慶應義塾研究者情報データベース

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• ライフサイエンス / 人体病理学

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• Effectiveness of color correction on the quantitative analysis of histopathological images acquired by different whole-slide scanners

  Aziz M., Nakamura T., Yamaguchi M., Kiyuna T., Yamashita Y., Abe T., Hashiguchi A., Sakamoto M.

  Artificial Life and Robotics （Artificial Life and Robotics）  24 （ 1 ） 28 - 37 2019年03月

  ISSN  14335298

  　概要を見る

  © 2018, ISAROB. Advances in whole-slide scanning have led to research on digital pathology, including monitor-based diagnosis, feature quantification, and computer-aided diagnosis. The color variations due to the staining process and scanning device are a serious issue that should be solved in whole-slide imaging applications, and methods for color correction have been studied. Nevertheless, the effectiveness of color-correction methods in the quantitative analysis of histopathological images acquired by different whole-slide scanners (WSSs) has not been confirmed. In this work, several liver tissue samples were scanned by different WSSs, and a color-correction method for whole-slide images was applied to the digitized tissue specimens. A set of histological features were extracted from the histopathological images, both without and with color correction, to analyze the effectiveness of the color-correction method in feature quantification and cancer identification.

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• Accuracy of non-invasive scoring systems for diagnosing non-alcoholic steatohepatitis-related fibrosis: Multicenter validation study

  Itoh Y., Seko Y., Shima T., Nakajima T., Mizuno K., Kawamura Y., Akuta N., Ito K., Kawanaka M., Hiramatsu A., Sakamoto M., Harada K., Goto Y., Nakayama T., Kumada H., Okanoue T.

  Hepatology Research （Hepatology Research）  48 （ 13 ） 1099 - 1107 2018年12月

  ISSN  13866346

  　概要を見る

  © 2018 The Japan Society of Hepatology Aim: Hepatic fibrosis is the most important factor for estimating the prognosis of patients with non-alcoholic fatty liver disease (NAFLD). A novel non-invasive scoring system, the FM-fibro index, showed high accuracy in a pilot study. The purpose of this study was to validate the efficacy of the FM-fibro index in a multicenter cohort. Methods: Among 18 institutions, we analyzed 400 Japanese patients with biopsy-proven NAFLD. We evaluated the accuracies of the FM-fibro index, CA-fibro index, and European Liver Fibrosis (ELF) panel by area under the receiver operator characteristics curves (AUROC). The FM-fibro index includes three formulas for type IV collagen 7S, hyaluronic acid, and vascular cell adhesion molecule-1. Results: Among 400 patients, 205 were women, and the median age was 56 years. The histological distribution of Matteoni types 1, 2, 3, and 4 was 11, 40, 15, and 334, and the distribution of hepatic fibrosis stages 0 to 4 was 67, 183, 55, 63, and 32, respectively. The AUROCs of the FM-fibro index, CA-fibro index, and ELF panel for non-alcoholic steatohepatitis (NASH)-related fibrosis were 0.7178/0.7095/0.7065, 0.7093, and 0.7245, respectively. The sensitivity and specificity of the FM-fibro index for predicting NASH-related fibrosis was 0.5359/0.5210/0.4641 and 0.8333/0.8182/0.8788, respectively. The accuracy of the FM-fibro index was not significantly different from that of the CA-fibro index or the ELF panel. Conclusions: The FM-fibro index can predict NASH-related fibrosis with sufficient accuracy compared with previous scoring systems. Further analyses that verify the accuracy of the FM-fibro index to distinguish significant or advanced fibrosis in patients with NAFLD are awaited. (UMIN-CTR: UMIN000018158).

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• CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma

  Nishida H., Hayashi M., Morimoto C., Sakamoto M., Yamada T.

  Blood Cancer Journal （Blood Cancer Journal）  8 （ 11 ）  2018年11月

  　概要を見る

  © 2018, The Author(s). CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG1 monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.

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• Evaluation of pancreatic fibrosis with acoustic radiation force impulse imaging and automated quantification of pancreatic tissue components

  Fujita Y., Kitago M., Abe T., Itano O., Shinoda M., Abe Y., Yagi H., Hibi T., Ishii M., Nakano Y., Okuma K., Hashimoto M., Takeuchi A., Masugi Y., Jinzaki M., Sakamoto M., Kitagawa Y.

  Pancreas （Pancreas）  47 （ 10 ） 1277 - 1282 2018年11月

  ISSN  08853177

  　概要を見る

  © 2018 Wolters Kluwer Health, Inc. All rights reserved. Objectives The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). Methods Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. Results The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV (ρ = 0.440, P < 0.001 and ρ =-0.428, P < 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with clinically relevant POPF (P = 0.268 and 0.052, respectively). Conclusions We objectively quantified the pancreatic tissue components using an automatic image processing software. Shear wave velocity was significantly related to collagen fiber content and suggests that ARFI imaging can be useful for evaluating pancreatic fibrosis.

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• Immunohistochemical visualization of the signature of activated Hedgehog signaling pathway in cutaneous epithelial tumors

  Tanese K., Emoto K., Kubota N., Fukuma M., Sakamoto M.

  Journal of Dermatology （Journal of Dermatology）  45 （ 10 ） 1181 - 1186 2018年10月

  ISSN  03852407

  　概要を見る

  © 2018 Japanese Dermatological Association Activation of the Hedgehog (HH) signaling pathway plays a critical role in the development of basal cell carcinoma (BCC). HH signaling activity is produced by nuclear translocation of transcription factors, glioma-associated oncogene homolog (GLI). Among three GLI subfamilies, GLI1 is the only full-length transcriptional activator, and its nuclear localization is recognized as a signature event in HH signaling activation. However, limited published work has investigated the nuclear staining of GLI1 protein in human tumor tissue samples by immunohistochemical analysis. In this study, we performed immunohistochemical staining of GLI1 in 382 cases of cutaneous epithelial tumors, including 196 BCC cases, using rabbit monoclonal antihuman GLI1 antibody (C68H3). As a result, 98.2% cases of BCC showed a diffuse and strong nuclear staining pattern regardless of the histological subtype. Positive staining was mainly restricted to the tumor nests, while the overlying epidermis was negative suggesting specificity of the antibody. In further analysis of other cutaneous epithelial tumors, 100% (4/4) cases of trichoblastoma, 15.1% (5/33) Bowen's disease, 3.5% (1/28) actinic keratosis and 12.5% (4/32) squamous cell carcinoma showed the nuclear staining pattern of GLI1. This suggested that HH signaling is also dysregulated in some other cutaneous malignant tumors. In conclusion, the C68H3 antibody is a useful tool for revealing activation of HH signaling in immunohistochemical analysis.

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

• 胆道癌・肝内胆管癌・膵癌におけるsynuclein gamma発現の意義

  坂元, 亨宇

  科学研究費補助金研究成果報告書 2018年

• インターフェロンγが悪性黒色腫細胞のAKTシグナルを活性化する機序の検討

  坂元, 亨宇

  科学研究費補助金研究成果報告書 2017年

• 肝細胞癌の分子病理学的知見に基づくサブクラス分類の確立

  坂元, 亨宇

  科学研究費補助金研究成果報告書 2016年

• G蛋白共役型受容体GPR49/LGR5のヒト組織並びに疾患における発現・機能解析

  坂元, 亨宇

  科学研究費補助金研究成果報告書 2011年

• 消化器がん個性診断法の開発

  坂元, 亨宇

  科学研究費補助金研究成果報告書 2009年

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総説・解説等 【 表示 ／ 非表示 】

• The challenges and promises of quanifying liver fibrosis and steatosis evaluation of liver fibrosis: From the viewpoint of pathology

  Hatano M., Abe T., Hashiguchi A., Sakamoto M.

  Acta Hepatologica Japonica （Acta Hepatologica Japonica）  59 （ 8 ） 415 - 420 2018年

  ISSN  04514203

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• 肝細胞癌における多段階発癌とCyclase-associated protein-2(CAP2)の過剰発現

  森　泰昌、柴田　理恵、杜　&#38639;林、中馬　誠、後藤　政広、広橋　説雄、坂元　亨宇

  ワークショップ　第64回日本癌学会学術総会 （札幌） , 

  2005年09月

  , 

  口頭発表（一般）, 日本癌学会

• Overexpression of cyclase-associated protein 2 i multistage hepatocaricinogenesis

  森 泰昌</U

  AACR annual meeting （anaheim USA） , 

  2005年04月

  , 

  ポスター発表, AACR

• オリゴヌクレオチドマイクロアレイを用いた非小細胞肺癌の網羅的遺伝子発現解析

  花田　仁子、　坂元　亨宇、　前島　新史、　広橋説雄

  第44回日本肺癌学会総会、 （東京） , 

  2003年11月

  , 

  口頭発表（一般）

• 'DNA methyltransferase (DNMT) 1 protein expression is significantly increased in human hepatocellular carcinomas with malignant potential and may be a biological predictor of prognosis in hepatocellular carcinoma patients. The 54th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, Massachusetts, USA, October 24-28, 2003'

  坂元 亨宇

  'The 54th Annual Meeting of the American Association for the Study of Liver Diseases,' （'Boston, Massachusetts, USA,'） , 

  2003年10月

  , 

  ポスター発表

• Expression profiling in multistage hepatocarcinogenesis; identification of HSP70 as a molecular marker of early hepatocellular carcinoma.

  坂元 亨宇

  'The 54th Annual Meeting of the American Association for the Study of Liver Diseases,' （'Boston, Massachusetts, USA,'） , 

  2003年10月

  , 

  ポスター発表

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競争的研究費の研究課題 【 表示 ／ 非表示 】

競争的研究費の研究課題 【 表示 ／ 非表示 】

• 肝細胞癌の分子病理学的知見に基づくサブクラス分類の確立

  2014年04月

  -

  2017年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 坂元　亨宇, 基盤研究(B), 補助金,  研究代表者

  　研究概要を見る

  シグナル伝達系・表現型などの特徴を免疫組織学的に解析し、悪性度も反映する肝細胞癌の新たなサブクラス分類を確立した。幹細胞・胆管上皮マーカーを発現する症例群では治療標的の候補であるMAPK経路の活性化やグリピカン3の高発現と関連することが、WNTシグナル経路が活性化した症例群はMRI画像診断により検出可能であることが示された。今後、これらの臨床応用が期待される。

Works 【 表示 ／ 非表示 】

Works 【 表示 ／ 非表示 】

• 学務委員会委員

  2003年10月

  -

  2005年09月

  , 

  その他

• 教育委員会委員

  2003年10月

  -

  2005年09月

  , 

  その他

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担当授業科目 【 表示 ／ 非表示 】

• 病理学総論

  2024年度

• 病理学総論

  2023年度

• 病理学各論

  2023年度

• 病理学特論

  2022年度

• 病理学各論

  2022年度

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