2021/10/20 更新

写真a

マルヤマ サトシ
丸山 智
MARUYAMA Satoshi
所属
医歯学総合病院 口腔外科系歯科 顎顔面口腔外科 講師
医歯学総合研究科 口腔生命科学専攻 講師
職名
講師
外部リンク

学位

  • 歯学博士「歯学」 ( 2004年3月   新潟大学 )

研究キーワード

  • Oral Pathology

  • 口腔病理学

研究分野

  • ライフサイエンス / 常態系口腔科学

経歴

  • 新潟大学   医歯学総合病院 口腔外科系歯科   講師

    2012年11月 - 現在

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻   講師

    2009年2月 - 現在

  • 新潟大学   口腔外科   講師

    2009年2月 - 2012年11月

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻   助教

    2005年5月 - 2009年1月

  • 新潟大学   医歯学総合研究科   研究員

    2004年5月 - 2005年4月

学歴

  • 新潟大学

    - 1999年

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  • 新潟大学   歯学部   歯

    - 1999年

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    国名: 日本国

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所属学協会

 

論文

  • Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma. 査読 国際誌

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

    Oncology reports   40 ( 5 )   2487 - 2496   2018年11月

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    記述言語:英語  

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

    DOI: 10.3892/or.2018.6665

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  • Stromal mesenchymal stem cells facilitate pancreatic cancer progression by regulating specific secretory molecules through mutual cellular interaction. 査読 国際誌

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

    Journal of Cancer   9 ( 16 )   2916 - 2929   2018年

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    記述言語:英語  

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

    DOI: 10.7150/jca.24415

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

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

    EXPERIMENTAL AND MOLECULAR PATHOLOGY   102 ( 2 )   327 - 336   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Oral squamous cell carcinomas (SCCs) are frequently associated with pre-invasive lesions including carcinoma in-situ (CIS), and CISs further form lateral interfaces against surrounding normal or dysplastic epithelia (ND). At the interface where keratin (K) 17 positive (+) SCC/CIS cells are in contact with K13 + ND cells, "cell competition" must be evoked between two such different cell types. Thus, the aim of this study was to characterize the histopathology of the SCC/CIS-ND interface and to determine protein profiles around the interface by proteomics. A total of 112 lateral interfaces were collected from 55 CIS and 57 SCC foci, and they were investigated by immunohistochemistry and liquid chromatography-tandem mass spectrometry. The interfaces were morphologically classified into three types: vertical, oblique, and convex. There were several cellular changes characteristic to the interface, including apoptosis and hyaline bodies, which were more emphasized in SCC/CIS sides. The results suggested that ND cells were winners of cell competition against SCC/CIS cells. Then, the interfaces were divided into four vertical segments, and each segment was separately laser-microdissected from tissue sections with immunostaining for K13 or K17; the four segments included SCC/CIS away from(#1) or adjacent to (#2) the interface, and ND adjacent to (#3) or away from (#4) the interface. Proteome analyses revealed approximately 4000 proteins from SCC/CIS sides [#1 and #2] and 2800 proteins from ND sides [#3 and #4]. We quantitatively selected the top 25 proteins including ladinin-1 or interleukin-1 receptor antagonist protein, which were most contrastively increased or decreased in SCC/CIS or ND sides, respectively, and their specific immunohistochemical expression modes were confirmed in tissue sections as well as in cultured SCC cells. These molecules should be involved in the cellular crosstalk toward cell competition at the lateral interface of oral SCC/CIS and would be new candidates for histopathological distinction of oral malignancies. (C) 2017 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.yexmp.2017.02.018

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

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

    HUMAN PATHOLOGY   57   51 - 60   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2016.07.001

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

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

    PATHOLOGY   48 ( 3 )   219 - 227   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    To confirm our hypothesis that macrophages recruited to fight against oral squamous cell carcinoma (SCC) invasion are functionally differentiated within neoplastic stromata, we analysed arrangements of macrophage subtypes and cancer-associated fibroblasts (CAFs) in their association with blood vasculatures in the neoplastic stroma. Surgical specimens of oral SCC were immunohistochemically examined for macrophage phenotypes (CD68, CD163, and CD204) and stromal environments (perlecan, connexin 43, and CD31). Human monocytes were co-cultured with ZK-1 cells of oral SCC origin in different culture conditions. SCC stromata were divided into two types: fascicular (fibroblast rich) and reticular (perlecan-rich). Regardless of stromal types, CD68 positive (+)/CD163+/CD204+ macrophages were recruited when blood vessels were abundant. Connexin 43+ fibroblasts were enriched in the fascicular stroma, where blood vessels were depleted. In co-culture experiments, monocytes, in the presence of ZK-1 cells, showed TNF-alpha(low)/IL-12(low) and IL-10(high)/VEGF(high)/MMP-9(high) with increased expression levels for fibronectin and perlecan. With direct contact with monocytes, SCC cells also expressed CD68 and CD163. SCC stromata were characterised by CD163+/CD204+ tumour-associated macrophages (TAMs) and connexin 43+ CAFs. TAMs are differentiated from monocytes by the physical contact with oral SCC cells in the perlecan-rich neoplastic stroma, which is also induced by the cross-talk between SCC cells and stromal cells including TAMs.

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    The intercellular depdsit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1 were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells. (C) 2016 Elsevier GmbH. All rights reserved.

    DOI: 10.1016/j.prp.2016.02.016

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   44 ( 10 )   850 - 856   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundOral pemphigus vulgaris (PV), an autoimmune blistering disease, is mainly mediated by autoantibodies against desmoglein (Dsg) 3. However, no attention has been paid to IgG subclasses of the autoantibodies against Dsg3 in the diagnostic procedure for PV. Thus, our aim in this study was to investigate whether Dsg3 and any of IgG subclasses are immunohistochemically colocalized in tissue sections of PV oral mucosa.
    Materials and MethodsSerial sections cut from formalin-fixed paraffin blocks of biopsy specimens of 9 PV cases and those of normal buccal mucosa surgically removed for fibro-epithelial polyps were comparatively examined for immunohistochemical localizations for Dsg3, IgG4, and IgG.
    ResultsDsg3 was demonstrated in a dot-like pattern on the cell border and in the cytoplasm of the whole epithelial layer in both normal and PV specimens, while its staining was irregular among floating epithelial sheets of PV. IgG4 was also demonstrated in a punctuated fashion on the cell border among floating epithelial sheets, which was nearly identical to the immunohistochemical profile of Dsg3. In addition to being detected in the epithelial part, IgG4 signals were prominently localized in plasma cells scattered in the granulation tissue, where ratios of IgG4-positive (+) plasma cells to IgG+ cells were extraordinarily higher (mean 28%) than those in normal mucosa.
    DiscussionThese findings confirmed for the first time that autoantibodies against Dsg3 are mainly composed of IgG4 in oral PV and that the combined immunohistochemistry for Dsg3 and IgG4 can be a valuable aid in confirming a histopathological diagnosis of PV.

    DOI: 10.1111/jop.12290

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

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

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY   120 ( 2 )   227 - 237   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Objective. The aim of this study was to characterize the histologic and immunohistochemical profiles of paradental cystlining epithelia to clarify its histopathogenesis.
    Study Design. Ten surgical specimens of paradental cysts were examined for clinical profiles and to determine the histopathologic characteristics of the lining epithelia. Immunohistochemical profiles for keratin (K) subtypes, as well as for perlecan, UEA-I lectin binding, and proliferating cell nuclear antigen (PCNA), were determined and compared.
    Results. The paradental cyst was clinically characterized by its occurrence in young adults (mean age, 36.8 years; male, 42.8, female 27.8). Eight of the 10 cases arose in the retromolar area. The cyst wall was basically granulation tissue that was attached to the periodontal ligament space. Thin irregular anastomosing epithelial cords lined the cyst walls of immature granulation tissue with vascular dilation and hemorrhage. The intercellular space of the lining epithelia was widened with inflammatory cell infiltrates. Immunohistochemically, the lining was positive for K13, K14, K17, K19, UEA-I binding, and perlecan, suggesting its junctional/sulcular epithelial character.
    Conclusion. The results showed that the paradental cyst was lined by epithelial cells with characteristics of the junctional/sulcular epithelium. The cyst can thus be considered as a kind of inclusion cyst arising in the periodontal pocket, most frequently of the mandibular third molars of young adults.

    DOI: 10.1016/j.oooo.2015.04.001

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

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

    HUMAN PATHOLOGY   46 ( 7 )   991 - 999   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1- dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2 activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2015.03.003

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

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

    VIRCHOWS ARCHIV   466 ( 5 )   559 - 569   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Expression of keratin (K) 13 is replaced with that of K17 when squamous cells of the oral mucosa transform from normal and dysplastic epithelia to carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Since 14-3-3 sigma is functionally associated with K17, we examined possible relationships between expression of K17 and 14-3-3 sigma in oral CIS and SCC tissues by immunohistochemistry. We furthermore examined whether or not K17 expression or knockdown by small interfering RNA (siRNA) modulates the behavior of SCC cells in culture in terms of cell proliferation and migration. In tissue specimens of oral SCC and CIS, the pattern of cytoplasmic expression of 14-3-3 sigma and K17 was similar but neither was expressed in normal or dysplastic epithelia. Both proteins were demonstrated in the cytoplasm of control oral SCC ZK-1 cells, but expression of 14-3-3 sigma changed from cytoplasmic to nuclear upon knockdown of K17. In carcinoma cells, therefore, cytoplasmic localization of 14-3-3 sigma seems to accompany expression of K17. In K17-knockdown cells, proliferation was significantly suppressed at 4 days after seeding. In addition, the cell size of K17-knockdown cells was significantly smaller than that of control cells; as a result of which in the migration experiments, we found delayed closure of scratch wounds but migration as such was not affected. We conclude that K17 expression promotes SCC cell growth and cell size but does not affect cell migration. K17 expression is accompanied by cytoplasmic expression of 14-3-3 sigma, indicative of their functional relationship.

    DOI: 10.1007/s00428-015-1735-6

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

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

    LABORATORY INVESTIGATION   94 ( 11 )   1260 - 1272   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Milk fat globule-epidermal growth factor (EGF)-factor VIII (MFG-E8) is a secreted glycoprotein that promotes clearance of apoptotic cells by bridging phosphatidylserine on apoptotic cells and integrin alpha beta 3/5 on phagocytes. High expression of MFG-E8 has been reported in various types of cancer in humans. Apoptotic figures are frequently found in the surgical samples of oral squamous cell carcinoma (SCC) and carcinoma in situ, and we have often observed apoptotic carcinoma cells engulfed by macrophages or even by neighboring carcinoma cells. Thus we hypothesized that MFG-E8 might promote engulfment of apoptotic carcinoma cells by living carcinoma cells and that MFG-E8 expressed by carcinoma cells could contribute to tumor progression. The aim of this study was to elucidate the biological role of MFG-E8 in oral SCC. Fifty-three surgical specimens of oral SCC were used for immunohistochemistry for MFG-E8, and the expression profiles were correlated with clinicopathological properties. Also, we examined the MFG-E8 expression patterns and functions using three human oral SCC cell lines. Most of the cases had MFG-E8-positive SCC cells, and the expression of MFG-E8 was correlated with such clinicopathological features as tumor size, pathological stage, locoregional recurrence, scattering invasion pattern, and SCC cell figures engulfing apoptotic SCC cells. The MFG-E8 staining was enhanced in apoptotic SCC cells, some of which were apparently engulfed by the neighboring SCC cells. ZK-1 cells showed high MFG-E8 expression, and its localization was found in the cytoplasm and the cell surface. Transient MFG-E8 knockdown by siRNA in ZK-1 decreased cell proliferation and invasiveness and increased cell death. Thus we have demonstrated that MFG-E8 promotes tumor progression in oral SCC and that it might be involved in the clearance of apoptotic SCC cells by living SCC cells.

    DOI: 10.1038/labinvest.2014.108

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   43 ( 10 )   778 - 784   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundWe have reported that neutrophilic infiltration was associated with round-shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in situ and that those inflammatory cells are recruited from intra-epithelially entrapped blood vessels. Based on these lines of evidence, we have formulated a hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm this hypothesis, we investigated immunohistochemically stepwise degradation of keratin pearls in oral squamous cell carcinoma (SCC) to clarify any other type scavenger cells in addition to neutrophils are involved in this particular degradation process.
    MethodsNeutrophils (neutrophil elastase) and macrophage subpopulations (CD68, CD163 and CD204) were immunohistochemically localized in 30 cases of oral SCC with typical round-shaped keratin pearls. SCC cells were revealed by immunohistochemistry for keratin (K) 17, and blood vessels were demonstrated by CD31.
    ResultsKeratin pearl degradation process was divided into four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage infiltration but focal neutrophilic infiltration within the pearls; (iii) neutrophil predominant stage: dense neutrophil infiltration with minimal macrophages and segregated keratinized cancer cells strongly positive for K17; and (iv) macrophage predominant stage: dense infiltration of CD68-, CD163 (mononuclear)- and CD204 (multinucleated)-positive macrophages engulfing detached keratinized SCC cells.
    ConclusionKeratin pearl degradation in oral SCC is strictly regulated by two types of scavenger cells: neutrophils, which perform initial tasks, and macrophages, which reciprocally take over from neutrophils the role to finalize the degradation processes.

    DOI: 10.1111/jop.12197

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

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

    HISTOCHEMISTRY AND CELL BIOLOGY   142 ( 3 )   297 - 305   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The aim of this study was to demonstrate the presence of intraepithelial stroma represented by extracellular matrix (ECM) deposits in the junctional epithelium to clarify its function as a scaffold for leukocyte migration through epithelial cells. Twenty-three biopsy specimens from the gingiva including the junctional epithelium were examined to determine comparative protein and gene level expression profiles for keratin and ECM molecules between the junctional epithelium and the gingival epithelium using immunohistochemistry and in situ hybridization. Intraepithelial leukocyte types and frequencies were also determined and compared between the junctional and gingival epithelia. In the junctional epithelium, which was positive for keratin 19, perlecan was strongly deposited in intercellular space of the whole epithelial layer, while it was faintly positive around the parabasal layer of the gingival epithelium. Perlecan mRNA signals were enhanced to a greater degree in both epithelial and inflammatory cells within the junctional epithelium. In the junctional epithelium, greater numbers of neutrophils and macrophages were found as compared with the gingival epithelium. Our results showed that perlecan is the primary ECM molecule comprising intraepithelial stroma of the junctional epithelium, in which leukocytes may migrate on ECM scaffolds in intercellular space toward the surface of the gingival sulci or pockets.

    DOI: 10.1007/s00418-014-1198-x

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   43 ( 8 )   627 - 636   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BACKGROUND: We have demonstrated the induction of perlecan-rich stroma of oral squamous cell carcinoma (SCC) on and after its start of invasion. However, it remains unknown how such a neoplastic stroma is actually arranged in tumor tissues.
    METHODS: To this end, tissue microarray samples, in which keratin and perlecan were contrastively labeled by immunohistochemistry, were three-dimensionally analyzed using digital images and image analysis software to demonstrate the relationship between SCC foci and the perlecan-positive stromal space or that between carcinoma in situ (CIS) and invasive SCC foci.
    RESULTS: The three-dimensional (3D) reconstruction demonstrated three kinds of perlecan profiles for inside (I) and outside (O) areas of the carcinoma cell focus: mode 1, 1(+)/O-; mode 2, 1(+)/O+; and mode 3, 1(-)/O+. Mode 1 was seen in CIS as well as SCC tumor massifs in the surface part. Mode 2 was seen in small SCC foci, which seemed isolated in 2D sections but were mostly continuous with the tumor massif in 3D reconstructions. Mode 3 was limited to small SCC foci, which were truly segregated from the tumor massif.
    CONCLUSIONS: The results indicated that the 2D SCC focus isolation could not be regarded as invasion but that the SCC foci surrounded by perlecan-positive stroma (modes 2 and 3) could be regarded as a more objective measure for invasion of SCC. This is the first 3D tissue-level demonstration of the neoplastic stroma space induced with oral SCC invasion, the presence of which we have predicted based on our previous 2D and tissue culture evidence.

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

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

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY   118 ( 1 )   E12 - E18   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Hybrid odontogenic tumors including 2 or more different histologic types have been documented, but their occurrences are not very common. We present a case of hybrid odontogenic tumor composed of ameloblastoma and adenomatoid odontogenic tumor (AOT) arising in the mandibular molar region of a 31-year-old Japanese woman who had a history of familial adenomatous polyposis. The tumor, measuring 10 mm in diameter, was surgically removed from the alveolar bone. Histopathologically, the tumor consisted of both follicular and plexiform types of ameloblastoma in which multiple and smaller foci of AOT were intermingled. There have been 3 reported cases of hybrid ameloblastoma and AOT, all of which presented unicystic types as ameloblastoma components. This, however, is the first report of a hybrid tumor containing an authentic solid-type ameloblastoma compartment and an AOT compartment in a patient with a background of familial adenomatous polyposis.

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

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

    HUMAN PATHOLOGY   45 ( 1 )   110 - 118   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Keratocystic odontogenic tumor (KCOT), a developmental jaw cyst previously referred to as odontogenic keratocyst (OKC), typically arises in the jawbone. In this article, however, we report a case of KCOT located within the temporalis muscle. We compared its immunohistochemical profiles with those of authentic jaw KCOT, orthokeratinized odontogenic cyst, and epidermoid cyst in order to consider whether a soft tissue counterpart of KCOT could be a separate disease entity. The patient was a 46-year-old man with a well-defined cystic lesion within the left temporalis muscle. On computed tomographic images, the lesion was recognized as a cystic lesion, although KCOT was not included in, the clinical differential diagnoses. The location of the lesion was not within bone but, rather; within the temporalis muscle that was attached to the jawbones. Our review of the literature has disclosed more than 20 peripheral KCOT cases of the oral mucosa and more than 10 cases of the skin, but only 1 case, arising in muscle. Immunohistochemical investigation of the present intramuscular case reveals KCOT-characteristic profiles distinct from the other 3 types of cysts investigated. The results indicate that KCOT-like lesions can arise within soft tissues, although use of the term odontogenic might seem inappropriate in those cases. (C) 2014 Elsevier Inc. All rights reserved.

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

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

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

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    記述言語:英語   出版者・発行元:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    We report a rare case of radiation-induced undifferentiated high-grade pleomorphic sarcoma (UPS) (malignant fibrous histiocytoma, MFH) in the right mandible of a 44-year-old woman. The patient had suffered from osteomyelitis of the same region of the mandible for several years, which was considered to be due to radiotherapy for a malignant lymphoma in her right neck 19 years before. The tumor appeared as an exophytic and invasive growth in the molar region of the mandible. Histopathologically, the tumor consisted of an interlacing proliferation of vimentin-immunopositive spindle-shaped fibroblastic cells with bizarre nuclei with high Ki-67 labeling scores, and tumor cells showed storiform patterns mixed with pleomorphic cells. Taking the history of radiation into consideration, we diagnosed the lesion as radiation-induced MFH/UPS. Including the present case, there have been only 14 documented cases of radiation-induced UPS in the jawbone, and this is the first UPS case arising in the follow-up period of long-standing osteomyelitis. (C) 2014 Elsevier GmbH. All rights reserved.

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

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

    JOURNAL OF CELLULAR PHYSIOLOGY   228 ( 10 )   1977 - 1988   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Although the histopathogenetic process of keratin pearls is still poorly understood, acceleration of keratinization in squamous cell carcinoma (SCC) cells may represent one possible therapeutic avenue. Based on our histopathological observations, we have hypothesized that SCC cells are keratinized by phagocytosis of extravasated erythrocytes. To confirm this hypothesis, we firstly examined immature keratin pearls in oral carcinoma in situ (CIS) and mature ones in SCC by immunohistochemistry. Concentric dyskeratotic cells in CIS keratin pearls became positive for keratin (K) 10, K17, heme oxygenase-1 (HO-1), or protease activated receptor-2 (PAR-2), a candidate regulator for hemophagocytosis. When ZK-1 cells, an SCC cell system, were incubated with human peripheral blood erythrocytes, or with crude and purified hemoglobins (Hbs), their erythro-hemophagocytotic activities were confirmed by immunofluorescence. Immunofluorescence signals for K10, K17, and HO-1 were enhanced due to hemophagocytosis in time-dependent manners. mRNA expression levels for the three molecules were most enhanced by purified Hb, followed by crude Hb and erythrocytes. K17/K10 mRNA expression levels were more elevated when PAR-2 was activated in ZK-1 cells. The results indicated that immature and mature keratin pearls in CIS and SCC were generated by oxidative stresses derived from erythro-hemophagocytosis, which might mediate HO-1 expression and be regulated by PAR-2. Thus, hemorrhage from the rupture of blood vessels can be one of the triggers for keratin pearl formation in oral CIS and SCC. J. Cell. Physiol. 228: 1977-1988, 2013. (c) 2013 Wiley Periodicals, Inc.

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

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

    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology   116 ( 4 )   485 - 491   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objectives To examine the histopathological characteristics of inflammatory lesions containing Actinomyces based on DNA sequencing. Furthermore, case reports of actinomycosis in the maxillofacial region are summarized by a review of the literature. Study design The study comprised 12 cases of inflammatory lesions containing Actinomyces as diagnosed by DNA analysis. The average age of the subjects was 59 ± 15 years (6 males
    6 females). Results The distribution of causative bacteria was: Actinomyces israelii in 9 cases, Actinomyces gerencseriae in 2 cases, and Actinomyces naeslundii in 1 case. Four cases diagnosed by DNA sequencing were positive for "Druse," a known morphological diagnostic characteristic of actinomycosis, and 8 cases lacked typical colony formation. Conclusions DNA analysis using paraffin-embedded samples is effective for both early and accurate diagnosis of oral lesions containing Actinomyces. © 2013 Elsevier Inc. All rights reserved.

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

    Tomita T, Kubota T, Nakasone N, Morozumi T, Abe D, Maruyama S, Shimizu T, Horimizu M, Saku T, Yoshie H

    Archives of oral biology   58 ( 8 )   1014 - 1020   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

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

    LABORATORY INVESTIGATION   93 ( 8 )   921 - 932   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Podoplanin (PDPN), one of the representative mucin-like type-I transmembrane glycoproteins specific to lymphatic endothelial cells, is expressed in various cancers including squamous cell carcinoma (SCC). On the basis of our previous studies, we have developed the hypothesis that PDPN functions in association with the extracellular matrix (ECM) from the cell surface side. The aim of this study was to elucidate the molecular role of PDPN in terms of cell adhesion, proliferation, and migration in oral SCC cells. Forty-four surgical specimens of oral SCC were used for immunohistochemistry for PDPN, and the expression profiles were correlated with their clinicopathological properties. Using ZK-1, a human oral SCC cell system, and five other cell systems, we examined PDPN expression levels by immunofluorescence, western blotting, and real-time PCR. The effects of transient PDPN knockdown by siRNA in ZK-1 were determined for cellular functions in terms of cell proliferation, adhesion, migration, and invasion in association with CD44 and hyaluronan. Cases without PDPN-positive cells were histopathologically classified as less-differentiated SCC, and SCC cells without PDPN more frequently invaded lymphatics. Adhesive properties of ZK-1 were significantly inhibited by siRNA, and PDPN was shown to collaborate with CD44 in cell adhesion to tether SCC cells with hyaluronan-rich ECM of the narrow intercellular space as well as with the stromal ECM. There was no siRNA effect in migration. We have demonstrated the primary function of PDPN in cell adhesion to ECM, which is to secondarily promote oral SCC cell proliferation.

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

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

    Biochemical and Biophysical Research Communications   434 ( 1 )   124 - 130   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In previous studies, we have shown several lines of evidence that podoplanin (PDPN) plays an important role in cell adhesion via its association with extracellular components in neoplastic conditions, though there has been no trial to search for PDPN-interaction molecules in the extracellular milieu. To screen for those molecules, we performed proteomics-based analysis using liquid chromatography-tandem mass spectrometry followed by co-immunoprecipitation for PDPN in ZK-1, an oral squamous cell carcinoma (SCC) cell system whose cell membrane molecules were cross-linked with each other in their extracellular compartments, and we identified heat shock protein (HSP) A9 as one of the extracellular PDPN bound molecules. Effects of transient PDPN knockdown by siRNA in ZK-1 were also comparatively examined for cellular behaviors in terms of HSPA9 expression and secretion. Finally, HSPA9 expression modes were immunohistochemically visualized in oral SCC tissue specimens. HSPA9 was secreted from ZK-1 cells, and the expression and secretion levels of HSPA9 gene and protein were well coordinated with those of PDPN. Immunohistochemically, HSPA9 and PDPN were co-localized in ZK-1 cells and oral SCC foci, especially in the peripheral zone. In conclusion, the results indicate that HSPA9 secreted by oral SCC cells interacts with PDPN on their cell surface in an autocrine manner and regulates their growth and invasiveness. © 2013 Elsevier Inc.

    DOI: 10.1016/j.bbrc.2013.03.057

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

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

    VIRCHOWS ARCHIV   462 ( 3 )   297 - 305   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The expression of podoplanin, one of the representative immunohistochemical markers for lymphatic endothelium, is upregulated in various kinds of cancers. Based on our previous studies, we have developed a hypothesis that podoplanin plays a role in cell adhesion via its association with extracellular matrix (ECM). Since salivary pleomorphic adenoma is histologically characterized by its ECM-enriched stroma, we firstly wanted to explore the expression modes of podoplanin in pleomorphic adenoma and related salivary tumors by immunohistochemistry. In normal salivary gland, podoplanin was specifically localized in myoepithelial cells, which were also positively labeled by antibodies against P63, of the intercalated duct as well as acini. In pleomorphic adenoma, podoplanin was colocalized with P63 and CD44 in basal cells of glandular structures as well as in stellate/spindle cells in myxochondroid matrices, where perlecan and hyaluronic acid were enriched. The expression of podoplanin was confirmed at both protein and mRNA levels in pleomorphic adenoma cell systems (SM-AP1 and SM-AP4) by using immunofluorescence, western blotting, and reverse transcription polymerase chain reaction. Podoplanin was localized on the cell border as well as in the external periphery of the cells. Moreover, podoplanin expression was also confirmed in tumor cells with myoepithelial differentiation in myoepithelioma and intraductal papilloma. The results indicate that podoplanin can be regarded as a novel myoepithelial marker in salivary gland tumors and suggest that podoplanin's communication with ECM molecules is essential to phenotypic differentiation to myoepithelial cells.

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

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

    HISTOPATHOLOGY   61 ( 5 )   910 - 920   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aims: We investigated a group of oral mucosal lesions with characteristic hyperorthokeratotic foci, which we termed orthokeratotic dysplasia (OKD), to determine if it could be identified as a distinct histopathological entity.
    Methods and results: We screened 282 surgical specimens from 200 patients with oral leucoplakia-type squamous cell carcinoma (SCC) or carcinoma in situ (CIS). OKD was defined as an oral mucosal lesional focus in which hyperorthokeratosis was predominant in the presence of the granular cell layer. A total of 84 OKD foci from 62 cases found among the 200 SCC/CIS cases were analysed. According to its rete ridge shapes, OKD was classified into three subtypes: flat (14.3%), leg (63.1%) and intermediate (22.6%). Eighty per cent of OKD foci were adjacent to the main foci of SCC or CIS, and they were demarcated sharply from each other. Most of the OKD constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. Numbers of Ki-67-positive cells in the first basal layer were greater in OKD than in normal epithelia.
    Conclusions: The findings indicate that OKD is a distinct variant of epithelial dysplasia related to malignancies, and hence that it is important to recognize its existence.

    DOI: 10.1111/j.1365-2559.2012.04283.x

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

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

    HUMAN PATHOLOGY   43 ( 11 )   1973 - 1981   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    It is poorly understood which cell type, tumor cells, or stromal cells are responsible for the production of extracellular matrix molecules in the neoplastic stroma. We studied the expression of 4 extracellular matrix molecules at the protein and messenger RNA levels in monocellular and 2 kinds of coculture systems between human squamous cell carcinoma (ZK-1) and fibroblast (OF-1) cell lines, which may correspond to carcinoma in situ and squamous cell carcinoma, respectively. Squamous cell carcinoma and carcinoma in situ tissue sections were also investigated by immunohistochemistry and in situ hybridization for extracellular matrix. Immunohistochemically, perlecan and tenascin C were localized in carcinoma cells in carcinoma in situ, whereas they were in the stromal space in squamous cell carcinoma. In monocellular culture conditions, expression levels for perlecan, tenascin C, and laminin were more predominant in ZK-1 than in OF-1, although those for fibronectin were more enhanced in OF-1. However, these extracellular matrix expression levels of OF-I were elevated, whereas those of ZK-1 dropped when they were in coculture conditions. The differences between ZK-1 and OF-I were significantly more evident in direct contact (ZK-1/OF-1, 56%-22%) than in indirect contact (63%-39%). These results indicate that oral squamous cell carcinoma cells produce extracellular matrix in the absence of stromal fibroblasts (or in carcinoma in situ) and that they stop producing extracellular matrix in the presence of fibroblasts (or in squamous cell carcinoma). It is hence suggested that stromal fibroblasts after direct contact with invading squamous cell carcinoma cells are more responsible than squamous cell carcinoma cells for the formation of neoplastic stroma, whereas carcinoma in situ cells have to produce and deposit extracellular matrix by themselves to form intraepithelial microstromal spaces. (C) 2012 Elsevier Inc. All rights reserved.

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

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

    MODERN PATHOLOGY   25 ( 6 )   784 - 794   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in-situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events. Modern Pathology (2012) 25, 784-794; doi:10.1038/modpathol.2011.218; published online 3 February 2012

    DOI: 10.1038/modpathol.2011.218

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   41 ( 5 )   372 - 378   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    OBJECTIVES: A precancerous condition is a lesion that, if left untreated, leads to cancer or can be induced to become malignant. In the oral region, leukoplakia is a lesion that has been regarded as precancerous. In cases of oral carcinoma, we have frequently noticed that a type of leukoplakia histologically demonstrating hyper-orthokeratosis and mild atypia (ortho-keratotic dysplasia; OKD) is often associated with carcinoma, either synchronously or metachronously. Therefore, we consider OKD-type leukoplakia to be a true precancerous lesion. MATERIALS AND METHODS: In an attempt to clarify the relationship between OKD as a precancerous condition in the oral mucosa and telomere length, we estimated telomere lengths in this type of leukoplakia using quantitative fluorescence in situ hybridization, and also quantified the frequency of anaphase-telophase bridges (ATBs) in comparison with squamous cell carcinoma in situ (CIS) and the background tissues of CIS and OKD. RESULTS: Ortho-keratotic dysplasia was frequently associated with squamous cell carcinoma (45.0%) and showed significantly shorter telomeres than normal control epithelium, CIS, or the background of CIS or OKD. The frequency of ATBs was much higher in OKD than in control epithelium or CIS. CONCLUSION: Ortho-keratotic dysplasia appears to be frequently associated with carcinoma, chromosomal instability, and excessively shortened telomeres, not only in the lesion itself but also in the surrounding background. Therefore, when this type of leukoplakia is recognized in the oral region, strict follow-up for oral squamous cell carcinoma is necessary, focusing not only on the areas of leukoplakia, but also the surrounding background.

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

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

    VIRCHOWS ARCHIV   460 ( 5 )   473 - 480   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    It can be difficult to make a certain diagnosis in case of an oral borderline malignant lesion on hematoxylin-eosin-stained sections only. Furthermore, assessment of surgical margins of borderline lesions is difficult with the naked eye. We set out to determine the topographical distribution of capillary blood vessels within the epithelial zone and to assess its use as an aid for histopathological diagnosis and a framework for clinical assessment of lesional margins using optical techniques, such as narrow-band imaging (NBI) endoscopy. Capillary blood vessels entrapped in the epithelial compartment, which we have designated as intraepithelially entrapped blood vessels (IEBVs), were examined for their frequency, location, and shape in normal mucosa, dysplasia, and carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and type IV collagen. When counted per unit length of epithelial surface, IEBVs increased in number significantly in CIS (5.6 +/- 2.8), which was two times more than in normal (1.9 +/- 1.6) and dysplastic (2.4 +/- 1.5) epithelia. In addition, IEBVs in CIS had compressed shapes with occasional obstruction or collapse with hemorrhage and were arranged perpendicular to and extending up to the epithelial surface. These characteristic IEBVs in CIS were considered to be generated by complex expansion of rete ridges due to carcinoma cell proliferation within the limited epithelial space determined by the basement membrane. The recognition of IEBVs was helpful in the differential diagnosis of oral CIS, and the present data provide a valuable frame of reference for detecting oral CIS areas using such NBI-based optical devices.

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    Podoplanin, a representative immunohistochemical marker for lymphatic endothelial cells, is also expressed in many other kinds of cancer cells, although its pathophysiological function is largely unknown. Our aim was to determine immunolocalization modes of podoplanin among odontogenic tumors to discuss possible roles of podoplanin in their characteristic tissue architecture formation. Immunohistochemical profiles of podoplanin were investigated in 40 surgical specimens from ameloblastoma (AM), adenomatoid odontogenic tumor (AOT), calcifying cystic odontogenic tumor (CCOT), and keratocystic odontogenic tumor (KCOT) in comparison with those of proliferating cell nuclear antigen (PCNA), integrin beta 1, fibronectin, and matrix metalloproteinase 9 (MMP-9). Podoplanin was localized in the basal cell layer or in the peripheral zone of AM foci. It was found in spindle-shaped tumor cells of AOT, in both the basal and polyhedral cells of CCOT, and in the basal and parabasal cells of KCOT linings. Podoplanin-positive (+) cells were located within areas of PCNA+ cells, and integrin beta 1 was localized in the cell membrane of podoplanin+ cells in the intercellular space where fibronectin and MMP-9 were deposited. In conclusion, podoplanin+ cells and areas in odontogenic tumors are in close associations with extracellular matrix signalings as well as cell proliferation. (C) 2012 Elsevier GmbH. All rights reserved.

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  • Differential expression of perlecan receptors, α-dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma. 査読

    Ahsan MS, Yamazaki M, Maruyama S, Kobayashi T, Ida-Yonemochi H, Hasegawa M, Henry Ademola A, Cheng J, Saku T

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology   40 ( 7 )   552 - 559   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    Alvarado CG, Maruyama S, Cheng J, Ida-Yonemochi H, Kobayashi T, Yamazaki M, Takagi R, Saku T

    Histopathology   59 ( 2 )   283 - 291   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1365-2559.2011.03929.x

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

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

    ORAL ONCOLOGY   47 ( 6 )   497 - 503   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    To evaluate differential expressions for keratin (K) subtypes 13 and 17 in oral borderline malignancies, we examined 67 surgical specimens of the oral mucosa for their immunohistochemical profiles. From those specimens, 173 foci of epithelial dysplasia, 152 foci of carcinoma in situ (CIS), and 82 foci of squamous cell carcinoma (SCC) were selected according to our diagnostic criteria, along with 20 areas of normal epithelia. In normal epithelia, there was no K17 positivity (0%), whereas definite K13 positivity (100%) was observed. The same tendencies were obtained in mild (undefined) and moderate (true) epithelial dysplasias (K17: 0%; K13: 100%). In contrast, all CIS (100%) had K17 positivities, while K13 positivities were lost in many of them (7%). Similar tendencies were confirmed in invasive SCC (K17: 100%, K13: 4%). Simultaneous immunopositivities for K17 and K13 were found only in SCC (7%) and CIS (4%) foci with distinct keratinization. These foci also showed K10 positivities, though K10 positive areas were not identical to K13 positive areas. The results indicate that expressions of K17 and K13 are reciprocal in oral epithelial lesions and that the K17 emergence is related to malignancies. (C) 2011 Elsevier Ltd. All rights reserved.

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

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

    MICROSCOPY RESEARCH AND TECHNIQUE   74 ( 3 )   264 - 268   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    For histopathological assessment of oral borderline malignancies, it is important to carefully detect subtle epithelial changes on fully stretched tissue sections. However, it is not generally easy to obtain wrinkle-free sections when using formalin-fixed paraffin-embedded oral mucosal samples. Since acetic acid treatment is already utilized for large brain tissue sections, we examined whether that treatment was also effective for oral mucosal tissues containing normal to malignant epithelial lesions. Paraffin sections were floated in various concentrations of acetic acid for 10 min after stretching in water for 1 min, then wrinkle formations were examined using hematoxylin and eosin staining, as well as for staining intensity with keratin immunohistochemistry. Wrinkles were formed in both epithelial and connective tissue zones of sections treated with less than a 40-mM (0.25%) concentration of acetic acid. In contrast, treatments with concentrations at 80 mM (0.5%) and higher resulted in cracking between the epithelial layer and lamina propria, as well as poor immunohistochemical results for keratins 13 and 17, even though the wrinkles completely disappeared. These results indicate that 40 mM is the optimal concentration of acetic acid solution to prevent wrinkles in the epithelial layer while maintaining the immunohistochemical qualities of oral mucosa tissue sections, especially those containing borderline malignant epithelial lesions. Microsc. Res. Tech. 74: 264-268,2011. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/jemt.20900

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   40 ( 1 )   20 - 26   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    The occurrence of oral cancer is not clearly known in Myanmar, where betel quid chewing habits are widely spread. Since betel quid chewing has been considered to be one of the important causative factors for oral cancer, the circumstantial situation for oral cancer should be investigated in this country. We surveyed oral cancer cases as well as whole body cancers from two cancer registries from Yangon and Mandalay cities, both of which have representative referral hospitals in Myanmar, and we showed that oral cancer stood at the 6th position in males and 10th in females, contributing to 3.5% of whole body cancers. There was a male predominance with a ratio of 2.1:1. Their most frequent site was the tongue, followed by the palate, which was different from that in other countries with betel quid chewing habits. About 90% of male and 44% of female patients had habitual backgrounds of chewing and smoking for more than 15 years. The results revealed for the first time reliable oral cancer frequencies in Myanmar, suggesting that longstanding chewing and smoking habits are etiological backgrounds for oral cancer patients.

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

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

    PATHOBIOLOGY   78 ( 3 )   171 - 180   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Objective: Podoplanin, a known lymphatic endothelial cell marker, has been reported to be expressed in various types of cancer. To elucidate the expression of podoplanin in precancerous lesions, we examined the immunohistochemical profiles of podoplanin in oral squamous epithelial lesions. Method: We studied a total of 298 foci of squamous cell carcinoma (SCC), carcinoma in situ (CIS), epithelial dysplasia, and hyperplastic and/or normal epithelial lesions by immunohistochemistry using D2-40. Results: There was no positivity for podoplanin in normal or hyperplastic epithelia, while all of the CIS and SCC foci stained positive. Approximately one third of the mild dysplasia foci (10 of 36 foci, 28%) and 80% of moderate dysplasia foci (78/98) showed grade 1 positive reactions (positive only in the 1st layer). Grade 2 reactions (up to 4th layer) were seen in 4 of 98 moderate dysplasia foci (4%), 29 of 74 CIS foci (39%), and 3 of 30 SCC foci (10%). Grade 3 reactions (to more than 5th layer) were found in 35 (47%) CIS foci and 26 (87%) SCC foci. Conclusions: The relationship between the present histological categorization and podoplanin grade was statistically significant. D2-40 expression is considered to be related to the severity of oral precancerous lesions. Copyright (C) 2011 S. Karger AG, Basel

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

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

    HISTOPATHOLOGY   57 ( 6 )   806 - 813   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology
    Aims:
    Histopathological distinction of cystic jaw lesions, including odontogenic tumours, is challenging because their lining epithelia, which are basically stratified squamous epithelia, resemble each other, especially when they become hyperplastic from inflammatory reaction. The aim of this study was to seek practical measures to differentiate such lesions.
    Methods and results:
    Nineteen surgical specimens from unicystic ameloblastomas (UAs), 17 from keratocystic odontogenic tumours (KCOTs), 13 from dentigerous cysts (DCs), 10 from lateral periodontal cysts (LPCs) and 20 from radicular cysts (RCs), all of which contained both typical flat and rete-peg-shaped lining epithelia, were examined for their immunohistochemical profiles. Among them, keratin (K) 10, K17, perlecan, proliferating cell nuclear antigen (PCNA) and UEA-I lectin binding (UEA) were selected as useful immunohistochemical markers for their differential diagnosis. K10 was positive (+) in KCOT and DC. K17 was not present in RC. Perlecan was found in UA, KCOT and LPC. PCNA+ cells were found frequently in UA and KCOT. These localization patterns were constant even when linings were not flat.
    Conclusions:
    Using a combination of six kinds of immunohistochemical pattern, it is now possible to discriminate reliably and objectively these five cystic jaw lesions in routine practice.

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

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

    PATHOLOGY INTERNATIONAL   60 ( 3 )   156 - 166   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    To make reproducible diagnoses for oral carcinoma in situ (CIS), combined immunohistochemistry directed at the positioning of squamous cell proliferation (Ki-67) and differentiation (keratin (K) 13 and K19) was used, both of which support histological evaluations by providing biological evidence. Normal/hyperplastic epithelia was defined by K19+ cells only in the first basal layer, K13+ cells in the third basal and upper layers, and sporadic Ki-67+ cells in the second basal layer. These profiles indicated that a proliferating center of the oral epithelium is located in the parabasal cell layer, and K19 and K13 can be regarded as markers for basal and prickle cells, respectively. Epithelial dysplasia was characterized by irregular stratification of Ki-67+ cells and the absence of K19/K13 in proliferating cells. Irregular emerging of K19+ and K13+ cells in proliferating foci with unique stratification of atypical Ki-67+ cells indicated CIS. When the definition was applied, surgical margins in 172 recurrent cases were shown to contain CIS (39.4%) and squamous cell carcinoma (55.8%), indicating that the new diagnostic criteria for CIS reflected clinical behaviors of the cases. The results indicate that oral CIS contain more histological variations, especially those with definite keratinization, than what had been previously defined.

    DOI: 10.1111/j.1440-1827.2009.02499.x

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

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

    CANCER GENETICS AND CYTOGENETICS   196 ( 1 )   14 - 22   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Overall modes of differential gene expressions were analyzed between human oral/salivary carcinoma cell systems with (MK-1 and ACCM) and without (ZK-1/ZK-2 and ACC2/ACC3) metastatic potential by using micro-array analysis with cancer-associated DNA chips to determine the kinds of genes associated with metastatic behaviors. MK-1 and/or ACCM showed lower levels of gene expression in extracellular matrix-related molecules, such as collagen type IV, laminin, and adhesion molecules such as cadherin 2, but higher levels of genes which control extracellular matrix degradation, such as MMP 9, as well as cell growth and cycle, such as FGF7 and cyclin D1. Among the differentially expressed genes, similar protein expression tendencies for FGF7, laminin, cyclin D1, and collagen type IV were confirmed by immunofluorescence. Metastatic potentials of oral/salivary carcinoma cells seem to have resulted from certain combinations of over-/underexpression of the genes, which were responsible for extracellular matrix metabolism and cell growth in particular. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cancergencyto.2009.08.002

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

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

    CANCER GENETICS AND CYTOGENETICS   194 ( 2 )   75 - 81   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Solitary fibrous tumor (SFT) is an uncommon spindle-cell neoplasm of mesenchymal origin. Because the pathogenetic background of SFT is still controversial, cytogenetic analysis could help in tumor diagnosis and prognosis. In this study, cultured SFT cells from a lower lip lesion that presented characteristic immunopositivity for CD34, vimentin, CD99, and BCL2 showed a unique cytogenetic finding: 46,XX,inv(2)(p21q35),t(3;12)(q25;q15). To our knowledge, this is the third report of cytogenetic result of a case involving the oral cavity. The SFT cells in culture that maintained their immunohistochemical expression of diagnostic molecules, showed unique chromosomal changes previously unreported when compared with already documented ones. Our data suggest that the complicated pathogenetic nature of SFT is possibly tumor- or organ-related. (C) 2009 Elsevier Inc. All rights reserved.

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

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

    BMC CANCER   9   247   2009年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Among the salivary gland carcinomas, carcinoma in pleomorphic adenoma has been regarded as a representative carcinoma type which arises secondarily in the background of a pre-existent benign pleomorphic adenoma. It is still poorly understood how and which benign pleomorphic adenoma cells transform into its malignant form, carcinoma ex pleomorphic adenoma.
    Methods: We have established five cell systems from a benign pleomorphic adenoma of the parotid gland of a 61-year-old woman. They were characterized by immunofluorescence, classical cytogenetics, p53 gene mutational analysis, fluorescence in-situ hybridization, and histopathological and immunohistochemical examinations of their xenografts, to demonstrate their potency of secondary transformation.
    Results: We established and characterized five cell systems (designated as SM-AP1 to SM-AP5) from a benign pleomorphic adenoma of the parotid gland. SM-AP1 to SM-AP3 showed polygonal cell shapes while SM-AP4 and SM-AP5 were spindle-shaped. SM-AP1-3 cells were immunopositive for keratin only, indicating their duct-epithelial or squamous cell differentiation, while SM-AP4/5 cells were positive for both keratin and S-100 protein, indicating their myoepithelial cell differentiation. Chromosome analyses showed numeral abnormalities such as 5n ploidies and various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9;13)(p13.3;q12.3) was shared by all five of the cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which resulted in generation of its nonsense gene product. Transplanted cells in nude mice formed subcutaneous tumors, which had histological features of squamous cell carcinoma with apparent keratinizing tendencies. In addition, they had ductal arrangements or plasmacytoid appearances of tumor cells and myxoid or hyaline stromata, indicating some characteristics of pleomorphic adenoma.
    Conclusion: This study demonstrates in vitro that certain cell types from pleomorphic adenoma are able to clone and survive over a long term and develop subcutaneous tumors in nude mice. The histological features of squamous cell carcinoma from the transplanted cell systems in nude mice might suggest a secondary onset of malignancy from a pre-existing benign adenoma.

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

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

    HUMAN PATHOLOGY   40 ( 5 )   683 - 692   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Sixty-four cases of lymphoepithelial cysts of the parotid gland, the largest scale collection in the literature, were clinicopathologically analyzed for their possible pathogenesis. All 64 cases were unilateral, 27 left and 37 right. There were 28 male and 36 female patients with a ratio of 1:1.3. The mean age of the patients was 52.0 years, and their average duration of symptoms was 29.3 months. The mean longest diameter of the cysts was 3.0 cm. Histologically, lymphoepithelial cysts were classified into 3 subtypes: type I, a cystic dilation of ducts within parotid glands (9 cases, 14.1%); type II, partially demarcated cystic lesions with lymphoid stroma (27, 42.2%); type III, well-encapsulated cystic lesions with lymphoid stroma containing lymph follicular structures (28, 43.8%). Based on immunohistochemical results for lymphocyte/macrophage (CD20/CD45RO/IgG4), cell cycle (Ki-67), and lymphatic (D2-40) markers, the lymphoid stroma was shown to have neither the usual lymph follicular distributions of T/B cells nor lymph sinus structures. No viral infection was confirmed. The results seemed to indicate that the lymphoid stroma were induced along with the growth of the cystic dilatation of ducts within sialadenitis, which were neither induced by Epstein-Barr virus nor HIV infections, and that the formation of lymphoepithelial cysts was completed by demarcation, which should have been a kind of granulation tissue reaction, from the parotid parenchyma but did not arise from intraparotid lymph nodes. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2008.10.012

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   38 ( 4 )   377 - 385   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Capsular invasion is often observed in daily pathologic diagnosis of pleomorphic adenomas, although neither actual information about its occurrence nor molecular mechanisms leading to their invasive activities have been reported. In this study, our aim was to elucidate the mode and the frequency of capsular invasion in this tumor and to characterize the tumor cell arrangement at the site of capsular invasion.
    The mode and frequency of capsular invasion of salivary pleomorphic adenomas were histopathologically examined in 104 surgical specimens of pleomorphic adenoma, and stromal characteristics, and tumor cell arrangements at the sites of capsular invasion were immunohistochemically investigated.
    A total of 353 areas with capsular invasive changes were collected from 104 cases. The mode of capsular invasion was classified into two types: type I: intracapsular invasion (247 areas, 70%) and type II: capsular penetration (106 areas, 30%). Myxoid stroma, which was perlecan-immunopositive (+), was shared by both type I and type II sites, while tumor cell foci containing ductal structures were predominant in type II sites. These foci were composed of KGF(+) and FGFR2(+) cells. In addition, apparent vascular involvement was recognized in 31 tumors (29.8%).
    The results suggest that pleomorphic adenoma cells are able to invade into the capsule and involve blood vessels when they are situated in perlecan-rich milieu, which accelerate KGF signaling.

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   37 ( 5 )   287 - 293   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    BACKGROUND: The intraepithelial deposit of perlecan, a basement membrane-type heparan sulfate (HS) proteoglycan, has been demonstrated in neoplastic conditions such as salivary gland tumors, odontogenic tumors, and oral carcinoma in situ. Our aim was to determine whether perlecan turnover was enhanced in the lining cells of keratocystic odontogenic tumor (KCOT), which had been recently renamed from odontogenic keratocyst because of its accumulated evidence of neoplasm, as a possible background for neoplastic proliferation.
    METHODS: Ten surgical specimens from each of KCOT, dentigerous cyst, and radicular cyst were examined for the expressions of perlecan core protein, HS chains, heparanase, and Ki-67 by immunohistochemistry and in situ hybridization.
    RESULTS: In KCOT, perlecan core protein and HS chains were localized on the cell border from the parabasal to subkeratinized layers of the lining epithelium. Heparanase was localized in a similar fashion to those for perlecan and HS chains but was within the cytoplasm. mRNA signals for perlecan core protein and heparanase were mostly compatible with their protein signals. Ki-67-positive cells were localized mainly in the second basal cell layers with definitely higher labeling indices (approximately 31.3%, second layer). In contrast to KCOT, dentigerous cysts and radicular cysts had no perlecan, HS chains, and heparanase deposition in their linings with extremely lower Ki-67 indices (0.4-0.8%).
    CONCLUSION: The result suggests that the characteristic intra-lining-epithelial deposit of perlecan in KCOT, which has never been seen in other cystic jaw lesions, is a new evidence supporting the neoplastic nature of KCOT.

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

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

    INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH   17 ( 3 )   185 - 195   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    To study the association of qat chewing with the occurrence of oral cancer, the frequency of oral cancer among whole body cancers and the patients' histories of tobacco consumption and qat chewing were examined in Yemen where qat chewing has been most popular. All primary malignant tumors listed in the surgical pathology files at Al-Thawra Hospital, University of Sana'a, in the year 2004 were analyzed, and the patients' histories of tobacco consumption and qat chewing were examined. A total of 649 cases of primary malignant tumors (348, 53.6% males and 301, 46.4% females) were extracted. Oral cancer was the most frequent body cancer in both males (17.2%) and females (19.6%). Squamous cell carcinoma (SCC) was the most frequent oral cancer (84%), and the tongue (42%), gingiva (23%) and buccal mucosa (20%) were the most common sites. Among the 119 patients with oral cancer, information on chewing habits and smoking was obtained in 92 patients (77.3%). There were 70 tobacco chewers (76.1%), 55 qat chewers (59.8%), and 22 smokers (23.9%). Simultaneous chewing of tobacco and qat was found in 48 cases (52.2%). The present survey has disclosed for the first time that oral SCC is the most frequent cancer in this study area in Yemen, and that the high relative frequency of oral SCC may be related to the habits of chewing tobacco and qat.

    DOI: 10.1080/09603120701254813

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  • Lymphatic involvement in the histopathogenesis of mucous retention cyst

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    Mucous retention cyst results from extravasation of saliva. Our intent was to study the role of lymphatics in its pathogenesis.
    Twenty-three surgical specimens of mucous retention cyst of the lip were examined for involvement of lymphatic vessels by a comparative immunohistochemical demonstration of lymphatic and blood vascular endothelial cells, as well as lymphatic and salivary contents.
    Mucous retention cysts were histopathologically classified into three stages: early, intermediate, and advanced. In the early stage, there was diffuse extravasation of mucous material in the interstitium of the lamina propria or the submucosal layer of the oral mucosa. In the intermediate stage, lymphatics, which were clearly revealed and immunohistochemically distinguished from blood vessels by monoclonal antibody D2-40, were dilated and finally ruptured, leaving fragments of lymphatic walls in the periphery of mucous pools. In the advanced stage, thick cyst walls of granulation tissue were formed around mucous retention. Lymphatics were no longer involved in the granulation tissue wall, which was actively driven by blood vessel formation.
    The results suggest that the lymphatic rupture seems to contribute to the enlargement in the pathogenesis of mucous retention cyst. (c) 2006 Elsevier GmbH. All rights reserved.

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

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

    JOURNAL OF ORAL PATHOLOGY & MEDICINE   34 ( 8 )   498 - 507   2005年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown.
    METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization.
    RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas.
    CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.

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

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

    VIRCHOWS ARCHIV   446 ( 6 )   653 - 662   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    To better understand the poorly vascularized background of the stroma of pleomorphic adenomas, we attempted to determine the expression of molecules related to blood vessels and hypoxic conditions in pleomorphic adenoma. Surgical specimens and tumor cells in primary culture of salivary pleomorphic adenomas were used for immunohistochemistry for CD31, vascular endothelial growth factor (VEGF) and its receptors Flk-1 and Flt-1, as well as for hypoxia markers, such as hypoxia-inducible factor-1 alpha (HIF-1 alpha) and lactate dehydrogenase-1 (LDH). At the same time, alternative splicing modes of the VEGF gene and expression levels of the HIF-1 alpha gene were analyzed in surgical specimens by means of reverse-transcription polymerase chain reaction (RT-PCR) and direct sequencing of the PCR products. In addition to co-immunolocalization with CD31+ vascular endothelial cells, VEGF and its receptors were demonstrated in normal duct epithelial and myoepithelial cells as well as in tumor cells in ductal structures and in myxochondroid stromata. Immunolocalizations for HIF-1 alpha and LDH were confirmed in the VEGF-positive area. Immunofluorescence signals for VEGF and others were confirmed in pleomorphic adenoma cells in culture. RT-PCR results showed that there were at least four splicing modes of the VEGF gene, among which VEGF(121) was most enhanced, and higher HIF-1 alpha levels in pleomorphic adenomas. The results suggest that pleomorphic adenoma cells produce VEGF in several functional forms for their own proliferation or differentiation, and that the VEGF expression is controlled by hypoxic circumstances of poorly vascularized pleomorphic adenomas.

    DOI: 10.1007/s00428-005-1219-1

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

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

    Pathol Int   55 ( 6 )   331 - 342   2005年

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

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

    Oral Oncology Extra   40 ( 10 )   107 - 112   2004年

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    記述言語:英語   出版者・発行元:Elsevier BV  

    A case of solitary fibrous tumor of the Lip is described. A 65-year-old Japanese woman had a painless mass in her lower lip that gradually increased in size and finally ulcerated. Computed tomography revealed a well-demarcated submucosal mass. On the cut surface, the tumor was well-circumscribed, solid, and yellowish-white with small cystic spaces. Histopathologically, it was encapsulated and consisted of an interlacing proliferation of spindle-shaped cells immunopositive for CD34, vimentin, Bcl-2, and CD99, with scattered salivary glandular structures with irregular cellular arrangements. This is the first case report of solitary fibrous tumor of the lip with reactive hyperplasia of minor salivary gland components based on our review of the literature. © 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.ooe.2004.06.002

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

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

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS   93 ( 3 )   305 - 310   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY, INC  

    A case of Castleman's disease occurring in the buccal mucosa is described. An 84-year-old woman noticed that a mass in the left buccal mucosa that had been present for half a year. Computed tomography revealed a well-demarcated submucosal tumor, measuring 4.0 x 3.0 x 2.0 cm. The patient received no treatment at this time, and continued growth of the mass was observed. After incisional biopsy, the lesion was surgically removed. Histologically, the tumor consisted of an enlarged lymph node with conspicuous lymph follicles, in which vascular channels and deposits of eosinophilic material were noted. Laboratory examination showed an increase of serum antibody level of cytomegalovirus but of no other viruses. The patient was followed up for 11/2 years, with no clinical evidence of recurrence. This is the first report of Castleman's disease presenting in an oral site.

    DOI: 10.1067/moe.2002.120026

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

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

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A case of sebaceous lymphadenoma occurring in the lip of a 73-year-old female is described. The patient had noticed a painless mass in the region of her upper lip for a year. The surgically removed tumor, measuring about 10mm in diameter, was located just beneath the lip mucosa, expanding into the submucosal and muscle layer. Histologically, the tumor was well encapsulated and consisted of scattered round-shaped islands of small squamous epithelial cells with focal but apparent sebaceous differentiation in a background of lymphoid stroma. This is the first case report of sebaceous lymphadenoma of minor salivary gland origin.

    DOI: 10.1034/j.1600-0714.2002.310409.x

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MISC

  • Periosteal osteosarcoma of the jawbones: a clinicopathological review

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

    Oral Med Pathol   12 ( 1 )   3 - 10   2007年

  • 上顎悪性神経鞘腫

    丸山 智, 中里隆之, 小山純市, 鈴木 誠

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

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  • Carcinoma in-situ of the oral mucosa has a definite tendency towards keratinization

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

    Oral Med Pathol   8 ( 2 )   43 - 44   2003年

  • 舌癌—舌癌と胃癌が重複した1例—

    丸山 智, 林 孝文, 川上美貴

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

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  • A case of trisomy 13 syndrome with bilateral cleft lip and palate

    Jpn. J. Oral Maxillofac. Surg.   47 ( 4 )   2001年

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共同研究・競争的資金等の研究

  • Histopathological study of oral cancer

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    資金種別:競争的資金

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  • 口腔癌の病理組織学的研究

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    資金種別:競争的資金

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  • 基礎科学演習

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