(男性28例、女性17例、年齢28〜68歳)を対象として、CRTへの組織病理学的反応の評価における[18F]fluoro-2-deoxyglucose positron emission tomography(FDG-PET)の有用性について検討した。なお、FDG-PETは術前CRTの前後に実施し、最大標準化取込値(SUVmax)とSUVmax減衰率(ΔSUV%)を術前CRTに対する反応性の評価に用い、SUVmax、組織病理学的反応、腫瘍抗原Ki-67および低酸素誘導因子1α(HIF-1α)の発現における相関性についても解析を行った。その結果、術前CRTは腫瘍内FDG取り込みを有意に減少させ、CRT前後のSUVは、病理学的完全奏効(pCR)患者において、非pCR患者に比べ有意に低いことが示された。またCRT前SUVでは、治療前生検検体において、Ki-67およびHIF-1α発現と有意な関連性が認められ、Ki-67、HIF-1αの発現は、pCR患者において、非pCR患者よりも有意に低いことが確認された。以上の所見から、CRT前後のSUVおよびΔSUV%は、術前CRTに対する良好な組織病理学的反応を予測可能であり、CRT治療前の生検検体におけるKi-67およびHIF-1αは、術前CRTに対する組織病理学的反応の予測因子となることが示唆された。

  • Sasahira T, Kirita T, Yamamoto K, Ueda N, Kurihara M, Matsushima S, Bhawal UK, Bosserhoff AK, Kuniyasu H .  Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma. .  European journal of cancer (Oxford, England : 1990)50 ( 12 ) 2142 - 51   2014.8

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  • Luo Y, Yoneda J, Ohmori H, Sasaki T, Shimbo K, Eto S, Kato Y, Miyano H, Kobayashi T, Sasahira T, Chihara Y, Kuniyasu H .  Cancer usurps skeletal muscle as an energy repository. .  Cancer research74 ( 1 ) 330 - 40   2014.1

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  • Sasahira T, Kurihara M, Yamamoto K, Ueda N, Nakashima C, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H .  HuD promotes progression of oral squamous cell carcinoma. .  Pathobiology : journal of immunopathology, molecular and cellular biology81 ( 4 ) 206 - 14   2014

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  • Sasahira T, Kirita T, Kuniyasu H .  Update of molecular pathobiology in oral cancer: a review. .  International journal of clinical oncology19 ( 3 ) 431 - 6   2014

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  • Sasahira T, Ueda N, Yamamoto K, Kurihara M, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H .  Prox1 and FOXC2 act as regulators of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma. .  PloS one9 ( 3 ) e92534   2014

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  • Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H .  Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma. .  Human pathology44 ( 6 ) 1098 - 106   2013.6

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  • Kurihara M, Kirita T, Sasahira T, Ohmori H, Matsushima S, Yamamoto K, Bosserhoff AK, Kuniyasu H .  Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma. .  British journal of cancer108 ( 7 ) 1460 - 9   2013.4

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    Language：English  

    DOI： 10.1038/bjc.2013.27

    PubMed

  • Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H .  High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. .  European journal of cancer (Oxford, England : 1990)49 ( 3 ) 741 - 51   2013.2

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  • Sasahira T, Ueda N, Yamamoto K, Bhawal UK, Kurihara M, Kirita T, Kuniyasu H .  Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma. .  Clinical & experimental metastasis30 ( 2 ) 165 - 76   2013.2

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  • Shimomoto T, Ohmori H, Luo Y, Chihara Y, Denda A, Sasahira T, Tatsumoto N, Fujii K, Kuniyasu H .  Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer. .  Clinical & experimental metastasis29 ( 8 ) 915 - 25   2012.12

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  • 玉置 盛浩, 山中 康嗣, 下村 弘幸, 笹平 智則, 山川 延宏, 柳生 貴裕, 青木 久美子, 今井 裕一郎, 桐田 忠昭 .  唾液腺原発粘表皮癌の臨床病理学的検討 .  日本口腔腫瘍学会誌24 ( 4 ) 137 - 145   2012.12

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    Publisher：(一社)日本口腔腫瘍学会  

    1995年から2010年までに当科で加療した唾液腺原発粘表皮癌12例(男性6例、女性6例、平均年齢59.3歳)に対して臨床病理学的検討を行ったので報告する。Goode分類による病理組織学的悪性度は低悪性度8例、高悪性度4例であった。年齢と病理組織学的悪性度との関連は、低悪性度の平均年齢は55.1歳、高悪性度は67.5歳で年齢差を認めなかった。性別との関連では、低悪性度は女性が多く、高悪性度は男性に多かった。頸部リンパ節転移との関連では、低悪性度はN0が多く、高悪性度はN1-3が多かった。臨床病期分類との関連では、低悪性度はstage Iが多く、高悪性度はstage IVAが多かった。原発巣制御率との関連では、低悪性度75.0%に対して高悪性度の制御率は25.0%と低下していた。生存率は、低悪性度の5年死因特異的累積生存率87.5%に対して高悪性度は25.0%と不良であった。同様に5年無病累積生存率も低悪性度72.9%に対して高悪性度は22.0%と不良であった。Goode分類は粘表皮癌の予後予測として有用な病理組織学的悪性度分類であると思われた。(著者抄録)

  • Shimomoto T, Luo Y, Ohmori H, Chihara Y, Fujii K, Sasahira T, Denda A, Kuniyasu H .  Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet. .  Journal of gastroenterology47 ( 10 ) 1073 - 83   2012.10

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  • Bhawal UK, Ito Y, Tanimoto K, Sato F, Fujimoto K, Kawamoto T, Sasahira T, Hamada N, Kuniyasu H, Arakawa H, Kato Y, Abiko Y .  IL-1β-mediated up-regulation of DEC1 in human gingiva cells via the Akt pathway. .  Journal of cellular biochemistry113 ( 10 ) 3246 - 53   2012.10

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  • Shimomoto Takasumi, Luo Yi, Ohmori Hitoshi, Chihara Yoshitomo, Fujii Kiyomu, Sasahira Tomonori, Denda Ayumi, Kuniyasu Hiroki .  糖化最終産物(AGE)は高リノール酸食および高グルコース食摂取のアゾキシメタン注入Fisher 344ラット結腸粘膜においてAGE受容体を誘導する(Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet) .  Journal of Gastroenterology47 ( 10 ) 1073 - 1083   2012.10

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    Publisher：シュプリンガー・ジャパン(株)  

    Fischer 344ラットに対照食(C群)、15%リノール酸(LA)含有食(L群)、対照食+10%グルコース液(G群)または15%LA食+10%グルコース液(L+G群)を投与し、アゾキシメタン(AOM)を注入したモデルにおける糖化最終産物(AGE)およびAGE受容体(RAGE)量を測定した。体重、血糖値、血清インスリン値はL+G群で最も増加していた。L+G群では異常腺窩巣(ACF)および癌が最も多く発生し、RAGEおよびAGE増加を伴っていた。AOM処理したIEC6ラット腸管上皮細胞ではRAGE発現が増加し、この増加はメトフォルミンないしロサルタンにより阻害された。AOMを投与されたラット結腸癌モデルにおいて、L+G群ではRAGEおよびAGE量、ACFと癌の発生がメトフォルミンないしロサルタンにより抑制され、AGE-RAGEの抑制が結腸癌の化学的予防の標的となりうると考えられた。

  • Sasahira T, Kurihara M, Bhawal UK, Ueda N, Shimomoto T, Yamamoto K, Kirita T, Kuniyasu H .  Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer. .  British journal of cancer107 ( 4 ) 700 - 6   2012.8

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    Language：English  

    DOI： 10.1038/bjc.2012.330

    PubMed

  • Ito Y, Bhawal UK, Sasahira T, Toyama T, Sato T, Matsuda D, Nishikiori H, Kobayashi M, Sugiyama M, Hamada N, Arakawa H, Kuniyasu H .  Involvement of HMGB1 and RAGE in IL-1β-induced gingival inflammation. .  Archives of oral biology57 ( 1 ) 73 - 80   2012.1

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  • Bhawal UK, Sato F, Arakawa Y, Fujimoto K, Kawamoto T, Tanimoto K, Ito Y, Sasahira T, Sakurai T, Kobayashi M, Kashima I, Kijima H, Kuniyasu H, Abiko Y, Kato Y, Sato S .  Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1. .  The Journal of pathology224 ( 3 ) 420 - 9   2011.7

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  • Sasahira T, Kurihara M, Yamamoto K, Bhawal UK, Kirita T, Kuniyasu H .  Downregulation of runt-related transcription factor 3 associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland. .  Cancer science102 ( 2 ) 492 - 7   2011.2

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  • Sasahira Tomonori, Kurihara Miyako, Yamamoto Kazuhiko, Bhawal Ujjal K., Kirita Tadaaki, Kuniyasu Hiroki .  唾液腺の腺様嚢胞癌および粘表皮癌の予後不良と関連するrunt関連転写因子3のダウンレギュレーション(Downregulation of runt-related transcription factor 3 associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland) .  Cancer Science102 ( 2 ) 492 - 497   2011.2

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    Publisher：John Wiley & Sons Australia, Ltd  

    唾液腺の多形腺腫(PA)、腺様嚢胞癌(ACC)および粘表皮癌(MEC)におけるRUNX3の発現およびメチル化状態を調べた。PA、ACCおよびMECの細胞質におけるRUNX3発現頻度はそれぞれ65%(13/20)、22.2%(8/36)、20.6%(7/34)であった。ACCおよびMECにおけるRUNX3の低発現および欠損は腫瘍進行および予後不良と関連した。microdissection法によるcDNAの検討にて、PAおよび非腫瘍唾液腺と比べてACCおよびMECでRUNX3 mRNA発現が低いことが分かった。RUNX3の過剰メチル化の頻度は非腫瘍唾液腺(0/8、0%)と比べてPA(2/8、25%)、ACC(6/8、75%)およびMEC(7/8、87.5%)で高かった。唾液腺腫瘍におけるRUNX3の低発現および欠損は唾液腺ACCおよびMECにおける腫瘍原性、腫瘍進行および予後不良に関係すると考えられた。

  • Yamanaka Y, Tamaki S, Shimomura H, Imai Y, Sasahira T, Kirita T .  [A case of advanced upper gingival carcinoma responding completely to concurrent chemoradiotherapy with S-1]. .  Gan to kagaku ryoho. Cancer & chemotherapy38 ( 1 ) 89 - 92   2011.1

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  • 山中 康嗣, 玉置 盛浩, 下村 弘幸, 今井 裕一郎, 笹平 智則, 桐田 忠昭 .  進行上顎歯肉癌に対してS-1と放射線同時療法が著効した1例 .  癌と化学療法38 ( 1 ) 89 - 92   2011.1

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    Publisher：(株)癌と化学療法社  

    症例は83歳、男性。対側頸部リンパ節転移を伴い、左側上顎骨を破壊し、上顎洞内、頬粘膜部まで進行した左側上顎歯肉癌(T4aN2cM0)である。患者および家族は手術療法を希望しなかったため、S-1と放射線同時併用療法を施行した。治療として、入院下でS-1 80mg/body/dayによる化学療法(2週間連続投与後1週間休薬)を繰り返し、同時に放射線治療を週5日間、1日2Gy、計60Gy行った。治療中の有害事象として軽度の白血球減少とgrade 2の口内炎が認められたが、治療中止になるまでには至らなかった。結果として、肉眼、画像所見において原発巣は消失し、病理組織学的にもcomplete response(CR)を得た。また転移リンパ節も触診、画像所見にて消失し、CRと判断した。その後、S-1は維持化学療法として1年間施行した。現在、約2年を経過するが、再発、転移は認められず、経過良好である。(著者抄録)

  • Luo Y, Ohmori H, Shimomoto T, Fujii K, Sasahira T, Chihara Y, Kuniyasu H .  Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells. .  Pathobiology : journal of immunopathology, molecular and cellular biology78 ( 5 ) 285 - 90   2011

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  • Sasahira T, Kirita T, Kurihara M, Yamamoto K, Bhawal UK, Bosserhoff AK, Kuniyasu H .  MIA-dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma. .  European journal of cancer (Oxford, England : 1990)46 ( 12 ) 2285 - 94   2010.8

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  • Luo Y, Ohmori H, Fujii K, Moriwaka Y, Sasahira T, Kurihara M, Tatsumoto N, Sasaki T, Yamashita Y, Kuniyasu H .  HMGB1 attenuates anti-metastatic defence of the liver in colorectal cancer. .  European journal of cancer (Oxford, England : 1990)46 ( 4 ) 791 - 9   2010.3

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  • Kuniyasu H, Luo Y, Fujii K, Sasahira T, Moriwaka Y, Tatsumoto N, Sasaki T, Yamashita Y, Ohmori H .  CD10 enhances metastasis of colorectal cancer by abrogating the anti-tumoural effect of methionine-enkephalin in the liver. .  Gut59 ( 3 ) 348 - 56   2010.3

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    Language：English  

    DOI： 10.1136/gut.2009.178376

    PubMed

  • Luo Y, Takaki M, Misawa H, Matsuyoshi H, Sasahira T, Chihara Y, Fujii K, Ohmori H, Kuniyasu H .  Determinants of the epithelial-muscular axis on embryonic stem cell-derived gut-like structures. .  Pathobiology : journal of immunopathology, molecular and cellular biology77 ( 5 ) 253 - 9   2010

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  • Ohmori H, Luo Y, Fujii K, Sasahira T, Shimomoto T, Denda A, Kuniyasu H .  Dietary linoleic acid and glucose enhances azoxymethane-induced colon cancer and metastases via the expression of high-mobility group box 1. .  Pathobiology : journal of immunopathology, molecular and cellular biology77 ( 4 ) 210 - 7   2010

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  • Moriwaka Y, Luo Y, Ohmori H, Fujii K, Tatsumoto N, Sasahira T, Kuniyasu H .  HMGB1 attenuates anti-metastatic defense of the lymph nodes in colorectal cancer. .  Pathobiology : journal of immunopathology, molecular and cellular biology77 ( 1 ) 17 - 23   2010

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  • Fujii K, Luo Y, Sasahira T, Denda A, Ohmori H, Kuniyasu H .  Co-treatment with deoxycholic acid and azoxymethane accelerates secretion of HMGB1 in IEC6 intestinal epithelial cells. .  Cell proliferation42 ( 5 ) 701 - 9   2009.10

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    Language：English  

    DOI： 10.1111/j.1365-2184.2009.00624.x

    PubMed

  • Ohmori H, Fujii K, Sasahira T, Luo Y, Isobe M, Tatsumoto N, Kuniyasu H .  Methionine-enkephalin secreted by human colorectal cancer cells suppresses T lymphocytes. .  Cancer science100 ( 3 ) 497 - 502   2009.3

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  • Ohmori Hitoshi, Fujii Kiyomu, Sasahira Tomonori, Luo Yi, Isobe Mamoru, Tatsumoto Naokuni, Kuniyasu Hiroki .  ヒト大腸癌細胞によって分泌されたメチオニン-エンケファリンはTリンパ球を抑制する(Methionine-enkephalin secreted by human colorectal cancer cells suppresses T lymphocytes) .  Cancer Science100 ( 3 ) 497 - 502   2009.3

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    Publisher：John Wiley & Sons Australia, Ltd  

    大腸癌(CRC)における免疫モジュレーターとしてのメチオニン-エンケファリン(MENK)の役割を検討した。MENKはCT26、IEC6A、Colo320、HT29 CRC細胞株で産生されたが、小腸細胞のIEC6では産生されなかった。MENK分泌は、同系げっ歯類モデルのCRC細胞の腫瘍形成能や転移と関連していた。CT26とIEC6A CRC細胞の皮下腫瘍におけるMENK濃度は、腫瘍浸潤Tリンパ球数と逆相関を示した。MENKは濃度依存的にMOLT-4-Tリンパ芽球細胞の成長を阻害した。さらに、MENKはMOLT-4細胞において、c-jun N末端キナーゼのリン酸化レベルを亢進し、アポトーシスを誘導した。MENK誘導アポトーシスはc-jun N末端キナーゼ阻害剤によって抑制された。免疫組織化学的解析によりCRC試料61例中33例でMENKの中等度から強度の発現が認められた。MENK発現はDukes病期分類、リンパ節転移、肝転移と関連していた。腫瘍組織におけるMENK濃度はDukes分類B症例よりDukes分類C症例において高かった。MENK発現は腫瘍浸潤Tリンパ球、特にCD4+細胞サブセットに属するリンパ球と関連していた。CRC細胞によって分泌されるMENKが免疫の影響から宿主を逸脱させたことを示唆していた。

  • Kuniyasu H, Oue N, Sasahira T, Yi L, Moriwaka Y, Shimomoto T, Fujii K, Ohmori H, Yasui W .  Reg IV enhances peritoneal metastasis in gastric carcinomas. .  Cell proliferation42 ( 1 ) 110 - 21   2009.2

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    Language：English  

    DOI： 10.1111/j.1365-2184.2008.00577.x

    PubMed

  • Luo Y, Fujii K, Ohmori H, Sasahira T, Moriwaka Y, Isobe M, Kuniyasu H .  Antisense phosphorothioate oligodeoxynucleic acid for CD10 suppresses liver metastasis of colorectal cancer. .  Pathobiology : journal of immunopathology, molecular and cellular biology76 ( 5 ) 267 - 73   2009

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  • Kusume A, Sasahira T, Luo Y, Isobe M, Nakagawa N, Tatsumoto N, Fujii K, Ohmori H, Kuniyasu H .  Suppression of dendritic cells by HMGB1 is associated with lymph node metastasis of human colon cancer. .  Pathobiology : journal of immunopathology, molecular and cellular biology76 ( 4 ) 155 - 62   2009

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  • Sasahira T, Oue N, Kirita T, Luo Y, Bhawal UK, Fujii K, Yasui W, Kuniyasu H .  Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland. .  Histopathology53 ( 6 ) 667 - 75   2008.12

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    Language：English  

    DOI： 10.1111/j.1365-2559.2008.03188.x

    PubMed

  • Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Ohmori H, Luo Y, Yasui W, Bosserhoff AK, Kuniyasu H .  High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. .  Cancer science99 ( 9 ) 1806 - 12   2008.9

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  • Sasahira Tomonori, Kirita Tadaaki, Oue Naohide, Bhawal Ujjal Kumar, Yamamoto Kazuhiko, Fujii Kiyomu, Ohmori Hitoshi, Luo Yi, Yasui Wataru, Bosserhoff Anja Katrin, Kuniyasu Hiroki .  High mobility group box-1誘導メラノーマ阻害活性は口腔扁平上皮癌におけるリンパ節転移およびリンパ管形成に関連する(High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma) .  Cancer Science99 ( 9 ) 1806 - 1812   2008.9

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    Publisher：John Wiley & Sons Australia, Ltd  

    メラノーマ阻害活性(MIA)は、種々のヒト悪性腫瘍において浸潤と転移とに相関を示す悪性黒色腫細胞から分離された11-kDaの分泌蛋白質である。免疫組織化学的方法により口腔扁平上皮癌(OSCC)62株におけるMIA発現を検討した。MIA発現は、リンパ節転移と有意に関連し、またhigh mobility group box-1(HMGB1)の発現とリンパ管密度とも関連を示した。MIA、HMGB1、核因子κB(NFκB) p65の発現レベルとHMGB1-NFκB p65の結合率は、転移性ヒトOSCC細胞株(HSC3)で非転移性OSCC細胞株(HSC4)に比して有意に高かった。Receptor for advanced glycation end product(RAGE)アンチセンスまたは低分子干渉RNAとヒト遺伝子組み換えHMGB1(hrHMGB1)を用いた処理はMIA発現に影響を与えなかった一方で、HMGB1アンチセンスまたはsiRNA処理はHSC3細胞におけるMIA発現を低下させた。HMGB1はRAGEリガンドとしてではなくNFκB共因子としてMIA発現を亢進させた。MIA抗体によるMIA中和は細胞外シグナル関連キナーゼ1/2リン酸化を亢進したが、p38リン酸化と血管内皮増殖因子(VEGF)-C、-Dの発現は低下させた。p38阻害剤による処理はHSC3細胞におけるVEGF-C、-Dの発現を低下させた。これらの結果は、OSCCにおいてMIA発現が細胞内HMGB1とNFκBp65の相互作用により亢進し、MIAがVEGF-CとVEGF-Dの増加により腫瘍進行およびリンパ節転移に強く関与することを示唆していた。

  • Fujii K, Sasahira T, Moriwaka Y, Oue N, Yasui W, Kuniyasu H .  Protection of telomeres 1 protein levels are associated with telomere length in gastric cancer. .  International journal of molecular medicine21 ( 5 ) 599 - 604   2008.5

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  • Ohmori H, Sasahira T, Fujii K, Yi L, Shimomoto T, Kuniyasu H .  Linoleic-acid-induced growth suppression induces quiescent cancer cell nests in nude mice. .  Pathobiology : journal of immunopathology, molecular and cellular biology75 ( 4 ) 226 - 32   2008

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  • Yagyuu T, Kirita T, Sasahira T, Moriwaka Y, Yamamoto K, Kuniyasu H .  Recurrence of keratocystic odontogenic tumor: clinicopathological features and immunohistochemical study of the Hedgehog signaling pathway. .  Pathobiology : journal of immunopathology, molecular and cellular biology75 ( 3 ) 171 - 6   2008

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  • 笹平 智則, 桐田 忠昭, 山中 康嗣, 國安 弘基 .  唾液腺原発腺様嚢胞癌におけるReg IVの発現 .  頭頸部癌33 ( 4 ) 489 - 492   2007.12

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    Publisher：(一社)日本頭頸部癌学会  

    Reg IV(Regenerating gene type IV)は炎症性腸疾患や、胃癌、大腸癌でも発現亢進していることが知られている。さらにはホルモン療法に転移性前立腺癌との関連や早期の膵管癌における血清マーカーとしての有用性についても報告されている。今回25例の唾液腺原発腺様嚢胞癌症例におけるReg IVの発現を免疫組織化学的に検討した結果、Reg IVは腺様嚢胞癌のリンパ節転移および術後の遠隔転移に関与することを見出した。これらのことより、Reg IVは腺様嚢胞癌の転移及び予後予測マーカーとして有用である可能性が示唆された。(著者抄録)

  • Bhawal UK, Tsukinoki K, Sasahira T, Sato F, Mori Y, Muto N, Sugiyama M, Kuniyasu H .  Methylation and intratumoural heterogeneity of 14-3-3 sigma in oral cancer. .  Oncology reports18 ( 4 ) 817 - 24   2007.10

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  • Yuri M, Sasahira T, Nakai K, Ishimaru S, Ohmori H, Kuniyasu H .  Reversal of expression of 15-lipoxygenase-1 to cyclooxygenase-2 is associated with development of colonic cancer. .  Histopathology51 ( 4 ) 520 - 7   2007.10

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    Language：English  

    DOI： 10.1111/j.1365-2559.2007.02799.x

    PubMed

  • Sasahira T, Kirita T, Bhawal UK, Yamamoto K, Ohmori H, Fujii K, Kuniyasu H .  Receptor for advanced glycation end products (RAGE) is important in the prediction of recurrence in human oral squamous cell carcinoma. .  Histopathology51 ( 2 ) 166 - 72   2007.8

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    Language：English  

    DOI： 10.1111/j.1365-2559.2007.02739.x

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  • Sasahira T, Kirita T, Bhawal UK, Ikeda M, Nagasawa A, Yamamoto K, Kuniyasu H .  The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma. .  Virchows Archiv : an international journal of pathology450 ( 3 ) 287 - 95   2007.3

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  • Hirai K, Sasahira T, Ohmori H, Fujii K, Kuniyasu H .  Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice. .  International journal of cancer120 ( 3 ) 500 - 5   2007.2

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  • Chihara Y, Fujimoto K, Kondo H, Moriwaka Y, Sasahira T, Hirao Y, Kuniyasu H .  Anti-tumor effects of liposome-encapsulated titanium dioxide in nude mice. .  Pathobiology : journal of immunopathology, molecular and cellular biology74 ( 6 ) 353 - 8   2007

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  • 野々村 昭孝, 笠井 孝彦, 榎本 泰典, 武田 麻衣子, 田村 智美, 中峯 寛和, 堤 幹宏, 小西 登, 笹平 智則, 齋藤 能彦, 森井 武志, 吉治 仁志, 川原 誠, 成清 道博, 三島 秀明, 長阪 重雄, 西尾 健治, 前田 光一, 丹羽 欣正, 西久保 敏也, 池 寛子, 古西 満, 米田 淳平, 時間外病理解剖のあり方を考えるワーキンググループ .  病理解剖に関するアンケート調査結果と剖検に関する一考察 .  Journal of Nara Medical Association57 ( 6 ) 175 - 184   2006.12

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    Publisher：奈良医学会  

    最近、殆どの医療機関で剖検率が低下している。最新の平成15年のデータによると大学医学部附属病院80とその分院などの関連機関37施設、合計117施設の平均剖検率は14.3%である。奈良医科大学では「時間外病理解剖のあり方を考えるワーキンググループ」で時間外剖検のあり方を検討してきたので、病理解剖の目的、病理解剖に関する法的事項、医療関連死と剖検、病理解剖以外の解剖について、剖検率、大学附属病院における病理解剖の現状、患者の死亡時刻について考察した。大学附属病院における現状は65大学附属病院に対して行ったアンケート調査結果に基づいて報告した。

  • Sakai Y, Sasahira T, Ohmori H, Yoshida K, Kuniyasu H .  Conjugated linoleic acid reduced metastasized LL2 tumors in mouse peritoneum. .  Virchows Archiv : an international journal of pathology449 ( 3 ) 341 - 7   2006.9

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  • Sasaki T, Fujii K, Yoshida K, Shimura H, Sasahira T, Ohmori H, Kuniyasu H .  Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells. .  Virchows Archiv : an international journal of pathology448 ( 4 ) 422 - 7   2006.4

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  • Kuniyasu H, Yoshida K, Sasaki T, Sasahira T, Fujii K, Ohmori H .  Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. .  International journal of cancer118 ( 3 ) 571 - 6   2006.2

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  • Sasaki T, Yoshida K, Shimura H, Ichiba M, Sasahira T, Shimomoto T, Denda A, Kuniyasu H .  Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment. .  International journal of cancer118 ( 3 ) 593 - 9   2006.2

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  • Yamamoto K, Kitayama W, Denda A, Sasahira T, Kuniyasu H, Kirita T .  Expression of receptor for advanced glycation end products during rat tongue carcinogenesis by 4-nitroquinoline 1-oxide and effect of a selective cyclooxygenase-2 inhibitor, etodolac. .  Pathobiology : journal of immunopathology, molecular and cellular biology73 ( 6 ) 317 - 24   2006

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  • Ohmori H, Fujii K, Sasahira T, Ukai R, Ikeda M, Kobayashi K, Maruyama A, Kuniyasu H .  Determinants for prediction of malignant potential by metalloproteinase:E-cadherin ratio in prostate core needle biopsy. .  Pathobiology : journal of immunopathology, molecular and cellular biology73 ( 2 ) 98 - 104   2006

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    Language：English  

    DOI： 10.1159/000094494

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  • Sasaki T, Shimura H, Sasahira T, Fujii K, Kuniyasu H .  High concentration of deoxycholic acid abrogates in vitro transformation of IEC6 intestinal cells by azoxymethane. .  Journal of experimental & clinical cancer research : CR24 ( 4 ) 625 - 31   2005.12

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    Language：English  

    PubMed

  • Sasahira T, Akama Y, Fujii K, Kuniyasu H .  Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. .  Virchows Archiv : an international journal of pathology446 ( 4 ) 411 - 5   2005.4

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  • Kuniyasu H, Yano S, Sasaki T, Sasahira T, Sone S, Ohmori H .  Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages. .  The American journal of pathology166 ( 3 ) 751 - 60   2005.3

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  • Sasahira T, Sasaki T, Kuniyasu H .  Interleukin-15 and transforming growth factor alpha are associated with depletion of tumor-associated macrophages in colon cancer. .  Journal of experimental & clinical cancer research : CR24 ( 1 ) 69 - 74   2005.3

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    Language：English  

    PubMed

  • Bhawal UK, Ozaki Y, Nishimura M, Sugiyama M, Sasahira T, Nomura Y, Sato F, Fujimoto K, Sasaki N, Ikeda MA, Tsuji K, Kuniyasu H, Kato Y .  Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma. .  Oncology69 ( 3 ) 246 - 55   2005

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  • 笹平 智則, 桐田 忠昭, 山本 一彦, 國安 弘基 .  口腔扁平上皮癌におけるReceptor for Advanced Glycation End Products(RAGE)発現の意義 .  頭頸部癌30 ( 4 ) 646 - 650   2004.12

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    Publisher：(一社)日本頭頸部癌学会  

    口腔扁平上皮癌74例(男40例,女34例)を対象にreceptor for advanced glycation end products(RAGE)発現の意義を検討した.部位は舌39例,歯肉27例,頬粘膜,硬口蓋各4例,分化度は高分化50例,中分化21例,低分化3例,臨床病期はStage Iが4例,IIが21例,IIIが28例,IVが21例であった.癌切除標本の免疫組織化学的検討で,RAGE陽性は61例,82.4%であり,過去に検討した胃癌,大腸癌,前立腺癌に比較して高率であった.RAGE発現と分化度,所属リンパ節転移とは関連を認めなかったが,臨床病期とRAGE発現との間には有意差を認め,Stage IIIおよびIVで高かった.また術後再発を来たした30例では全例RAGE発現を認めた.Coxの比例ハザードモデルによる多変量解析を他の臨床病理学的因子を含めて行ったところ,「RAGE発現」のみが有意な予後と関わる独立因子であった.無病生存期間との関連ではRAGE陽性例が陰性例に比較して有意に予後不良であり,特に強陽性30例が不良であった.RAGEが口腔扁平上皮癌の進展および予後予測マーカーとして有用である可能性が示唆された

  • Sasaki T, Sasahira T, Shimura H, Ikeda S, Kuniyasu H .  Effect of Nma on growth inhibition by TGF-betaa in human gastric carcinoma cell lines. .  Oncology reports11 ( 6 ) 1219 - 23   2004.6

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  • Kuniyasu H, Sasaki T, Sasahira T, Chihara Y, Ohmori H .  Repression of MLH1 and MGMT genes in colon mucosa adjacent to implanted cancer in athymic mouse. .  Journal of experimental & clinical cancer research : CR23 ( 2 ) 317 - 23   2004.6

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    PubMed

  • Sasaki T, Sasahira T, Shimura H, Ikeda S, Kuniyasu H .  Effect of human noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines. .  Hepato-gastroenterology51 ( 57 ) 912 - 5   2004.5

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  • Kuniyasu H, Sasaki T, Sasahira T, Ohmori H, Takahashi T .  Depletion of tumor-infiltrating macrophages is associated with amphoterin expression in colon cancer. .  Pathobiology : journal of immunopathology, molecular and cellular biology71 ( 3 ) 129 - 36   2004

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  • Kuniyasu H, Ohmori H, Sasaki T, Sasahira T, Yoshida K, Kitadai Y, Fidler IJ .  Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis. .  Clinical cancer research : an official journal of the American Association for Cancer Research9 ( 13 ) 4802 - 10   2003.10

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Books

  • Oral cancer Reviewed

    Sasahira T et al.（ Role： Joint author ,  Molecular biology of the oral cancer）

    Springer  2015 

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    Responsible for pages：63-81  

  • Recent Advances in Metastasis of Gastrointestinal Cancers Reviewed

    Sasahira T et al.（ Role： Joint author ,  Angiogenesis and lymphangiogenesis in oral cancer）

    Transworld Research Network  2010 

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    Responsible for pages：23-40  

MISC

  • 多彩な進展様式が混在した上顎粘表皮癌の1例

    宮腰 昌明, 阿部 浩志, 萩元 綾, 川島 雄介, 川畑 義裕, 犬童 寛子, 比地岡 浩志, 嶋 香織, 杉浦 剛, 笹平 智則, 田中 達朗

    歯科放射線   63 ( 1 )   20 - 24   2023.9

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    Language：Japanese   Publisher：(NPO)日本歯科放射線学会  

  • 上顎に生じたPrimordial odontogenic tumorの2例

    嶋 香織, Nguyen Phuong Thao, 下拾石 雄大, 笹平 智則

    診断病理   40 ( 3 )   265 - 271   2023.7

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

    症例は,過去の標本を再検討し,2017年に新規疾患としてWHO分類に追加された稀な歯原性腫瘍であるPrimordial odontogenic tumorの病理組織像を呈した2例である。いずれも小児の上顎に生じ,Ameloblastic fibroma疑い病名と診断されていた。組織像では,歯乳頭様の線維性組織の分葉状増殖がみられ,その最外層を全周,エナメル器にみられる内エナメル上皮様の極性を持つ高円柱状細胞が被覆していた。1例では,上皮直下に好酸性基質の沈着が認められた。(著者抄録)

  • 口腔癌の特性を規定する新規マーカーの分子病理学的探索

    笹平 智則

    南九州歯学会雑誌   3 ( 1 )   8 - 17   2022.9

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    Language：Japanese   Publisher：南九州歯学会  

    頭頸部癌は全世界で6番目に多い悪性腫瘍であり,なかでも口腔癌が一般的である。口腔癌は局所浸潤性やリンパ節転移能が強いため予後は過去30年間ほぼ改善されないままであり,全5年生存率は50%未満に過ぎない。早期の口腔癌は適切な治療により80%以上が制御可能であるのに対し,進行癌の約70%は治癒困難である。さらに,口腔癌はしばしば咀嚼・嚥下障害,発声・構音異常,審美性の低下を引き起こす。したがって,口腔癌の制圧や口腔機能と審美性の維持のためにはさらなるがんの分子機構の解明が緊急の課題である。一般的に,口腔癌は飲酒,喫煙,ある種のウイルス感染,炎症といったような慢性的な刺激に曝露されることで発生,進展すると考えられている。近年の著しい分子生物学の発展・進歩により口腔癌の発生,浸潤,転移に関する分子機構が明らかになりつつあるが,残念ながら口腔癌の早期発見,治療に有用なマーカーは現在まで開発されておらず,分子標的を明らかにすることは不可欠である。本総説では口腔癌の分子病理学に関する我々の最近の知見のうち,特にparticular focus on mucin 20(MUC20),sushi repeat containing protein X-linked 2(SRPX2),serpin peptidase inhibitor,clade E,member 2(SERPINE2),miR-29b-1-5pに焦点を絞って概説する。(著者抄録)

Presentations

  • Nguyen Thao、嶋　香織、下拾石雄大、笹平智則   Amlification of the nuclear important receptor KPNA7 is associated with poor overall survival in head and　 　　　　neck cancer.  

    第82回日本癌学会総会  2023.9 

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    Event date： 2023.9

    Presentation type：Poster presentation  

    Venue：横浜  

  • 下拾石雄大、Nguyen Phuong Thao、嶋 香織、石田喬之、笹平智則   口腔扁平上皮癌における癌抑制遺伝子としてのEGR−１の機能解析  

    第65回歯科基礎医学会学術大会  2023.9 

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    Event date： 2023.9

    Presentation type：Poster presentation  

    Venue：東京  

  • 笹平智則   口腔癌の特性を規定する新規分子の探索  

    第65回歯科基礎医学会学術大会  2023.9 

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    Event date： 2023.9

    Presentation type：Symposium, workshop panel (nominated)  

    Venue：東京  

  • 嶋 香織、Nguyen Phuong Thao、下拾石雄大、笹平智則   口腔扁平上皮癌におけるm6AメチルトランスフェラーゼMETTL5の発現解析  

    第65回歯科基礎医学会学術大会  2023.9 

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    Event date： 2023.9

    Presentation type：Poster presentation  

    Venue：東京  

  • 柳生貴裕、舟山直希、財前美希、栗原　都、笹平智則、桐田忠昭　   口腔潜在的悪性疾患からの癌化における遺伝子異常：次世代シーケンサーによるゲノム解析  

    第34回日本臨床口腔病理学会総会  2023.8 

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    Event date： 2023.8

    Presentation type：Oral presentation (general)  

    Venue：大阪  

  • 嶋　香織、野間優作、別府真広、萩本　綾、田中達朗、廣瀬勝俊、豊澤　悟、笹平智則   下顎骨病変  

    第34回日本臨床口腔病理学会総会  2023.8 

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    Event date： 2023.8

    Presentation type：Poster presentation  

    Venue：大阪  

  • 口腔扁平上皮癌におけるMETTL5の発現と機能の解析   口腔扁平上皮癌におけるMETTL5の発現と機能の解析  

    第112回日本病理学会総会  2023.4 

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    Event date： 2023.4

    Presentation type：Poster presentation  

    Venue：下関  

  • 冨嶋彩未、Nguyen Phuong Thao、嶋 香織、下拾石雄大、笹平智則　   口腔癌における MCTP1 と MCTP2 の機能的な差異についての検討  

    第112回日本病理学会総会  2023.4 

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    Event date： 2023.4

    Presentation type：Poster presentation  

    Venue：下関  

  • Cytoplasmic TCF19 translocation impairs DNA damage repair in HNSCC  

    2023.4 

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    Event date： 2023.4

    Presentation type：Poster presentation  

  • Nguyen Phuong Thao、嶋　香織、下拾石雄大、笹平智則   Impacts of KPNA7 amplification and overexpression on tumor infiltrating immune cells of HNSCCs  

    第112回日本病理学会総会  2023.4 

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    Event date： 2023.4

    Presentation type：Poster presentation  

    Venue：下関  

  • Nguyen Phuong Thao、嶋 香織、下拾石雄大、笹平智則   EPS8L3 mediates YAP nuclear translocation and promotes liver tumorigenesis  

    第112回日本病理学会総会  2023.4 

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    Event date： 2023.4

    Presentation type：Poster presentation  

    Venue：下関  

  • 東 友太郎、久米健一、松村吉晃、別府真広、杉浦 剛、高田耕児、嶋 香織、笹平智則   口腔扁平上皮癌患者における循環腫瘍細胞の DNA 解析  

    第58回日本口腔組織培養学会  2022.12 

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    Event date： 2022.12

    Presentation type：Oral presentation (general)  

    Venue：鹿児島  

  • Nguyen Thao 、嶋　香織、笹平智則   New insights into YAP nuclear translocation to promote liver tumorginesis  

    第81回日本癌学会総会  2022.9 

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    Event date： 2022.9 - 2022.10

    Presentation type：Poster presentation  

    Venue：横浜  

  • 嶋　香織、下拾石雄大、杉浦 剛、中村典史、笹平智則   口腔粘膜病変における擦過細胞診の有用性について  

    第4回南九州歯学会総会  2022.8 

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    Event date： 2022.8

    Presentation type：Oral presentation (general)  

    Venue：Web  

  • 嶋　香織、近藤智之、笹平智則   多発性口腔扁平上皮癌におけるRNAメチル化関連因子の検索  

    第111回日本病理学会総会  2022.4 

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    Event date： 2022.4

    Presentation type：Poster presentation  

    Venue：神戸  

  • 近藤智之、嶋　香織、笹平智則   自己免疫疾患モデルにおけるPD-1陽性T細胞増加による大腸化学発癌の亢進  

    第111回日本病理学会総会  2022.4 

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    Event date： 2022.4

    Venue：神戸  

  • 下拾石雄大、石田喬之、吉村卓也、野村綾子、東　翔太朗、高山大生、平野憂花、嶋　香織、宮脇昭彦、 　　　　比地岡浩志、久米健一、野添悦郎、笹平智則、中村典史   切除標本を用いた術中迅速病理診断の有用性  

    第40回日本口腔腫瘍学会総会  2022.2 

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    Event date： 2022.2 - 2022.3

    Presentation type：Oral presentation (general)  

    Venue：Web  

  • 小野裕右、石畑清秀、岐部俊郎、嶋 香織、近藤智之、渕上貴央、野添悦郎、笹平智則、中村典史   当科開設後40年間の新分類（WHO: 2017年）による歯原性腫瘍の臨床統計的検討  

    第66回日本口腔外科学会総会 

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    Event date： 2021.11

  • 笹平智則   Hallmarks of Oral Cancer: 新たな分子マーカーの探索  

    2021.9 

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    Event date： 2021.9

  • 近藤智之、 嶋 香織、 吉村卓也、 野添悦郎、 中村典史、 笹平智則   診断に苦慮した頬粘膜 mucoepidermoid carcinoma の一例  

    第3回南九州歯学会議  2021.9 

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    Event date： 2021.9

  • 笹平智則   口腔癌の特性を規定する分子マーカーの探索  

    第3回南九州歯学会  2021.9 

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    Event date： 2021.9

    Language：Japanese  

  • 嶋　香織、近藤智之、別府真広、杉浦　剛、笹平智則   顎下部腫瘍  

    第32回日本臨床口腔病理学会 

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    Event date： 2021.8

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Awards

  • 高橋産業経済研究財団助成

    2024.4  

    笹平智則

  • 日本病理学会学術奨励賞

    2013.6  

  • 日本臨床口腔病理学会奨励賞（実験病理分野）

    2011.8  

  • 日本病理学会学術研究賞

    2007.11  

Research Projects

  • 時空間的多様性を捕捉する微小環境選択的な口腔癌診断・治療システムの開発

    Grant number：24K02647  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    笹平 智則, 美島 健二, 工藤 保誠, 森 泰昌, 嶋 香織, NGUYEN THAO

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    Grant amount：\18460000 （ Direct Cost: \14200000 、 Indirect Cost：\4260000 ）

  • 運動によるmyokineを介した口腔癌微小環境・免疫機能改善と癌細胞への直接作用

    Grant number：22K10152  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    吉村 卓也, 谷本 昭英, 鈴木 甫, 中村 典史, 大澤 匡弘, 笹平 智則

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

  • PXDNによるがん代謝と微小環境を標的とした口腔癌の治療ストラテジー

    Grant number：21K10077  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    栗原 都, 笹平 智則

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

    がん細胞と間質細胞との相互作用により形成される微小環境が、がん細胞の増殖・浸潤・転移や治療抵抗性にも深く関わることが明らかとなっている。申請者らはperoxidasin（PXDN）ga
    口腔癌局所の乳酸とATPの産生亢進とROSの産生、ならびにHO-1との相互作用により微小環境の形成に寄与することを既に報告している。
    本年度はPXDNがんの微小環境を形成する機構についての検討をおこなった。その結果、small proline-rich protein 1B (SPRR1B)を見いだした。SPRR1Bは扁平上皮への分化に関わるマーカーと考えられており、扁平上皮化生を示す気管支粘膜では高発現しているのに対し、胃や肺の腺癌では発現レベルが低いことが示されている。SPRR1Bは高分化型の口腔癌細胞であるHSC4細胞でより高発現しており、 SPPRR1BをノックダウンしたHSC4細胞ではケラチノサイトのマーカーであるinvolucrinとkeratin 1の発現と培養上清中への分泌が低下した。また、SPRR1BはMAPK p38のリン酸化レベルを誘導することで細胞増殖にも関与することも明らかとなった。口腔癌検体を用いた検討では、高分化型扁平上皮癌において有意に高いSPRR1Bの発現が確認された。
    これらの結果、高分化型口腔扁平上皮癌はSPRR1Bにより角化が亢進するだけでなく、MAPKを介した細胞増殖を誘導する可能性が示唆された。細胞分化を指標とした新たな口腔癌治療の展開が期待される。

  • 新規口腔癌特異的遺伝子であるSTOX2の機能解明と診断・治療への応用の模索

    Grant number：20K09912  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    笹平 智則, 栗原 都, 桐田 忠昭

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

    Melanoma inhibitory activity (MIA) はメラノーマ等の進展を促進する血清タンパクであり、口腔癌においても所用促進性の分泌タンパクとして機能してている。申請者らはMIAの新たな下流シグナルとしてstorkhead-box protein 2 (STOX2) を見いだした。STOX2はMIAと相互作用することで口腔癌促進的に作用する
    本年度はSRPX2に関連するシグナルとして、（serpin family E member 2）SERPINE2を見いだした。口腔癌細胞株においてSERPINE2の発現を抑制すると培養上清中への分SERPINE2の泌が抑制され、口腔癌検体を用いた検討においても正常粘膜よりも高いレベルでのSERPINE2の分泌がELISAで確認された。さらに、in vitroにおいて脈管新生能への影響を調べたところ、SERPINE2により血管/リンパ管内皮細胞の増殖能、遊走能、管腔形成能が誘導され、口腔癌細胞と内皮細胞の相互作用も促されることが明らかとなった。167例のFFPE標本による免疫組織化学においてSERPINE2の発現率は38.9%（65/167）であり、その発現は浸潤の深さ、MVD、LVDと相関していた。さらに、多変量解析では独立した予後不良因子となることが示された。
    以上より、SERPINE2は口腔癌における新たな脈管新生分子であることが明らかとなり、本分子を標的とした新たな口腔癌治診断、治療の可能性が期待される。

  • New Developments in Molecular Diagnosis and Therapy of Oral Cancer by Targeting MIA2-related Signals

    Grant number：18K09796  2018.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kurihara Miyako

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

    Melanoma inhibitory activity (MIA family) is a secreted protein involved in the progression of oral cancer. During the course of this study, the applicants newly identified pyruvate kinase (PKM), miR29b-1-5p, non-SMC condensin I complex subunit H (NCAPH), and mucin20 (MUC20) as signals related to the MIA family. The results of this study are as follows. Although these molecules have different functions, they were all found to be factors that promote the progression of oral cancer.

  • Elucidation of the pre-metastasis niche formation mechanism of oral cancer by TANGO

    Grant number：17K11621  2017.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Sasahira Tomoonori

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

    TANGO acts tumor-promotingly in oral cancer. We have conducted detailed studies on the functions and signal pathways of TANGO in oral cancer using clinical specimen and oral cancer cell line. As a result, NCAPH, mast cell chymase, SRPX2, PXDN, MUC20, etc. were newly identified as new molecules related to TANGO. Among these, DHRS9 acts on tumor inhibitory properties in oral cancer, but other molecules act as oncgene in oral cancer. It was also revealed that some of them are detected as secretory proteins not only in tumors but also in serum. It is expected that it may be a molecular marker in oral cancer

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Teaching Experience

  • 病理学Ⅱ

    2021.12
    -
    2021.2
    Institution：鹿児島大学

  • 総合歯科学

    2021.10
    -
    2021.11

  • 病理学

    2021.4
    -
    2021.9
    Institution：奈良県立医科大学

  • 臨床予備実習

    2021.4
    Institution：鹿児島大学

  • 病理学Ⅰ

    Institution：鹿児島大学