2022/12/01 更新

写真a

アベ タツヤ
阿部 達也
ABE Tatsuya
所属
教育研究院 医歯学系 歯学系列 助教
医歯学総合研究科 口腔生命科学専攻 顎顔面再建学 助教
職名
助教
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外部リンク

学位

  • 博士(歯学) ( 2016年3月   新潟大学 )

研究分野

  • ライフサイエンス / 人体病理学  / 口腔病理学

経歴(researchmap)

  • 新潟大学   大学院 医歯学総合研究科 口腔病理学分野   助教

    2020年4月 - 現在

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  • 新潟大学   医学部 臨床病理学分野   特任助教

    2017年7月 - 2020年3月

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  • 新潟大学医歯学総合病院   病理検査室(歯科)   医員

    2012年4月 - 2017年6月

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経歴

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻 顎顔面再建学   助教

    2020年4月 - 現在

  • 新潟大学   医歯学総合研究科   特任助教

    2017年7月 - 2020年3月

取得資格

  • 歯科医師

  • 日本病理学会認定 口腔病理専門医

  • 死体解剖資格

  • 日本臨床細胞学会認定 口腔細胞診専門歯科医

  • 日本バイオインフォマティクス学会認定技術者

 

論文

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

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

    Diagnostics   12 ( 10 )   2398 - 2398   2022年10月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

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

    DOI: 10.3390/diagnostics12102398

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

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

    Oncology letters   23 ( 3 )   76 - 76   2022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)  

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

    DOI: 10.3892/ol.2022.13196

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

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

    日本病理学会会誌   111 ( 1 )   278 - 278   2022年3月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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

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

    Oral Science International   2022年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/osi2.1130

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1130

  • Melanotic neuroectodermal tumor of infancy in the mandible: A case report. 国際誌

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

    Medicine   100 ( 50 )   e28001   2021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)  

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

    DOI: 10.1097/MD.0000000000028001

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  • [Laparoscopic Abdominoperineal Resection after Preoperative Chemoradiotherapy for Adenocarcinoma Associated with Anal Fistula].

    Kana Tanaka, Mae Nakano, Yoshifumi Shimada, Tatsuya Abe, Hajime Umezu, Akio Matsumoto, Michiru Arabiki, Kaoru Abe, Hidehito Oyanagi, Masato Nakano, Yumiko Hirai, Hikaru Ozeki, Daisuke Motegi, Koji Toge, Jun Yamamoto, Kohei Miura, Hiroshi Ichikawa, Kazuyasu Takizawa, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   48 ( 12 )   1515 - 1517   2021年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 72-year-old man had a chief complaint of anal pain and difficulty in defecation. He was diagnosed with adenocarcinoma by biopsy from a tumor of the anal canal. A computed tomography scan revealed neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa anal canal cancer. Preoperative capecitabine- based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. Digital rectal examination and imaging evaluation 8 weeks after preoperative CRT revealed that the tumor had shrunk. Fifteen weeks after preoperative CRT, laparoscopic abdominoperineal resection was performed. The pathological findings showed mucinous adenocarcinoma associated with anal fistula. At present, 12 months after the operation, no local recurrence and distant metastasis has been detected under follow-up evaluations.

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

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

    新潟歯学会雑誌   51 ( 2 )   114 - 115   2021年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • 口腔がん早期診断用マーカーの同定に向けた新規発がんモデルの作製

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

    新潟歯学会雑誌   51 ( 2 )   124 - 124   2021年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report. 国際誌

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

    Journal of medical case reports   15 ( 1 )   438 - 438   2021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)  

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

    DOI: 10.1186/s13256-021-03066-z

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

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

    Diagnostic pathology   16 ( 1 )   61 - 61   2021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)  

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

    DOI: 10.1186/s13000-021-01124-0

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  • 口腔領域に発症したOI-LPDの臨床病理学的解析

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

    日本口腔科学会雑誌   70 ( 2 )   147 - 147   2021年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

    Oral surgery, oral medicine, oral pathology and oral radiology   132 ( 6 )   687 - 697   2021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)  

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

    DOI: 10.1016/j.oooo.2021.05.015

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  • 口底部に発生した孤立性神経線維腫の1例

    野澤 舞, 三上 俊彦, 船山 昭典, 齋藤 大輔, 須田 大亮, 新美 奏恵, 阿部 達也, 田沼 順一, 新國 農, 西山 秀昌, 林 孝文, 小林 正治

    日本口腔診断学会雑誌   34 ( 1 )   73 - 74   2021年2月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔診断学会  

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  • Disseminated Varicella-zoster Virus Infection Causing Fatal Pneumonia in an Immunocompromised Patient with Chronic Interstitial Pneumonia: A Case Report

    Hiroshi Ueno, Masachika Hayashi, Shun Nagumo, Kosuke Ichikawa, Nobumasa Aoki, Yasuyoshi Ohshima, Satoshi Watanabe, Toshiyuki Koya, Tatsuya Abé, Riuko Ohashi, Yoichi Ajioka, Toshiaki Kikuchi

    Internal Medicine   2021年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.5396-20

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  • [A Case of Invasive Lobular Carcinoma of Accessory Mammary Gland That Was Difficult for Evaluate for Lesion Spread].

    Hikaru Ohzeki, Chie Toshikawa, Kazuki Moro, Haruka Hasegawa, Junko Tsuchida, Mayuko Ikarashi, Masayuki Nagahashi, Maya Katsumi, Yoriko Nakajima, Tatsuya Abe, Yusuke Tani, Jun Sakata, Hajime Umezu, Ken Matsuda, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 13 )   2044 - 2046   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 48-year-old female discovered a mass in her left axilla. A thorough examination resulted in a diagnosis of left invasive lobular carcinoma(ILC)of the accessory mammary gland with wide ductal spread. Considering the wide ductal spread, massive resection of the left axilla mass, left lymph node dissection, and a latissimus dorsi musculocutaneous flap procedure were performed. However, histological analysis revealed ILC measuring 80×50 mm with lymph node metastases(5/23)and extensive cancer spread, resulting in a positive surgical margin. It is important to recognize the characteristics of ILC, axillary accessory breast cancer, and the axilla in a treatment strategy.

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  • 口底部に発生した孤立性神経線維腫の1例

    野澤 舞, 三上 俊彦, 船山 昭典, 齋藤 大輔, 須田 大亮, 新美 奏恵, 阿部 達也, 田沼 順一, 新國 農, 西山 秀昌, 林 孝文, 小林 正治

    日本口腔内科学会雑誌   26 ( 2 )   121 - 122   2020年12月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔内科学会  

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  • 17年を経過して再減量手術を行った上顎骨線維性異形成症の1例

    伊藤 元貴, 児玉 泰光, 大貫 尚志, 高村 真貴, 林 孝文, 阿部 達也, 田沼 順一, 小林 正治, 高木 律男

    新潟歯学会雑誌   50 ( 2 )   79 - 85   2020年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

    線維性異形成症(FD)は正常な骨組織が線維性結合組織で置換され増殖することを特徴とする非腫瘍性骨病変である。骨格成長後にはFDの増殖が静止するとされているが、成人期でも増大をきたすことがある。今回、上顎骨FDの減量手術後再増大をきたし、再び減量手術が必要となった症例を経験したので報告する。患者は42歳の男性。25歳の時に上顎骨FDの減量手術を施行されるも受診が途絶え、再増大による顔面非対称をきたしたため17年後に当科初診となった。顔面非対称改善と病変増大による機能障害の予防のため、右側上顎骨頬側と口蓋側の2回に分けて減量手術を行った。削除量の目安としてCT画像から3次元実体モデルを利用してサージカルガイドを制作し、術中の対称性確認と手術時間の短縮を行った。術後3年経過した現在、明らかな再増大はない。今回もあくまで減量手術であり、病巣の残遺に伴う病態変化の可能性についての患者教育とともに長期の経過管理が重要と考えられた。(著者抄録)

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  • Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients 査読 国際誌

    Riuko Ohashi, Hajime Umezu, Ayako Sato, Tatsuya Abé, Shuhei Kondo, Kenji Daigo, Seijiro Sato, Norikazu Hara, Akinori Miyashita, Takeshi Ikeuchi, Teiichi Motoyama, Masashi Kishi, Tadahiro Nagaoka, Keiko Horiuchi, Atsushi Shiga, Shujiro Okuda, Tomoki Sekiya, Aya Ohtsubo, Kosuke Ichikawa, Hiroshi Kagamu, Toshiaki Kikuchi, Satoshi Watanabe, Jun-Ichi Tanuma, Peter Schraml, Takao Hamakubo, Masanori Tsuchida, Yoichi Ajioka

    Cells   9 ( 11 )   2409 - 2409   2020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:MDPI AG  

    Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called “ribosomopathies,” including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions −248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.

    DOI: 10.3390/cells9112409

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

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

    Scientific Reports   10 ( 1 )   14586 - 14586   2020年9月

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    担当区分:筆頭著者   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 Science and Business Media LLC  

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

    DOI: 10.1038/s41598-020-71496-8

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    その他リンク: http://www.nature.com/articles/s41598-020-71496-8

  • Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: A possible driving force for tumor progression. 査読 国際誌

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

    Experimental cell research   392 ( 1 )   112013 - 112013   2020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)  

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

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  • がん細胞による死細胞貪食は細胞遊走とDKK1発現を促進する

    山崎 学, 丸山 智, 阿部 達也, 朔 敬, 田沼 順一

    日本病理学会会誌   109 ( 1 )   396 - 396   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Serrated neoplasia pathwayにおけるSOX2発現の検討

    高村 佳緒里, 味岡 洋一, 阿部 達也, 大橋 瑠子, 谷 優佑, 近藤 修平, 田口 貴博, 佐藤 航, グリツン・タチアナ, 西川 直人

    日本病理学会会誌   109 ( 1 )   326 - 326   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Portal Vein Thrombosis Associated with Trousseau Syndrome due to Urinary Bladder Squamous Cell Carcinoma in a Liver Cirrhosis Patient 査読

    Kimura Naruhiro, Terai Shuji, Tsuchiya Atsunori, Oda Chiyumi, Kimura Atsushi, Hosaka Kazunori, Tominaga Kentaro, Hayashi Kazunao, Abé Tatsuya, Umezu Hajime

    Internal Medicine   59 ( 16 )   1971 - 1975   2020年

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    記述言語:英語   出版者・発行元:一般社団法人 日本内科学会  

    <p>A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis. </p>

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  • 下顎骨に発生した象牙質形成性幻影細胞腫の1例 査読

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

    日本口腔科学会雑誌   68 ( 2 )   188 - 188   2019年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • 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   掲載種別:研究論文(学術雑誌)  

    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.

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  • A Case of Panenteritis With Massive IgG4-Positive Plasma Cell Infiltration Developed 26 Years After Total Proctocolectomy for Ulcerative Colitis. 査読 国際誌

    Kentaro Tominaga, Atsunori Tsuchiya, Yutaka Honda, Tatsuya Abe, Junji Yokoyama, Hajime Umezu, Shuji Terai

    The American journal of gastroenterology   113 ( 2 )   173 - 173   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/ajg.2017.481

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

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

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   30 ( 5 )   422 - 427   2018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 Ltd  

    Synovial chondromatosis (SC) is a reactive joint disorder characterized by the development of metaplastic cartilaginous nodules floating within the joint space. We report a case of SC of the temporomandibular joint (TMJ) which had difficulty in diagnosis in a 40-year-old woman. The patient had TMJ pain with mandibular lateral deviation for two years. CT and MRI revealed well-defined and round-shaped bone resorption at the right mandibular fossa and an ovoid-shaped expansion of the superior articular cavity, which showed heterogeneous high signal intensity on T2-weighted MRI. Following a clinical diagnosis of benign TMJ tumor, the lesion was surgically removed. Histopathologically, it was diagnosed as SC in Milgram's stage 1, mainly involving the upper joint space. This is the first case report of SC in an early stage in which no cartilaginous nodules were generated but instead the mandibular fossa of the temporal bone was resorbed.

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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 Abé, 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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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

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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.

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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.

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

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

    Journal of Oral Pathology &amp; Medicine   44 ( 10 )   850 - 856   2015年11月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

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  • Mandibular osteonecrosis in a patient receiving Denosumab and Sunitinib. 査読

    Tanaka R, Saito M, Abé T, Ajima H, Saku T, Hayashi T

    6 ( 9 )   393 - 398   2015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)  

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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.

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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.

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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.

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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.

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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.

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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.

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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.

    DOI: 10.1016/j.oooo.2013.08.032

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

    Tatsuya Abé, 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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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.humpath.2013.08.011

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  • Intraoperative Assessment of Surgical Margins of Oral Squamous Cell Carcinoma Using Frozen Sections: A Practical Clinicopathological Management for Recurrences 査読

    Shun Miyota, Takanori Kobayashi, Tatsuya Abe, Hisashi Miyajima, Masaki Nagata, Hideyuki Hoshina, Tadaharu Kobayashi, Ritsuo Takagi, Takashi Saku

    BIOMED RESEARCH INTERNATIONAL   2014   823968   2014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:HINDAWI PUBLISHING CORPORATION  

    Background. Local recurrence remains a challenging clinical issue for the treatment of oral squamous cell carcinoma (SCC). We analyzed retrospectively how effective the frozen section technique (FS) was against recurrences of oral SCC. Methods. We screened 343 surgical samples from 236 patients who had oral SCC, carcinoma in situ (CIS), or epithelial dysplasia, and we followed up their clinical outcomes for at least 5 years. Histopathological states of surgical margins were compared between FS and surgical materials in relapse and relapse-free groups, respectively. Results. Among the 236 patients, 191 were classified into the relapse-free group, and 45 into the relapse group. FS was more frequently performed in the relapse-free group (128/191) than in the relapse group (83/152). Histopathologically, moderate dysplasia or CIS (borderline malignancies) and SCC were recognized in 55 samples of the relapse-free group and in 57 of the relapse group. For those surgical margins with borderline malignancies, additional incisions were performed in 38 of the 55 relapse-free cases, which reduced to 20 from the 38 margins with borderline malignancies (47.4% reduction), and in 39 of the 57 relapse cases, which reduced to only 3 of 39 (7.7% reduction). Conclusions. The intraoperative assessment of surgical margins by FS is essential in preventing recurrences of oral mucosal malignancies.

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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.

    DOI: 10.1016/j.prp.2014.06.028

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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.

    DOI: 10.1002/jcp.24364

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

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

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology   25 ( 3 )   294 - 298   2013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)  

    A case of solitary central neurofibroma of the mandible arising in a 70-year-old man is reported. The patient had a radiolucent lesion, measuring 16. mm in diameter, with central radiopaque freckles in the right incisor-canine region of the mandible, which was discovered incidentally during routine dental check-up. The lesion was persisted for 10 years without any symptoms or complication. It was clinically diagnosed as benign tumor and surgically removed under general anesthesia. Histologically, the removed tumor was relatively well demarcated and composed of a sparse proliferation of elongated spindle-shaped cells with wavy nuclei in loosely textured connective tissue stroma, which was associated with bone formation. Clinicopathological features of central neurofibroma of the jaw bone are reviewed from the literature. This is the first report of central neurofibroma arising in the anterior part of the mandible. © 2012 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI.

    DOI: 10.1016/j.ajoms.2012.12.002

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  • Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases 査読

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

    ORAL DISEASES   19 ( 4 )   415 - 424   2013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  

    Objective The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. Materials and methods Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. Results Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. Conclusions Two possible histopathogeneses of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele. Oral Diseases (2013) 19, 415-424

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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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  • 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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  • 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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  • アクチン分子を介した ladinin-1 の口腔扁平上皮癌細胞増殖・遊走制御機 構

    阿部達也, 味岡洋一, 山崎学, 丸山智

    日本病理学会会誌   108 ( 1 )   323 - 323   2019年

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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

    阿部 達也

    128 ( 1 )   e81 - e82   2019年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • マイクロスコープを用いた再歯根尖切除術の1例

    大倉 直人, 山本 信一, 阿部 達也, 竹内 亮祐, 遠間 愛子, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 1 )   29 - 35   2018年6月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

    根尖性歯周組織病変の難治化は、根尖部での複雑な解剖学的問題に加え、残存バイオフィルムによる細菌学的な影響もあるとされている。こうした様々な要因の改善策として外科的歯内療法が選択される。しかし、補綴処置を行う上で考慮する歯冠・歯根長比の問題で複数回に渡り歯根切断が行われることは稀である。今回は、歯根尖切除術を過去3度に渡って施行しても治癒しなかった症例に対して、マイクロスコープの使用下で再歯根尖切除術と根尖部の緊密な封鎖を目的としたmineral trioxide aggregate(以下MTA)による逆根管充填を含めた再外科的歯内療法が奏効した症例を報告する。患者は59歳の女性で、上顎右側中切歯および側切歯に対して打診痛、根尖部圧痛および瘻孔を認める慢性根尖膿瘍と診断し、最初に通常の感染根管治療を行った。その後、病変部の治癒が期待できなかったため歯根尖切除を行い、逆根管形成後にMTAで逆根管充填を行った。手術から1ヵ月後で瘻孔は消失し、さらに6ヵ月後のレントゲン写真では根尖部の透過像が消失しており、治癒傾向を認めた。(著者抄録)

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  • マイクロスコープを用いた再歯根尖切除術の1例

    大倉 直人, 山本 信一, 阿部 達也, 竹内 亮祐, 遠間 愛子, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 1 )   29 - 35   2018年6月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

    根尖性歯周組織病変の難治化は、根尖部での複雑な解剖学的問題に加え、残存バイオフィルムによる細菌学的な影響もあるとされている。こうした様々な要因の改善策として外科的歯内療法が選択される。しかし、補綴処置を行う上で考慮する歯冠・歯根長比の問題で複数回に渡り歯根切断が行われることは稀である。今回は、歯根尖切除術を過去3度に渡って施行しても治癒しなかった症例に対して、マイクロスコープの使用下で再歯根尖切除術と根尖部の緊密な封鎖を目的としたmineral trioxide aggregate(以下MTA)による逆根管充填を含めた再外科的歯内療法が奏効した症例を報告する。患者は59歳の女性で、上顎右側中切歯および側切歯に対して打診痛、根尖部圧痛および瘻孔を認める慢性根尖膿瘍と診断し、最初に通常の感染根管治療を行った。その後、病変部の治癒が期待できなかったため歯根尖切除を行い、逆根管形成後にMTAで逆根管充填を行った。手術から1ヵ月後で瘻孔は消失し、さらに6ヵ月後のレントゲン写真では根尖部の透過像が消失しており、治癒傾向を認めた。(著者抄録)

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  • 口腔扁平上皮癌における死細胞誘導性細胞増殖機構の解明

    山崎 学, 丸山 智, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   346 - 346   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌における死細胞誘導性細胞増殖機構の解明

    山崎 学, 丸山 智, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   346 - 346   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌細胞におけるladinin-1の機能解析

    阿部 達也, 丸山 智, 山崎 学, 味岡 洋一

    日本病理学会会誌   107 ( 1 )   458 - 458   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔粘膜悪性境界病変におけるp53免疫組織化学的検索の取り組み

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   459 - 459   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔粘膜悪性境界病変におけるp53免疫組織化学的検索の取り組み

    丸山 智, 山崎 学, 阿部 達也, 田沼 順一

    日本病理学会会誌   107 ( 1 )   459 - 459   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Ladinin-1 はアクチン分子動態の調整を介し、口腔扁平上皮癌細胞の増殖と遊走を制御する

    阿部達也, 山崎学, 丸山智, 味岡洋一

    第29回日本臨床口腔病理学会総会・学術大会 プログラム・抄録集   86 - 86   2018年

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    掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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  • 口腔扁平上皮癌におけるSOX 9細胞質発現は予後不良と関連する

    隅田 賢正, 山崎 学, 阿部 達也, 高木 律男, 丸山 智

    新潟歯学会雑誌   47 ( 2 )   120 - 121   2017年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • 感染性リンパ節腫脹との鑑別に苦慮した悪性リンパ腫の1例

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

    日本口腔科学会雑誌   66 ( 2 )   182 - 182   2017年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

    日本病理学会会誌   106 ( 1 )   295 - 295   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔表在性癌と非癌部粘膜上皮との界面におけるタンパク質動態解析

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

    日本病理学会会誌   106 ( 1 )   408 - 408   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌におけるSOX9の発現様式

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

    日本病理学会会誌   106 ( 1 )   364 - 364   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   106 ( 1 )   424 - 424   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • Le Fort I型骨切り術後に生じた正中上顎骨嚢胞の1例

    大貫 尚志, 阿部 達也, 児玉 泰光, 勝見 祐二, 西川 敦, 黒川 亮, 木口 哲郎, 程 くん, 林 孝文, 高木 律男

    日本口腔科学会雑誌   65 ( 2 )   152 - 152   2016年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

    日本病理学会会誌   105 ( 1 )   468 - 468   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔粘膜乳頭腫は粘液腺導管開口部に発生する

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

    日本病理学会会誌   105 ( 1 )   419 - 419   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   105 ( 1 )   424 - 424   2016年4月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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  • 口腔表在性癌と非癌部粘膜上皮との界面における細胞競合現象の解析

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

    日本病理学会会誌   105 ( 1 )   421 - 421   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 口腔扁平上皮癌における皮膚型角化の分化誘導と細胞増殖の調整機構

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

    新潟歯学会雑誌   45 ( 2 )   103 - 103   2015年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • 口腔表在性癌と非癌部粘膜上皮との界面における細胞競合現象

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

    新潟歯学会雑誌   45 ( 2 )   105 - 106   2015年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • 口腔扁平上皮癌および正角化型異型上皮における正角化関連分子の動態

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

    日本病理学会会誌   104 ( 1 )   467 - 467   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   104 ( 1 )   449 - 449   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   104 ( 1 )   469 - 469   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本口腔科学会雑誌   63 ( 4 )   414 - 415   2014年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

    丸山 智, 山崎 学, 阿部 達也, 程 クン, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   435 - 436   2014年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

    山崎 学, 程 クン, 丸山 智, 阿部 達也, 朔 敬

    日本口腔科学会雑誌   63 ( 4 )   387 - 387   2014年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

    日本病理学会会誌   103 ( 1 )   273 - 273   2014年3月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   103 ( 1 )   281 - 281   2014年3月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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  • 口腔異型上皮-扁平上皮癌シーケンスにおける正角化関連分子の発現動態

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

    日本病理学会会誌   103 ( 1 )   281 - 281   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   103 ( 1 )   296 - 296   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

    山崎 学, 程 くん, 丸山 智, 阿部 達也, 朔 敬

    日本病理学会会誌   103 ( 1 )   295 - 295   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 腫瘍を疑わせた顎関節炎の1例

    安島 久雄, 池田 順行, 嵐山 貴徳, 齋藤 太郎, 荒井 良明, 河村 篤志, 西山 秀昌, 阿部 達也, 朔 敬, 高木 律男

    日本顎関節学会雑誌   25 ( Suppl. )   79 - 79   2013年7月

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    記述言語:日本語   出版者・発行元:(一社)日本顎関節学会  

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  • 下顎窩骨吸収を主徴とした顎関節滑膜性軟骨腫症の1例 初期病像の認識

    加藤 祐介, 小林 正治, 三上 俊彦, 西山 秀昌, 阿部 達也, 林 孝文, 朔 敬, 齊藤 力

    日本顎関節学会雑誌   25 ( Suppl. )   78 - 78   2013年7月

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    記述言語:日本語   出版者・発行元:(一社)日本顎関節学会  

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  • 口腔扁平上皮癌の側方進展界面における細胞死

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

    日本病理学会会誌   102 ( 1 )   319 - 319   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • MFG-E8は口腔扁平上皮癌の進展と死細胞貪食を促進する

    山崎 学, 程 くん, 丸山 智, 阿部 達也, 朔 敬

    日本病理学会会誌   102 ( 1 )   360 - 360   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • 唾液腺多形性腺腫細胞における低酸素応答性の細胞外基質合成

    丸山 智, 山崎 学, 阿部 達也, 程 くん, 朔 敬

    日本病理学会会誌   102 ( 1 )   364 - 364   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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

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

    日本病理学会会誌   102 ( 1 )   361 - 361   2013年4月

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    記述言語:英語   出版者・発行元:(一社)日本病理学会  

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  • 東京大学医学部附属病院顎口腔外科における歯原性腫瘍の統計的観察

    阿部 達也, 安部 貴大, 古賀 陽子, 阿部 雅修, 末永 英之, 菅野 勇樹, 杉山 円, 瀬戸 一郎, 星 和人, 西條 英人, 森 良之, 高戸 毅

    日本口腔科学会雑誌   62 ( 1 )   65 - 65   2013年1月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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

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

    日本癌学会総会記事   71回   144 - 145   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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

    丸山 智, 山崎 学, 阿部 達也, 程 ジュン, 朔 敬

    日本癌学会総会記事   71回   144 - 144   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 脈管分布様式からみたワルチン腫瘍のリンパ性間質

    阿部 達也, 程 くん, 丸山 智, 朔 敬

    日本病理学会会誌   98 ( 1 )   398 - 398   2009年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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▶ 全件表示

共同研究・競争的資金等の研究

  • 口腔扁平上皮癌の間質浸潤と側方上皮内進展:その相反的制御と分子基盤

    研究課題/領域番号:21K09841  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    阿部 達也

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 口腔癌細胞の側方浸潤界面における非癌細胞との競合現象:新たな制癌戦略への基礎研究

    研究課題/領域番号:19K10101  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    朔 敬, 北河 憲雄, 阿部 達也, 吉本 尚平

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    口腔扁平上皮癌の浸潤に伴って細胞競合が生じることを想定して、以下の実験を実施してそれぞれの成果が得られた。
    (1)細胞競合で生じる細胞死の実態とその分子機序を解析したところ、癌死細胞を癌細胞がRac1依存的に貪食すること、その結果として癌細胞の遊走能が高まることが判明し、同機序が制癌戦略に応用可能性が見出されたとして、同成果を報文として専門誌に投稿した。
    (2)細胞競合の生じる癌浸潤界面で高発現することの判明している分子のLAD-1について、細胞骨格アクチンあるいは浸潤時に形成される糸状・葉状仮足形成との関連の上でその機能を解析したところ、LAD-1は遊走先端に生じる仮足に形成されるアクチンアークと同様の分布、すなわちアクチン線維束基部に配置して、仮足形成による細胞運動に関与していることが明らかになった。概要を取りまとめて、論文原稿の作成中である。
    (3)口腔扁平上皮癌の側方浸潤界面には癌側に硝子体が形成されることを見いだしたが、これと同様な形態の構造体が口腔扁平苔癬に生じることを見いだした。それはシバット小体と呼ばれてきたもので、ケラチン17陽性を示した。その背景として、同病変では上皮細胞がケラチン17を発現しており、その細胞死過程でシバット小体に濃縮すると解釈し、異角化を通した非アポトーシス細胞死経路の存在を予測した。論文を作成して専門誌に投稿した。
    (4)口腔扁平上皮癌ならびに口腔上皮内癌の細胞診基準として先に提唱した五指標方式が高分化型症例のみならず広く口腔癌に応用可能であることを示した。その一部は日本臨床細胞学会で口演発表した。

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  • 口腔扁平上皮癌の非癌上皮細胞との衝突界面におけるアクチン重合配置の分子制御

    研究課題/領域番号:18K09550  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    阿部 達也, 丸山 智, 柿原 嘉人

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    口腔扁平上皮癌の癌-非癌界面における蛋白質網羅的解析により, 癌界面部組織に特異的に増加した蛋白質である LAD1 の機能解析を行った. 前年度までに, siRNA による LAD1 発現抑制細胞において, LAD1 が acitn 分子動態に関連する可能性が示唆されたことから, PCR array による細胞運動性に関連する遺伝子発現の詳細な検討を行ったところ, caveolin-1 などの遺伝子発現の減少が明らかとなった. 特にこの caveolin-1 は, 細胞の平面的運動と三次元的運動において, 異なった局在を示すことが報告されており, 前年までに得られた, LAD1 発現抑制細胞における wound-healing assay での細胞遊走阻害と transwell migration assay での細胞遊走促進という, 相反する細胞運動性評価結果に関連しうる有力な候補因子と考えられた.
    また, 上皮-間葉転換 (EMT) に関連した遺伝子発現の変動を PCR array によって検討したところ, EMT 様の表現型が顕れている可能性が見いだされ, なかでも EMT および細胞平面極性に関わる蛋白質をコードする遺伝子の発現上昇が有意にみられた. このことから, 上記の caveolin-1 とともに, 細胞極性制御も LAD1 抑制細胞の運動性に重要な役割を果たしている可能性が示唆された.
    これらの結果から, LAD1 は口腔扁平上皮癌において, actin 分子制御に関わり, 細胞運動性を制御している可能性とともに, EMT 様の表現型の発現調整にも関連している可能性が示唆された.

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  • 唾液腺腫瘍の低酸素レベル細胞外環境におけるエネルギー代謝調節機構

    研究課題/領域番号:15K11069  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    丸山 智, 阿部 達也, 山崎 学, 程 クン, 朔 敬

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    唾液腺多形性腺腫の間質は乏血管性の特徴があることから、低酸素環境下でのがん細胞の生存・増殖を可能にしているエネルギー代謝調節機構を明らかにするために、多形性腺腫由来細胞におけるHIF-1に関連したがんの代謝に重要な因子であるMYCの発現レベルおよび細胞機能に果たす役割を検討した。HIF-1α遺伝子・蛋白質は48時間低酸素培養下で高発現し、MYCともに核への局在がみられた。 MYC発現を抑制すると細胞増殖のみだけでなく遊走も抑制された。以上より、多形性腺腫細胞はMYCを高発現することで、低酸素状態での細胞の生存・増殖を維持していることが示唆された。

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  • 同種アポトーシス細胞貪食によって誘導される口腔扁平上皮癌の細胞活性化機序

    研究課題/領域番号:15K11006  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    山崎 学, 阿部 達也, 丸山 智, 程 クン, 朔 敬

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    病理組織標本でがん細胞による同種アポトーシス細胞貪食がしばしば見出されるが、本現象の生物学的意義は不明である。そこで「がん細胞は同種のアポトーシス細胞を貪食することで、自身の細胞機能を活性化する」という仮説を立て、検証した。アポトーシスを誘導した培養細胞を同種生活細胞と共培養すると、多くの生活細胞がアポトーシス細胞を細胞質内に取り込んだ。アポトーシス細胞は貪食細胞のファゴソームに局在しており、貪食はRac1阻害剤により抑制された。さらに、がん細胞の遊走浸潤能はアポトーシス細胞貪食後に亢進した。これより、同種アポトーシス細胞貪食によるがん細胞機能活性化が示され、新規治療標的として期待される。

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  • 口腔扁平上皮癌の浸潤界面における細胞競合現象のプロテオーム解析

    研究課題/領域番号:15K20384  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    阿部 達也

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    口腔扁平上皮癌・上皮内癌が非癌上皮との間に形成する明瞭な上皮内界面が、病理組織標本上でしばしば観察される。この癌‐非癌界面は生体内での細胞競合現象の場であると仮説を立て、検証した。病理組織標本の検討で、界面に面する癌組織にアポトーシスや硝子体、細胞傷害との関連を示唆する組織・細胞変化を認めた。病理組織標本から選択採取した癌・非癌組織それぞれの界面近接・非近接組織を材料に、LC-MS/MSによるプロテオーム解析を行ったところ、癌あるいは非癌界面近接組織で特異的発現増減を示す7分子を同定した。以上より、これらの分子が、癌細胞が敗者となりうる細胞競合現象メカニズムに関わっている可能性が示唆された。

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  • 口腔扁平上皮癌細胞におけるヘモグロビン誘導性角化機序と角化細胞死への経路

    研究課題/領域番号:15K15693  2015年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    朔 敬, 程 クン, 丸山 智, 山崎 学, 阿部 達也, 田中 昭男

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    配分額:3510000円 ( 直接経費:2700000円 、 間接経費:810000円 )

    口腔扁平上皮癌における角化は形態学的には皮膚型の正角化で特徴づけられ、分子レベルではケラチン17の発現亢進で規定されることを確定した。異角化特異的ケラチン17の発現は、血管外漏出した赤血球由来のヘモグロビン貪食によって惹起され、ヘモグロビン刺激は口腔扁平上皮癌細胞にケラチン17のみならず、OH-1、PAR-2、14-3-3σ、YAPなどの機能分子の発現を誘導し、細胞死経路への誘導のみならず細胞増殖と細胞遊走・浸潤性にも寄与していた。この異角化分子機序は当初は想定外の口腔扁平苔癬における細胞死誘導に適用され、角化を指標にした細胞診断への応用にまで展開し、挑戦的萌芽研究に相応しい成果となった。

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  • ミャンマーにおける噛みタバコ習慣関連口腔がん発症に関する分子病理疫学的研究

    研究課題/領域番号:26305032  2014年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    朔 敬, 田中 昭男, 山崎 学, 丸山 智, 阿部 達也, 稲井 哲一朗, 程 クン

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    配分額:15990000円 ( 直接経費:12300000円 、 間接経費:3690000円 )

    口腔癌と上皮内癌を含む前癌病変症例をミャンマーの研究協力者の支援により収集し、わが国の症例を加えて、それら病理組織標本についてバーチャルスライドを利用した双方向検討で、上皮内癌の診断根拠となる病理組織所見を抽出し、同所見を口腔癌細胞の生物学的特性の解析実験から説明し、科学的根拠に基づいて病理診断精度を高めることができた。ミャンマーでの調査では、噛みタバコ常習者担癌患者群・非常習者からななる対照群について解析し、黄緑色野菜・果物摂取量の高い対照群で口腔粘膜病変の頻度が低く、血中βカロチン高レベルとの相関も判明した。ミクロ・マクロ双方向アプローチで口腔癌の診断と予防に関する提言を行うことができた。

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  • アジア民族間の口腔表在性癌発症背景の分子病理疫学的比較研究

    研究課題/領域番号:25305035  2013年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    程 クン, 丸山 智, 山崎 学, 阿部 達也, 朔 敬

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    配分額:18200000円 ( 直接経費:14000000円 、 間接経費:4200000円 )

    高齢化社会への移行に伴い口腔がん、とりわけ表在性扁平上皮癌、が増加しているが、その発生背景を究明するため、アジア諸国とわが国の口腔表在性癌症例を比較検討することを計画しして、各地で症例を収集した。まず、科学的根拠に基づく病理診断基準を確立し、その基準にしたがった診断法を各地の研究施設間で均霑化した。ついで、口腔表在性癌の病因は各地で大きく相違するにも関わらず、特定分子の発現を客観的指標に診断を実践することの正当性を証明した。とくに、口腔表在性癌に特徴的に高分化傾向はケラチン(K)17発現で規定される皮膚型正角化という特異的共通項で括られるという事実を確認し、その細胞生物学的意義も説明しえた。

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  • 口腔扁平上皮癌の浸潤開始スイッチ関連分子のプロテオーム解析

    研究課題/領域番号:25462849  2013年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    程 クン, 丸山 智, 山崎 学, 阿部 達也, 朔 敬

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    口腔扁平上皮癌の浸潤性が獲得される機序の詳細は未だ不明である。そこで、非浸潤性の上皮内癌と明瞭な遊離胞巣を伴う浸潤癌の組織標本を用いて病巣周囲に発現している蛋白質を網羅的に解析して、腫瘍実質と周囲正常粘膜、腫瘍実質-間質界面で、癌細胞と非癌細胞または癌細胞と宿主間質細胞のあいだにどのようなクロストークが生じて浸潤性の決定がなされるのかを免疫組織化学法を応用して顕微組織分画した試料をプロテオーム解析した。その結果、浸潤界面形成を特徴づける蛋白質分子群を同定し、浸潤開始の機序を理解する端緒としえた。病理組織学的な浸潤レベルの認知・判定を科学的客観的に評価する方法にも展望が得られた。

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  • 口腔上皮内癌における細胞競合現象の認識とその病理学的意義の解明

    研究課題/領域番号:25861768  2013年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    阿部 達也

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    口腔上皮内癌CISおよび口腔扁平上皮癌SCCの病理診断では、癌組織は非癌組織との間に明瞭な界面を形成することがしばしば観察される。この界面部において細胞競合という現象が生じるという仮説を立て、検証することとした。明瞭な界面を形成するCISを含む病理組織標本の検討では、癌組織にアポトーシス小体(60%)、好酸性硝子体(36%)が高頻度だった。選択的に癌組織・非癌組織を採取し、LC/MS/MSで蛋白質の網羅的解析を行うと、癌細胞でインターフェロン応答性蛋白質の発現が明らかになった。癌細胞が非癌細胞に対して敗者となっている可能性とともに、その分子基盤にはサイトカインの関連が示唆された。

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  • 多形性腺腫細胞の低酸素応答性細胞外基質改変における転移形質獲得機構

    研究課題/領域番号:24592829  2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    丸山 智, 阿部 達也, 山崎 学, 程 珺, 朔 敬

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    配分額:5330000円 ( 直接経費:4100000円 、 間接経費:1230000円 )

    唾液腺多形性腺腫の間質表現は多彩かつ乏血管性であることから、低酸素環境下で細胞外基質(ECM)合成を亢進させて多彩な間質表現を実現し、生存・増殖を維持しているという仮説をたて、低酸素下でのECM合成能および細胞機能を検討した。HIF-1α遺伝子・蛋白質は48時間低酸素培養下で高発現・核移行し、腫瘍間質に豊富なECM分子のperlecan、fibronectinの合成が促進された。さらにsiRNA法でECM発現を抑制すると、細胞増殖が抑制された。以上より、多形性腺腫には低酸素刺激によってECM合成を亢進させることで、低酸素状態にも関わらず細胞増殖を維持する機構がそなわっていることが示唆された。

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  • アジア・アフリカの噛みタバコ習慣関連口腔がん発症に関する分子病理疫学的研究

    研究課題/領域番号:23406038  2011年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    朔 敬, 程 珺, 丸山 智, 山崎 学, 阿部 達也

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    配分額:14820000円 ( 直接経費:11400000円 、 間接経費:3420000円 )

    口腔扁平上皮癌の病因として関連づけられてきた噛みタバコ習慣の広がる地域の口腔癌症例を収集して病理疫学的に解析した。疫学的に噛みタバコ習慣者の非習慣者を対比したコホート調査をミャンマーで開始した。その結果、同習慣による口腔粘膜変化との関連、すなわち、口腔粘膜下線維症と異型上皮、上皮内癌等の前癌病変の随伴が確認された。そこで、それら前癌病変の病理組織学的特性について解析したところ、上皮内血管や正角化型異型上皮等の特徴的病態をみいだし、それらの生物学的意義について実験的に解析した。以上を総合して前癌病変の診断基準を見直し、われわれの基準が外科手術の予後等にも反映する客観性があることも判明した。

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  • 石灰化嚢胞性歯原性腫瘍由来CCOT細胞系における幻影細胞化と石灰化の分子機構

    研究課題/領域番号:22592033  2010年 - 2012年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    程 〓, 丸山 智, 山崎 学, 朔 敬, 阿部 達也

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    歯原性腫瘍に特徴的な幻影細胞が最も顕著な石灰化嚢胞性歯原性腫瘍(calcifying cystic odontogenic tumor, CCOT)の性格は十分に理解されていない。われわれは同腫瘍由来の細胞株樹立に成功したので、これを用いて幻影細胞成立、二次的悪性化機序を試験管内で検討した。その結果、幻影細胞の特徴的細胞像はパールカンなどの細胞外基質分子が細胞外に分泌されずに沈着することが原因であることをつきとめた。幻影細胞の特徴的な細胞質、脱核の機構など長年の懸案が説明でき、CCOT 由来細胞の腫瘍性格を明確にすることで、CCOTの診断から治療までの臨床的対応に科学的根拠をもってあたることができるようになった。

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担当経験のある授業科目

  • 歯の形態学

    2022年
    -
    現在
    機関名:新潟大学

  • 基礎歯学コースワーク(口腔病理学ベーシックコースII)

    2021年
    -
    現在
    機関名:新潟大学

  • 口腔分子病理学演習IIA

    2021年
    -
    現在
    機関名:新潟大学

  • 基礎歯学コースワーク(口腔病理学ベーシックコースI)

    2021年
    -
    現在
    機関名:新潟大学

  • 口腔分子病理学演習IB

    2021年
    -
    現在
    機関名:新潟大学

  • 口腔分子病理学演習IA

    2021年
    -
    現在
    機関名:新潟大学

  • 口腔分子病理学演習IIB

    2021年
    -
    現在
    機関名:新潟大学

  • 臨床口腔病理学演習IIA

    2021年
    機関名:新潟大学

  • 臨床口腔病理学演習IB

    2021年
    機関名:新潟大学

  • 臨床口腔病理学演習IA

    2021年
    機関名:新潟大学

  • 臨床口腔病理学演習IIB

    2021年
    機関名:新潟大学

  • 病理学総論

    2020年
    -
    現在
    機関名:新潟大学

  • 口腔病理学

    2020年
    -
    現在
    機関名:新潟大学

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