2022/12/01 更新

写真a

オオハシ リウコ
大橋 瑠子
OHASHI Riuko
所属
教育研究院 医歯学系 医学系列 准教授
医歯学総合研究科 分子細胞医学専攻 遺伝子制御 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 2015年3月   新潟大学 )

研究キーワード

  • 人体病理学

研究分野

  • ライフサイエンス / 人体病理学  / 腎癌

経歴(researchmap)

  • 医歯学総合研究科 分子細胞医学専攻 細胞機能   准教授

    2022年8月 - 現在

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    国名:日本国

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  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2015年12月 - 2022年7月

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  • 新潟大学   医歯学総合病院 病理部   特任助教

    2012年1月 - 2015年11月

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  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2008年6月 - 2011年12月

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  • 新潟大学医歯学総合病院病理部   Pathological Division, Medical and Dental Hospital   医員

    2003年8月 - 2008年5月

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経歴

  • 新潟大学   教育研究院 医歯学系 医学系列   准教授

    2022年8月 - 現在

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 遺伝子制御   准教授

    2022年8月 - 現在

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2015年12月 - 2022年7月

  • 新潟大学   医歯学総合病院 病理部   特任助教

    2012年1月 - 2015年11月

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2008年6月 - 2011年12月

学歴

  • 浜松医科大学   医学研究科   形態系専攻

    - 2003年7月

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    国名: 日本国

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  • 浜松医科大学   医学部   医学科

    - 2001年3月

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    国名: 日本国

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所属学協会

▶ 全件表示

留学歴

  • スイス連邦・チューリッヒ大学病院病理部   客員医師

    2017年3月 - 2018年5月

取得資格

  • 日本病理学会病理専門医・研修指導医

  • 医師

  • 日本臨床細胞学会細胞診専門医

 

論文

  • WHO 2022 landscape of papillary and chromophobe renal cell carcinoma. 国際誌

    João Lobo, Riuko Ohashi, Mahul B Amin, Daniel M Berney, Eva M Compérat, Ian A Cree, Anthony J Gill, Arndt Hartmann, Santosh Menon, George J Netto, Maria R Raspollini, Mark A Rubin, Puay Hoon Tan, Satish K Tickoo, Toyonori Tsuzuki, Samra Turajlic, Ming Zhou, John R Srigley, Holger Moch

    Histopathology   81 ( 4 )   426 - 438   2022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)  

    The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems contains relevant revisions and introduces a group of molecularly defined renal tumour subtypes. Herein we present the World Health Organization (WHO) 2022 perspectives on papillary and chromophobe renal cell carcinoma with emphasis on their evolving classification, differential diagnosis, and emerging entities. The WHO 2022 classification eliminated the type 1/2 papillary renal cell carcinoma (pRCC) subcategorization, given the recognition of frequent mixed tumour phenotypes and the existence of entities with a different molecular background within the type 2 pRCC category. Additionally, emerging entities such as biphasic squamoid alveolar RCC, biphasic hyalinising psammomatous RCC, papillary renal neoplasm with reverse polarity, and Warthin-like pRCC are included as part of the pRCC spectrum, while additional morphological and molecular data are being gathered. In addition to oncocytomas and chromophobe renal cell carcinoma (chRCC), a category of 'other oncocytic tumours' with oncocytoma/chRCC-like features has been introduced, including emerging entities, most with TSC/mTOR pathway alterations (eosinophilic vacuolated tumour and so-called 'low-grade' oncocytic tumour), deserving additional research. Eosinophilic solid and cystic RCC was accepted as a new and independent tumour entity. Finally, a highly reproducible and clinically relevant universal grading system for chRCC is still missing and is another niche of ongoing investigation. This review discusses these developments and highlights emerging morphological and molecular data relevant for the classification of renal cell carcinoma.

    DOI: 10.1111/his.14700

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  • Development and validation of a vascularity-based architectural classification for clear cell renal cell carcinoma: correlation with conventional pathological prognostic factors, gene expression patterns, and clinical outcomes. 国際誌

    Chisato Ohe, Takashi Yoshida, Mahul B Amin, Naho Atsumi, Junichi Ikeda, Kazuho Saiga, Yuri Noda, Yoshiki Yasukochi, Riuko Ohashi, Haruyuki Ohsugi, Koichiro Higasa, Hidefumi Kinoshita, Koji Tsuta

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   35 ( 6 )   816 - 824   2022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)  

    The prognostic significance of an architectural grading system for clear cell renal cell carcinoma (ccRCC) has recently been demonstrated. The present study aimed to establish a vascularity-based architectural classification using the cohort of 436 patients with localized ccRCC who underwent extirpative surgery and correlated the findings with conventional pathologic factors, gene expression, and prognosis. First, we assessed architectural patterns in the highest-grade area on hematoxylin and eosin-stained slides, then separately evaluated our surrogate score for vascularity. We grouped nine architectural patterns into three categories based on the vascular network score. "Vascularity-based architectural classification" was defined: category 1: characterized by enrichment of the vascular network, including compact/small nested, macrocyst/microcystic, and tubular/acinar patterns; category 2: characterized by a widely spaced-out vascular network, including alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary patterns; category 3: characterized by scattered vascularity without a vascular network, including solid sheets, rhabdoid and sarcomatoid patterns. Adverse pathological prognostic factors such as TNM stage, WHO/ISUP grade, and necrosis were significantly associated with category 3, followed by category 2 (all p < 0.001). We successfully validated the classification using The Cancer Genome Atlas (TCGA) cohort (n = 162), and RNA-sequencing data available from TCGA showed that the angiogenesis gene signature was significantly enriched in category 1 compared to categories 2 and 3, whereas the immune gene signature was significantly enriched in category 3 compared to categories 1 and 2. In univariate analysis, vascularity-based architectural classification showed the best accuracy in pathological prognostic factors for predicting recurrence-free survival (c-index = 0.786). The predictive accuracy of our model which integrated WHO/ISUP grade, necrosis, TNM stage, and vascularity-based architectural classification was greater than conventional risk models (c-index = 0.871 vs. 0.755-0.843). Our findings suggest that the vascularity-based architectural classification is prognostically useful and may help stratify patients appropriately for management based on their likelihood of post-surgical recurrence.

    DOI: 10.1038/s41379-021-00982-9

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  • Histologic-Based Tumor-Associated Immune Cells Status in Clear Cell Renal Cell Carcinoma Correlates with Gene Signatures Related to Cancer Immunity and Clinical Outcomes. 国際誌

    Chisato Ohe, Takashi Yoshida, Junichi Ikeda, Toyonori Tsuzuki, Riuko Ohashi, Haruyuki Ohsugi, Naho Atsumi, Ryosuke Yamaka, Ryoichi Saito, Yoshiki Yasukochi, Koichiro Higasa, Hidefumi Kinoshita, Koji Tsuta

    Biomedicines   10 ( 2 )   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The three-tier immunophenotype (desert, excluded, and inflamed) and the four-tier immunophenotype (cold, immunosuppressed, excluded, and hot) have been linked to prognosis and immunotherapy response. This study aims to evaluate whether immunophenotypes of clear cell renal cell carcinoma, identified on hematoxylin and eosin-stained slides, correlate with gene expression signatures related to cancer immunity, and clinical outcomes. We evaluated tumor-associated immune cells (TAICs) status using three methodologies: three-tier immunophenotype based on the location of TAICs, four-tier immunophenotype considering both the location and degree of TAICs and inflammation score focusing only on the degree of TAICs, using a localized clear cell renal cell carcinoma cohort (n = 436) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 162). We evaluated the association of the TAICs status assessed by three methodologies with CD8 and PD-L1 immunohistochemistry and immune gene expression signatures by TCGA RNA-sequencing data. All three methodologies correlated with immunohistochemical and immune gene expression signatures. The inflammation score and the four-tier immunophenotype showed similarly higher accuracy in predicting recurrence-free survival and overall survival compared to the three-tier immunophenotype. In conclusion, a simple histologic assessment of TIACs may predict clinical outcomes and immunotherapy responses.

    DOI: 10.3390/biomedicines10020323

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  • TSC/mTOR Pathway Mutation Associated Eosinophilic/Oncocytic Renal Neoplasms: A Heterogeneous Group of Tumors with Distinct Morphology, Immunohistochemical Profile, and Similar Genetic Background 招待 査読 国際誌

    Kristyna Pivovarcikova, Reza Alaghehbandan, Tomas Vanecek, Riuko Ohashi, Tomas Pitra, Ondrej Hes

    Biomedicines   10 ( 2 )   322 - 322   2022年1月

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

    A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.

    DOI: 10.3390/biomedicines10020322

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  • Onkozytäre Tumoren der Niere – neue Differenzialdiagnosen 招待 査読

    I. Polifka, R. Ohashi, H. Moch

    Der Pathologe   2021年9月

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    記述言語:ドイツ語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s00292-021-00979-w

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    その他リンク: https://link.springer.com/article/10.1007/s00292-021-00979-w/fulltext.html

  • Re: Svetlana Avulova, John C. Cheville, Christine M. Lohse, et al. Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis. Eur Urol 2021;79:225–31 査読 国際誌

    Riuko Ohashi, Arndt Hartmann, Guido Martignoni, Holger Moch

    European Urology   80 ( 1 )   e17 - e18   2021年7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:Elsevier BV  

    DOI: 10.1016/j.eururo.2021.03.025

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  • Chromophobe renal cell carcinoma: current and controversial issues 招待 査読 国際誌

    Holger Moch, Riuko Ohashi

    Pathology   53 ( 1 )   101 - 108   2021年1月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    It has been 35 years since Professor Thoenes and his colleagues discovered chromophobe renal cell carcinoma (RCC). Since then, our knowledge about this tumour entity has changed and novel tumour entities have been discovered. The aim of this review is to discuss recent molecular findings and open questions in diagnosing chromophobe-like/oncocytic neoplasms. The broader differential diagnosis of chromophobe-like and oncocytoma-like neoplasms includes SDH-deficient renal cell carcinoma, fumarate hydratase (FH) deficient RCC, epitheloid angiomyolipoma ('oncocytoma like'), MiT family translocation RCC and the emerging entity of eosinophilic solid and cystic renal cell carcinoma. After separation of these tumours from chromophobe RCC, it becomes evident that chromophobe RCC are low malignant tumours with a 5-6% risk of metastasis. Recent next generation sequencing (NGS) and DNA methylation profiling studies have confirmed Thoenes' theory of a distal tubule derived origin of chromophobe RCC and renal oncocytomas. Comprehensive genomic analyses of chromophobe RCC have demonstrated a low somatic mutation rate and identified TP53 and PTEN as the most frequently mutated genes, whereas 'unclassified' RCC with oncocytic or chromophobe-like features can show somatic inactivating mutations of TSC2 or activating mutations of MTOR as the primary molecular alterations. For the future, it would be desirable to create a category of 'oncocytic/chromophobe RCC, NOS' with the potential of further molecular studies for identification of TSC1/2 mutations in these rare tumours.

    DOI: 10.1016/j.pathol.2020.09.015

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  • Review of TFEB-amplified renal cell carcinoma with focus on clinical and pathobiological aspects. 国際誌

    Naoto Kuroda, Emiko Sugawara, Chisato Ohe, Fumiyoshi Kojima, Riuko Ohashi, Shuji Mikami, Yoji Nagashima, Kvetoslava Peckova, Michal Michal, Ondrej Hes

    Polish journal of pathology : official journal of the Polish Society of Pathologists   72 ( 3 )   197 - 199   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The disease entity of TFEB-amplified renal cell carcinoma (RCC) has been recently established. In this article, we review such cases. Clinically, the age of patients ranged from 28 to 83 years with a mean age of 62.8 years. The size of the tumor ranged from 1.9 to 19.5 cm with a mean size of 8.7 cm. The tumor demonstrated a variety of architectural patterns such as solid, alveolar, papillary, pseudopapillary, nested or tubular. The International Society of Urological Pathology (ISUP) grade usually corresponds to grade 3 or 4. Cytomorphology shows eosinophilic, clear, amphophilic or even oncocytic cytoplasm. Necrosis can be frequently observed. Neoplastic cells with TFEB-amplified RCC show diffuse or patchy positivity for TFEB. Fluorescence in situ hybridization frequently show the amplification of more than 10 or 20 copies of the TFEB gene. Most TFEB-amplified RCCs behave in an aggressive fashion. Metastasis frequently occurs. In conclusion, this tumor seems to be characterized by occurrence in older patients, frequent necrosis, papillary/pseudopapillary growth pattern, high-grade nuclear grade, TFEB gene amplification, and aggressive clinical behavior. In order to clarify whether this tumor is a distinct entity from previously described renal tumors or not, a further examination in a large scale study will be required in the future.

    DOI: 10.5114/pjp.2021.111769

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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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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 &lt; 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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  • Re: Multi-institutional Re-evaluation of Prognostic Factors in Chromophobe Renal Cell Carcinoma: Proposal of a Novel Two-tiered Grading Scheme 査読 国際誌

    Alessia Cimadamore, Liang Cheng, Riuko Ohashi, Marina Scarpelli, Antonio Lopez-Beltran, Holger Moch, Rodolfo Montironi

    European Urology   78 ( 1 )   114 - 116   2020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 BV  

    DOI: 10.1016/j.eururo.2020.02.016

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  • Chromophobe Renal Cell Carcinoma Aggressiveness and Immuno-oncology Therapy: How to Distinguish the Good One from the Bad One 査読

    Rodolfo Montironi, Alessia Cimadamore, Riuko Ohashi, Liang Cheng, Marina Scarpelli, Antonio Lopez-Beltran, Holger Moch

    European Urology Oncology   2020年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.euo.2020.02.011

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  • Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme 査読 国際誌

    Riuko Ohashi, Guido Martignoni, Arndt Hartmann, Anna Caliò, Diego Segala, Christine Stöhr, Sven Wach, Franziska Erlmeier, Wilko Weichert, Michael Autenrieth, Peter Schraml, Niels J. Rupp, Chisato Ohe, Yoshiro Otsuki, Takashi Kawasaki, Hiroshi Kobayashi, Kazuhiro Kobayashi, Tatsuhiko Miyazaki, Hiroyuki Shibuya, Hiroyuki Usuda, Hajime Umezu, Fumiyoshi Fujishima, Bungo Furusato, Mitsumasa Osakabe, Tamotsu Sugai, Naoto Kuroda, Toyonori Tsuzuki, Yoji Nagashima, Yoichi Ajioka, Holger Moch

    Virchows Archiv   476 ( 3 )   409 - 418   2020年3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  

    A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.

    DOI: 10.1007/s00428-019-02710-w

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    その他リンク: http://link.springer.com/article/10.1007/s00428-019-02710-w/fulltext.html

  • Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients 査読 国際誌

    Riuko Ohashi, Silvia Angori, Aashil A. Batavia, Niels J. Rupp, Yoichi Ajioka, Peter Schraml, Holger Moch

    Cancers   12 ( 2 )   465 - 465   2020年2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:MDPI AG  

    Chromophobe renal cell carcinoma (chRCC) patients have good prognosis. Only 5%–10% patients die of metastatic disease after tumorectomy, but tumor progression cannot be predicted by histopathological parameters alone. chRCC are characterized by losses of many chromosomes, whereas gene mutations are rare. In this study, we aim at identifying genes indicating chRCC progression. A bioinformatic approach was used to correlate chromosomal loss and mRNA expression from 15287 genes from The Cancer Genome Atlas (TCGA) database. All genes in TCGA chromophobe renal cancer dataset (KICH) for which a significant correlation between chromosomal loss and mRNA expression was shown, were identified and their associations with outcome was assessed. Genome-wide DNA copy-number alterations were analyzed by Affymetrix OncoScan® CNV FFPE Microarrays in a second cohort of Swiss chRCC. In both cohorts, tumors with loss of chromosomes 2, 6, 10, 13, 17 and 21 had signs of tumor progression. There were 4654 genes located on these chromosomes, and 13 of these genes had reduced mRNA levels, which was associated with poor outcome in chRCC. Decreased CDKN1A expression at mRNA (p = 0.02) and protein levels (p = 0.02) were associated with short overall survival and were independent predictors of prognosis (p &lt; 0.01 and &lt;0.05 respectively). CDKN1A expression status is a prognostic biomarker independent of tumor stage. CDKN1A immunohistochemistry may be used to identify chRCC patients at greater risk of disease progression.

    DOI: 10.3390/cancers12020465

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  • Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses than Seen in the Eosinophilic Subtype 査読 国際誌

    Ohashi, Schraml, Angori, Batavia, Rupp, Ohe, Otsuki, Kawasaki, Kobayashi, Kobayashi, Miyazaki, Shibuya, Usuda, Umezu, Fujishima, Furusato, Osakabe, Sugai, Kuroda, Tsuzuki, Nagashima, Ajioka, Moch

    Cancers   11 ( 10 )   1492 - 1492   2019年10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:MDPI AG  

    Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan® CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p &lt; 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC.

    DOI: 10.3390/cancers11101492

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  • Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma 査読 国際誌

    Riuko Ohashi, Peter Schraml, Aashil Batavia, Silvia Angori, Patrik Simmler, Niels Rupp, Yoichi Ajioka, Esther Oliva, Holger Moch

    Translational Oncology   12 ( 9 )   1131 - 1137   2019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:Elsevier BV  

    Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes have been recently identified as the most enriched class of copy-number associated gene dependencies in human cancer. These genes are cell essential and render tumor cells highly sensitive to the expression of the remaining copy. Chromophobe renal cell carcinoma (chRCC) is characterized by frequent chromosomal deletions, but the relevance of CYCLOPS genes in this tumor subtype is unclear. We found 39 (31%) of 124 recently published candidate CYCLOPS genes (B. Paolella et al., eLife 2017;6:e23268) located on 7 autosomes that are frequently lost in chRCC. GISTIC and RNA-seq data obtained from the TCGA-KICH database showed that 62% of these CYCLOPS genes had significantly lower expression levels in samples with deletion of the respective gene. As copy number (CN) loss of the CYCLOPS gene SF3B1 (Splicing factor 3B subunit 1) has been recently reported in 71% chRCC, we explored the relevance of SF3B1 CN alteration and SF3B1 expression in a set of chRCC and additional oncocytic renal neoplasms. The frequency of SF3B1 CN loss (65%) was similar to that obtained from the TCGA-KICH database and correlated significantly with both lower SF3B1 mRNA (P < .05) and protein expression (P < .001). Other tumor subtypes with oncocytic cytoplasm had normal SF3B1 CN and displayed strong SF3B1 protein expression. These results suggest that CN loss of CYCLOPS genes is a characteristic feature in chRCC. Since many CYCLOPS genes code for components of proteasomes and transcriptional regulation, their alteration could make chRCC vulnerable to targeted drugs.

    DOI: 10.1016/j.tranon.2019.05.005

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  • Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma 査読 国際誌

    Svenja Bihr, Riuko Ohashi, Ariane L. Moore, Jan H. Rüschoff, Christian Beisel, Thomas Hermanns, Axel Mischo, Claudia Corrò, Jörg Beyer, Niko Beerenwinkel, Holger Moch, Peter Schraml

    Neoplasia   21 ( 2 )   247 - 256   2019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)   出版者・発行元:Elsevier BV  

    Bi-allelic inactivation of the VHL gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in SETD2, BAP1 and PBRM1, all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression. We analyzed PBRM1 and BAP1 protein expression as well as the tri-methylation state of H3K36 as a surrogate marker for SETD2 activity in more than 700 RCC samples. In ccRCC loss of nuclear PBRM1 (68%), BAP1 (40%) and H3K36me3 (47%) expression was significantly correlated with each other, advanced tumor stage, poor tumor differentiation (P < .0001 each), and necrosis (P < .005) Targeted next generation sequencing of 83 ccRCC samples demonstrated a significant association of genetic mutations in PBRM1, BAP1, and SETD2 with absence of PBRM1, BAP1, and HEK36me3 protein expression (P < .05, each). By assigning the protein expression patterns to evolutionary subtypes, we revealed similar clinical phenotypes as suggested by TRACERx Renal. Given their important contribution to tumor suppression, we conclude that combined functional inactivation of PBRM1, BAP1, SETD2 and pVHL is critical for ccRCC progression.

    DOI: 10.1016/j.neo.2018.12.006

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  • Morphological clues to the appropriate recognition of hereditary renal neoplasms 招待 査読 国際誌

    Holger Moch, Riuko Ohashi, Jatin S. Gandhi, Mahul B. Amin

    Seminars in Diagnostic Pathology   35 ( 3 )   184 - 192   2018年5月

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

    An important emerging role of the surgical pathologist besides the traditional tasks of establishment of the diagnosis and documentation of prognostic and predictive factors, is to recognize the possibility of a hereditary condition in cases where the histology is suggestive for a familial cancer syndrome. In recent years, the knowledge regarding all of the above roles, including the role of recognition of familial cancer, has particularly expanded in renal neoplasms with the close scrutiny to morphology, molecular correlates and clinical features of the different sub-types of renal cell carcinoma. Awareness of these clinically distinctive sub-types and their associated histologic clues will prompt the pathologist for further immunohistochemical or molecular work up, to look for clinical information to support the suspected diagnosis of familial cancer, to alert managing physician/s to look for stigmata of history of familial cancer, which will permit triaging patients and their families for appropriate genetic counseling. This review provides a comprehensive review of the known sub-types of renal cell carcinoma that have a predilection to occur in the setting of hereditary disease
    examples include renal cancers occurring in the background of von Hippel Lindau disease, hereditary leiomyomatosis and renal cell carcinoma syndrome, tuberous sclerosis, Birt Hogg Dube syndrome and succinate dehydrogenase deficiency. Herein we focus on diagnostic clues for renal tumors occurring in a non-pediatric setting that should prompt their correct recognition and reiterate the importance of the correct diagnosis.

    DOI: 10.1053/j.semdp.2018.01.005

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  • A Case Report of Occupational Lung Disease Caused by Exposure to Polytetrafluoroethylene.

    Ami Aoki, Akira Saito, Kenjiro Shima, Yosuke Kimura, Katsuaki Asakawa, Riuko Ohashi, Hajime Umezu, Takuro Sakagami, Hiroshi Moriyama, Toshiaki Kikuchi

    Internal medicine (Tokyo, Japan)   2022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)  

    We herein report a 45-year-old-man with multiple foreign body granulomas in the lungs caused by polytetrafluoroethylene (PTFE). A mass in the right lower lobe of the lung and bilateral centrilobular lung nodules were found unexpectedly during the patient's visit to a hospital for a respiratory infection. The patient's occupation for 26 years involved spraying PTFE. A lung biopsy using bronchoscopy revealed granulomatous lesions and giant cells. The presence of fluorine in the granulomatous lesions was confirmed using an electron probe microanalyzer with wavelength dispersive spectrometer. Fluorine is a component of PTFE and is not found in normal lung tissue.

    DOI: 10.2169/internalmedicine.9008-21

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  • Correction to: Development and validation of a vascularity-based architectural classification for clear cell renal cell carcinoma: correlation with conventional pathological prognostic factors, gene expression patterns, and clinical outcomes. 国際誌

    Chisato Ohe, Takashi Yoshida, Mahul B Amin, Naho Atsumi, Junichi Ikeda, Kazuho Saiga, Yuri Noda, Yoshiki Yasukochi, Riuko Ohashi, Haruyuki Ohsugi, Koichiro Higasa, Hidefumi Kinoshita, Koji Tsuta

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   35 ( 5 )   708 - 708   2022年5月

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  • Synchronous Occurrence of Advanced Gastric Carcinoma with Retroperitoneal Liposarcoma: A Case Report. 国際誌

    Hiroshi Kobayashi, Riuko Ohashi, Masuo Ujita, Kana Ueki, Ryouya Seki, Shintaro Fukuda, Brian Rubin

    The American journal of case reports   23   e934586   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND Gastric carcinoma (GC) remains one of the most common and deadly neoplasms in the world. Liposarcoma (LPS) is the most common sarcoma of adults. However, synchronous or metachronous occurrence of GC with LPS seems to be very rare. Tumor staging and differential diagnosis with these cases are extremely difficult. CASE REPORT The patient was a man in his 70s, who reported anorexia and weight loss of 4 kg over 2 months. Gastroscopy demonstrated a large tumor of Borrmann type 3, of which histology was moderately to poorly differentiated adenocarcinoma. The clinical stage was initially defined as IVb due to a 11×6 cm retroperitoneal (RP) tumor. Despite chemotherapy for GC, the RP tumor rapidly enlarged. Endoscopic ultrasound-guided fine-needle aspiration biopsy showed that it was an undifferentiated sarcoma. He died of hepatorenal failure secondary to severe jaundice. The autopsy revealed a synchronous occurrence of GC and RP sarcoma. GC had no areas admixed with sarcoma. Histology of RP sarcoma showed that it mainly consisted of undifferentiated sarcoma and focally of well-differentiated LPS characterized by well-differentiated adipocytes admixed with scattered atypical stromal cells. The tumor cells in both areas were positive for MDM2 and CDK4 by immunohistochemistry. The diagnosis of the RP sarcoma was revised to dedifferentiated LPS. CONCLUSIONS There were no previous case reports of synchronous occurrence of GC with LPS in the English and Japanese literature. GC and LPS pose challenging problems in their diagnoses, staging, and treatments when they occur synchronously or metachronously.

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  • The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth 査読 国際誌

    João Lobo, Riuko Ohashi, Birgit M. Helmchen, Niels J. Rupp, Jan H. Rüschoff, Holger Moch

    Biomedicines   9 ( 10 )   1418 - 1418   2021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:MDPI AG  

    Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic “type 1 versus type 2” classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.

    DOI: 10.3390/biomedicines9101418

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  • [Retracted] Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. 国際誌

    Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Pavel V Korita, Yasunobu Matsuda, Masaaki Takamura, Riuko Ohashi, Masayuki Nagahashi, Yoichi Ajioka, Katsuyoshi Hatakeyama

    International journal of oncology   59 ( 4 )   2021年10月

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    記述言語:英語  

    Following the publication of this paper, the Journal was alerted by an investigation committee of Niigata University to the fact that the paper had been identified as a duplicate publication, which had already been published. Therefore, in accordance with the rules of Niigata University Fraud Investigation committee, a request was made that the paper be retracted. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 38: 1227-1236, 2011; DOI: 10.3892/ijo.2011.959].

    DOI: 10.3892/ijo.2021.5258

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  • Altered Microbiota by a High-Fat Diet Accelerates Lethal Myeloid Hematopoiesis Associated with Systemic Socs3 Deficiency 国際誌

    Kaori Cho, Takashi Ushiki, Hajime Ishiguro, Suguru Tamura, Masaya Araki, Tatsuya Suwabe, Takayuki Katagiri, Mari Watanabe, Yoko Fujimoto, Riuko Ohashi, Yoichi Ajioka, Ippei Shimizu, Shujiro Okuda, Masayoshi Masuko, Yoshimi Nakagawa, Hideyo Hirai, Warren S. Alexander, Hitoshi Shimano, Hirohito Sone

    iScience   24 ( 10 )   103117 - 103117   2021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:Elsevier BV  

    The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

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  • Mood Disorder in Systemic Lupus Erythematosus Induced by Antiribosomal P Protein Antibodies Associated with Decreased Serum and Brain Tryptophan 査読 国際誌

    Takamasa Cho, Hiroe Sato, Ayako Wakamatsu, Riuko Ohashi, Yoichi Ajioka, Toshio Uchiumi, Shin Goto, Ichiei Narita, Yoshikatsu Kaneko

    The Journal of Immunology   206 ( 8 )   1729 - 1739   2021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:The American Association of Immunologists  

    Antiribosomal P protein (anti-P) autoantibodies commonly develop in patients with systemic lupus erythematosus. We have previously established hybridoma clones producing anti-P mAbs. In this study, we explored the pathogenesis of behavioral disorders induced by anti-P Abs using these mAbs. New Zealand Black × New Zealand White F1, New Zealand White, C57BL/6, and BALB/c mice were treated with 1 mg of anti-P Abs once every 2 wk. The behavioral disorder was evaluated by the tail suspension test, forced swim test, and open field test. Following administration of anti-P Abs, New Zealand Black × New Zealand White F1 and C57BL/6 mice developed depressive behavior and showed increased anxiety with elevated serum TNF-α and IL-6 levels. Anti-P Abs were not deposited in the affected brain tissue; instead, this mood disorder was associated with lower serum and brain tryptophan concentrations. Tryptophan supplementation recovered serum tryptophan levels and prevented the behavioral disorder. TNF-α and IL-6 were essential for the decreased serum tryptophan and disease development, which were ameliorated by treatment with anti-TNF-α neutralizing Abs or dexamethasone. Peritoneal macrophages from C57BL/6 mice produced TNF-α, IL-6, and IDO-1 via interaction with anti-P Abs through activating FcγRs, which were required for disease development. IVIg, which has an immunosuppressive effect partly through the regulation of FcγR expression, also prevented the decrease in serum tryptophan and disease development. Furthermore, serum tryptophan concentrations were decreased in the sera of systemic lupus erythematosus patients with anti-P Abs, and lower tryptophan levels correlated with disease activity. Our study revealed some of the molecular mechanisms of mood disorder induced by anti-P Abs.

    DOI: 10.4049/jimmunol.2000260

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  • Klippel-Trenaunay-Weber症候群の一例

    中村 真衣, 大橋 瑠子, 長谷川 剛, 梅津 哉, 小林 寛, 吉田 朗彦, 味岡 洋一

    日本病理学会会誌   110 ( 1 )   281 - 281   2021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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  • Osteoclastogenic Potential of Tissue-Engineered Periosteal Sheet: Effects of Culture Media on the Ability to Recruit Osteoclast Precursors 査読 国際誌

    Kohya Uematsu, Takashi Ushiki, Hajime Ishiguro, Riuko Ohashi, Suguru Tamura, Mari Watanabe, Yoko Fujimoto, Masaki Nagata, Yoichi Ajioka, Tomoyuki Kawase

    International Journal of Molecular Sciences   22 ( 4 )   2169 - 2169   2021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)   出版者・発行元:MDPI AG  

    Cell culture media influence the characteristics of human osteogenic periosteal sheets. We have previously found that a stem cell medium facilitates growth and collagen matrix formation in vitro and osteogenesis in vivo. However, it has not yet been demonstrated which culture medium is superior for osteoclastogenesis, a prerequisite for reconstruction of normal bone metabolic basis. To address this question, we compared chemotaxis and osteoclastogenesis in tissue-engineered periosteal sheets (TPSs) prepared with two types of culture media. Periosteal tissues obtained from adult volunteers were expanded with the conventional Medium 199 or with the stem cell medium, MesenPRO. Hematopoietic enhanced-green-fluorescent-protein (EGFP)-nude mice were prepared by γ-irradiation of Balb/c nu/nu mice and subsequent transplantation of bone marrow cells from CAG-EGFP C57BL/6 mice. TPSs were implanted subcutaneously into the chimeric mice and retrieved after intervals for immunohistopathological examination. EGFP+ cells were similarly recruited to the implantation site in both the TPSs prepared, whereas the distribution of CD11b+ cells was significantly lower in the TPS prepared with the stem cell medium. Instead, osteoclastogenesis was higher in the TPS prepared with the stem cell medium than in the one prepared with the conventional medium. These findings suggest that the stem cell medium is preferable for the preparation of more functional TPSs.

    DOI: 10.3390/ijms22042169

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

    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   60 ( 7 )   1077 - 1082   2021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:Japanese Society of Internal Medicine  

    Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

    DOI: 10.2169/internalmedicine.5396-20

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  • Predicting Cervical Lymph Node Metastasis Following Endoscopic Surgery in Superficial Head and Neck Carcinoma. 国際誌

    Ryuichi Okabe, Yushi Ueki, Riuko Ohashi, Manabu Takeuchi, Satoru Hashimoto, Takeshi Takahashi, Ryusuke Shodo, Keisuke Yamazaki, Hiroshi Matsuyama, Hajime Umezu, Shuji Terai, Yoichi Ajioka, Arata Horii

    Frontiers in surgery   8   813260 - 813260   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Early detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection. METHODS: Sixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined. RESULTS: The 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness. CONCLUSION: The treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

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  • An Autopsy Case of an Elderly Patient with Classic Hodgkin Lymphoma Presenting with a Plethora of Clinical Symptoms and Signs 査読 国際誌

    Hiroshi Kobayashi, Ryouya Seki, Masuo Ujita, Kana Hirayama, Satoshi Yamada, Riuko Ohashi, Yoshiro Otsuki, Takuya Watanabe, Tadashi Yoshino

    American Journal of Case Reports   21   e926177   2020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:International Scientific Information, Inc.  

    BACKGROUND Hodgkin lymphoma (HL) is a potentially curable disease with favorable outcomes. However, elderly patients with HL usually have more adverse prognostic factors and hence a much worse prognosis than younger patients. CASE REPORT The patient was a woman in her 80s. She reported high fever, anorexia, and a weight loss of 8 kg within 5 months. She had been on treatment for diabetes mellitus and hypertension. She had undergone percutaneous coronary intervention and pacemaker implantation to treat acute coronary syndrome and sinus arrhythmia, respectively. Blood tests showed elevation of alkaline phosphatase, C-reactive protein, leukocyte count, CA 19-9, and carcinoembryonic antigen. Computed tomography did not show tumors in the liver, and cholangitis and sepsis were suspected. Aspartate transaminase, alanine aminotransferase, and total bilirubin gradually increased through the course of the patient's hospital stay. Despite treatment, her condition deteriorated and she died 22 days after hospital admission. At autopsy, we found stage IV HL with lymph node swelling on both sides of the diaphragm, as well as diffusely disseminated nodules in the liver and spleen. CONCLUSIONS Our patient had several poor prognostic factors including B symptoms, comorbidity, advanced stage, Epstein-Barr virus infection, and expression of programmed death-ligand 1 and interleukin-6, all of which were closely connected with her advanced age. Her age and comorbidities may have been the most adverse prognostic factors for her illness. An effective HL screening method for elderly individuals should be developed to ameliorate poor prognosis and adverse outcomes.

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  • Photosensitizer With Illumination Enhances In Vivo Antitumor Effect of Anti-ROBO1 Immunotoxin on Maxillary Sinus Squamous Cell Carcinoma 査読 国際誌

    NORIKO KOMATSU, MIKU KOMATSU, RIUKO OHASHI, AKIRA HORII, KAZUTO HOSHI, TSUYOSHI TAKATO, TAKAHIRO ABE, TAKAO HAMAKUBO

    Anticancer Research   40 ( 7 )   3793 - 3799   2020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:Anticancer Research USA Inc.  

    BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide. Our study focused on the axon guidance receptor roundabout guidance receptor 1 (ROBO1) as a target for monoclonal antibody therapy of HNSCC. We previously showed that saporin-conjugated anti-ROBO1 (B5209B) immunotoxin (IT-ROBO1) enhanced cytotoxic effects on HNSCC cells in combination with the photosensitizer aluminum phthalocyanine disulphonate (AlPcS2a) and illumination. We examined the effects of this combination therapy in a mouse xenograft model. MATERIALS AND METHODS: IT-ROBO1 was intraperitoneally administered to HSQ-89 (derived from Japanese maxillary sinus squamous carcinoma, RCB0789; RIKEN, Tsukuba, Japan) xenografted mice. After 3 days, AlPcS2a was injected subcutaneously around the tumor and the area was illuminated at 650 nm for 30 min. The growth of the tumor was evaluated and the effects on the tumor were examined. RESULTS: Pronounced anti-tumor effects were elicited by the administration of IT-ROBO1 and AlPcS2a with light illumination on tumor size and pathological characteristics. CONCLUSION: The results showed that photosensitizer treatment with illumination robustly enhanced the antitumor effect of the IT-ROBO1 immunotoxin.

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  • Low bone mineral density due to secondary hyperparathyroidism in theGlatmTg(CAG‐A4GALT)mouse model of Fabry disease 査読 国際誌

    Hiroki Maruyama, Atsumi Taguchi, Mariko Mikame, Hongmei Lu, Norihiro Tada, Muneaki Ishijima, Haruka Kaneko, Mariko Kawai, Sawako Goto, Akihiko Saito, Riuko Ohashi, Yuji Nishikawa, Satoshi Ishii

    FASEB BioAdvances   2 ( 6 )   365 - 381   2020年6月

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

    Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG-A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG-A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro-X-ray-computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+-not plasma fibroblast growth factor 23 (FGF-23) elevation-by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF-23 levels with phosphaturic action. The expression of 1α-hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24-hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.

    DOI: 10.1096/fba.2019-00080

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fba.2019-00080

  • Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma 査読 国際誌

    Noriko Komatsu, Miku Komatsu, Riuko Ohashi, Akira Horii, Kazuto Hoshi, Tsuyoshi Takato, Takahiro Abe, Takao Hamakubo

    Journal of Oncology   2020   1 - 8   2020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:Hindawi Limited  

    Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. The standard treatment of surgery, chemotherapy, and radiotherapy can result in long-term complications which lower the patient’s quality of life, such as eating disorders, speech problems, and disfiguring or otherwise untoward cosmetic issues. Antibody therapy against cancer-specific antigens is advantageous in terms of its lesser side effects achieved by its greater specificity, though the antitumor activity is still usually not enough to obtain a complete cure. Robo1, an axon guidance receptor, has received considerable attention as a possible drug target in various cancers. We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti-Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. Considering the light source, which has only limited tissue penetrance, we examined the drug internalization effect of saponin. Treatment with saponin facilitated significant cytotoxic effects of IT-Robo1 on HSQ-89 cells. Saponin exerts its own nonspecific cytotoxicity, which may cover the actual extent of the internalization effect. We thus examined whether a flashed treatment with saponin exerted a significant specific cytotoxic effect on cancer cells. The combination of an immunotoxin with saponin also exhibited a significant tumor-suppressive effect on mice HSQ-19 xenografts. These results suggest the utility of saponin treatment as an enhancer of immunotoxin treatment in cancer.

    DOI: 10.1155/2020/9593516

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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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  • Correction to: Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme. 国際誌

    Riuko Ohashi, Guido Martignoni, Arndt Hartmann, Anna Caliò, Diego Segala, Christine Stöhr, Sven Wach, Franziska Erlmeier, Wilko Weichert, Michael Autenrieth, Peter Schraml, Niels J Rupp, Chisato Ohe, Yoshiro Otsuki, Takashi Kawasaki, Hiroshi Kobayashi, Kazuhiro Kobayashi, Tatsuhiko Miyazaki, Hiroyuki Shibuya, Hiroyuki Usuda, Hajime Umezu, Fumiyoshi Fujishima, Bungo Furusato, Mitsumasa Osakabe, Tamotsu Sugai, Naoto Kuroda, Toyonori Tsuzuki, Yoji Nagashima, Yoichi Ajioka, Holger Moch

    Virchows Archiv : an international journal of pathology   476 ( 3 )   419 - 422   2020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)  

    The legends of Figs. 1 and 3 in the published original version of the above article are incorrect.

    DOI: 10.1007/s00428-020-02786-9

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  • Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature. 査読 国際誌

    Morita S, Kamimura K, Abe H, Watanabe-Mori Y, Oda C, Kobayashi T, Arao Y, Tani Y, Ohashi R, Ajioka Y, Terai S

    World journal of gastroenterology   25 ( 48 )   6949 - 6958   2019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)  

    DOI: 10.3748/wjg.v25.i48.6949

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  • Detection of Hepatitis Virus B And C in Archival Autopsy Specimens of Liver Cirrhosis 査読

    Yutaka Tsutsumi, Kazuya Shiogama, Hidemi Teramoto, Shinichi Aishima, Yoshinao Oda, Riuko Ohashi, Yoichi Ajioka, Makoto Naito

    Biomedical Journal of Scientific & Technical Research   22 ( 3 )   2019年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Biomedical Research Network, LLC  

    DOI: 10.26717/bjstr.2019.22.003757

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  • An Autopsy Case of Pulmonary Capillary Hemangiomatosis with an Electron Microscopy Study 査読 国際誌

    Hiroshi Kobayashi, Yoshiro Otsuki, Misako Yamaguchi, Kento Ko, Shogo Mizuno, Masuo Ujita, Riuko Ohashi, Takao Sato, Hideo Sato, Toshimitsu Suzuki

    American Journal of Case Reports   20   1551 - 1557   2019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:International Scientific Information, Inc.  

    BACKGROUND Pulmonary capillary hemangiomatosis (PCH) and pulmonary veno-occlusive disease (PVOD) are rare diseases that share clinical, X-ray, and histological features. Most patients have poor prognosis due to severe respiratory impairment. Recently, EIF2AK4 mutations were found in some patients with PCH and PVOD, but the role of this mutation is still unknown. We report an autopsy case of PCH and discuss a mechanism of respiratory dysfunction based on an electron microscopy study. CASE REPORT The patient was a Japanese man in his sixties. He suffered from acute exacerbation of dyspnea during treatment of COPD. Respiratory function testing revealed DLCO' 32.1% and DLCO'/VA 23.6%. Echocardiography demonstrated findings consistent with pulmonary hypertension. A CT scan showed mild emphysema and small ground-glass opacity in the lungs. However, we could not find the exact cause of his respiratory failure and he died 28 days after admission. At autopsy, the histology showed multilayering capillary proliferation within the alveolar walls. Electron microscopy examination revealed prominent widening of the air-blood barrier, scarce fusion of the epithelial and capillary basement membranes, and frequent narrowing of the capillary lumen. CONCLUSIONS We reported an autopsy case with PCH with no histological findings of PVOD. Whether PCH and PVOD are 2 different histological patterns of the same disease remains to be verified. The changes in the air-blood barrier detected by electron microscopy may explain the respiratory impairment and pulmonary arterial hypertension.

    DOI: 10.12659/ajcr.918375

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  • 潰瘍性大腸炎の炎症性発癌早期病変におけるSOX2発現

    渡邉 佳緒里, 味岡 洋一, 大橋 瑠子, 谷 優佑, 渡邉 玄

    日本大腸肛門病学会雑誌   72 ( 5 )   242 - 242   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 原発性小腸進行癌の臨床病理学的特徴と粘液形質について

    近藤 修平, Aye Pa Pa Tun, 味岡 洋一, 高村 佳緒里, 谷 優佑, 大橋 瑠子, 加藤 卓, 杉野 英明, 田口 貴博, 佐藤 航

    日本大腸肛門病学会雑誌   72 ( 5 )   322 - 322   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations 査読 国際誌

    Miyuki Sato, Satoshi Watanabe, Hiroshi Tanaka, Koichiro Nozaki, Masashi Arita, Miho Takahashi, Satoshi Shoji, Kosuke Ichikawa, Rie Kondo, Nobumasa Aoki, Masachika Hayashi, Yasuyoshi Ohshima, Toshiyuki Koya, Riuko Ohashi, Yoichi Ajioka, Toshiaki Kikuchi

    PLOS ONE   14 ( 4 )   e0215292 - e0215292   2019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:Public Library of Science (PLoS)  

    Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.

    DOI: 10.1371/journal.pone.0215292

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  • 多臓器転移と肺癌性リンパ管症を来した6mm大の胃原発小絨毛癌の1剖検例

    谷 優佑, 味岡 洋一, 大橋 瑠子, 加藤 卓, 高村 佳緒里, 杉野 英明, 阿部 達也, 近藤 修平, 田口 貴博, 佐藤 航

    日本病理学会会誌   108 ( 1 )   367 - 367   2019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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  • 原発巣の特定に苦慮した甲状腺扁平上皮癌が疑われた一例

    今西 明, 安樂 匠, 三ツ間 友里恵, 矢口 雄大, 鈴木 達郎, 山田 貴穂, 曽根 博仁, 植木 雄志, 茂木 聡子, 梅津 哉, 大橋 瑠子, 佐々木 健太, 平田 哲大, 丸山 克也

    日本内分泌学会雑誌   95 ( 1 )   464 - 464   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors. 査読

    Yamagishi T, Kawashima H, Ogose A, Ariizumi T, Oike N, Sasaki T, Hatano H, Ohashi R, Umezu H, Ajioka Y, Endo N

    The Tohoku journal of experimental medicine   248 ( 2 )   87 - 97   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1620/tjem.248.87

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  • 原発性小腸癌の粘液形質について

    近藤 修平, Aye Pa Pa Tun, 味岡 洋一, 高村 佳緒里, 谷 優佑, 大橋 瑠子, 加藤 卓, 杉野 英明, 田口 貴博

    日本病理学会会誌   107 ( 1 )   425 - 425   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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  • 原発性小腸癌におけるCytokeratin7、20の発現パターン

    Aye Pa Pa Tun, 近藤 修平, 味岡 洋一, 高村 佳緒里, 谷 優佑, 大橋 瑠子, 加藤 卓, 杉野 英明, 田口 貴博

    日本病理学会会誌   107 ( 1 )   425 - 425   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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  • Fatal visceral disseminated varicella zoster infection during initial remission induction therapy in a patient with lupus nephritis and rheumatoid arthritis - Possible association with mycophenolate mofetil and high-dose glucocorticoid therapy: A case report 査読 国際誌

    Masato Habuka, Yoko Wada, Yoichi Kurosawa, Suguru Yamamoto, Yusuke Tani, Riuko Ohashi, Yoichi Ajioka, Masaaki Nakano, Ichiei Narita

    BMC Research Notes   11 ( 1 )   165 - 165   2018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:BioMed Central Ltd.  

    Background: Visceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient. Case presentation: A 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C). Although initial remission-induction therapy with prednisolone and tacrolimus was started, her serum creatinine level and urinary protein excretion were elevated. Methylprednisolone pulse therapy was added, and tacrolimus was switched to MMF. Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed. Laboratory examinations demonstrated rapid exacerbation of severe acute liver failure and coagulation abnormalities despite immediate multidisciplinary treatment, and she died of hemorrhagic shock 7 days after the onset of abdominal pain. A serum sample collected at the time of admission revealed that she had recursive VZV infection. Conclusions: MMF together with high-dose glucocorticoid therapy may increase the risk of VZV infection in Asian patients with SLE. Accumulation of evidence for parameters of safety, such as the area under the blood concentration-time curve of mycophenolic acid, should be urgently considered in order to establish a safer protocol for remission induction therapy in Asian patients with LN.

    DOI: 10.1186/s13104-018-3271-3

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  • HRCT texture analysis for pure or part-solid ground-glass nodules: distinguishability of adenocarcinoma in situ or minimally invasive adenocarcinoma from invasive adenocarcinoma 査読

    Takuya Yagi, Motohiko Yamazaki, Riuko Ohashi, Rei Ogawa, Hiroyuki Ishikawa, Norihiko Yoshimura, Masanori Tsuchida, Yoichi Ajioka, Hidefumi Aoyama

    Japanese Journal of Radiology   36 ( 2 )   113 - 121   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)   出版者・発行元:Springer Tokyo  

    Purpose: To distinguish between adenocarcinoma in situ (AIS)–minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) showing pure or part-solid ground-glass nodules (GGNs) by high-resolution computed tomography (HRCT) texture analysis. Materials and methods: This retrospective study included 101 consecutive patients with 115 pure or part-solid GGNs ≤ 3 cm diameter, which were surgically resected and pathologically diagnosed with AIS, MIA, or IAC (48 AIS–MIA and 67 IAC) between April 2011 and March 2015. Each tumor was manually segmented on axial CT images, and the following texture features were calculated: volume, mass, mean CT value, variance, skewness, kurtosis, entropy, uniformity, and percentile CT numbers (10th, 25th, 50th, 75th, 90th, 95th percentiles). The differences between AIS–MIA and IAC were statistically evaluated using univariate, multivariate, and receiver operating characteristic analysis. Results: Compared with IAC, AIS–MIA had significantly greater skewness, kurtosis, and uniformity, whereas in the other parameters, AIS–MIA demonstrated significantly lower values than those of IAC. Multivariate analysis revealed that independent differentiators were the 90th percentile CT numbers (P &lt
     0.001) and entropy (P = 0.005) with an excellent accuracy (area under the curve, 0.90). Conclusions: The 90th percentile CT numbers and entropy can accurately distinguish AIS–MIA from IAC.

    DOI: 10.1007/s11604-017-0711-2

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  • 肺動脈塞栓として初期治療を受け、18F FDG-PET/CTで鑑別できた肺動脈肉腫の1例

    山田 美佳, 佐藤 卓, 石川 浩志, 堀井 陽祐, 八木 琢也, 山崎 元彦, 塩谷 基, 吉村 宣彦, 青山 英史, 佐藤 征二郎, 小池 輝元, 土田 正則, 名村 理, 大橋 瑠子, 梅津 哉

    Japanese Journal of Radiology   36 ( Suppl. )   7 - 7   2018年2月

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    記述言語:日本語   出版者・発行元:(公社)日本医学放射線学会  

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  • An autopsy case of mesenteric panniculitis with massive pleural effusions 査読 国際誌

    Hiroshi Kobayashi, Kenji Notohara, Tadashi Otsuka, Yuka Kobayashi, Masuo Ujita, Yuuki Yoshioka, Naomasa Suzuki, Ryuji Aoyagi, Riuko Ohashi, Toshimitsu Suzuki

    American Journal of Case Reports   19   13 - 20   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Scientific Information, Inc.  

    Objective: Rare disease Background: Mesenteric panniculitis (MP) is an idiopathic chronic inflammatory condition of the mesentery. The main symptoms include abdominal pain, abdominal distention, weight loss, fever, nausea, and vomiting. The patients also present with chylous ascites in 14% of the cases and chylous pleural effusion (CPE) in very rare occasions. Despite the previous view of excellent prognosis of MP, two recent papers reported several fatal cases. However, there are still only a few autopsy case reports that describe the macroscopic and histological details of MP cases. Case Report: The patient was an 81-year-old Japanese woman. She complained of edema of her lower legs and face, general fatigue, and dyspnea. She was overweight and had type 2 diabetes (T2D). Computerized tomography (CT) demonstrated massive bilateral pleural effusions, with mild pericardial effusion and mild ascites. There was no pulmonary, cardiac or hepatic condition to explain the effusions. However, MP was suspected based on her CT. She gradually deteriorated into respiratory failure. The autopsy revealed CPEs (left 1,300 mL, right 1,400 mL) and MP in the mesentery of the small intestine. Neither neoplasia nor inflammatory conditions other than MP were detected. Conclusions: In rare occasions, patients with MP present with CPE or chylothorax. We thought that a possible mechanism of the CPEs was a diaphragmatic defect. We suspected that being overweight and T2D had an etiological relationship with MP in our patient’s case. Adipose tissue of the mesentery is the main focus of MP. We believed that MP would be the best umbrella term of the many synonyms.

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  • 潰瘍性大腸炎(UC)以外の炎症性腸疾患大腸粘膜におけるDNA損傷・修復応答

    谷 優佑, 味岡 洋一, 渡邉 佳緒里, 渡邉 玄, 大橋 瑠子, 加藤 卓, 杉野 英明, 福田 睦, 近藤 修平, 横田 陽子

    日本病理学会会誌   106 ( 1 )   308 - 308   2017年3月

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  • 潰瘍性大腸炎の炎症性発癌早期病変におけるSOX2発現

    渡邉 佳緒里, 味岡 洋一, 大橋 瑠子, 渡邉 玄, 谷 優佑, 加藤 卓, 福田 睦, 近藤 修平

    日本病理学会会誌   106 ( 1 )   309 - 309   2017年3月

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  • 若年者に発症し副結節をともなった硬化性血管腫の1例

    押金 智哉, 山崎 元彦, 石川 浩志, 八木 琢也, 吉村 宣彦, 青山 英史, 北原 哲彦, 佐藤 征二郎, 小池 輝元, 土田 正則, 大橋 瑠子, 梅津 哉

    Japanese Journal of Radiology   35 ( Suppl. )   8 - 8   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本医学放射線学会  

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  • 多発肺結節を呈したメトトレキセート関連リンパ増殖性疾患の1例

    山名 加菜子, 山崎 元彦, 石川 浩志, 八木 琢也, 吉村 宣彦, 青山 英史, 坂上 拓郎, 北原 哲彦, 佐藤 征二郎, 小池 輝元, 土田 正則, 大橋 瑠子, 梅津 哉

    Japanese Journal of Radiology   35 ( Suppl. )   8 - 8   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本医学放射線学会  

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  • Non-bacterial thrombotic endocarditis in the right atrium caused by pectus excavatum. 査読 国際誌

    Sugimoto A, Shiraishi S, Watanabe M, Moon J, Ohashi R, Takahashi M, Tsuchida M

    Surgical case reports   2 ( 1 )   105 - 105   2016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)  

    DOI: 10.1186/s40792-016-0236-4

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  • Solitary pulmonary MALT lymphoma presenting crystal-storing histiocytosis. 査読

    Nagaharu K, Kageyama Y, Watanabe T, Yamaguchi T, Ito R, Baba Y, Masuya M, Ohashi R, Kawakami K

    [Rinsho ketsueki] The Japanese journal of clinical hematology   57 ( 8 )   1032 - 1037   2016年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11406/rinketsu.57.1032

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  • A case of gastric crystal-storing histiocytosis 査読

    Yoshiaki Isono, Youichirou Baba, Hiroki Tanaka, Hiroaki Kumazawa, Tomomasa Tochio, Shinpei Matsuzaki, Tomohiro Sase, Tomonori Saito, Hiroshi Okano, Katsumi Mukai, Riuko Ohashi

    Journal of Japanese Society of Gastroenterology   113 ( 6 )   968 - 974   2016年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Gastroenterology  

    A 54-year-old male patient underwent upper gastrointestinal endoscopy, which revealed a 25-mm brown region in the angular section of the greater curvature of the stomach. The region was histologically determined to be gastric mucosa with an accumulation of histiocytes containing eosinophilic substances in the cytoplasm and chronic inflammatory cell infiltration. Histiocytes were immunohistologically positive for CD68, IgG, and κ. Based on these findings, the patient was diagnosed with gastric crystal-storing histiocytosis comprised of histiocytes phagocytosing IgG-κ-type immunoglobulin. This is a rare disease of which there have been no previous reports that included long-term follow-up. Here, we report the case with a literature review.

    DOI: 10.11405/nisshoshi.113.968

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  • Clinicopathological features in anterior visual pathway in neuromyelitis optica 査読

    Mariko Hokari, Akiko Yokoseki, Musashi Arakawa, Etsuji Saji, Kaori Yanagawa, Fumihiro Yanagimura, Yasuko Toyoshima, Kouichirou Okamoto, Satoshi Ueki, Tetsuhisa Hatase, Riuko Ohashi, Takeo Fukuchi, Kohei Akazawa, Mitsunori Yamada, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa, Izumi Kawachi

    ANNALS OF NEUROLOGY   79 ( 4 )   605 - 624   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:WILEY-BLACKWELL  

    ObjectiveNeuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd.
    MethodsThirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
    ResultsThe AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Muller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON.
    InterpretationSevere and widespread neuroaxonal damage and unique dynamics of astrocytes/Muller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. Ann Neurol 2016;79:605-624

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  • A Case of Ectopic ACTH-Producing Pulmonary Carcinoid Arising in an Extralobar Pulmonary Sequestration 査読

    Seijiro Sato, Akihiko Kitahara, Terumoto Koike, Takehisa Hashimoto, Riuko Ohashi, Yoichi Kameda, Masanori Tsuchida

    INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY   24 ( 2 )   130 - 134   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:SAGE PUBLICATIONS INC  

    Ectopic adrenocorticotrophic hormone (ACTH)-producing bronchopulmonary carcinoid arising in a bronchopulmonary sequestration is extremely rare. The case of a 67-year-old woman with a 1.7-cm nodule in the mediastinal side of the left lower lobe is presented. At 52 years of age, she was diagnosed as having ACTH-dependent Cushing's syndrome (CS). However, no ectopic source of ACTH-secretion was detected. Seven years later, she underwent a bilateral adrenalectomy because of aggravation of her health condition. This time, tumor excision was performed by thoracoscopic surgery. The tumor adhered sparsely to the mediastinal pleura and the left lower lobe and was bluntly separated from these tissues. Pathologically, the tumor was a typical carcinoid arising in an extralobar pulmonary sequestration. Immunohistochemical staining confirmed the secretion of ACTH by bronchopulmonary carcinoid tumor cells. After surgery, the serum ACTH level was almost normalized, and the dexamethasone (1 mg) suppression test showed significant suppression of ACTH.

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  • 潰瘍性大腸炎(UC)の炎症性発癌におけるDNA損傷応答の意義

    谷 優佑, 味岡 洋一, 渡辺 佳緒里, 渡邉 玄, 大橋 瑠子, 加藤 卓, 杉野 英明, 福田 睦, 近藤 修平

    日本病理学会会誌   105 ( 1 )   339 - 339   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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  • バレット粘膜より先行する、扁平上皮下粘膜固有層内デスミン陽性線維

    渡邉 玄, 味岡 洋一, 加藤 卓, アネンコフ・アレクセイ, 大橋 瑠子, 渡辺 佳緒里, 谷 優佑, 福田 睦, 近藤 修平, 横田 陽子

    日本病理学会会誌   105 ( 1 )   407 - 407   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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  • Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model 査読

    Hiroyuki Abe, Kenya Kamimura, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Riuko Ohashi, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

    MOLECULAR THERAPY-NUCLEIC ACIDS   5   e276   2016年1月

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

    Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of similar to 5 pg/ml (P &lt; 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P &lt; 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P &lt; 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.

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  • Resection of a large ectopic parathyroid adenoma: A case report 査読

    Seijiro Sato, Akihiko Kitahara, Terumoto Koike, Takehisa Hashimoto, Riuko Ohashi, Noriko Motoi, Masanori Tsuchida

    INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS   23   8 - 11   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 SCI LTD  

    INTRODUCTION: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. However, cases of parathyroid adenomas greater than 4 cm with osteitis fibrosa cystica are extremely rare. Herein, we report a case of resection of a large ectopic mediastinal parathyroid adenoma.CASE PRESENTATIONS: A 46-year-old female with chief complaints of bone pain and gait disturbance was referred to our hospital. Physical examination revealed many mobile teeth in her oral cavity, distortion of the vertebral body, and bowlegs. Laboratory tests showed hypercalcemia, hypophosphatemia, and elevated serum levels of intact parathyroid hormone. Chest CT revealed a 42-mm well-defined, enhancing mass in front of the left-sided tracheal bifurcation. Her findings were diagnosed as primary hyperparathyroidism due to an ectopic mediastinal parathyroid tumor. We performed a median sternotomy and resected the tumor. The tumor was a solid, yellowish-brown mass measuring 42 42 mm. Pathologically, the tumor consisted mainly of chief cells with some oxyphil cells; there were no necrotic areas or nuclear atypia, and few mitotic figures. We diagnosed the tumor as an ectopic mediastinal parathyroid adenoma. Eight months after the resection, her serum calcium, phosphorus, and intact PTH levels were normal.DISCUSSION AND CONCLUSIONS: Parathyroid adenomas and parathyroid carcinomas have disparate natural histories, but they can be difficult to differentiate on the basis of preoperative clinical characteristics. We believe that long-term follow-up of these cases is required because there have been few reports on the postoperative natural history of large parathyroid adenomas. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

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  • Effective Prevention of Liver Fibrosis by Liver-Targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in Rat Liver Fibrosis Model 査読

    Abe Hiroyuki, Kamimura Kenya, Kobayashi Yuji, Ohtsuka Masato, Miura Hiromi, Ohashi Riuko, Yokoo Takeshi, Kanefuji Tsutomu, Suda Takeshi, Tsuchida Masanori, Aoyagi Yutaka, Zhang Guisheng, Liu Dexi, Terai Shuji

    MOLECULAR THERAPY   23   S234   2015年5月

  • Differential expression of pentraxin 3 in neutrophils 査読

    Olga Razvina, Shuying Jiang, Koichi Matsubara, Riuko Ohashi, Go Hasegawa, Takashi Aoyama, Kenji Daigo, Tatsuhiko Kodama, Takao Hamakubo, Makoto Naito

    EXPERIMENTAL AND MOLECULAR PATHOLOGY   98 ( 1 )   33 - 40   2015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)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Pentraxins belong to the superfamily of conserved proteins that are characterized by a cyclic multimeric structure. Pentraxin 3 (PTX3) is a long pentraxin which can be produced by different cell types upon exposure to various inflammatory signals. Inside the neutrophil PTX3 is stored in form of granules localized in the cytoplasm. Neutrophilic granules are divided into three types: azurophilic (primary) granules, specific (secondary) granules and gelatinase (tertiary) granules. PTX3 has been considered to be localized in specific (secondary) granules. Immunofluorescent analyses using confocal laser microscopic examination were performed to clarify the localization of all three groups of granules within the cytoplasm of the mature neutrophils and neutrophils stimulated with IL-8. Furthermore, PTX3 was localized in primary granules of promyelocyte cell line HL-60. As a result, we suggest that PTX3 is localized not only in specific granules, but is also partly expressed in primary and tertiary granules. After the stimulation with IL-8, irregular reticular structures called neutrophil extracellular traps (NETs) were formed, three types of granules were trapped by NETs and PTX3 showed partial colocalization with these granular components. PTX3 localized in all three types of granules in neutrophils may play important roles in host defense. (C) 2014 Elsevier Inc. All rights reserved.

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  • Foregut cystに発生した異所性ACTH産生カルチノイドの1例

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則, 大橋 瑠子, 梅津 哉

    肺癌   54 ( 7 )   1003 - 1003   2014年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Protective effect of the long pentraxin PTX3 against histone-mediated endothelial cell cytotoxicity in sepsis 査読

    Kenji Daigo, Makoto Nakakido, Riuko Ohashi, Rie Fukuda, Koichi Matsubara, Takashi Minami, Naotaka Yamaguchi, Kenji Inoue, Shuying Jiang, Makoto Naito, Kouhei Tsumoto, Takao Hamakubo

    SCIENCE SIGNALING   7 ( 343 )   ra88   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:AMER ASSOC ADVANCEMENT SCIENCE  

    Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Extracellular histones are considered to be the main cause of septic death because of their cytotoxic effect on endothelial cells, which makes them a potential therapeutic target. We found that PTX3 interacted with histones to form coaggregates, which depended on polyvalent interactions and disorder in the secondary structure of PTX3. PTX3 exerted a protective effect, both in vitro and in vivo, against histone-mediated cytotoxicity toward endothelial cells. Additionally, the intraperitoneal administration of PTX3 reduced mortality in mouse models of sepsis. The amino-terminal domain of PTX3, which was required for coaggregation with histones, was sufficient to protect against cytotoxicity. Our results suggest that the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. This long pentraxin-specific effect provides a potential basis for the treatment of sepsis directed at protecting cells from the toxic effects of extracellular histones.

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  • LXRαの核小体への局在とリボソームDNA転写制御 査読

    大橋 瑠子

    新潟医学会雑誌   128 ( 9 )   447 - 461   2014年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:新潟医学会  

    LXRα (Liver X receptor α)はLDL (low density lipoprotein)など酸化ステロールの受容体として機能し, 脂質代謝, 胆汁酸代謝などに関与する核内受容体である. しかし特異性の高い抗体がこれまでなかったためmRNAレベルの研究が多く, その組織細胞内局在や機能については不明な点が多い. 本研究では最近作製されたLXRαに対する特異的抗体を用いて, LXRαの細胞内局在とこれまで知られていなかったリボソーム生合成への関与について解析を行ったので報告する. LXRαは核小体内においてfibrillarin, UBFおよびRNA polymerase I (RNA pol I)の転写活性の高い領域, すなわちdense fibrillar componentと呼ばれる領域に局在することがわかった. HepG2細胞においてRNA pol Iの転写活性をActinomycin D投与によって抑制すると, LXRαは核小体内に局在できず核質へ移行したことからLXRαの核小体内局在はRNA pol Iの転写活性に依存していることがわかった. クロマチン免疫沈降法を用いた検討の結果, LXRαは18S rDNAと28S rDNAに結合することが判明した. さらに, HepG2細胞に対してLXRαを活性化する合成リガンドであるT0901317を投与するとリボゾーム前駆体47S/45S rRNAの転写が促進されたが, LXRαをsiRNAでノックダウンすると転写促進が起こらなかった. 以上の結果より, LXRαはリボソーム生合成において重要な役割を担っていることが示唆された.

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    その他リンク: http://hdl.handle.net/10191/43896

  • Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors 査読

    Taro Sasaki, Akira Ogose, Hiroyuki Kawashima, Tetsuo Hotta, Hiroshi Hatano, Takashi Ariizumi, Hajime Umezu, Riuko Ohashi, Tsuyoshi Tohyama, Naohito Tanabe, Naoto Endo

    BMC CANCER   14   468   2014年6月

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

    Background: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL.
    Methods: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage.
    Results: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P &lt; 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P &lt; 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test).
    Conclusion: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

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  • The Wnt/Planar Cell Polarity Pathway Component Vangl2 Induces Synapse Formation through Direct Control of N-Cadherin 査読

    Tadahiro Nagaoka, Riuko Ohashi, Ayumu Inutsuka, Seiko Sakai, Nobuyoshi Fujisawa, Minesuke Yokoyama, Yina H. Huang, Michihiro Igarashi, Masashi Kishi

    CELL REPORTS   6 ( 5 )   916 - 927   2014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:CELL PRESS  

    Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by beta-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell adhesions at the synapse.

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  • Identification of Wilms' Tumor 1-associating Protein Complex and Its Role in Alternative Splicing and the Cell Cycle 査読

    Keiko Horiuchi, Takeshi Kawamura, Hiroko Iwanari, Riuko Ohashi, Makoto Naito, Tatsuhiko Kodama, Takao Hamakubo

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 46 )   33292 - 33302   2013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:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Background: WTAP is a ubiquitously expressed nuclear protein that is required for mammalian early embryo development and cell cycle progression. Results: WTAP forms a complex with several splicing regulators. Conclusion: WTAP regulates both the cell cycle and alternative splicing by the formation of a protein complex. Significance: Characterization of this protein complex will help to elucidate the critically important function of WTAP in alternative splicing and cell proliferation.
    Wilms' tumor 1-associating protein (WTAP) is a putative splicing regulator that is thought to be required for cell cycle progression through the stabilization of cyclin A2 mRNA and mammalian early embryo development. To further understand how WTAP acts in the context of the cellular machinery, we identified its interacting proteins in human umbilical vein endothelial cells and HeLa cells using shotgun proteomics. Here we show that WTAP forms a novel protein complex including Hakai, Virilizer homolog, KIAA0853, RBM15, the arginine/serine-rich domain-containing proteins BCLAF1 and THRAP3, and certain general splicing regulators, most of which have reported roles in post-transcriptional regulation. The depletion of these respective components of the complex resulted in reduced cell proliferation along with G(2)/M accumulation. Double knockdown of the serine/arginine-rich (SR)-like proteins BCLAF1 and THRAP3 by siRNA resulted in a decrease in the nuclear speckle localization of WTAP, whereas the nuclear speckles were intact. Furthermore, we found that the WTAP complex regulates alternative splicing of the WTAP pre-mRNA by promoting the production of a truncated isoform, leading to a change in WTAP protein expression. Collectively, these findings show that the WTAP complex is a novel component of the RNA processing machinery, implying an important role in both posttranscriptional control and cell cycle regulation.

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  • Proteomic analysis of native hepatocyte nuclear factor-4 alpha (HNF4 alpha) isoforms, phosphorylation status, and interactive cofactors (vol 286, pg 674, 2011) 査読

    Daigo Kenji, Kawamura Takeshi, Ohta Yoshihiro, Ohashi Riuko, Katayose Satoshi, Tanaka Toshiya, Aburatani Hiroyuki, Naito Makoto, Kodama Tatsuhiko, Ihara Sigeo, Hamakubo Takao

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 33 )   24161   2013年8月

  • Phosphatidylinositol 3-Phosphatase Myotubularin-related Protein 6 (MTMR6) Is Regulated by Small GTPase Rab1B in the Early Secretory and Autophagic Pathways 査読

    Yasuhiro Mochizuki, Riuko Ohashi, Takeshi Kawamura, Hiroko Iwanari, Tatsuhiko Kodama, Makoto Naito, Takao Hamakubo

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 2 )   1009 - 1021   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.

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  • The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps 査読

    Kenji Daigo, Naotaka Yamaguchi, Takeshi Kawamura, Koichi Matsubara, Shuying Jiang, Riuko Ohashi, Yukio Sudou, Tatsuhiko Kodama, Makoto Naito, Kenji Inoue, Takao Hamakubo

    MOLECULAR & CELLULAR PROTEOMICS   11 ( 6 )   M111.015073   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Pentraxin 3 (PTX3), a long pentraxin subfamily member in the pentraxin family, plays an important role in innate immunity as a soluble pattern recognition receptor. Plasma PTX3 is elevated in sepsis (similar to 200 ng/ml) and correlates with mortality. The roles of PTX3 in sepsis, however, are not well understood. To investigate the ligands of PTX3 in sepsis, we performed a targeted proteomic study of circulating PTX3 complexes using magnetic bead-based immunopurification and shotgun proteomics for label-free relative quantitation via spectral counting. From septic patient fluids, we successfully identified 104 candidate proteins, including the known PTX3-interacting proteins involved in complement activation, pathogen opsonization, inflammation regulation, and extracellular matrix deposition. Notably, the proteomic profile additionally showed that PTX3 formed a complex with some of the components of neutrophil extracellular traps. Subsequent biochemical analyses revealed a direct interaction of bactericidal proteins azurocidin 1 (AZU1) and myeloperoxidase with PTX3. AZU1 exhibited high affinity binding (K-D = 22 +/- 7.6 nM) to full-length PTX3 in a calcium ion-dependent manner and bound specifically to an oligomer of the PTX3 N-terminal domain. Immunohistochemistry with a specific monoclonal antibody generated against AZU1 revealed a partial co-localization of AZU1 with PTX3 in neutrophil extracellular traps. The association of circulating PTX3 with components of the neutrophil extracellular traps in sepsis suggests a role for PTX3 in host defense and as a potential diagnostic target. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.015073, 1-12, 2012.

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  • 自然に縮小した肺癌の2例

    山崎 元彦, 石川 浩志, 國井 亮祐, 麻谷 美奈, 青山 英史, 篠原 博彦, 橋本 毅久, 土田 正則, 大橋 瑠子, 梅津 哉

    Japanese Journal of Radiology   30 ( Suppl.I )   1 - 1   2012年2月

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    記述言語:日本語   出版者・発行元:(公社)日本医学放射線学会  

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  • Hypogammaglobulinemic Patient with Polyarthritis Mimicking Rheumatoid Arthritis Finally Diagnosed as Septic Arthritis Caused by Mycoplasma hominis 査読

    Hiroe Sato, Noriaki Iino, Riuko Ohashi, Takako Saeki, Tomoyuki Ito, Maki Saito, Yutaka Tsubata, Suguru Yamamoto, Shuichi Murakami, Takeshi Kuroda, Yoshinari Tanabe, Junichi Fujisawa, Takehiro Murai, Masaaki Nakano, Ichiei Narita, Fumitake Gejyo

    INTERNAL MEDICINE   51 ( 4 )   425 - 429   2012年

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

    Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA). As polyarthritis remained after immunoglobulin replacement therapy and there was no finding indicating any infection at that time, a diagnosis of RA was made. Prednisolone and etanercept were started. However, his polyarthritis did not improve and he developed meningitis and massive brain ischemia. Finally, a diagnosis of disseminated Mycoplasma hominis infection was made. The differential diagnosis of polyarthritis in patients with hypogammaglobulinemia should strictly exclude Mycoplasma infection by culture with special media or longer anaerobic culture, and molecular methods for mycoplasma.

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  • Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. 査読

    Wakai Toshifumi, Shirai Yoshio, Sakata Jun, Korita Pavel V, Matsuda Yasunobu, Takamura Masaaki, Ohashi Riuko, Nagahashi Masayuki, Ajioka Yoichi, Hatakeyama Katsuyoshi

    Int J Oncol   38 ( 5 )   1227 - 1236   2011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)  

    P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P&lt;0.001). Of the 14 tumor

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  • Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma 査読

    Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Pavel V. Korita, Yasunobu Matsuda, Masaaki Takamura, Riuko Ohashi, Masayuki Nagahashi, Yoichi Ajioka, Katsuyoshi Hatakeyama

    INTERNATIONAL JOURNAL OF ONCOLOGY   38 ( 5 )   1227 - 1236   2011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:SPANDIDOS PUBL LTD  

    P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA. double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P&lt;0.001). Of the 14 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear Foci of 53BP1 (53BP1 activation). All 11 tumor specimens of invasive carcinoma showed 53BP1 inactivation. Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation (median index, 0% vs. 22%; P&lt;0.001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (60% vs. 0% at 5 years; P=-0.020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.

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  • Long pentraxin 3 (PTX3) expression and release by neutrophils in vitro and in ulcerative colitis 査読

    Alexander S. Savchenko, Akira Inoue, Riuko Ohashi, Shuying Jiang, Go Hasegawa, Toshiya Tanaka, Takao Hamakubo, Tatsuhiko Kodama, Yutaka Aoyagi, Tatsuo Ushiki, Makoto Naito

    PATHOLOGY INTERNATIONAL   61 ( 5 )   290 - 297   2011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  

    Pentraxin 3 protein was found to be present following release upon IL-8 stimulation in cultured neutrophils together with lactoferrin+-specific granules localized in neutrophil extracellular traps (NETs) formed by extruded DNA. Neutrophils in colonic mucosal tissue of patients with ulcerative colitis were the main cellular source of PTX3 protein, the expression of which is correlated well with the histological grades of inflammation. Immunofluorescence analysis against anti-lactoferrin antibody revealed the formation of NETs released from neutrophils within crypt abscess lesions, which were found to be activated through the expression of IL-8 receptor B (CXCR2). Of interest, neutrophils depleted of PTX3 protein were displayed, supporting the release of PTX3 from neutrophils in crypt abscess. We suspected that PTX3 protein may contribute to cell-mediated immune defense in inflamed colon tissue, and in particular in crypt abscess lesions, of patients with ulcerative colitis.

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  • 11歳女児に発生した右乳房巨大葉状腫瘍 査読

    塚田 真実, 窪田 正幸, 奥山 直樹, 小林 久美子, 佐藤 佳奈子, 仲谷 健吾, 小山 諭, 畠山 勝義, 大橋 瑠子

    日小外会誌   47 ( 2 )   251 - 255   2011年4月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本小児外科学会  

    症例は11歳,女児.右乳房に腫瘤を自覚し徐々に増大してきたため,3か月後に前医受診し,当科紹介受診となる.右乳房全体を占める12×12×9cm大の弾性軟,辺縁平滑,可動性を有する腫瘤を認めた.穿刺吸引細胞診では悪性像は認めず,CEA,CA15-3は正常範囲内であった.画像診断上は線維線腫,葉状腫瘍(phyllodes tumor)などの良性腫瘍が考えられたため,乳房下縁inframammary foldに沿った皮膚切開をおき,可能な限り乳腺を含む周囲組織を温存した右乳房腫瘤核出術を施行した.術中迅速組織診断では良性葉状腫瘍との診断のため,追加切除やリンパ節郭清は施行しなかった.病理診断でも良性葉状腫瘍と診断された.術後3年現在,再発なく乳腺の軽度の発育を認めている.

    DOI: 10.11164/jjsps.47.2_251

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  • Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors. 査読

    Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, Aburatani H, Naito M, Kodama T, Ihara S, Hamakubo T

    The Journal of biological chemistry   286 ( 1 )   674 - 686   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M110.154732

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  • イマチニブ不耐容・耐性GIST患者に対するスニチニブ治療

    神田 達夫, 藤森 芳郎, 矢島 和人, 松田 至晃, 大橋 瑠子, 廣田 誠一, 間島 寧興, 松木 淳, 小杉 伸一, 畠山 勝義

    ENDOSCOPIC FORUM for digestive disease   26 ( 1 )   66 - 66   2010年6月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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  • 神経芽腫におけるGATA2の発現

    林 和直, 大橋 瑠子, 姜 淑英, 長谷川 剛, 内藤 眞

    日本病理学会会誌   99 ( 1 )   271 - 271   2010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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  • イマチニブ耐性・不耐容消化管間質腫瘍患者に対するスニチニブ・リンゴ酸の治療成績

    松木 淳, 神田 達夫, 大橋 瑠子, 間島 寧興, 羽入 隆晃, 矢島 和人, 小杉 伸一, 畠山 勝義

    新潟医学会雑誌   124 ( 3 )   178 - 178   2010年3月

  • Expression of liver X receptor alpha and lipid metabolism in granulocyte-macrophage colony-stimulating factor-induced human monocyte-derived macrophage 査読

    Toshihiro Kazawa, Takashi Kawasaki, Azusa Sakamoto, Masaru Imamura, Riuko Ohashi, Shuying Jiang, Toshiya Tanaka, Hiroko Iwanari, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Makoto Naito

    PATHOLOGY INTERNATIONAL   59 ( 3 )   152 - 160   2009年3月

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

    Liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. The foam cell transformation of macrophages (M phi) is considered a critical process in atherosclerotic lesions. The relationship, however, of the foam cell transformation of M phi and LXR is not fully understood. The purpose of the present study was to examine the expression of LXR alpha, retinoid X receptor (RXR)alpha, ATP-binding cassette transporter (ABCA1), and macrophage scavenger receptor A (MSR-A), and lipid accumulation in human monocyte-derived M phi. The expression of LXR alpha, ABCA1, MSR-A in 7 day cultured granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced M phi (GM-M phi) was significantly higher than that in 7 day cultured M-CSF-induced M phi (M-M phi). The expression levels of LXR alpha, ABCA1 and MSR-A protein decreased from 48 h to 5 days after the addition of lipopolysaccharide (LPS) in GM-M phi, but only MSR-A protein decreased at 5 days after the addition of LPS in M-M phi. Intracellular lipid accumulation was clearly observed when GM-M phi was pre-stimulated with LPS for 48 h and incubated with oxidized LDL for an additional 5 days. These findings suggest that the inhibitory activity of LXR alpha, ABCA1 and MSR-A by LPS may be related to the transformation of M phi s, especially GM-M phi into foam cells.

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  • GATAファミリーのヒト・ラット組織における発現

    林 和直, 姜 淑英, 長谷川 剛, 大橋 瑠子, 内藤 眞

    日本病理学会会誌   98 ( 1 )   368 - 368   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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  • Protein expression of nuclear receptors in human and murine tissues 査読

    So Takegoshi, Shuying Jiang, Riuko Ohashi, Alexander S. Savchenko, Hiroko Iwanari, Toshiya Tanaka, Go Hasegawa, Takao Hamakubo, Tatsuhiko Kodama, Makoto Naito

    PATHOLOGY INTERNATIONAL   59 ( 2 )   61 - 72   2009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)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Nuclear receptors (NR) are transcriptional regulators expressed in a variety of tissues and they play important roles in embryonic development, organogenesis and metabolic homeostasis. In order to investigate the tissue-specific expression pattern of NR, mouse anti-human monoclonal antibodies newly generated against various NR. Specificities of the antibodies were confirmed on immunoblotting using overexpressed proteins. Most of the antibodies recognized intrinsic protein. Among 60 monoclonal antibodies generated, 32 were applicable for immunohistochemistry. The expression pattern of NR in human liver and pancreas was confirmed on immunohistochemical staining using these antibodies. The P2 promoter-driven hepatocyte nuclear factor 4 alpha (HNF4 alpha) isoform and progesterone receptor were expressed in pancreatic alpha-cells, but not beta-cells in the human pancreas, suggesting an unknown role of these NR in diabetes mellitus. These antibodies were also useful for immunohistochemistry of the murine liver and pancreas. Immunoblotting using these antibodies produced similar corresponding bands both in human and mouse tissues. These monoclonal antibodies may serve as powerful tools to detect tissue-specific localization of NR and provide a platform for future studies of NR in human and murine tissues.

    DOI: 10.1111/j.1440-1827.2008.02330.x

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  • Expression of the nerve growth factor-induced gene B-β in the developing rat brain and retina 査読

    Yingmin Li, Riuko Ohashi, Makoto Naito

    Archives of Histology and Cytology   72 ( 1 )   23 - 34   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The nerve growth factor-induced gene B-β (NGFI-Bβ, Nurr1) is a member of the nuclear receptor superfamily that is expressed predominantly in the central nervous system. We used an antibody against the human NGFI-Bβ to observe the protein expression in neuronal cells in the retina, cerebral neocortex, and midbrain of humans and rats. To provide further insight into the role of NGFI-Bβ in the differentiation of neuronal cells, we also examined the expression of NGFI-Bβ in rat ontogeny. A few cells in the midbrain showed the expression of NGFI-Bβ from 12 days of gestation, and NGFI-Bβ positive cells increased in the neocortex, claustrum, thalamus and hypothalamus in the subsequent fetal days. NGFI-Bβ-positive cells appeared in the inner nuclear layer of the retina at 18 days of gestation and also in the ganglion cell layer after birth. An immunohistochemical study on the expression of proliferating cell nuclear antigen (PCNA) demonstrated that NGFI-Bβ-positive cells were not proliferating cells. These findings suggest that NGFI-Bβ plays an important role during the postmitotic differentiation of neuronal cells in the brain and retina.

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  • Inverse Relationship Between the Length of the EGFR CA Repeat Polymorphism in Lung Carcinoma and Protein Expression of EGFR in the Carcinoma 査読

    Masaya Suzuki, Shinji Kageyama, Kazuya Shinmura, Koji Okudela, Tomoyasu Bunai, Kiyoko Nagura, Hisaki Igarashi, Shinichiro Kiyose, Hiroki Mori, Hong Tao, Masanori Coto, Kazuya Takamochi, Takahiro Mochizuki, Kazuya Suzuki, Riuko Ohashi, Hiroshi Ogawa, Takeshi Yamada, Hiroshi Niwa, Toshihiro Tsuneyoshi, Haruhiko Sugimura

    JOURNAL OF SURGICAL ONCOLOGY   98 ( 6 )   457 - 461   2008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-LISS  

    Background and Objectives: There is a CA dinucleotide repeat polymorphism in the first intron of the epidermal growth factor receptor (EGFR) gene. Our aim was to examine the relationship between the CA repeat length in lung carcinoma and EGFR mutation. EGFR gene copy number, and EGFR protein expression level in the carcinoma.
    Methods: We examined 168 lung carcinomas for the length of the CA repeat polymorphism by PCR-polyacrylamide gel electrophoresis analysis, for EGFR mutations by sequencing analysis, for EGFR gene copy number by fluorescence in situ hybridization analysis, and for EGFR protein expression by immunohistochemical analysis.
    Results: When the carcinomas were divided into two groups according to the length of their CA repeat polymorphism. the EGFR protein expression level was found to he significantly higher in the shorter allele group than in the longer allele group (P=0.0116), but its length was not associated with EGFR somatic mutations. high EGFR gene copy numbers, or clinicopathological factors, such as histological type or stage.
    Conclusions: The results suggested that the length of the EGFR CA repeat polymorphism in lung carcinoma is inversely related with level of EGFR protein expression in the carcinoma. J. Surg. Oncol. 2008:98:457-461. (c) 2008 Wiley-Liss, Inc.

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  • Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion 査読

    Takashi Yamamoto, Chikako Kaizu, Takashi Kawasaki, Go Hasegawa, Hajime Umezu, Riuko Ohashi, Junko Sakurada, Shuying Jiang, Leonard Shultz, Makoto Naito

    CELL AND TISSUE RESEARCH   332 ( 2 )   245 - 256   2008年5月

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

    We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red pulp macrophages were reduced. Repopulation of Kupffer cells and splenic macrophages was observed in littermate (op/+) mice liver by 14 days after depletion. However, in op/op mice, repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op mice until 56 days after depletion, whereas splenic red pulp macrophages repopulated and recovered to the level of control op/op mice by 10 days after depletion. Single injection of M-CSF was effective for the induction of the repopulation of Kupffer cells, and daily administration of M-CSF induced remarkable repopulation and maturation of Kupffer cells and proliferation of macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice. These results suggest that Kupffer cells are completely M-CSF-dependent tissue macrophages, whereas splenic red pulp macrophages are composed of M-CSF-dependent macrophages and M-CSF-independent macrophages. This mouse model provides a useful tool for the study of effects of growth factor on Kupffer cell differentiation in vivo.

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  • Expression of pentraxin 3 (PTX3) in human atherosclerotic lesions 査読

    A. S. Savchenko, M. Imamura, R. Ohashi, S. Jiang, T. Kawasaki, G. Hasegawa, I. Emura, H. Iwanari, M. Sagara, T. Tanaka, T. Hamakubo, T. Kodama, M. Naito

    JOURNAL OF PATHOLOGY   215 ( 1 )   48 - 55   2008年5月

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

    Pentraxin 3 (PTX3) and C-reactive protein (CRP) are members of the pentraxin superfamily. PTX3 expression is induced in response to inflammatory signals, and is produced at sites of inflammation by several types of cell, primarily monocytes/macrophages, dendritic cells (DCs), endothelial cells, smooth muscle cells (SMCs), and fibroblasts, but is not produced by hepatocytes, which are a major source of CRP. The aim of our study was to investigate the expression pattern of PTX3 in human atherosclerotic lesions using a novel monoclonal antibody against PTX3. We examined coronary arterial thrombi containing an atherosclerotic plaque component removed from patients with acute myocardial infarction and human aortic tissues with various degrees of atherosclerosis sampled from autopsy cases. Immunohistochemical study of paraffin and frozen sections indicated that macrophages, mainly foam cells, expressed PTX3 in advanced atherosclerotic lesions. Interestingly, we also clearly observed PTX3-positive neutrophils infiltrating into atherosclerotic plaques, suggesting that PTX3 derived from neutrophils as well as macrophages plays an important role in atherogenesis. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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  • PIK3CA mutation and amplification in human lung cancer (vol 57, pg 664, 2007) 査読

    Okudela Koji, Suzuki Masaya, Kageyama Shinji, Bunai Tomoyasu, Nagura Kiyoko, Igarashi Hisaki, Takamochi Kazuya, Suzuki Kazuya, Yamada Takeshi, Niwa Hiroshi, Ohashi Riuko, Ogawa Hiroshi, Mori Hiroki, Kitamura Hitoshi, Kaneko Takeshi, Tsuneyoshi Toshihiro, Sugimura Haruhiko

    PATHOLOGY INTERNATIONAL   57 ( 11 )   757   2007年11月

  • PIK3CA mutation and amplification in human lung cancer 査読

    Koji Okudela, Masaya Suzuki, Shinji Kageyama, Tomoyasu Bunai, Kiyoko Nagura, Hisaki Igarashi, Kazuya Takamochi, Kazuya Suzuki, Takeshi Yamada, Hiroshi Niwa, Riuko Ohashi, Hiroshi Ogawa, Hiroki Mori, Hitoshi Kitamura, Takeshi Kaneko, Toshihiro Tsuneyoshi, Haruhiko Sugimura

    PATHOLOGY INTERNATIONAL   57 ( 10 )   664 - 671   2007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:BLACKWELL PUBLISHING  

    To explore the significance of phosphatidylinositol-3-kinase, catalytic, alpha (PIK3CA) in the carcinogenesis in human lung, mutations and copy number changes were investigated in 148 Japanese patients with primary cancer of the lung. For biological validation, the effects of exogenously expressed wild-type and mutated PIK3CA were studied in an immortalized human airway epithelial cell line. Mutations in PIK3CA were found in five (3.6%) of the 139 available patients, and copy number gains were found in 21 (18.3%) of 115 patients, respectively. Overall, mutations or copy number gains were detected in 24 of the 106 patients (22.6%) for whom results in both analyses were available. The prevalence of copy number gains was higher in men, smokers, and in patients with squamous cell carcinoma than in the opposite categories. The copy number changes showed a trend toward higher prevalence in the earlier stages (P = 0.038). Interestingly, the presence of mutations and of copy number alterations were mutually exclusive in the present patients, implying that both entail equivalent oncogenic potential. Over-expressed wild-type PIK3CA and its two common mutants, K545E and H1047R, significantly enhanced the anchorage-independent growth activity and migration activity of immortalized airway epithelium 16HBE14o- cells, but the effects of the K545E and H1047R mutants were more remarkable than those of the wild-type. The present demonstrates an important role of PIK3CA in human lung carcinogenesis.

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  • Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages 査読

    Masaru Imamura, Takashi Kawasaki, Alexander S. Savchenko, Riuko Ohashi, Shuying Jiang, Kyoko Miyamoto, Yukio Ito, Hiroko Iwanari, Mina Sagara, Toshlya Tanaka, Takao Hamakubo, Tatsuhiko Kodama, Makoto Uchlyama, Makoto Naito

    CELLULAR IMMUNOLOGY   248 ( 2 )   86 - 94   2007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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by various cells, such as monocytes/macrophages (M phi s) in response to lipopolysaccharide (LPS) and proinflammatory signals. We performed immunoblotting, immunohistochemical staininig. reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) of PTX3 in human monocyte-derived M phi s and neutrophils. PTX3 expression was observed in the cytoplasm of both GM-CSF induced monocyte-derived M phi (GM-M phi) and M-CSF induced monocyte-derived M phi (M-M phi). PTX3 level in both M phi s was up-regulated at 24 It after LPS stimulation. Moreover, we confirmed PTX3 expression in freshly isolated neutrophils, and PTX3 level was distinctly up-regulated at 6 and 24 It after LPS stimulation. These findings suggested that PTX3 expression, not only in M phi s, but also in neutrophils, may reflect the role of PTX3 in inflammation. We believe that PTX3 can contribute as a diagnostic tool to evaluate inflammation at peripheral sites. (C) 2007 Elsevier Inc. All rights reserved.

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  • Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8 査読

    Koichi Sumi, Toshiya Tanaka, Aoi Uchida, Kenta Magoori, Yasuyo Urashima, Riuko Ohashi, Hiroto Ohguchi, Masashi Okamura, Hiromi Kudo, Kenji Daigo, Takashi Maejima, Noriaki Kojima, Iori Sakakibara, Shuying Jiang, Go Hasegawa, Insook Kim, Timothy F. Osborne, Makoto Naito, Frank J. Gonzalez, Takao Hamakubo, Tatsuhiko Kodama, Juro Sakai

    MOLECULAR AND CELLULAR BIOLOGY   27 ( 12 )   4248 - 4260   2007年6月

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

    Cholesterol homeostasis is maintained by coordinate regulation of cholesterol synthesis and its conversion to bile acids in the liver. The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. The genes for these two proteins are closely linked and divergently transcribed from a common intergenic promoter region. Here, we identified a binding site for hepatocyte nuclear factor 4 alpha (HNF4 alpha) in the ABCG5/ABCG8 intergenic promoter, through which HNF4 alpha strongly activated the expression of a reporter gene in both directions. The HNF4ci-responsive element is flanked by two conserved GATA boxes that were also required for stimulation by HNF4 alpha. GATA4 and GATA6 bind to the GATA boxes, coexpression of GATA4 and HNF4 alpha leads to a striking synergistic activation of both the ABCG5 and the ABCG8 promoters, and binding sites for HNF4a and GATA were essential for maximal synergism. We also show that HNF4a, GATA4, and GATA6 colocallize in the nuclei of HepG2 cells and that a physical interaction between HNF4 alpha and GATA4 is critical for the synergistic response. This is the first demonstration that HNF4 alpha acts synergistically with GATA factors to activate gene expression in a bidirectional fashion.

    DOI: 10.1128/MCB.01894-06

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  • Expression of liver X receptor alpha in rat fetal tissues at different developmental stages 査読

    Azusa Sakamoto, Takashi Kawasaki, Toshihiro Kazawa, Riuko Ohashi, Shuying Jiang, Takashi Maejima, Toshiya Tanaka, Hiroko Iwanari, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Makoto Naito

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   55 ( 6 )   641 - 649   2007年6月

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

    The liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. Using a novel LXR alpha-specific antibody for immunohistochemistry, we evaluated cellular expression of LXR alpha in fetal rat tissues. In the fetal liver, LXR alpha-positive macrophages appeared at 12 days and their number peaked at 18 days of gestation. In contrast, hepatocytes expressed LXR alpha during the later stage of gestation, suggesting the functional development of the liver during ontogeny. Later, macrophages in spleen and thymus expressed LXR alpha, and some mononuclear cells in the vascular lumen compatible to primitive/fetal macrophages in the fetal circulation were found to express LXR alpha. In vitro, rat monocytes did not express LXR alpha, but monocyte-derived macrophages cultured in the presence of macrophage-colony stimulating factor revealed the distinct expression of LXR alpha in nucleoli. These findings suggest that LXR alpha plays a role in the differentiation of fetal macrophages, particularly hepatic macrophages, in rat development.

    DOI: 10.1369/jhc.6A7120.2007

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  • Downregulated P1 promoter-driven hepatocyte nuclear factor-4 alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis 査読

    Tomoko Oshima, Takashi Kawasaki, Riuko Ohashi, Go Hasegawa, Shuying Jiang, Hajime Umezu, Yutaka Aoyagi, Hiroko Iwanari, Toshiya Tanaka, Takao Hamakubo, Tatsuhiko Kodama, Makoto Naito

    PATHOLOGY INTERNATIONAL   57 ( 2 )   82 - 90   2007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)   出版者・発行元:BLACKWELL PUBLISHING  

    Liver metastases are the most critical prognostic factors for patients with colorectal carcinomas (CRC). It has been reported that the dysregulation of hepatocyte nuclear factor-4 alpha (HNF4 alpha) expression is linked to the development of CRC, gastric cancer and hepatocellular carcinoma. The purpose of the present paper was to examine the P1 and P2 promoter-driven HNF4 alpha (P1 and P2) expression in surgically resected CRC. Immunohistochemically, P1, P2, MUC1 and CD10 expression were evaluated in 63 cases of primary CRC. Positive staining with P1, P2, MUC1 and CD10 antibodies were observed in 37 (59%), 63 (100%), 42 (67%) and 27 (43%) cases, respectively. Loss or decreased P1 expression was observed with respect to the depth of the tumor invasion. The frequency of P1-positive expression in Dukes' C and D tumors was significantly lower than that in Dukes' A and B tumors. There was a relationship between the loss of P1 expression and metachronous liver metastases, and the survival rate of the P1-negative patients without liver metastasis at the time of the primary CRC resection tended to be worse than that of the P1-positive patients. These findings suggest that downregulation of P1 expression is involved in tumor metastasis and a worse prognosis.

    DOI: 10.1111/j.1440-1827.2006.02061.x

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  • Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. 査読

    Tanaka T, Jiang S, Hotta H, Takano K, Iwanari H, Sumi K, Daigo K, Ohashi R, Sugai M, Ikegame C, Umezu H, Hirayama Y, Midorikawa Y, Hippo Y, Watanabe A, Uchiyama Y, Hasegawa G, Reid P, Aburatani H, Hamakubo T, Sakai J, Naito M, Kodama T

    The Journal of pathology   208 ( 5 )   662 - 672   2006年4月

  • SOX6 attenuates glucose-stimulated insulin secretion by repressing PDX1 transcriptional actvity and is down-regulated in hyperinsulinemic obese mice 査読

    H Iguchi, Y Ikeda, M Okamura, T Tanaka, Y Urashima, H Ohguchi, S Takayasu, N Kojima, S Iwasaki, R Ohashi, SY Jiang, G Hasegawa, RX Ioca, K Magoori, K Sumi, T Maejima, A Uchida, M Naito, TF Osborne, M Yanagisawa, TT Yamamoto, T Kodama, J Sakai

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 45 )   37669 - 37680   2005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:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    In obesity-related insulin resistance, pancreatic islets compensate for insulin resistance by increasing secretory capacity. Here, we report the identification of sex-determining region Y-box 6 (SOX6), a member of the high mobility group box superfamily of transcription factors, as a co-repressor for pancreatic-duodenal homeobox factor-1 (PDX1). SOX6 mRNA levels were profoundly reduced by both a long term high fat feeding protocol in normal mice and in genetically obese ob/ob mice on a normal chow diet. Interestingly, we show that SOX6 is expressed in adult pancreatic insulin-producing beta-cells and that overexpression of SOX6 decreased glucose-stimulated insulin secretion, which was accompanied by decreased ATP/ADP ratio, Ca2+ mobilization, proinsulin content, and insulin gene expression. In a complementary fashion, depletion of SOX6 by small interfering RNAs augmented glucose-stimulated insulin secretion in insulinoma mouse MIN6 and rat INS-1E cells. These effects can be explained by our mechanistic studies that show SOX6 acts to suppress PDX1 stimulation of the insulin II promoter through a direct protein/protein interaction. Furthermore, SOX6 retroviral expression decreased acetylation of histones H3 and H4 in chromatin from the promoter for the insulin II gene, suggesting that SOX6 may decrease PDX1 stimulation through changes in chromatin structure at specific promoters. These results suggest that perturbations in transcriptional regulation that are coordinated through SOX6 and PDX1 in beta-cells may contribute to the beta-cell adaptation in obesity-related insulin resistance.

    DOI: 10.1074/jbc.M505392200

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  • Expression of the LXR alpha protein in human atherosclerotic lesions 査読

    Y Watanabe, SY Jiang, W Takabe, R Ohashi, T Tanaka, Y Uchiyama, K Katsumi, H Iwanari, N Noguchi, M Naito, T Hamakubo, T Kodama

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   25 ( 3 )   622 - 627   2005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:LIPPINCOTT WILLIAMS & WILKINS  

    Objective - Liver X - activated receptor alpha ( LXR alpha) regulates multiple genes controlling cholesterol metabolism and transport. To clarify its role in atherogenesis, we established a monoclonal antibody recognizing native human LXRalpha protein and studied the expression pattern in human atherosclerotic lesions.
    Methods and Results - A novel monoclonal antibody PPZ0412 was raised against the ligand-binding domain of LXRalpha, which can be used for immunostaining of human LXRalpha protein. LXRalpha protein was detected in the nucleus of macrophages in the liver, spleen, or lung and also in hepatocytes and adipocytes. In atherosclerotic lesions, the LXRalpha protein was detected in macrophages positive for scavenger receptor class A and/or CD68.
    Conclusions - In the human body, the LXRalpha protein is highly expressed in macrophage lineage cells and foam cells in atherosclerotic lesions and is identified as a target for intervention in atherosclerotic disease.

    DOI: 10.1161/01.ATV.0000154489.53077.4e

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  • Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2 査読

    M Tanaka, R Ohashi, R Nakamura, K Shinmura, T Kamo, R Sakai, H Sugimura

    EMBO JOURNAL   23 ( 5 )   1075 - 1088   2004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:NATURE PUBLISHING GROUP  

    Bidirectional signals mediated by Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, play pivotal roles in the formation of neural networks by induction of both collapse and elongation of neurites. However, the downstream molecular modules to deliver these cues are largely unknown. We report here that the interaction of a Rac1-specific guanine nucleotide-exchanging factor, Tiam1, with ephrin-B1 and EphA2 mediates neurite outgrowth. In cells coexpressing Tiam1 and ephrin-B1, Rac1 is activated by the extracellular stimulation of clustered soluble EphB2 receptors. Similarly, soluble ephrin-A1 activates Rac1 in cells coexpressing Tiam1 and EphA2. Cortical neurons from the E14 mouse embryos and neuroblastoma cells significantly extend neurites when placed on surfaces coated with the extracellular domain of EphB2 or ephrin-A1, which were abolished by the forced expression of the dominant-negative mutant of ephrin-B1 or EphA2. Furthermore, the introduction of a dominant-negative form of Tiam1 also inhibits neurite outgrowth induced by the ephrin-B1 and EphA2 signals. These results indicate that Tiam1 is required for neurite outgrowth induced by both ephrin-B1-mediated reverse signaling and EphA2-mediated forward signaling.

    DOI: 10.1038/sj.emboj.7600128

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書籍等出版物

  • Urinary and Male Genital Tumours (Who Classification of Tumours)

    Who Classification of Tumours Editorial Board

    World Health Organization  2022年7月  ( ISBN:9283245121

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    総ページ数:576   記述言語:英語

    CiNii Books

    ASIN

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  • 気管支肺胞洗浄(BAL)法の手引き改訂3版

    日本呼吸器学会びまん性肺疾患学術部会, 厚生労働省難治性疾患政策研究事業びまん性肺疾患に関する調査研究班編, 編集責任者, 中田光, 石井芳樹( 担当: 分担執筆)

    克誠堂出版  2017年10月 

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    担当ページ:25-49   記述言語:日本語 著書種別:教科書・概説・概論

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共同研究・競争的資金等の研究

  • 嫌色素性腎細胞癌の臨床病理・分子統合的新規グレード分類の提案と治療戦略への展開

    研究課題/領域番号:20K07404  2020年4月 - 2023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)

    大橋 瑠子, 味岡 洋一

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    担当区分:研究代表者 

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

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  • ヒト悪性腫瘍を対象としたリボソーム遺伝子変異解析

    2014年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    大橋 瑠子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 核内受容体の組織・細胞内局在の系統的解析

    2007年4月 - 2009年3月

    日本学術振興会  科学研究費助成事業  若手研究(B)

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    資金種別:競争的資金

    核内受容体ファミリーはステロイドホルモンや低分子脂溶性物質をリガンドとする転写因子群であり、多くの受容体が広く炎症、代謝、発癌などに関わり創薬分野で最近注目されている。さまざまなヒト正常組織や癌細胞を対象に核内受容体の組織・細胞内局在について蛍光イメージング技術を用いた検討を行うとともに、病理診断への応用法について検討を行っている。

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