Updated on 2025/07/07

写真a

 
MIZUKAMI Yusuke
 
Organization
School of Medicine Medical Course Clinical Medicine Internal Medicine [Division of Gastroenterology ]
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Degree

  • MD, PhD ( 2001.9   Asahikawa Medical College )

Research Interests

  • Cancer Genetics

  • tumor biology

  • Clonal evolution

  • Gastroenterology

  • pancreatic cancer

  • Intraductal Papillary Mucinous Neoplasm

  • Biomarker

Research Areas

  • Life Science / Tumor biology

  • Life Science / Genome biology

  • Life Science / Gastroenterology

Education

  • Asahikawa Medical College   School of Medicine

    1987.4 - 1993.3

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Research History

  • National Institutes of Biomedical Innovation, Health and Nutrition   Center for Intractable Diseases and ImmunoGenomics (CiDIG)   Project Leader

    2024.9

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    Country:Japan

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  • Asahikawa Medical College   Professor

    2023.10

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  • Asahikawa Medical University   Cancer Genetics, Division of Gastroenterology and Hematology/Oncology, Department of Medicine   Professor

    2020.6 - 2023.9

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    Country:Japan

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  • Massachusetts General Hospital and Harvard Medical School   Gastrointestinal Unit   Part-time Lecturer

    2017.7

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    Country:United States

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  • Asahikawa Medical College   Department of Medicine   Associate Professor

    2017.1 - 2020.6

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  • Massachusetts General Hispital   Center for Cancer Research   Assistant in Biochemistry

    2011.8 - 2016.6

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  • Sapporohigashi Tokushukai Hospital   Institute of Biomedical Rsearch   Director

    2011.6 - 2016.12

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  • Asahikawa Medical College   Department of Medicine   Assistant Professor

    2008.4 - 2011.5

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Committee Memberships

  • 日本膵臓学会   評議員  

    2025.4   

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    Committee type:Academic society

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  • The Japanese Society of Gastroenterology   Board of Councilors  

    2022.1   

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  • The Japanese Cancer Association   Board of Councilors  

    2022.1   

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  • Japan Pancreas Society   Board Certified Trainer  

    2020.1   

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    Committee type:Academic society

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  • 日本消化器病学会   機関誌編集委員会  

    2019.6 - 2025.5   

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Studying abroad experiences

  • 2011.8 - 2014.6   Center for Cancer Research, Massachusetts General Hospital   Assistant in Biochemisctry

Papers

  • Current status of molecular diagnostic approaches using liquid biopsy. Invited Reviewed

    Kenji Takahashi, Yohei Takeda, Yusuke Ono, Hajime Isomoto, Yusuke Mizukami

    Journal of Gastroenterology   2023.7

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)  

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity.

    DOI: 10.1007/s00535-023-02024-4

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  • Serine/Threonine Kinase 11 Plays a Canonical Role in Malignant Progression of KRAS -Mutant and GNAS -Wild-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas Reviewed International journal

    Yuko Omori, Yusuke Ono, Takanori Morikawa, Fuyuhiko Motoi, Ryota Higuchi, Masakazu Yamamoto, Yuko Hayakawa, Hidenori Karasaki, Yusuke Mizukami, Michiaki Unno, Toru Furukawa

    Annals of Surgery   277 ( 2 )   E384 - E395   2023.2

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    DOI: 10.1097/SLA.0000000000004842

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  • Predictors of Long-Term Survival in Pancreatic Ductal Adenocarcinoma after Pancreatectomy: TP53 and SMAD4 Mutation Scoring in Combination with CA19-9 Reviewed International journal

    Masato Ono, Yusuke Ono, Toru Nakamura, Takahiro Tsuchikawa, Tomotaka Kuraya, Shota Kuwabara, Yoshitsugu Nakanishi, Toshimichi Asano, Aya Matsui, Kimitaka Tanaka, Yuma Ebihara, Yo Kurashima, Takehiro Noji, Soichi Murakami, Toshiaki Shichinohe, Tomoko Mitsuhashi, Yuko Omori, Toru Furukawa, Kenzui Taniue, Mayumi Suzuki, Ayumu Sugitani, Hidenori Karasaki, Yusuke Mizukami, Satoshi Hirano

    Annals of Surgical Oncology   29 ( 8 )   5007 - 5019   2022.4

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a fatal cancer for which even unfavorable clinicopathological factors occasionally fail to preclude long-term survival. We sought to establish a scoring system that utilizes measurable pre-intervention factors for predicting survival following surgical resection. METHODS: We retrospectively analyzed 34 patients who died from short-term recurrences and 32 long-term survivors among 310 consecutively resected patients with PDA. A logistic regression model was used to define factors related to clinical parameters, molecular profiles of 18 pancreatic cancer-associated genes, and aberrant expression of major tumor suppressors. RESULTS: Carbohydrate antigen 19-9 (CA19-9) had the best ability to classify patients with short-term recurrence and long-term survivors [odds ratio 21.04, 95% confidence interval (CI) 4.612-96.019], followed by SMAD4 and TP53 mutation scoring (odds ratio 41.322, 95% CI 3.156-541.035). Missense TP53 mutations were strongly associated with the nuclear expression of p53, whereas truncating mutations were associated with the absence of nuclear p53. The former subset was associated with a worse prognosis. The combination of aberrant SMAD4 and mutation types of TP53 exhibited a better resolution for distinguishing patients with short-term recurrences from long-term survivors (compared with the assessment of the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes). Calibration of mutation scores combined with CA19-9 in a logistic regression model setting demonstrated a practical effect in classifying long survivors and patients with early recurrence (c-statistic = 0.876). CONCLUSIONS: Genetic information, i.e., TP53 mutation types and SMAD4 abnormalities, combined with CA19-9, will be a valuable tool for improving surgical strategies for pancreatic cancer.

    DOI: 10.1245/s10434-022-11630-0

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    Other Link: https://link.springer.com/article/10.1245/s10434-022-11630-0/fulltext.html

  • Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway. Reviewed

    Hidemasa Kawabata, Yusuke Ono, Nobue Tamamura, Kyohei Oyama, Jun Ueda, Hiroki Sato, Kenji Takahashi, Kenzui Taniue, Tetsuhiro Okada, Syugo Fujibayashi, Akihiro Hayashi, Takuma Goto, Katsuro Enomoto, Hiroaki Konishi, Mikihiro Fujiya, Keita Miyakawa, Mishie Tanino, Yuji Nishikawa, Daisuke Koga, Tsuyoshi Watanabe, Chiho Maeda, Hidenori Karasaki, Andrew S Liss, Yusuke Mizukami, Toshikatsu Okumura

    Journal of Gastroenterology   57 ( 3 )   208 - 220   2022.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. METHODS: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. RESULTS: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. CONCLUSIONS: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.

    DOI: 10.1007/s00535-021-01846-4

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  • Genomic medicine for the early detection of pancreatic cancer Invited Reviewed

    佐藤裕基, 高橋賢治, 水上裕輔

    膵臓(Web)   37 ( 1 )   2022

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    J-GLOBAL

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  • Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance. Reviewed

    Tetsuhiro Okada, Yusuke Mizukami, Yusuke Ono, Hiroki Sato, Akihiro Hayashi, Hidemasa Kawabata, Kazuya Koizumi, Sakue Masuda, Shinichi Teshima, Kuniyuki Takahashi, Akio Katanuma, Yuko Omori, Hirotoshi Iwano, Masataka Yamada, Tomoki Yokochi, Shingo Asahara, Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto, Katsuro Enomoto, Takuma Goto, Junpei Sasajima, Mikihiro Fujiya, Jun Ueda, Seiji Matsumoto, Kenzui Taniue, Ayumu Sugitani, Hidenori Karasaki, Toshikatsu Okumura

    Journal of Gastroenterology   55 ( 12 )   1183 - 1193   2020.12

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00535-020-01724-5

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  • 【IPMN大全】IPMNの分子生物学 IPMNと併存膵癌のクローン進化

    大森 優子, 水上 裕輔, 古川 徹

    胆と膵   41 ( 臨増特大 )   1245 - 1252   2020.11

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    Language:Japanese   Publisher:医学図書出版(株)  

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  • Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection Reviewed International journal

    Nagai, K., Mizukami, Y., Omori, Y., Kin, T., Yane, K., Takahashi, K., Ono, Y., Sugitani, A., Karasaki, H., Shinohara, T., Furukawa, T., Hayashi, T., Okumura, T., Maguchi, H., Katanuma, A.

    Modern Pathology   33 ( 5 )   971 - 980   2020

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41379-019-0405-7

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  • Pathways of Progression From Intraductal Papillary Mucinous Neoplasm to Pancreatic Ductal Adenocarcinoma Based on Molecular Features Reviewed International journal

    Omori, Y., Ono, Y., Tanino, M., Karasaki, H., Yamaguchi, H., Furukawa, T., Enomoto, K., Ueda, J., Sumi, A., Katayama, J., Muraki, M., Taniue, K., Takahashi, K., Ambo, Y., Shinohara, T., Nishihara, H., Sasajima, J., Maguchi, H., Mizukami, Y., Okumura, T., Tanaka, S.

    Gastroenterology   156 ( 3 )   647 - 661   2019

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1053/j.gastro.2018.10.029

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  • Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism Reviewed

    Krushna C. Patra, Yasutaka Kato, Yusuke Mizukami, Sebastian Widholz, Myriam Boukhali, Iulia Revenco, Elizabeth A. Grossman, Fei Ji, Ruslan I. Sadreyev, Andrew S. Liss, Robert A. Screaton, Kei Sakamoto, David P. Ryan, Mari Mino-Kenudson, Carlos Fernandez-del Castillo, Daniel K. Nomura, Wilhelm Haas, Nabeel Bardeesy

    Nature Cell Biology   20 ( 7 )   1 - 12   2018.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Publishing Group  

    DOI: 10.1038/s41556-018-0122-3

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    Other Link: http://orcid.org/0000-0002-1068-7024

  • Diversity of Precursor Lesions For Pancreatic Cancer: The Genetics and Biology of Intraductal Papillary Mucinous Neoplasm Reviewed

    Krushna C. Patra, Nabeel Bardeesy, Yusuke Mizukami

    CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY   8 ( 4 )   2017.4

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ctg.2017.3

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    Other Link: http://orcid.org/0000-0002-1068-7024

  • Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas Reviewed

    Gala, M.K., Mizukami, Y., Le, L.P., Moriichi, K., Austin, T., Yamamoto, M., Lauwers, G.Y., Bardeesy, N., Chung, D.C.

    Gastroenterology   146 ( 2 )   520 - +   2014

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    DOI: 10.1053/j.gastro.2013.10.045

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  • Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results Reviewed

    S. Tanno, Y. Nakano, T. Nishikawa, K. Nakamura, J. Sasajima, M. Minoguchi, Y. Mizukami, N. Yanagawa, T. Fujii, T. Obara, T. Okumura, Y. Kohgo

    GUT   57 ( 3 )   339 - 343   2008.3

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    DOI: 10.1136/gut.2007.129684

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    Other Link: http://orcid.org/0000-0002-1068-7024

  • Hypoxia inducible factor-1-independent pathways in tumor angiogenesis Reviewed

    Yusuke Mizukami, Yutaka Kohgo, Daniel C. Chung

    CLINICAL CANCER RESEARCH   13 ( 19 )   5670 - 5674   2007.10

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

    DOI: 10.1158/1078-0432.CCR-07-0111

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    Other Link: http://orcid.org/0000-0002-1068-7024

  • Induction of interleukin-8 preserves the angiogenic response in HIF-1α–deficient colon cancer cells

    Yusuke Mizukami, Won-Seok Jo, Eva-Maria Duerr, Manish Gala, Jingnan Li, Xiaobo Zhang, Michael A Zimmer, Othon Iliopoulos, Lawrence R Zukerberg, Yutaka Kohgo, Maureen P Lynch, Bo R Rueda, Daniel C Chung

    Nature Medicine   11 ( 9 )   992 - 997   2005.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm1294

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    Other Link: http://www.nature.com/articles/nm1294

  • Highly multiplexed digital PCR assay for simultaneous quantification of variant allele frequencies and copy number alterations of KRAS and GNAS in pancreatic cancer precursors Reviewed

    Junko Tanaka, Tatsuo Nakagawa, Yusuke Ono, Yoshio Kamura, Takeshi Ishida, Hidemasa Kawabata, Kenji Takahashi, Hiroki Sato, Andrew S. Liss, Yusuke Mizukami, Takahide Yokoi

    Molecular Oncology   2025.3

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    DOI: 10.1002/1878-0261.70011

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  • Cognitive and ataxic adverse events following entrectinib treatment in NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma: a case report. Reviewed

    Kazuya Koyama, Hidetaka Iwamoto, Kenji Takahashi, Tetsuhiro Okada, Hidemasa Kawabata, Yohei Kitano, Hiroki Tanabe, Mikihiro Fujiya, Toshikatsu Okumura, Yusuke Mizukami

    Clinical journal of gastroenterology   18 ( 1 )   183 - 187   2024.12

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    We report the rare case of severe cognitive disorder and ataxia caused by entrectinib in a patient with NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma. The case was a 56-year-old woman after nine courses of GCS therapy. The patient experienced grade 1 muscle weakness on day 4 and grade 3, cognitive disorder on day 7 after receiving entrectinib, which led to hospitalization. The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

    DOI: 10.1007/s12328-024-02076-w

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  • High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics Reviewed

    Hiroki Tanabe, Yasuyuki Koshizuka, Kazuyuki Tanaka, Kenji Takahashi, Masami Ijiri, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Takeo Sarashina, Kentaro Moriichi, Kenrokuro Mitsube, Yusuke Mizukami, Mikihiro Fujiya, Yoshio Makita

    Human Genome Variation   11 ( 1 )   46   2024.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

    DOI: 10.1038/s41439-024-00301-z

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    Other Link: https://www.nature.com/articles/s41439-024-00301-z

  • 【EUS-FNA/Bの進歩と課題】EUS-FNA/B検体を用いた分子・ゲノム診断の現状

    河端 秀賢, 湯澤 明夏, 高橋 賢治, 谷野 美智枝, 水上 裕輔

    膵臓   39 ( 5 )   316 - 324   2024.10

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本膵臓学会  

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J02025&link_issn=&doc_id=20241105300004&doc_link_id=10.2958%2Fsuizo.39.316&url=https%3A%2F%2Fdoi.org%2F10.2958%2Fsuizo.39.316&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • ゲノム解析と胆道疾患診療 胆管癌診断時の生検検体における遺伝子変異解析の意義 Reviewed

    岡田 哲弘, 高橋 賢治, 水上 裕輔

    胆道   38 ( 3 )   314 - 314   2024.9

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本胆道学会  

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  • Three Molecular Developmental Pathways of Remnant Pancreatic Cancer after Resection Reviewed

    Shuji Suzuki, Yuko Omori, Yusuke Ono, Katsuya Hirose, Taito Itoh, Hidenori Karasaki, Mitsugi Shimoda, Yuichi Nagakawa, Ryota Higuchi, Itaru Endo, Toshiki Rikiyama, Michiaki Unno, Tsutomu Fujii, Yuki Sunagawa, Hidetoshi Eguchi, Hideki Sasanuma, Takahiro Akahori, Keiichi Okano, Masaji Tani, Satoshi Hirano, Yasuhiro Shimizu, Minoru Kitago, Shugo Mizuno, Tomohisa Yamamoto, Masayuki Furukawa, Masayuki Ohtsuka, Motokazu Sugimoto, Akira Matsushita, Kenichi Hakamada, Hisato Igarashi, Tamotsu Kuroki, Satoshi Tanno, Yoshihisa Tsuji, Atsushi Masamune, Kazuhiro Mizumoto, Yoshiki Hirooka, Hiroki Yamaue, Kazuichi Okazaki, Sohei Satoi, Yoshifumi Takeyama, Yusuke Mizukami, Toru Furukawa

    Annals of Surgery   2024.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    Objective:

    This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection.

    Summary Background Data:

    Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown.

    Methods:

    Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated.

    Results:

    These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=-0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways.

    Conclusion:

    Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

    DOI: 10.1097/sla.0000000000006444

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  • 膵癌の長期予後向上を目指して 1-膵癌早期発見の戦略と精緻診断 高異型度PanIN/膵上皮内癌・小径膵癌の分子進化モデル Reviewed

    伊藤 泰斗, 大森 優子, 小野 裕介, 高橋 賢治, 國米 崇, 正宗 淳, 海野 倫明, 水上 裕輔, 古川 徹

    膵臓   39 ( 3 )   A172 - A172   2024.7

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  • 残膵癌における先行膵癌との分子病理学的および臨床病理学的検討 Reviewed

    鈴木 修司, 大森 優子, 廣瀬 勝也, 小野 裕介, 唐崎 秀則, 下田 貢, 永川 裕一, 水上 裕輔, 古川 徹

    膵臓   39 ( 3 )   A149 - A149   2024.7

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    Authorship:Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本膵臓学会  

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  • 膵疾患のトランスレーショナル・リサーチ マルチレイヤー核酸解析による膵癌リキッドバイオプシー体系の構築 Reviewed

    高橋 賢治, 小山 一也, 梶浦 麻未, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   39 ( 3 )   A252 - A252   2024.7

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本膵臓学会  

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  • Clonal analysis of metachronous double biliary tract cancers. Reviewed International journal

    Yuko Omori, Shuichi Aoki, Yusuke Ono, Takashi Kokumai, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kei Nakagawa, Yusuke Mizukami, Toru Furukawa, Michiaki Unno

    The Journal of pathology   263 ( 1 )   113 - 127   2024.5

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    The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

    DOI: 10.1002/path.6265

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  • Genomic insights into familial adenomatous polyposis: unraveling a rare case with whole APC gene deletion and intellectual disability. Reviewed International journal

    Hiroki Tanabe, Masami Ijiri, Kenji Takahashi, Honoka Sasagawa, Tomomi Kamanaka, Shohei Kuroda, Hiroki Sato, Takeo Sarashina, Yusuke Mizukami, Yoshio Makita, Toshikatsu Okumura

    Human genome variation   11 ( 1 )   13 - 13   2024.3

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    A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

    DOI: 10.1038/s41439-024-00270-3

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  • New gel immersion endoscopic ultrasonography technique for accurate periampullary evaluation. Reviewed International journal

    Hiroki Sato, Hidemasa Kawabata, Hidetaka Iwamoto, Tetsuhiro Okada, Shugo Fujibayashi, Kenji Takahashi, Yohei Kitano, Takuma Goto, Yusuke Mizukami, Toshikatsu Okumura, Mikihiro Fujiya

    Surgical endoscopy   38 ( 4 )   2297 - 2304   2024.3

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    BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

    DOI: 10.1007/s00464-024-10762-6

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  • A familial case of extramammary Paget disease: Analysis of whole-exome sequencing Reviewed

    Takuya Maeda, Teruki Yanagi, Shinya Kitamura, Hiroshi Nishihara, Yusuke Ono, Yusuke Mizukami, Shinya Tanaka, Hideyuki Ujiie

    EJC Skin Cancer   2024.3

  • Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle–Encapsulated Long Noncoding RNA HEVEPA Reviewed

    Kenji Takahashi, Tatsutoshi Inuzuka, Yuta Shimizu, Kazuki Sawamoto, Kenzui Taniue, Yusuke Ono, Fumi Asai, Kazuya Koyama, Hiroki Sato, Hidemasa Kawabata, Hidetaka Iwamoto, Keisuke Yamakita, Yohei Kitano, Takashi Teramoto, Mikihiro Fujiya, Satoshi Fujii, Yusuke Mizukami, Toshikatsu Okumura

    Pancreas   53 ( 5 )   e395 - e404   2024.2

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    Objectives

    The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)–encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs.

    Materials and Methods

    Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR.

    Results

    Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone.

    Conclusions

    Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

    DOI: 10.1097/mpa.0000000000002315

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  • Comparison between hangeshashinto and dexamethasone for IL-1α and β-defensin 1 production by human oral keratinocytes Reviewed

    Hiroyuki Hato, Atsushi Kaneko, Chiho Maeda, Ken-ichiro Sakata, Yusuke Ono, Yusuke Mizukami, Toru Kono, Yoshimasa Kitagawa

    Journal of Oral Biosciences   66 ( 1 )   188 - 195   2024.1

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    DOI: 10.1016/j.job.2024.01.007

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  • Monitoring mutant KRAS in plasma cell-free DNA can predict disease progression in a patient with multiple myeloma: A case report. Reviewed International journal

    Masayo Yamamoto, Motohiro Shindo, Takuya Funayama, Chihiro Sumi, Takeshi Saito, Yasumichi Toki, Mayumi Hatayama, Yusuke Ono, Kazuya Sato, Yusuke Mizukami, Toshikatsu Okumura

    Clinica chimica acta; international journal of clinical chemistry   551   117590 - 117590   2023.10

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    BACKGROUND AND AIMS: Multiple myeloma (MM), a neoplasm of plasma cells (PCs), is a highly heterogeneous disease with multifocal dissemination throughout the body. Minimal residual disease (MRD) detected using PCs in bone marrow (BM) is important for MM management; however, frequent invasive examinations impose a significant burden on patients. METHODS: Analysis using plasma cell-free DNA (cfDNA) might represent an alternative tool for disease monitoring. In this study, we observed the disease status in a patient with MM by examining the KRAS mutation allele frequency (MAF) in plasma cfDNA using digital PCR. RESULTS: During treatment, the MAF was correlated with serum immunoglobulin A and free light chain-kappa levels. After the second autologous peripheral blood stem cell transplantation, the KRAS MAF became immediately positive after confirming MRD negativity using PCs from BM. Shortly thereafter, the patient experienced clinical relapse primarily involving bone lesions. CONCLUSION: Mutant KRAS monitoring in cfDNA using serial blood collection might reflect the disease status more accurately than invasive BM examinations, especially in patients with MM whose primary lesions have extra-BM locations. It could also help predict treatment responses and outcomes.

    DOI: 10.1016/j.cca.2023.117590

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  • Gene rearrangement and expression of PRKACA and PRKACB governs morpho-biology of pancreatobiliary oncocytic neoplasms Reviewed

    Taito Itoh, Yuko Omori, Mitsuru Seino, Katsuya Hirose, Fumiko Date, Yusuke Ono, Yusuke Mizukami, Shuichi Aoki, Masaharu Ishida, Masamichi Mizuma, Takanori Morikawa, Ryota Higuchi, Goro Honda, Yasunobu Okamura, Kengo Kinoshita, Michiaki Unno, Toru Furukawa

    Modern Pathology   37 ( 1 )   100358 - 100358   2023.10

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    DOI: 10.1016/j.modpat.2023.100358

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  • ASO Visual Abstract: Predictors of Long-Term Survival in Pancreatic Ductal Adenocarcinoma After Pancreatectomy-TP53 and SMAD4 Mutation Scoring in Combination with CA19-9. Reviewed International journal

    Masato Ono, Yusuke Ono, Toru Nakamura, Takahiro Tsuchikawa, Tomotaka Kuraya, Shota Kuwabara, Yoshitsugu Nakanishi, Toshimichi Asano, Aya Matsui, Kimitaka Tanaka, Yuma Ebihara, Yo Kurashima, Takehiro Noji, Soichi Murakami, Toshiaki Shichinohe, Tomoko Mitsuhashi, Yuko Omori, Toru Furukawa, Kenzui Taniue, Mayumi Suzuki, Ayumu Sugitani, Hidenori Karasaki, Yusuke Mizukami, Satoshi Hirano

    Annals of surgical oncology   29 ( 8 )   5007 - 5019   2023.9

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    DOI: 10.1245/s10434-023-13451-1

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  • 細胞外小胞EV内RNAに着目した膵癌バイオマーカー探索 Reviewed

    高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A320 - A320   2023.7

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  • IPMNの発癌機構と治療方針決定 IPMN関連膵癌におけるGNAS遺伝子の病態解明からみた治療戦略 Reviewed

    河端 秀賢, 高橋 賢治, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 北野 陽平, 大森 優子, 古川 徹, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A213 - A213   2023.7

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  • 急性膵炎の致命率改善への集学的治療 DIC合併重症急性膵炎の臨床的アウトカムに関する検討 Reviewed

    岩本 英孝, 高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    膵臓   38 ( 3 )   A171 - A171   2023.7

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  • 残膵癌における先行膵癌との分子病理学的および臨床病理学的検討 Reviewed

    鈴木 修司, 大森 優子, 廣瀬 勝也, 小野 裕介, 唐崎 秀則, 下田 貢, 永川 裕一, 水上 裕輔, 古川 徹

    膵臓   38 ( 3 )   A289 - A289   2023.7

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  • Assessment for the timing of comprehensive genomic profiling tests in patients with advanced solid cancers. Reviewed International journal

    Kanako Hagio, Junko Kikuchi, Kohichi Takada, Hiroki Tanabe, Minako Sugiyama, Yoshihito Ohhara, Toraji Amano, Satoshi Yuki, Yoshito Komatsu, Takahiro Osawa, Kanako C Hatanaka, Yutaka Hatanaka, Takashi Mitamura, Ichiro Yabe, Yoshihiro Matsuno, Atsushi Manabe, Akihiro Sakurai, Atsushi Ishiguro, Masato Takahashi, Hiroshi Yokouchi, Hirohito Naruse, Yusuke Mizukami, Hirotoshi Dosaka-Akita, Ichiro Kinoshita

    Cancer science   114 ( 8 )   3385 - 3395   2023.5

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    Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

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  • Two Cases of SMARCA4-Deficient Non-small Cell Lung Cancer (NSCLC) with Improved Performance Status (PS) after Treatment with Immune Checkpoint Inhibitors (ICIs) Reviewed

    Akiko Koizumi, Yukiho Tamura, Ryohei Yoshida, Chie Mori, Yusuke Ono, Mishie Tanino, Yusuke Mizukami, Takaaki Sasaki

    Cureus   15 ( 4 )   e37656   2023.4

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    DOI: 10.7759/cureus.37656

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  • Low-grade papillary Schneiderian carcinoma with TP53 mutation: a case report and review of the literature Reviewed

    Sayaka Yuzawa, Tomohiko Michizuka, Rika Kakisaka, Yusuke Ono, Manami Hayashi, Miki Takahara, Akihiro Katada, Yusuke Mizukami, Mishie Tanino

    Diagnostic Pathology   18 ( 1 )   2023.4

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    Abstract

    Background

    Low-grade papillary Schneiderian carcinoma (LGPSC) is a relatively new entity of the sinonasal tract and is characterized by a bland morphology simulating sinonasal papilloma, invasive growth pattern with pushing borders, and aggressive clinical behavior with multiple recurrences and metastatic potential. Recently, DEK::AFF2 fusions were identified in LGPSC. However, some LPGSCs lack DEK::AFF2 fusion, and the molecular features of these tumors have not been clarified.

    Case presentation

    A 69-year-old man presented with a discharge of pus from his left cheek. Computed tomography revealed a mass involving the left maxillary sinus, ethmoid sinus, and nasal cavity with the destruction of the orbital wall. The biopsy specimens showed that the tumor had a predominantly exophytic, papillary growth and did not have an apparent stromal invasion. The tumor was composed of multilayered epithelium that showed bland morphology with a round to polygonal shape, abundant eosinophilic cytoplasm, and uniform nuclei. Dense neutrophilic infiltrates were focally present. Immunohistochemically, CK5/6 was strongly and diffusely positive, and p16 was negative. p63 was mainly positive in the basal layer, and EMA was predominantly expressed in the outermost cell layer. DNA-based targeted sequencing showed TP53 R175H mutation, whereas neither EGFR nor KRAS mutation was identified. Reverse transcription polymerase chain reaction and fluorescence in situ hybridization revealed no DEK::AFF2 fusion.

    Conclusions

    We describe the first case of TP53-mutant LGPSC and review the literature. LGPSC is a genetically heterogeneous entity, and the recognition of this rare entity and comprehensive assessment of clinicopathological and molecular findings are crucial for the correct pathological diagnosis and clinical management.

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  • Multiplex digital PCR assay to detect multiple KRAS and GNAS mutations associated with pancreatic carcinogenesis from minimal specimen amounts Reviewed

    Maeda Chiho, Yusuke Ono, Akihiro Hayashi, Kenji Takahashi, Kenzui Taniue, Rika Kakisaka, Miyuki Mori, Takahiro Ishii, Hiroki Sato, Tetsuhiro Okada, Hidemasa Kawabata, Takuma Goto, Nobue Tamamura, Yuko Omori, Kuniyuki Takahashi, Akio Katanuma, Hidenori Karasaki, Andrew Scott Liss, Yusuke Mizukami

    The Journal of Molecular Diagnostics   25 ( 6 )   367 - 377   2023.3

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    DOI: 10.1016/j.jmoldx.2023.02.007

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  • Molecular comparison of concurrent components of high-grade dysplasia, adenocarcinoma, and sarcomatoid carcinoma in a case of sarcomatoid carcinoma of the gallbladder Reviewed

    Katsuya Hirose, Yuko Omori, Yusuke Ono, Yusuke Mizukami, Yoshiki Kaneko, Tsunehiko Maruyama, Haruo Ohtani, Toru Furukawa

    Virchows Archiv   483 ( 2 )   261 - 266   2023.3

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    DOI: 10.1007/s00428-023-03524-7

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  • Local recurrence after successful endoscopic submucosal dissection for rectal mucinous mucosal adenocarcinoma: A case report Reviewed

    Yuki Murakami, Hiroki Tanabe, Yusuke Ono, Yuya Sugiyama, Yu Kobayashi, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Sayaka Yuzawa, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    World Journal of Gastrointestinal Oncology   15 ( 1 )   186 - 194   2023.1

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    DOI: 10.4251/wjgo.v15.i1.186

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  • GATA6 and CK5 stratify the survival of patients with pancreatic cancer undergoing neoadjuvant chemotherapy Reviewed

    Takashi Kokumai, Yuko Omori, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Maeda Chiho, Yusuke Ono, Yusuke Mizukami, Shin Miura, Kiyoshi Kume, Atsushi Masamune, Takanori Morikawa, Michiaki Unno, Toru Furukawa

    Modern Pathology   36 ( 5 )   100102 - 100102   2023.1

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    DOI: 10.1016/j.modpat.2023.100102

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  • Cytomegalovirus infection in patients with malignant lymphomas who have not received hematopoietic stem cell transplantation. Reviewed International journal

    Kazuya Sato, Sho Igarashi, Nodoka Tsukada, Junki Inamura, Masayo Yamamoto, Motohiro Shindo, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Yoshihiro Torimoto

    BMC cancer   22 ( 1 )   944 - 944   2022.9

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    BACKGROUND: Life-threatening cytomegalovirus infection (CMVI) has been reported even in patients with malignant lymphoma (ML) who have not received hematopoietic stem cell transplantation (w/o HSCT) but had been treated with chemotherapy or radiotherapy. However, the CMVI incidence and risk factors (RFs) in patients with ML w/o HSCT have not been fully elucidated. This study aimed to evaluate the clinical aspects, including incidence and RFs, of CMVI in patients with ML w/o HSCT. METHODS: We retrospectively reviewed all patients with ML who received chemotherapy or radiotherapy in our department from 2005 to 2013. The overall survival (OS), incidence and RFs of CMVI, and other characteristics of patients with CMVI were analyzed. RESULTS: Overall, 236 patients with ML w/o HSCT were evaluated. Of these, 5.5% (13/236) developed CMVI; 54% (7/13) received steroid pretreatment before primary therapy (PT) for ML; and 62% (8/13) received > 2 therapeutic regimens for ML. The OS curve of patients with CMVI was significantly worse than that of patients without CMVI (p < 0.0001, log-rank test). A univariate analysis identified B symptoms (p = 0.00321), serum albumin < 3.5 g/dL (p = 0.0007837), C-reactive protein level > the upper limit of normal (p = 0.0006962), steroid pretreatment before PT for ML (p = 0.0004262), > 2 therapeutic regimens for ML (p = 0.0000818), T cell lymphoma (p = 0.006406), and non-complete remission (p = 0.02311) as RFs for CMVI. A multivariate analysis identified steroid pretreatment before PT for ML [odds ratio (OR): 4.71 (95% confidence interval [CI]: 1.06-21.0); p = 0.0419] and > 2 therapeutic regimens for ML [OR: 9.25 (95% CI: 2.33-36.8); p = 0.00159] as independent RFs for CMVI in patients with ML w/o HSCT. CONCLUSIONS: Attention should be paid to CMVI development in patients with ML w/o HSCT pretreated with steroids or who had multiple therapeutic regimens.

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  • STK11が変化した膵管内乳頭粘液性腫瘍は特有の臨床病理学的特徴を示す(STK11-aletered intraductal papillary mucinous neoplasms develop characteristic clinico-patho-biology) Reviewed

    Omori Yuko, Ono Yusuke, Itoh Taito, Date Fumiko, Morikawa Takanori, Motoi Fuyuhiko, Higuchi Ryota, Honda Goro, Karasaki Hidenori, Mizukami Yusuke, Unno Michiaki, Furukawa Toru

    膵臓   37 ( 3 )   A391 - A391   2022.9

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  • PRKACA/Bの再配列と発現が膵胆管好酸性腫瘍の表現型を規定する(Rearrangement and expression of PRKACA/B governs phenotypes of pancreato-biliary oncocytic neoplasms) Reviewed

    Itoh Taito, Omori Yuko, Seino Mitsuru, Hirose Katsuya, Date Fumiko, Ono Yusuke, Mizukami Yusuke, Mizuma Masamichi, Morikawa Takanori, Higuchi Ryota, Honda Goro, Unno Michiaki, Furukawa Toru

    膵臓   37 ( 3 )   A392 - A393   2022.9

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  • 膵腫瘍に対するgenomicsにおける進歩 残存膵癌の三つの分子発生経路が切除後の生存率に影響する(Advances in genomics for pancreatic neoplasms Three molecular development pathways of remnant pancreatic cancer impact survival after resection) Reviewed

    Suzuki Shuji, Omori Yuko, Hirose Katsuya, Ono Yusuke, Karasaki Hidenori, Shimoda Mitsugi, Nagakawa Yuichi, Tsuchida Akihiko, Mizukami Yusuke, Furukawa Toru

    膵臓   37 ( 3 )   A191 - A192   2022.9

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  • ASO Author Reflections: Constructed Scoring System Using TP53 and SMAD4 Mutations Combined with Carbohydrate Antigen 19-9 in Pancreatic Ductal Adenocarcinoma. Reviewed International journal

    Masato Ono, Toru Nakamura, Yusuke Mizukami, Satoshi Hirano

    Annals of Surgical Oncology   29 ( 8 )   5020 - 5021   2022.8

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    DOI: 10.1245/s10434-022-11735-6

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  • Severe immune checkpoint inhibitor-associated gastritis: A case series and literature review. Reviewed International journal

    Yuya Sugiyama, Hiroki Tanabe, Taisuke Matsuya, Yu Kobayashi, Yuki Murakami, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Mishie Tanino, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Endoscopy International Open   10 ( 7 )   E982-E989   2022.7

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    Background and study aims  Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Patients and methods  Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Results  Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. Conclusions  IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.

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  • Artificial intelligence-assisted detection of colorectal polyps in Lynch syndrome. Reviewed International journal

    Hiroki Tanabe, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Gastrointestinal Endoscopy   95 ( 6 )   1276 - 1277   2022.6

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  • Late-onset posttransplant Epstein-Barr virusrelated lymphoproliferative disease after cord blood transplantation for chronic active Epstein Barr virus infection: A case report. Reviewed International journal

    Masayo Yamamoto, Motohiro Shindo, Takuya Funayama, Chihiro Sumi, Takeshi Saito, Yasumichi Toki, Mayumi Hatayama, Ken-Ichi Imadome, Yusuke Mizukami, Toshikatsu Okumura

    Medicine   101 ( 12 )   e29055   2022.3

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    INTRODUCTION: Posttransplant lymphoproliferative disease (PTLD) is a critical complication of hematopoietic stem cell transplantation (HSCT). PTLD is classified into early and late-onset PTLDs. In post-HSCT patients, late-onset PTLD is rare, particularly PTLD after HSCT for Epstein-Barr virus (EBV)-related lymphoproliferative disease. Here, we report the case of a patient diagnosed with late-onset EBV-related hemophagocytic lymphohistiocytosis (HLH), that of PTLD, after HSCT for chronic active EBV infection (CAEBV), that of EBV related lymphoproliferative disease, probably because of EBV reactivation. PATIENT CONCERNS AND DIAGNOSIS: A 22-year-old woman with abdominal fullness visited our hospital. Blood examination showed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed slight hemophagocytosis with increased natural-killer cells (NK cells). As serum antibodies against EBV were atypical, we calculated the EBV-DNA level in peripheral blood and this level was significantly high. EBV was infected with NK cells, and EBV's monoclonality in NK cells was confirmed. Thus, the patient was diagnosed with CAEBV. INTERVENTIONS AND OUTCOMES: The patient received chemotherapy and cord blood cell transplantation (CBT); CAEBV was well controlled. Approximately 6years from CBT for CAEBV, she visited our hospital because of fever. Blood examination revealed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed hemophagocytosis with increased B and T cell counts without increased NK cell count. Additionally, serum antibody titers against EBV were atypical, and the EBV-DNA level in the peripheral blood was high. EBV was infected with only B cells, and EBV's monoclonality was confirmed. A more detailed analysis indicated that EBV-specific cytotoxic T lymphocytes were inactive. Therefore, she was diagnosed with late-onset EBV-related HLH. She received extensive treatment, but EBV-related HLH did not improve. Finally, she died about 3 weeks after diagnosis. CONCLUSION: PTLD, including HLH, is a life-threatening complication after transplantation, including HSCT. To our knowledge, this is the first case of late-onset EBV-related HLH after CBT for CAEBV. Late-onset PTLD has an indolent clinical course, but our patient's disease course was extremely aggressive. Therefore, late-onset EBV-related PTLD may be life-threatening.

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  • Distinct effects of TU-100 (daikenchuto) on long-lasting dysbiosis in the small intestine in patients with colorectal cancer and inflammatory bowel disease. Reviewed International journal

    Toru Kono, Taku Maejima, Yusuke Ono, Takahiro Ito, Shigeru Furukawa, Mitsue Nishiyama, Masahiro Yamamoto, Ayumu Sugitani, Hidenori Karasaki, Yusuke Mizukami, Atsuo Maemoto

    Gene   820   146266 - 146266   2022.2

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    The profile of the human small intestinal microbiota remains to be uncovered primarily due to sampling difficulties. Ileostomy provides the intestinal luminal contents as ileostomy effluents (IE) that offer opportunity for performing extensive analyses of nutrients, gastrointestinal fluids, metabolites, and microbiome. In the present study, we evaluated changes in the microbiome, pH, and bacterial short-chain fatty acids (SCFAs) in IE obtained from patients who had undergone ileostomy following surgical resection of colon cancer and inflammatory bowel disease (IBD). We enrolled 11 patients who varied in the duration of ileostomy from 3 days to >5 years after surgery and had no inflammation in the small intestine. The analyses suggested that IE from patients previously having IBD had less diversity and greater intraday and interday fluctuations, and increased pH and decreased levels of propionic acid and acetic acid than those in IE from patients previously having cancer. Furthermore, correlation analysis suggested a possible effect of the intestinal microbiome on luminal pH, presumably via SCFA production. The present study suggested that inflammation in the colon may induce long-term dysbiosis in the small intestine even after removal of diseased parts of the colon. Moreover, pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) was found to have beneficial effects on postoperative bowel dysfunction and the human small intestinal microbiota. Taken together, these results suggest the necessity of a direct remedy for dysbiosis and the treatment of gastrointestinal lesions to achieve favorable outcomes for chronic gastrointestinal disorders.

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  • RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival. Reviewed International journal

    Kenzui Taniue, Tanzina Tanu, Yuki Shimoura, Shuhei Mitsutomi, Han Han, Rika Kakisaka, Yusuke Ono, Nobue Tamamura, Kenji Takahashi, Youichiro Wada, Yusuke Mizukami, Nobuyoshi Akimitsu

    International Journal of Molecular Sciences   23 ( 1 )   2022.1

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    The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies' datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.

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  • Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC). Reviewed International journal

    Kazuyuki Tanaka, Hiroki Tanabe, Hiroki Sato, Chisato Ishikawa, Mitsuru Goto, Naoyuki Yanagida, Hiromitsu Akabane, Shiro Yokohama, Kimiharu Hasegawa, Yohei Kitano, Yuya Sugiyama, Kyoko Uehara, Yu Kobayashi, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Keisuke Sato, Sayaka Yuzawa, Mishie Tanino, Masaki Taruiishi, Yasuo Sumi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Cancer Medicine   11 ( 2 )   406 - 416   2022.1

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    BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

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  • Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study. Reviewed International journal

    Kohichi Takada, Tomohiro Kubo, Junko Kikuchi, Makoto Yoshida, Ayako Murota, Yohei Arihara, Hajime Nakamura, Hiroyuki Nagashima, Hiroki Tanabe, Shintaro Sugita, Yumi Tanaka, Ayana Miura, Yoshihito Ohhara, Atsushi Ishiguro, Hiroshi Yokouchi, Yasuyuki Kawamoto, Yusuke Mizukami, Hirofumi Ohnishi, Ichiro Kinoshita, Akihiro Sakurai

    Frontiers in oncology   12   988527 - 988527   2022

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    Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

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  • Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis Reviewed International journal

    Hiroki Sato, Takeshi Saito, Hiroshi Horii, Mami Kajiura, Noriaki Kikuchi, Nobuhisa Takada, Koichi Taguchi, Mika Yoshida, Masakazu Hasegawa, Hiroyuki Taguchi, Yukinori Yoshida, Katsuyoshi Ando, Mikihiro Fujiya, Yuko Omori, Thomas Hank, Andrew S. Liss, Manish A. Gala, Yoshio Makita, Yusuke Ono, Yusuke Mizukami, Toshikatsu Okumura

    Frontiers in Genetics   12   608324 - 608324   2021.9

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    Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for &amp;gt;3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed <italic>TP53</italic> Q192X mutation, whereas <italic>SMAD4</italic> S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in <italic>TP53</italic>. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the <italic>TP53</italic> gene might have occurred during the differentiation of the founder clone into NEC, while a <italic>SMAD4</italic> mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

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  • リキッドバイオプシー、内視鏡下採取検体による分子プロファイリング EUS-FNA検体と血清を用いた膵癌診断における長鎖ノンコーディングRNAの有用性 Reviewed

    高橋 賢治, 小山 一也, 川尻 はるな, 佐藤 裕基, 藤林 周吾, 林 明宏, 河端 秀賢, 岩本 英孝, 後藤 拓磨, 山北 圭介, 北野 陽平, 水上 裕輔, 奥村 利勝

    膵臓   36 ( 3 )   A252 - A252   2021.8

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  • Generation of combined hepatocellular-cholangiocarcinoma through transdifferentiation and dedifferentiation in p53-knockout mice. Reviewed International journal

    Yang Liu, Bing Xin, Masahiro Yamamoto, Masanori Goto, Takako Ooshio, Yuki Kamikokura, Hiroki Tanaka, Lingtong Meng, Yoko Okada, Yusuke Mizukami, Yuji Nishikawa

    Cancer Science   112 ( 8 )   3111 - 3124   2021.8

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    The two principal histological types of primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma, can coexist within a tumor, comprising combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Although the possible involvement of liver stem/progenitor cells has been proposed for the pathogenesis of cHCC-CCA, the cells might originate from transformed hepatocytes that undergo ductular transdifferentiation or dedifferentiation. We previously demonstrated that concomitant introduction of mutant HRASV12 (HRAS) and Myc into mouse hepatocytes induced dedifferentiated tumors that expressed fetal/neonatal liver genes and proteins. Here, we examine whether the phenotype of HRAS- or HRAS/Myc-induced tumors might be affected by the disruption of the Trp53 gene, which has been shown to induce biliary differentiation in mouse liver tumors. Hepatocyte-derived liver tumors were induced in heterozygous and homozygous p53-knockout (KO) mice by hydrodynamic tail vein injection of HRAS- or Myc-containing transposon cassette plasmids, which were modified by deleting loxP sites, with a transposase-expressing plasmid. The HRAS-induced and HRAS/Myc-induced tumors in the wild-type mice demonstrated histological features of HCC, whereas the phenotype of the tumors generated in the p53-KO mice was consistent with cHCC-CCA. The expression of fetal/neonatal liver proteins, including delta-like 1, was detected in the HRAS/Myc-induced but not in the HRAS-induced cHCC-CCA tissues. The dedifferentiation in the HRAS/Myc-induced tumors was more marked in the homozygous p53-KO mice than in the heterozygous p53-KO mice and was associated with activation of Myc and YAP and suppression of ERK phosphorylation. Our results suggest that the loss of p53 promotes ductular differentiation of hepatocyte-derived tumor cells through either transdifferentiation or Myc-mediated dedifferentiation.

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  • Prognostic significance of skeletal muscle decrease in unresectable pancreatic cancer: Survival analysis using the Weibull exponential distribution model. Reviewed International journal

    Hiroki Sato, Takuma Goto, Akihiro Hayashi, Hidemasa Kawabata, Tetsuhiro Okada, Shuhei Takauji, Junpei Sasajima, Katsuro Enomoto, Mikihiro Fujiya, Kyohei Oyama, Yusuke Ono, Ayumu Sugitani, Yusuke Mizukami, Toshikatsu Okumura

    Pancreatology   21 ( 5 )   892 - 902   2021.8

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    BACKGROUND/OBJECTIVES: Decrease in skeletal muscle mass and function is associated with a poor prognosis following surgical resection of pancreatic ductal adenocarcinomas (PDAs). This study evaluated whether skeletal muscle mass decrease affects PDA outcomes. METHODS: Data of 112 patients with advanced and unresectable PDA who underwent chemotherapy in a single institution were retrospectively analyzed. Information on age, sex, hematological investigations, including systemic inflammation-based markers and nutritional assessment biomarkers, and imaging parameters of skeletal muscle mass and visceral adipose tissue were retrieved from the patients' medical records. The efficiency of the Cox, Weibull, and standardized exponential models were compared using hazard ratios and the Akaike Information Criterion (AIC). RESULTS: Results from the Weibull, Cox, and standardized exponential model analyses indicated that low skeletal muscle mass, Eastern Cooperative Oncology Group performance status (PS), and the requirement of biliary drainage were associated with the highest risk of death, followed by carcinoembryonic antigen (CEA) levels and the presence of ascites. The AIC value from the four significant parameters was lowest for the Weibull-exponential distribution (222.3) than that of the Cox (653.7) and standardized exponential models (265.7). We developed a model for estimating the 1-year survival probability using the Weibull-exponential distribution. CONCLUSIONS: Low-skeletal muscle index, PS, requirement of biliary drainage, CEA levels, and presence of ascites are independent factors for predicting poor patient survival after chemotherapy. Improved survival modeling using a parametric approach may accurately predict the outcome of patients with advanced-stage PDA.

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  • 膵多発SPN(solid-pseudopapillary neoplasm)の1例 Reviewed

    林 明宏, 佐藤 裕基, 藤林 周吾, 河端 秀賢, 岩本 英孝, 高橋 賢治, 後藤 拓磨, 山北 圭介, 北野 陽平, 水上 裕輔, 奥村 利勝

    膵臓   36 ( 3 )   A405 - A405   2021.8

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  • Trial protocol: a randomised controlled trial to verify the non-inferiority of a partially covered self-expandable metal stent to an uncovered self-expandable metal stent for biliary drainage during neoadjuvant therapy in patients with pancreatic cancer with obstructive jaundice (PUN-NAC trial). Reviewed International journal

    Masaki Kuwatani, Kazumichi Kawakubo, Kazuya Sugimori, Hiroyuki Inoue, Hideki Kamada, Hirotoshi Ishiwatari, Shin Kato, Takuji Iwashita, Makoto Yoshida, Shinichi Hashimoto, Masahiro Itonaga, Yusuke Mizukami, Yusuke Nomura, Akio Katanuma, Naoya Sakamoto

    BMJ Open   11 ( 7 )   e045698   2021.7

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    INTRODUCTION: Neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (NAC/NACRT) for resectable/borderline resectable pancreatic cancers was recently performed to improve clinical outcomes and led to good results, although it remains controversial whether NAC/NACRT is beneficial for resectable pancreatic cancer. A few recent studies revealed longer patency and lower cost related to the stent occlusion of a metal stent than those of a plastic stent during NAC/NACRT. It also remains controversial which type of self-expandable metal stent (SEMS) is the most suitable for patients with resectable/borderline resectable pancreatic cancer during NAC/NACRT: an uncovered SEMS (USEMS), a fully covered SEMS (FCSEMS) or a partially covered SEMS (PCSEMS). So far, two randomised controlled trials indicated that a USEMS and an FCSEMS were similar in preoperative stent dysfunction and adverse event rate. Thus, we aimed to verify the non-inferiority of a PCSEMS to a USEMS in this multicentre randomised controlled trial. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial, for which we will recruit 100 patients with resectable/borderline resectable pancreatic cancer and distal biliary obstruction scheduled for NAC/NACRT from 13 high-volume institutions. Patients will be randomly allocated to the PCSEMS group or USEMS group. The primary outcome measure is the preoperative biliary event rate. Data will be analysed after completion of the study. We will calculate the 95% CIs of the incidence of preoperative biliary events in each group and analyse whether the difference between them is within the non-inferiority margin (10%). ETHICS AND DISSEMINATION: This study has been approved by the institutional review board of Hokkaido University Hospital. The results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000041737; jRCT1012200002.

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  • Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria. International journal

    Hiroki Tanabe, Yusuke Mizukami, Hidehiro Takei, Nobue Tamamura, Yuhi Omura, Yu Kobayashi, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Sayaka Yuzawa, Kimiharu Hasegawa, Yasuo Sumi, Mishie Tanino, Mikihiro Fujiya, Toshikatsu Okumura

    The Journal of Pathology. Clinical Research   7 ( 4 )   397 - 409   2021.7

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    Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein-Barr virus (EBV) and microsatellite-unstable tumors are considered to be the two major subtypes as they are clearly defined by well-established methodologies, such as in situ hybridization and polymerase chain reaction-based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re-evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low- and high-grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re-evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV-positive (11.1%), 7 MSI-high (MSI-H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI-H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death-ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI-H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV-positive carcinomas were poorly differentiated (83.8%), and MSI-H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV-positive subtype presented with high-grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.

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  • Large-duct pattern invasive adenocarcinoma of the pancreas-a variant mimicking pancreatic cystic neoplasms: A minireview. Reviewed International journal

    Hiroki Sato, Andrew Scott Liss, Yusuke Mizukami

    World Journal of Gastroenterology   27 ( 23 )   3262 - 3278   2021.6

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    Pancreatic cancer currently has no subtypes that inform clinical decisions; hence, there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics. Nonetheless, accumulating studies to date have revealed the large-duct type variant, a unique subtype of pancreatic ductal adenocarcinoma (PDA) with cystic features. This subtype often radiographically mimics intraductal papillary mucinous neoplasms (IPMNs) and involves multiple small cysts occasionally associated with solid masses. The "bunch-of-grapes" sign, an imaging characteristic of IPMNs, is absent in large-duct PDA. Large-duct PDA defines the mucin profile, and genetic alterations are useful in distinguishing large-duct PDA from IPMNs. Histologically, neoplastic ducts measure over 0.5 mm, forming large ductal elements. Similar to classic PDAs, this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions, and KRAS mutations in codon 12 are nearly ubiquitous. Despite such morphological similarities with IPMNs, the prognosis of large-duct PDA is equivalent to that of classic PDA. Differential diagnosis is therefore essential.

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  • Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas. Reviewed

    Toshikazu Kobayashi, Yuko Omori, Yusuke Ono, Hidenori Karasaki, Yusuke Mizukami, Naohiko Makino, Fuyuhiko Motoi, Michiaki Unno, Yoshiyuki Ueno, Toru Furukawa

    Journal of Gastroenterology   56 ( 6 )   581 - 592   2021.6

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    BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN. METHODS: We obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas. RESULTS: Gastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as "progressive", "divergent", and "independent". The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently. CONCLUSION: These findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.

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  • Monitoring epidermal growth factor receptor C797S mutation in Japanese non-small cell lung cancer patients with serial cell-free DNA evaluation using digital droplet PCR. International journal

    Ryo Ariyasu, Ken Uchibori, Takaaki Sasaki, Mika Tsukahara, Kazuma Kiyotani, Ryohei Yoshida, Yusuke Ono, Satoru Kitazono, Hironori Ninomiya, Yuichi Ishikawa, Yusuke Mizukami, Noriko Yanagitani, Naoya Fujita, Makoto Nishio, Ryohei Katayama

    Cancer Science   112 ( 6 )   2371 - 2380   2021.6

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    Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is effective in treating both naïve and T790M-mutated EGFR-TKI-resistant non-small cell lung cancer patients. The EGFR C797S mutation is the major osimertinib resistance mechanism. The present study monitored the EGFR C797S mutation during osimertinib treatment in Japanese patients using droplet digital PCR (ddPCR). In our first cohort, C797S detection was validated with tumor specimens and/or plasma samples from 26 patients using ddPCR with custom-designed probes detecting and discriminating T790M and C797S in cis and trans positions. In our second cohort, 18 patients with EGFR-T790M who were going to start osimertinib were analyzed using ddPCR by collecting the plasma samples every month from the beginning of the course of osimertinib. In the first cohort, C797S was detected in 15.4% of patients. C797S and T790M in cis and trans positions were distinguished using ddPCR. In the second cohort, serial cfDNA evaluation revealed that the rate of EGFR mutation changes with disease state. Increases of EGFR mutation were detected, including C797S several months before the diagnosis of disease progression. As with the first cohort, C797S and T790M in cis and trans position were distinguished by ddPCR at disease progression. Coincidentally, in the first cohort, next generation sequencing detected NRAS Q61K mutation and the resistance with NRAS Q61K mutation was overcome by trametinib. In the second cohort, serial cfDNA analysis was useful for evaluating bone oligo-progression and local radiation therapy.

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  • The feasibility of circulating tumor DNA analysis as a marker of recurrence in triple-negative breast cancer. International journal

    Satoshi Okazaki, Takaaki Sasaki, Shunsuke Yasuda, Masahiro Abe, Nana Yoshida, Ryohei Yoshida, Kei Ishibashi, Yoshinori Minami, Shunsuke Okumura, Shinichi Chiba, Hidehiro Takei, Ryusuke Hayashi, Toshihiro Nagato, Hiroya Kobayashi, Ayumu Sugitani, Yusuke Ono, Yusuke Mizukami, Masahiro Kitada, Yoshinobu Ohsaki

    Oncology Letters   21 ( 5 )   420 - 420   2021.5

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    Triple-negative breast cancer (TNBC) has a poorer prognosis than other breast cancer subtypes; therefore, identifying markers of early recurrence is important. The present study aimed to establish a liquid biopsy protocol for droplet digital PCR-based detection of frequently mutated genes in patients with TNBC. Tumor DNA from 36 patients with TNBC who relapsed within 2 years after surgical resection was retrospectively analyzed. Somatic mutational profiles were evaluated using targeted sequencing to identify frequently mutated genes and genes associated with molecularly targeted therapies. The association between genetic alterations and associated protein phosphorylation was investigated using immunohistochemical analysis. Recurrent hot spot mutations in the plasma were monitored over time. Mutation-specific probes were used to successfully detect mutations in the blood samples of patients who were positive for PIK3CA H1047R and AKT1 E17K mutations. Somatic mutations in AKT1 (14.9%) and PIK3CA (25.5%) were frequently identified in the data. Robust phosphorylation of AKT and S6RP was more common in tumors with PIK3CA H1047R and AKT1 E17K mutational background than in tumors with wild-type PIK3CA and AKT1. In conclusion, the present study evaluated a high-sensitivity detection system for frequently mutated genes that was also applicable for cell-free DNA. The PI3K/AKT pathway was revealed to be activated in patients harboring PIK3CA H1047R and AKT1 E17K mutations; therefore, the PI3K/AKT pathway may be a promising candidate for targeted therapy in these patients.

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  • Ampullary tumor with a rare etiology: A new lesion in the residual ampulla following curative resection of the perihilar cholangiocarcinoma. International journal

    Haruka Toyonaga, Yusuke Mizukami, Akio Katanuma

    Gastroenterology   161 ( 6 )   e6-e9   2021.4

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    DOI: 10.1053/j.gastro.2021.04.049

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  • Acquired hemophilia A associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report. International journal

    Masayo Yamamoto, Motohiro Shindo, Chihiro Sumi, Sho Igarashi, Takeshi Saito, Nodoka Tsukada, Yasumichi Toki, Mayumi Hatayama, Junki Inamura, Kazuya Sato, Yusuke Mizukami, Yoshihiro Torimoto, Toshikatsu Okumura

    Medicine   100 ( 16 )   e25518   2021.4

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    INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD. HISTORY: A 69-year-old man visited our hospital because of general fatigue. Blood examination showed pancytopenia, and computed tomography revealed whole-body lymphadenopathy, but there were no findings indicating hematological malignancy from bone marrow aspiration and cervical lymph node biopsy. The level of EBV DNA in peripheral blood was extremely high, and he was diagnosed with EBV-T/NK-LPD. EBV-T/NK-LPD improved with prednisolone (PSL) administration. Seventeen months after starting treatment, the patient complained of back and right leg pain. At that time, he had been treated with low-dose PSL, and EBV-T/NK-LPD was well controlled. Imaging revealed hematoma of the right iliopsoas muscle. Prolonged activated partial thromboplastin time (APTT) was the only abnormal finding in a screening coagulation test. FVIII coagulant activity was below detection limit, and FVIII inhibitor level was increased. From these results, he was diagnosed with AHA.A higher dose of PSL was administered, and, after 1 month of treatment, FVIII activity gradually increased, and FVIII inhibitor level became undetectable. APTT also normalized, and complete remission was achieved and maintained for 13 months with low-dose PSL. During treatment, EBV-T/NK-LPD was well controlled. CONCLUSION: It is speculated that proliferating lymphocytes interfere with normal immune functions and that abnormal autoantibodies are produced from those lymphocytes in patients with LPD. Therefore, we speculate that EBV-infected and proliferating monoclonal NK cells might have modulated the immune system and produced autoantibodies against FVIII, thus causing AHA in this patient with EBV-T/NK-LPD.

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  • Intracholecystic papillary neoplasm arising in the cystic duct and extending into common bile duct: a case report.

    Masahiro Iseki, Masamichi Mizuma, Yasutaka Aoki, Shuichi Aoki, Tatsuo Hata, Tatsuyuki Takadate, Kei Kawaguchi, Kunihiro Masuda, Masaharu Ishida, Hideo Ohtsuka, Kei Nakagawa, Hiroki Hayashi, Takanori Morikawa, Takashi Kamei, Kiyoshi Kume, Atsushi Kanno, Atsushi Masamune, Yuko Omori, Yusuke Ono, Yusuke Mizukami, Toru Furukawa, Michiaki Unno

    Clinical Journal of Gastroenterology   14 ( 2 )   668 - 677   2021.4

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    An 83-year-old man without specific symptoms was referred to our hospital for further evaluation and treatment of apparent double primary tumors of the cystic duct and common bile duct. Computed tomography showed contrast-enhanced solid tumors in the cystic duct and common bile duct. Magnetic resonance imaging showed that the bile duct tumor was isointense on T1-weighted images and had low intensity on T2-weighted images. In addition, the bile duct tumor showed high intensity on diffusion-weighted images. Endoscopic ultrasonography revealed the tumor of the common bile duct and endoscopic retrograde cholangiopancreatography demonstrated a filling defect in the bile duct. The cystic duct was not identified on endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography. Transpapillary biopsy of the bile duct tumor showed adenocarcinoma. The patient was diagnosed with double primary tumors of the cystic duct and the common bile duct and underwent subtotal stomach-preserving pancreaticoduodenectomy. Microscopic examination with molecular profiling of the tumors revealed a high-grade noninvasive intracholecystic papillary neoplasm of the cystic duct extending into the common bile duct and forming a tubulopapillary neoplasm with invasion of the common bile duct.

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  • Polyphosphate, Derived from Lactobacillus brevis, Modulates the Intestinal Microbiome and Attenuates Acute Pancreatitis. International journal

    Shuhei Takauji, Hiroaki Konishi, Mikihiro Fujiya, Nobuhiro Ueno, Hiroki Tanaka, Hiroki Sato, Shotaro Isozaki, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura

    Digestive Diseases and Sciences   66 ( 11 )   3872 - 3884   2021.1

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    BACKGROUND: We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. AIMS: We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. METHODS: Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. RESULTS: The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. CONCLUSIONS: Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.

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  • Successful Treatment of Myeloid Sarcoma in an Elderly Patient with Myelodysplastic Syndrome with Reduced-Dose Azacitidine. International journal

    Kazuya Sato, Nodoka Tsukada, Junki Inamura, Shigetsuna Komatsu, Keisuke Sato, Masayo Yamamoto, Motohiro Shindo, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Yoshihiro Torimoto, Toshikatsu Okumura

    Case Reports in Hematology   2021   6640597 - 6640597   2021

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    Myeloid sarcoma (MS), which involves extramedullary lesions, is classified as a unique subtype of acute myeloid leukemia (AML). At present, no standard treatments for MS have been established. The patient was an 89-year-old man with myelodysplastic syndrome-excess blast-2 (MDS-EB-2) with a 2-year history of intermittent treatment with azacitidine (AZA) during a 4-year history of MDS. He developed painful cutaneous tumors 8 months after the second discontinuation of AZA. They were refractory for antibiotics and topical tacrolimus hydrate. A tumor biopsy was performed, and the histological findings of the tumor lesion showed a proliferation of tumor cells that were positive for myeloperoxidase and CD68 and negative for CD4 and CD123. The patient was diagnosed with MDS-associated MS. MDS-EB-2 quickly progressed to AML with the appearance of peripheral blood blasts and 25% bone marrow blasts. Monotherapy with reduced-dose AZA (37.5 mg/m2 for 7 days, every 4-6 weeks) was restarted, and the MS quickly disappeared. The patient's MS was successfully treated with 16 cycles of AZA treatment over a 22-month period. There have been 10 reported cases in which MS was successfully treated with AZA. Among the 10 cases, the patient in the present case was the oldest. Treatment with reduced-dose AZA should be considered as a therapeutic option for MS in elderly patients with MDS, especially patients who are ineligible for intensive chemotherapy.

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  • Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer. Reviewed International journal

    Kenji Takahashi, Kenzui Taniue, Yusuke Ono, Mikihiro Fujiya, Yusuke Mizukami, Toshikatsu Okumura

    Frontiers in Molecular Biosciences   8   717890 - 717890   2021

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    Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

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  • A Case of Adult Pancreatoblastoma With Novel APC Mutation and Genetic Heterogeneity. International journal

    Yamato Suemitsu, Yusuke Ono, Yusuke Mizukami, Juanjuan Ye, Keiko Yamakawa, Takeshi Takamoto, Yuko Nakano-Narusawa, Yuri Mukai, Manabu Takamatsu, Atsuko Nakazawa, Mari Mino-Kenudson, Toshio Kumasaka, Yoko Matsuda

    Frontiers in oncology   11   725290 - 725290   2021

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    Background: Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT/β-catenin pathway, such as CTNNB1 mutation. However, the molecular abnormalities in adult pancreatoblastoma are not well known. Case Presentation: An elderly man, who underwent elective distal pancreatectomy and splenectomy, was referred to our hospital with a mass in the tail of the pancreas. Histologically, the lesion revealed proliferation of clear, basophilic, and cartilaginous tumor cells with lymphatic metastasis. Each of the morphologically distinct tumor components showed different immunohistochemical patterns, indicating heterogeneous differentiation, including epithelial (both acinar and ductal), mesenchymal, and neuroendocrine differentiation. All tumor components showed nuclear expression of β-catenin and cyclin D1. Per next-generation sequencing (NGS), the clear and basophilic tumor cells shared mutations in APC, GRM8, LAMP1, and AKA9. Among the mutations, APC, c.1816_1817insA showed the highest frequency in both cell types, indicating that APC mutation was a driver mutation of the tumor. A diagnosis of PB was rendered. Summary: In conclusion, the clear and basophilic cells of the tumor were supposedly derived from the same clone and subsequently acquired additional mutations. This is the first report of clonal evolution in pancreatoblastoma.

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  • Serrated adenomas with a BRAF mutation in a young patient with familial adenomatous polyposis Reviewed International journal

    Kentaro Moriichi, Hiroki Tanabe, Yusuke Ono, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Hidehiro Takei, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    International Journal of Colorectal Disease   35 ( 10 )   1967 - 1972   2020.10

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    DOI: 10.1007/s00384-020-03657-0

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  • Genetic alteration of colorectal adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis Reviewed International journal

    Hiroki Tanabe, Kentaro Moriichi, Keitaro Takahashi, Yusuke Ono, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Hidehiro Takei, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Molecular Genetics and Genomic Medicine   8 ( 9 )   e1348   2020.9

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  • 【膵疾患の病理学的診断の現状と課題】膵癌の初期発生とリキッドバイオプシーによる分子診断

    岡田 哲弘, 水上 裕輔, 林 明宏, 河端 秀賢, 佐藤 裕基, 河本 徹, 後藤 拓磨, 谷上 賢瑞, 小野 裕介, 唐崎 秀則, 奥村 利勝

    膵臓   35 ( 4 )   302 - 312   2020.8

  • Time-saving method for directly amplifying and capturing a minimal amount of pancreatic tumor-derived mutations from fine-needle aspirates using digital PCR. Reviewed International journal

    Yusuke Ono, Akihiro Hayashi, Chiho Maeda, Mayumi Suzuki, Reona Wada, Hiroki Sato, Hidemasa Kawabata, Tetsuhiro Okada, Takuma Goto, Hidenori Karasaki, Yusuke Mizukami, Toshikatsu Okumura

    Scientific Reports   10 ( 1 )   12332 - 12332   2020.7

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    It is challenging to secure a cytopathologic diagnosis using minute amounts of tumor fluids and tissue fragments. Hence, we developed a rapid, accurate, low-cost method for detecting tumor cell-derived DNA from limited amounts of specimens and samples with a low tumor cellularity, to detect KRAS mutations in pancreatic ductal carcinomas (PDA) using digital PCR (dPCR). The core invention is based on the suspension of tumor samples in pure water, which causes an osmotic burst; the crude suspension could be directly subjected to emulsion PCR in the platform. We examined the feasibility of this process using needle aspirates from surgically resected pancreatic tumor specimens (n = 12). We successfully amplified and detected mutant KRAS in 11 of 12 tumor samples harboring the mutation; the positive mutation frequency was as low as 0.8%. We used residual specimens from fine-needle aspiration/biopsy and needle flush processes (n = 10) for method validation. In 9 of 10 oncogenic KRAS pancreatic tumor samples, the "water-burst" method resulted in a positive mutation call. We describe a dPCR-based, super-sensitive screening protocol for determining KRAS mutation availability using tiny needle aspirates from PDAs processed using simple steps. This method might enable pathologists to secure a more accurate, minimally invasive diagnosis using minute tissue fragments.

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    Other Link: http://www.nature.com/articles/s41598-020-69221-6

  • REDD1 loss reprograms lipid metabolism to drive progression of RAS mutant tumors Reviewed

    Qiao, S., Koh, S.-B., Vivekan, an, V., Salunke, D., Patra, K.C., Zaganjor, E., Ross, K., Mizukami, Y., Jeanfavre, S., Chen, A., Mino-Kenudson, M., Ramaswamy, S., Clish, C., Haigis, M., Bardeesy, N., Ellisen, L.W.

    Genes &amp; development   34 ( 11-12 )   2020

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  • How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression Reviewed International journal

    Omori, Y., Ono, Y., Kobayashi, T., Motoi, F., Karasaki, H., Mizukami, Y., Makino, N., Ueno, Y., Unno, M., Furukawa, T.

    Virchows Archiv   477 ( 1 )   21 - 31   2020

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    DOI: 10.1007/s00428-020-02806-8

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  • Genetic Tracing of Clonal Expansion and Progression of Pancreatic Ductal Adenocarcinoma: A Case Report and Multi-Region Sequencing Analysis Reviewed

    Tachibana, S., Mizukami, Y., Ono, Y., Sugiyama, Y., Okada, T., Kitazaki, A., Sasajima, J., Tominaga, M., Sakamoto, J., Kimura, K., Omori, Y., Furukawa, T., Kimura, T., Tanaka, S., Nagashima, K., Karasaki, H., Ohta, T., Okumura, T.

    Frontiers in Oncology   10   2020

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    DOI: 10.3389/fonc.2020.00728

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  • Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes Reviewed International journal

    Aoki, Y., Mizuma, M., Hata, T., Aoki, T., Omori, Y., Ono, Y., Mizukami, Y., Unno, M., Furukawa, T.

    Journal of Pathology   251 ( 1 )   38 - 48   2020

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  • Resection for pancreatic cancer metastases contributes to survival: A case report with sequential tumor genotype profiling during the long-term postoperative course Reviewed

    Sato, H., Sasajima, J., Okada, T., Hayashi, A., Kawabata, H., Goto, T., Koizumi, K., Tamamura, N., Tanabe, H., Fujiya, M., Chiba, S.-I., Tanino, M., Ono, Y., Mizukami, Y., Okumura, T.

    Medicine   99 ( 25 )   e20564 - e20564   2020

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  • Genetic analysis of postoperative recurrence of pancreatic cancer potentially owing to needle tract seeding during EUS-FNB. Reviewed International journal

    Hidemasa Kawabata, Yuki Miyazawa, Hiroki Sato, Tetsuhiro Okada, Akihiro Hayashi, Takuya Iwama, Shugo Fujibayashi, Takuma Goto, Junpei Sasajima, Shuhei Takauji, Mikihiro Fujiya, Yoshihiro Torimoto, Mishie Tanino, Yuko Omori, Yusuke Ono, Hidenori Karasaki, Yusuke Mizukami, Toshikatsu Okumura

    Endoscopy International Open   7 ( 12 )   E1768-E1772   2019.12

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    Background and study aims  Needle tract seeding during endoscopic ultrasound fine-needle biopsy (EUS-FNB) remains a concern. We investigated whether such seeding occurred in a patient with pancreatic ductal adenocarcinoma (PDA). Patient and methods  Surgically resected and EUS-FNB-derived specimens were genotyped to determine if a gastric wall tumor that emerged 3 years after curative resection of an early-stage PDA was clonally related to the original tumor. Results  The gastric tumor histologically resembled the primary PDA; the lesions also shared KRAS , SMAD4 , and RNF43 mutations. Genotyping of the preoperative EUS-FNB specimen, in which cancer was not detected, nevertheless revealed mutations that were identical to those in the resected primary and recurrent tumors. While the primary PDA had a low frequency of mutant SMAD4 , such mutations were highly prevalent in both the EUS-FNB and recurrent tumor specimens. Conclusions  The genetic lineages of sampled tissues from our patient revealed that needle tract seeding may have incidentally occurred when a subset of neoplastic cells within a heterogeneous tumor ( i. e. , an aggressive clone) was targeted during EUS-FNB.

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  • Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient Reviewed International journal

    Kashima, S., Tanabe, H., Tanino, M., Kobayashi, Y., Murakami, Y., Iwama, T., Sasaki, T., Kunogi, T., Takahashi, K., Ando, K., Ueno, N., Moriichi, K., Fukudo, M., Tasaki, Y., Hosokawa, M., Mizukami, Y., Fujiya, M., Okumura, T.

    Frontiers in Oncology   9   1375 - 1375   2019

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    DOI: 10.3389/fonc.2019.01375

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  • Clinical course of conservative management for isolated superior mesenteric arterial dissection Reviewed International journal

    Sosogi, S., Sato, R., Wada, R., Saito, H., Takauji, S., Sakamoto, J., Kimura, K., Karasaki, H., Mizukami, Y., Ohta, T.

    European Journal of Radiology Open   6   192 - 197   2019

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    DOI: 10.1016/j.ejro.2019.05.004

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  • Autofluorescence imaging reflects the nuclear enlargement of tumor cells as well as the cell proliferation ability and aberrant status of the p53, Ki-67, and p16 genes in colon neoplasms Reviewed

    Moriichi, K., Fujiya, M., Kobayashi, Y., Murakami, Y., Iwama, T., Kunogi, T., Sasaki, T., Ijiri, M., Takahashi, K., Tanaka, K., Sakatani, A., Ando, K., Nomura, Y., Ueno, N., Kashima, S., Ikuta, K., Tanabe, H., Mizukami, Y., Saitoh, Y., Okumura, T.

    Molecules   24 ( 6 )   2019

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  • A Case of Alpha-Fetoprotein-Producing Adenocarcinoma of the Esophagogastric Junction in which Long-Term Survival Was Achieved by Means of Individualized Multidisciplinary Therapy Reviewed

    Tanaka, K., Fujiya, M., Ijiri, M., Takahashi, K., Ando, K., Nomura, Y., Ueno, N., Kashima, S., Goto, T., Sasajima, J., Ito, T., Moriichi, K., Mizukami, Y., Tanabe, H., Okumura, T.

    Journal of Gastrointestinal Cancer   50 ( 3 )   617 - 620   2019

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    DOI: 10.1007/s12029-018-0078-3

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  • ARF6 and AMAP1 are major targets of KRAS and TP53 mutations to promote invasion, PD-L1 dynamics, and immune evasion of pancreatic cancer Reviewed

    Hashimoto, S., Furukawa, S., Hashimoto, A., Tsutaho, A., Fukao, A., Sakamura, Y., Parajuli, G., Onodera, Y., Otsuka, Y., Handa, H., Oikawa, T., Hata, S., Nishikawa, Y., Mizukami, Y., Kodama, Y., Murakami, M., Fujiwara, T., Hirano, S., Sabe, H.

    Proceedings of the National Academy of Sciences of the United States of America   116 ( 35 )   17450 - 17459   2019

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    DOI: 10.1073/pnas.1901765116

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  • Comparative genome-wide analysis of gastric adenocarcinomas with hyperplastic polyp components Reviewed International journal

    Takayama, Y., Ono, Y., Mizukami, Y., Itoh, H., Nakajima, N., Arai, H., Tanaka, S., Nobusawa, S., Yokoo, H., Onozato, Y.

    Virchows Archiv   475 ( 3 )   383 - 389   2019

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  • The Incidence and Risk Factors of Venous Thromboembolism in Patients with Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study Reviewed International journal

    Ando, K., Fujiya, M., Nomura, Y., Inaba, Y., Sugiyama, Y., Kobayashi, Y., Iwama, T., Ijiri, M., Takahashi, K., Ueno, N., Kashima, S., Moriichi, K., Tanabe, H., Mizukami, Y., Akasaka, K., Fujii, S., Yamada, S., Nakase, H., Okumura, T.

    Digestion   100 ( 4 )   229 - 237   2019

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  • Utility of "liquid biopsy" using pancreatic juice for early detection of pancreatic cancer. Reviewed International journal

    Okada T, Iwano H, Ono Y, Karasaki H, Sato T, Yamada M, Omori Y, Sato H, Hayashi A, Kawabata H, Goto T, Sasajima J, Takauji S, Nagashima K, Mizukami Y, Okumura T

    Endoscopy International Open   6 ( 12 )   E1454 - E1461   2018.12

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    Background  Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods  We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results  Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions  Our study indicates the potential of "endoscopic liquid biopsy" to capture the driver gene for PDA diagnosis.

    DOI: 10.1055/a-0721-1747

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  • Molecular basis of intraductal papillary mucinous neoplasm of the pancreas Invited

    Kawabata H, Mizukami Y, Okada T, Sato H, Hayashi A, Goto T, Ueda J, Ono Y, Karasaki H, Okumura T

    KAN・TAN・SUI (Japan)   77 ( 5 )   1003 - 1009   2018.11

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  • The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: a retrospective cohort study. Reviewed

    Ando K, Fujiya M, Nomura Y, Inaba Y, Sugiyama Y, Iwama T, Ijiri M, Takahashi K, Tanaka K, Sakatani A, Ueno N, Kashima S, Moriichi K, Mizukami Y, Okumura T

    Intestinal Research   16 ( 3 )   416 - 425   2018.7

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  • Takayasu's arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17 Reviewed

    Mikihiro Fujiya, Shin Kashima, Yuya Sugiyama, Takuya Iwama, Masami Ijiri, Kazuyuki Tanaka, Keitaro Takahashi, Katuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Takuma Goto, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura, Junpei Sasajima, Daisuke Fujishiro, Kensaku Okamoto, Yuichi Makino

    Gut Pathogens   10 ( 1 )   2018.6

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    DOI: 10.1186/s13099-018-0251-z

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  • An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker Reviewed

    Takuma Goto, Mikihiro Fujiya, Hiroaki Konishi, Junpei Sasajima, Shugo Fujibayashi, Akihiro Hayashi, Tatsuya Utsumi, Hiroki Sato, Takuya Iwama, Masami Ijiri, Aki Sakatani, Kazuyuki Tanaka, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Yutaka Kohgo, Toshikatsu Okumura

    BMC Cancer   18 ( 1 )   2018.1

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    DOI: 10.1186/s12885-018-4006-5

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  • Highly sensitive detection of ALK resistance mutations in plasma using droplet digital PCR Reviewed International journal

    Yoshida, R., Sasaki, T., Umekage, Y., Tanno, S., Ono, Y., Ogata, M., Chiba, S., Mizukami, Y., Ohsaki, Y.

    BMC Cancer   18 ( 1 )   1136 - 1136   2018

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    DOI: 10.1186/s12885-018-5031-0

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  • An improved digital polymerase chain reaction protocol to capture low-copy KRAS mutations in plasma cell-free DNA by resolving 'subsampling' issues Reviewed

    Yusuke Ono, Ayumu Sugitani, Hidenori Karasaki, Munehiko Ogata, Reo Nozaki, Junpei Sasajima, Tomoki Yokochi, Shingo Asahara, Kazuya Koizumi, Kiyohiro Ando, Katsunori Hironaka, Tsutomu Daito, Yusuke Mizukami

    MOLECULAR ONCOLOGY   11 ( 10 )   1448 - 1458   2017.10

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    DOI: 10.1002/1878-0261.12110

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  • Pancreatic metastasis of angiosarcoma (Stewart-Treves syndrome) diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report Reviewed

    Junpei Sasajima, Jiro Uehara, Takuma Goto, Shugo Fujibayashi, Kazuya Koizumi, Yusuke Mizukami, Akemi Ishida-Yamamoto, Mikihiro Fujiya, Toshikatsu Okumura

    MEDICINE   95 ( 33 )   2016.8

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    DOI: 10.1097/MD.0000000000004316

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  • mTORC2 signaling drives the development and progression of pancreatic cancer Reviewed

    Driscoll, D.R., Karim, S.A., Sano, M., Gay, D.M., Jacob, W., Yu, J., Mizukami, Y., Gopinathan, A., Jodrell, D.I., Evans, T.R.J., Bardeesy, N., Hall, M.N., Quattrochi, B.J., Klimstra, D.S., Barry, S.T., Sansom, O.J., Lewis, B.C., Morton, J.P.

    Cancer Research   76 ( 23 )   6911 - 6923   2016

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    DOI: 10.1158/0008-5472.CAN-16-0810

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  • Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC dependence in intrahepatic cholangiocarcinoma Reviewed

    Saha, S.K., Gordan, J.D., Kleinstiver, B.P., Vu, P., Najem, M.S., Yeo, J.-C., Shi, L., Kato, Y., Levin, R.S., Webber, J.T., Damon, L.J., Egan, R.K., Greninger, P., McDermott, U., Garnett, M.J., Jenkins, R.L., Rieger-Chris, K.M., Sullivan, T.B., Hezel, A.F., Liss, A.S., Mizukami, Y., Goyal, L., Ferrone, C.R., Zhu, A.X., Joung, J.K., Shokat, K.M., Benes, C.H., Bardeesy, N.

    Cancer Discovery   6 ( 7 )   727 - 739   2016

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    DOI: 10.1158/2159-8290.CD-15-1442

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  • Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas Reviewed

    Matsuzaka, S., Karasaki, H., Ono, Y., Ogata, M., Oikawa, K., Tamakawa, S., Chiba, S.-I., Muraki, M., Yokochi, T., Funakoshi, H., Kono, T., Nagashima, K., Mizukami, Y.

    Pancreas   45 ( 6 )   915 - 918   2016

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  • A Rare Case of Epidermoid Cyst in the Pancreatic Tail Invaginated from the Splenic Hilum: The Long-term Changes in the Imaging Findings Reviewed

    Yoshiaki Sugiyama, Toru Kawamoto, Junpei Sasajima, Kazuya Koizumi, Hidenori Karasaki, Yusuke Mizukami

    INTERNAL MEDICINE   55 ( 24 )   3591 - 3594   2016

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    DOI: 10.2169/internalmedicine.55.7466

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  • GLI2 PROTEIN EXPRESSION LEVEL IS A FEASIBLE MARKER OF LIGAND-DEPENDENT HEDGEHOG ACTIVATION IN PANCREATIC NEOPLASMS Reviewed

    Yoshiaki Sugiyama, Junpei Sasajima, Yusuke Mizukami, Kazuya Koizumi, Toru Kawamoto, Yusuke Ono, Hidenori Karasaki, Hiroki Tanabe, Mikihiro Fujiya, Yutaka Kohgo

    POLISH JOURNAL OF PATHOLOGY   67 ( 2 )   136 - 144   2016

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    DOI: 10.5114/PJP.2016.61449

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  • Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias (PanINs) Reviewed

    Imai, K., Karasaki, H., Ono, Y., Sasajima, J., Chiba, S.-I., Funakoshi, H., Muraki, M., Hanaoka, H., Furukawa, T., Furukawa, H., Kono, T., Nagashima, K., Mizukami, Y.

    Journal of Pathology: Clinical Research   1 ( 2 )   76 - 82   2015.2

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    DOI: 10.1002/cjp2.8

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  • Cyst Infection of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Management of a Rare Complication Reviewed

    Kenji Watanabe, Hidenori Karasaki, Yusuke Mizukami, Toru Kawamoto, Toru Kono, Koji Imai, Takahiro Einama, Masahiko Taniguchi, Yutaka Kohgo, Hiroyuki Furukawa

    PANCREAS   43 ( 3 )   478 - 481   2014.4

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  • Ex vivo activation of angiogenic property in human peripheral blood-derived monocytes by thrombopoietin Reviewed

    Toru Kawamoto, Junpei Sasajima, Yoshiaki Sugiyama, Kazumasa Nakamura, Hiroki Tanabe, Mikihiro Fujiya, Toshie Nata, Yasuyuki Iuchi, Toshifumi Ashida, Yoshihiro Torimoto, Yusuke Mizukami, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   98 ( 4 )   417 - 429   2013.10

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    DOI: 10.1007/s12185-013-1423-8

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  • Macrophages in pancreatic cancer: Starting things off on the wrong track Reviewed

    Xavier Deschenes-Simard, Yusuke Mizukami, Nabeel Bardeesy

    JOURNAL OF CELL BIOLOGY   202 ( 3 )   403 - 405   2013.8

  • Prostacyclin Stimulated Integrin-Dependent Angiogenic Effects of Endothelial Progenitor Cells and Mediated Potent Circulation Recovery in Ischemic Hind Limb Model Reviewed

    Yoko Aburakawa, Jun-ichi Kawabe, Motoi Okada, Atsushi Yamauchi, Akira Asanome, Maki Kabara, Motoki Matsuki, Naofumi Takehara, Naoki Nakagawa, Shunsuke Okumura, Yoshinori Minami, Yusuke Mizukami, Koh-ichi Yuhki, Fumitaka Ushikubi, Naoyuki Hasebe

    CIRCULATION JOURNAL   77 ( 4 )   1053 - 1062   2013.4

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    DOI: 10.1253/circj.CJ-12-0897

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  • Analysis of vanin-1 upregulation and lipid accumulation in hepatocytes in response to a high-fat diet and free fatty acids Reviewed

    Wataru Motomura, Takayuki Yoshizaki, Nobuhiko Takahashi, Shima Kumei, Yusuke Mizukami, Seong-Jae Jang, Yutaka Kohgo

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   51 ( 3 )   163 - 169   2012.11

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    DOI: 10.3164/jcbn.12-06

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  • Competence and sporulation factor derived from Bacillus subtilis improves epithelial cell injury in intestinal inflammation via immunomodulation and cytoprotection Reviewed

    Kotaro Okamoto, Mikihiro Fujiya, Toshie Nata, Nobuhiro Ueno, Yuhei Inaba, Chisato Ishikawa, Takahiro Ito, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Eugene B. Chang, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE   27 ( 8 )   1039 - 1046   2012.8

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    DOI: 10.1007/s00384-012-1416-8

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  • Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection Reviewed

    Kentaro Moriichi, Mikihiro Fujiya, Ryu Sato, Jiro Watari, Yoshiki Nomura, Toshie Nata, Nobuhiro Ueno, Shigeaki Maeda, Shin Kashima, Kentaro Itabashi, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Kotaro Okamoto, Hiroki Tanabe, Yusuke Mizukami, Yusuke Saitoh, Yutaka Kohgo

    BMC GASTROENTEROLOGY   12   2012.6

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    DOI: 10.1186/1471-230X-12-75

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  • Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines Reviewed

    Eva-Maria Duerr, Yusuke Mizukami, Kentaro Moriichi, Manish Gala, Won-Seok Jo, Hirotoshi Kikuchi, Ramnik J. Xavier, Daniel C. Chung

    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY   302 ( 10 )   G1223 - G1230   2012.5

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    DOI: 10.1152/ajpgi.00047.2011

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  • PSEUDO-DIVERTICULAR FORMATION DUE TO A CYTOMEGALOVIRUS INFECTION IN THE COLORECTUM Reviewed

    Momotaro Muto, Ryu Sato, Mikihiro Fujiya, Kazuyuki Tanaka, Shinya Serikawa, Akihiro Hayashi, Yohko Konno, Jun Sakamoto, Tomoya Nishikawa, Kensuke Oikawa, Nobuhiro Ueno, Katsuya Ikuta, Yusuke Mizukami, Satoshi Tanno, Jiro Watari, Yutaka Kohgo

    DIGESTIVE ENDOSCOPY   24 ( 3 )   193 - 193   2012.5

  • A pseudosarcomatous lesion resembling a malignant tumor of the esophagocardiac junction, diagnosed by a total biopsy with endoscopic surgery Reviewed

    K. Ando, M. Fujiya, T. Ito, R. Sugiyama, T. Nata, Y. Nomura, N. Ueno, S. Kashima, C. Ishikawa, Y. Inaba, K. Moriichi, K. Okamoto, K. Ikuta, H. Tanabe, Y. Tokusashi, N. Miyokawa, J. Watari, Y. Mizukami, Y. Kohgo

    ENDOSCOPY   44 ( SUPPL. 2 )   E21 - E22   2012.3

  • Autofluorescence imaging and the quantitative intensity of fluorescence for evaluating the dysplastic grade of colonic neoplasms Reviewed

    Kentaro Moriichi, Mikihiro Fujiya, Ryu Sato, Toshie Nata, Yoshiki Nomura, Nobuhiro Ueno, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Kotaro Okamoto, Hiroki Tanabe, Yusuke Mizukami, Jiro Watari, Yusuke Saitoh, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE   27 ( 3 )   325 - 330   2012.3

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  • Bone marrow-derived proangiogenic cells in pancreatic cancer Reviewed

    Yusuke Mizukami

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   27 ( SUPPL.2 )   23 - 26   2012.3

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    DOI: 10.1111/j.1440-1746.2011.07012.x

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  • Abnormal tumor vasculatures and bone marrow-derived pro-angiogenic cells in cancer Reviewed

    Yusuke Mizukami, Junpei Sasajima, Toshifumi Ashida, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   95 ( 2 )   125 - 130   2012.2

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  • Isoleucine, an Essential Amino Acid, Induces the Expression of Human β Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia. Reviewed

    Konno Y, Ashida T, Inaba Y, ItoT, Tanabe H, Maemoto A, Ayabe T, Mizukami Y, Fujiya M, Kohgo Y

    Food Nutrition Sciences   3 ( 4 )   548 - 555   2012

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  • Heat-killed Body of Lactobacillus brevis SBC8803 Ameliorates Intestinal Injury in a Murine Model of Colitis by Enhancing the Intestinal Barrier Function Reviewed

    Nobuhiro Ueno, Mikihiro Fujiya, Shuichi Segawa, Toshie Nata, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Naoyuki Kobayashi, Kazutoshi Ito, Yutaka Kohgo

    INFLAMMATORY BOWEL DISEASES   17 ( 11 )   2235 - 2250   2011.11

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  • The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma Reviewed

    R. Sato, M. Fujiya, J. Watari, N. Ueno, K. Moriichi, S. Kashima, S. Maeda, K. Ando, H. Kawabata, R. Sugiyama, Y. Nomura, T. Nata, K. Itabashi, Y. Inaba, K. Okamoto, Y. Mizukami, Y. Saitoh, Y. Kohgo

    ENDOSCOPY   43 ( 10 )   862 - 868   2011.10

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  • Obscure gastrointestinal bleeding occurring 50 years after an appendectomy Reviewed

    Shin Kashima, Toshie Nata, Mikihiro Fujiya, Kentaro Moriichi, Yoshiki Nomura, Nobuhiro Ueno, Kentaro Itabashi, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Kotaro Okamoto, Yusuke Mizukami, Yoshiaki Ebisawa, Naoyuki Chisato, Toru Kohno, Yoshihiko Tokusashi, Naoyuki Miyokawa, Masataka Yamada, Yutaka Kohgo

    GUT   60 ( 10 )   1344 - 1403   2011.10

  • Localization of the Most Severely Dysplastic/Invasive Lesions and Mucin Phenotypes in Intraductal Papillary Mucinous Neoplasm of the Pancreas Reviewed

    Hidenori Karasaki, Yusuke Mizukami, Yoshihiko Tokusashi, Kazuya Koizumi, Akira Ishizaki, Kouji Imai, Daitaro Yoshikawa, Shuichi Kino, Junpei Sasajima, Satoshi Tanno, Kakuya Matsumoto, Naoyuki Miyokawa, Toru Kono, Yutaka Kohgo, Hiroyuki Furukawa

    PANCREAS   40 ( 4 )   588 - 594   2011.5

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  • An unusual elevated lesion of the oesophagus Reviewed

    Koji Sawada, Katsuya Ikuta, Kentaro Itabashi, Yasuyuki Suzuki, Yusuke Mizukami, Mikihiro Fujiya, Koji Kubo, Yasuaki Tamura, Yoshihiro Torimoto, Yutaka Kohgo

    GUT   60 ( 4 )   441 - U172   2011.4

  • Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13) Reviewed

    Kazuya Sato, Yoshihiro Torimoto, Takaaki Hosoki, Katsuya Ikuta, Hiroyuki Takahashi, Masayo Yamamoto, Satoshi Ito, Naoka Okamura, Kazuhiko Ichiki, Hiroki Tanaka, Motohiro Shindo, Katsuyuki Hirai, Yusuke Mizukami, Takaaki Otake, Mikihiro Fujiya, Kastunori Sasaki, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   93 ( 3 )   311 - 318   2011.3

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  • Atypical tumour-like involvement of the colon in secondary systemic amyloidosis which vanished after 1 month of observation Reviewed

    Katuyoshi Ando, Mikihiro Fujiya, Takahiro Ito, Ryuji Sugiyama, Toshie Nata, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Chisato Ishikawa, Yuhiei Inaba, Kentaro Moriichi, Kotaro Okamoto, Katsuya Ikuta, Yusuke Mizukami, Yoshihiko Tokusashi, Naoyuki Miyokawa, Jiro Watari, Yutaka Kohgo

    BMJ Case Reports   2011

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    DOI: 10.1136/bcr.01.2011.3775

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  • Small intestinal intussusceptions due to the placement of a percutaneous endoscopic jejunostomy tube Reviewed

    Takayuki Satoh, Kazue Sawada, Miyuki Satoh, Kikuchi Yohko, Masataka Yamada, Masaaki Zaitsu, Tadahiro Osada, Reiji Sawaya, Toshie Nata, Nobuhiro Ueno, Kentaro Moriichi, Katsuya Ikuta, Yusuke Mizukami, Jiro Watari, Mikihiro Fujiya, Yutaka Kohgo

    BMJ Case Reports   2011

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  • Atypical tumour-like involvement of the colon in Henoch-Schönlein purpura successfully treated with the administration of factor XIII Reviewed

    Katuyoshi Ando, Mikihiro Fujiya, Ryuji Sugiyama, Toshie Nata, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Kentaro Moriichi, Kotaro Okamoto, Katsuya Ikuta, Jiro Watari, Yusuke Mizukami, Yutaka Kohgo

    BMJ Case Reports   2011

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    DOI: 10.1136/bcr.08.2010.3251

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  • Expression of the Antimicrobial Peptide alpha-Defensin/Cryptdins in Intestinal Crypts Decreases at the Initial Phase of Intestinal Inflammation in a Model of Inflammatory Bowel Disease, IL-10-deficient Mice Reviewed

    Yuhei Inaba, Toshifumi Ashida, Takahiro Ito, Chisato Ishikawa, Hiroki Tanabe, Atsuo Maemoto, Jiro Watari, Tokiyoshi Ayabe, Yusuke Mizukami, Mikihiro Fujiya, Yutaka Kohgo

    INFLAMMATORY BOWEL DISEASES   16 ( 9 )   1488 - 1495   2010.9

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  • Capsule endoscopy is a feasible procedure for identifying a Diphyllobothrium nihonkaiense infection and determining the indications for vermifuge treatment Reviewed

    Yoshiki Nomura, Mikihiro Fujiya, Takahiro Ito, Katuyoshi Ando, Ryuji Sugiyama, Toshie Nata, Nobuhiro Ueno, Shin Kashima, Chisato Ishikawa, Yuhei Inaba, Kentaro Moriichi, Kotaro Okamoto, Tetsuya Yanagida, Akira Ito, Katsuya Ikuta, Jiro Watari, Yusuke Mizukami, Yutaka Kohgo

    BMJ Case Reports   2010.8

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    DOI: 10.1136/bcr.05.2010.3023

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  • Transplanting Normal Vascular Proangiogenic Cells to Tumor-Bearing Mice Triggers Vascular Remodeling and Reduces Hypoxia in Tumors Reviewed

    Junpei Sasajima, Yusuke Mizukami, Yoshiaki Sugiyama, Kazumasa Nakamura, Toru Kawamoto, Kazuya Koizumi, Rie Fujii, Wataru Motomura, Kazuya Sato, Yasuaki Suzuki, Satoshi Tanno, Mikihiro Fujiya, Katsunori Sasaki, Norihiko Shimizu, Hidenori Karasaki, Toru Kono, Jun-ichi Kawabe, Masaaki Ii, Hiroki Yoshiara, Naohisa Kamiyama, Toshifumi Ashida, Nabeel Bardeesy, Daniel C. Chung, Yutaka Kohgo

    CANCER RESEARCH   70 ( 15 )   6283 - 6292   2010.8

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  • A case of pancreatic carcinoma presenting as pancreaticopleural fistula with pancreatic pleural effusion Reviewed

    Yoshiaki Sugiyama, Satoshi Tanno, Tomoya Nishikawa, Kazumasa Nakamura, Junpei Sasajima, Kazuya Koizumi, Yusuke Mizukami, Hidenori Karasaki, Shinichi Kasai, Yukinori Yoshida, Naomi Watanabe, Toshikatsu Okumura, Yutaka Kohgo

    Journal of Japanese Society of Gastroenterology   107 ( 5 )   784 - 791   2010.5

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    DOI: 10.11405/nisshoshi.107.784

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  • Immunoprecipitation of nucleosomal DNA is a novel procedure to improve the sensitivity of serum screening for the p16 hypermethylation associated with colon cancer Reviewed

    Jun Sakamoto, Mikihiro Fujiya, Kotaro Okamoto, Toshie Nata, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Jiro Watari, Toshifumi Ashida, Yutaka Kohgo

    CANCER EPIDEMIOLOGY   34 ( 2 )   194 - 199   2010.4

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  • Collagenous colitis appeared after 6-year administration of lansoprazole Reviewed

    Koji Sawada, Mikihiro Fujiya, Kentaro Itabashi, Yasuyuki Suzuki, Koji Kubo, Toshie Nata, Nobuhiro Ueno, Yuhei Inaba, Kentaro Moriichi, Kotaro Okamoto, Katsuya Ikuta, Hiroki Tanabe, Yusuke Mizukami, Yoshitake Takagi, Yutaka Kohgo

    Clinical Journal of Gastroenterology   3 ( 1 )   18 - 21   2010.2

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    DOI: 10.1007/s12328-009-0126-4

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  • Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells Reviewed

    Kazumasa Nakamura, Junpei Sasajima, Yusuke Mizukami, Yoshiaki Sugiyama, Madoka Yamazaki, Rie Fujii, Toru Kawamoto, Kazuya Koizumi, Kazuya Sato, Mikihiro Fujiya, Katsunori Sasaki, Satoshi Tanno, Toshikatsu Okumura, Norihiko Shimizu, Jun-ichi Kawabe, Hidenori Karasaki, Toru Kono, Masaaki Ii, Nabeel Bardeesy, Daniel C. Chung, Yutaka Kohgo

    PLOS ONE   5 ( 1 )   2010.1

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  • Pancreatic Ductal Adenocarcinomas in Long-Term Follow-Up Patients With Branch Duct Intraductal Papillary Mucinous Neoplasms Reviewed

    Satoshi Tanno, Yasuhiro Nakano, Kazuya Koizumi, Yoshiaki Sugiyama, Kazumasa Nakamura, Junpei Sasajima, Tomoya Nishikawa, Yusuke Mizukami, Nobuyuki Yanagawa, Tsuneshi Fujii, Toshikatsu Okumura, Takeshi Obara, Yutaka Kohgo

    PANCREAS   39 ( 1 )   36 - 40   2010.1

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  • Incidence of Synchronous and Metachronous Pancreatic Carcinoma in 168 Patients with Branch Duct Intraductal Papillary Mucinous Neoplasm Reviewed

    Satoshi Tanno, Yasuhiro Nakano, Yoshiaki Sugiyama, Kazumasa Nakamura, Junpei Sasajima, Kazuya Koizumi, Madoka Yamazaki, Tomoya Nishikawa, Yusuke Mizukami, Nobuyuki Yanagawa, Tsuneshi Fujii, Takeshi Obara, Toshikatsu Okumura, Yutaka Kohgo

    PANCREATOLOGY   10 ( 2-3 )   173 - 178   2010

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  • A case of small cell carcinoma of the oesophagus treated with endoscopic mucosal resection who remained in clinical remission for 18 months: Its endoscopic features with specific light spectra Reviewed

    Toshie Nata, Mikihiro Fujiya, Hiroki Tanabe, Nobuhiro Ueno, Youkou Konno, Chisato Ishikawa, Yuhiei Inaba, Takahiro Ito, Ryu Sato, Kentaro Moriichi, Kotaro Okamoto, Atsuo Maemoto, Yusuke Mizukami, Jiro Watari, Toshifumi Ashida, Yutaka Kohgo

    BMJ Case Reports   2009.12

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    DOI: 10.1136/bcr.06.2009.2048

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  • Risk of additional pancreatic cancer in patients with branch duct intraductal papillary-mucinous neoplasm Reviewed

    Satoshi Tanno, Takeshi Obara, Kazuya Koizumi, Yasuhiro Nakano, Manabu Osanai, Yusuke Mizukami, Yutaka Kohgo

    Clinical Journal of Gastroenterology   2 ( 6 )   365 - 370   2009.12

  • Tumor Doubling Time in Two Cases of Main Duct Intraductal Papillary-Mucinous Neoplasms of the Pancreas Reviewed

    Satoshi Tanno, Junpei Sasajima, Kazuya Koizumi, Nobuyuki Yanagawa, Yasuhiro Nakano, Manabu Osanai, Yusuke Mizukami, Tsuneshi Fujii, Takeshi Obara, Toshikatsu Okumura, Yutaka Kohgo

    HEPATO-GASTROENTEROLOGY   56 ( 94-95 )   1545 - 1548   2009.9

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  • Portal annular pancreas, a notable pancreatic malformation: Frequency, morphology, and implications for pancreatic surgery Reviewed

    Hidenori Karasaki, Yusuke Mizukami, Akira Ishizaki, Jyunichi Goto, Daitaro Yoshikawa, Shuichi Kino, Yoshihiko Tokusashi, Naoyuki Miyokawa, Tomonori Yamada, Toru Kono, Shinichi Kasai

    SURGERY   146 ( 3 )   515 - 518   2009.9

  • 血管前駆細胞移植は膵癌の腫瘍血管リモデリングを誘導し、腫瘍の低酸素環境を解除する(Transplantation of vascular progenitor cells leads to vascular remodeling and reduces tumor hypoxia in pancreatic cancer)

    笹島 順平, 水上 裕輔, 杉山 祥晃, 中村 和正, 鈴木 康秋, 佐藤 一也, 藤谷 幹浩, 丹野 誠志, 奥村 利勝, 河野 透, 伊井 正明, 神山 直久, 高後 裕

    日本癌学会総会記事   68回   434 - 435   2009.8

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  • HIF-1 alpha and HIF-2 alpha have divergent roles in colon cancer Reviewed

    Takaaki Imamura, Hirotoshi Kikuchi, Maria-Teresa Herraiz, Do-Youn Park, Yusuke Mizukami, Mari Mino-Kenduson, Maureen P. Lynch, Bo R. Rueda, Yair Benita, Ramnik J. Xavier, Daniel C. Chung

    INTERNATIONAL JOURNAL OF CANCER   124 ( 4 )   763 - 771   2009.2

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  • Gemcitabine in combination with S-1 or UFT in patients with advanced pancreatic cancer Reviewed

    Junpei Sasajima, Satoshi Tanno, Kazuya Koizumi, Yasuhiro Nakano, Atsuya Habiro, Atsushi Chiba, Tsuneshi Fujii, Yoshiaki Sugiyama, Kazumasa Nakamura, Tomoya Nishikawa, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    Japanese Journal of Cancer and Chemotherapy   36 ( 10 )   1657 - 1661   2009

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  • Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth Reviewed

    Kotoyo Fujiki, Eva-Maria Duerr, Hirotoshi Kikuchi, Aylwin Ng, Ramnik J. Xavier, Yusuke Mizukami, Takaaki Imamura, Matthew H. Kulke, Daniel C. Chung

    GASTROENTEROLOGY   135 ( 3 )   907 - 916   2008.9

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    DOI: 10.1053/j.gastro.2008.06.034

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  • Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells Reviewed

    Madoka Yamazaki, Kazumasa Nakamura, Yusuke Mizukami, Masaaki Ii, Junpei Sasajima, Yoshiaki Sugiyama, Tomoya Nishikawa, Yasuhiro Nakano, Nobuyuki Yanagawa, Kazuya Sato, Atsuo Maemoto, Satoshi Tanno, Toshikatsu Okumura, Hidenori Karasaki, Toru Kono, Mikihiro Fujiya, Toshifumi Ashida, Daniel C. Chung, Yutaka Kohgo

    CANCER SCIENCE   99 ( 6 )   1131 - 1138   2008.6

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    DOI: 10.1111/j.1349-7006.2008.00795.x

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  • Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis Reviewed

    Eva-Maria Duerr, Yusuke Mizukami, Aylwin Ng, Ramnik J. Xavier, Hirotoshi Kikuchi, Vikram Deshpande, Andrew L. Warshaw, Jonathan Glickman, Matthew H. Kulke, Daniel C. Chung

    ENDOCRINE-RELATED CANCER   15 ( 1 )   243 - 256   2008.3

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  • Two cases of pancreatic tumor with von Hippel-Lindau disease Reviewed

    Hidenori Karasaki, Akira Ishizaki, Nobuyuki Yanagawa, Yasuhiro Nakano, Jyunpei Sasajima, Yusuke Mizukami, Satoshi Tanno, Yoshihiko Tokusashi, Naoyuki Miyokawa, Mitsuhiro Obara, Junichi Goto, Shuichi Kino, Toru Kono, Shinichi Kasai

    Japanese Journal of Gastroenterology   105 ( 5 )   725 - 731   2008

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    DOI: 10.11405/nisshoshi.105.725

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  • Milk-of-calcium in a pseudocyst of the pancreas Reviewed

    Kazuya Koizumi, Satoshi Tanno, Nobuyuki Yanagawa, Manabu Osanai, Atsuya Habiro, Kazumasa Nakamura, Madoka Minoguchi, Yasuhiro Nakano, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    Japanese Journal of Gastroenterology   105 ( 1 )   93 - 98   2008

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    DOI: 10.11405/nisshoshi.105.93

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  • ヒト膵臓癌における内皮前駆細胞の活性化を介した血管形成のSonic hedgehogによる誘導(Sonic hedgehog induces angiogenesis through the activation of endothelial progenitor cells in human pancreatic cancer)

    中村 和正, 山崎 まどか, 水上 裕輔, 伊井 正明, 笹島 順平, 西川 智哉, 前本 篤男, 佐藤 一也, 丹野 誠志, 奥村 利勝, 蘆田 知史, 河野 透, 高後 裕

    日本癌学会総会記事   66回   93 - 93   2007.8

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  • Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells Reviewed

    Y. Nakano, S. Tanno, K. Koizumi, T. Nishikawa, K. Nakamura, M. Minoguchi, T. Izawa, Y. Mizukami, T. Okumura, Y. Kohgo

    BRITISH JOURNAL OF CANCER   96 ( 3 )   457 - 463   2007.2

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  • Hypoxia, angiogenesis, and colorectal cancer Reviewed

    Mizukami, Y., Chung, D.C.

    Current Colorectal Cancer Reports   3 ( 2 )   71 - 75   2007

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  • Hypoxic regulation of vascular endothelial growth factor through the induction of phosphatidylinositol 3-kinase/Rho/ROCK and c-Myc Reviewed

    Yusuke Mizukami, Kotoyo Fujiki, Eva-Maria Duerr, Manish Gala, Won-Seok Jo, Xiaobo Zhang, Daniel C. Chung

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 20 )   13957 - 13963   2006.5

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  • Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury Reviewed

    M Ii, H Takenaka, J Asai, K Ibusuki, Y Mizukami, K Maruyama, YS Yoon, A Wecker, C Luedemann, E Eaton, M Silver, T Thorne, DW Losordo

    CIRCULATION RESEARCH   98 ( 5 )   697 - 704   2006.3

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  • Erratum: Induction of interleukin-8 preserves the angiogenic response in HIF-1α-deficient colon cancer cells (Nature Medicine (2005) 12 (992-997)) Reviewed

    Mizukami, Y., Jo, W.-S., Duerr, E.-M., Gala, M., Li, J., Zhang, X., Zimmer, M.A., Iliopoulos, O., Zukerberg, L.R., Kohgo, Y., Lynch, M.P., Rueda, B.R., Chung, D.C.

    Nature Medicine   12 ( 2 )   253 - 253   2006

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  • A phase I study of oral uracil-tegafur prior to weekly intravenous gemcitabine in patients with advanced pancreatic cancer Reviewed

    S Tanno, Y Nakano, M Osanai, K Koizumi, T Izawa, A Habiro, Y Mizukami, N Yanagawa, T Fujii, T Okumura, Y Kohgo

    CHEMOTHERAPY   52 ( 2 )   98 - 102   2006

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  • Wnt signaling can repress thrombospondin-1 expression in colonic tumorigenesis Reviewed

    WS Jo, Y Mizukami, EM Duerr, LR Zukerberg, DC Chung

    CANCER BIOLOGY & THERAPY   4 ( 12 )   1361 - 1366   2005.12

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  • Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells Reviewed

    K Koizumi, S Tanno, Y Nakano, A Habiro, T Izawa, Y Mizukami, T Okumura, Y Kohgo

    ANTICANCER RESEARCH   25 ( 5 )   3347 - 3353   2005.9

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  • Oncogenic K-ras stimulates wnt signaling in colon cancer through inhibition of GSK-3 beta Reviewed

    JN Li, Y Mizukami, XB Zhang, WS Jo, DC Chung

    GASTROENTEROLOGY   128 ( 7 )   1907 - 1918   2005.6

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    DOI: 10.1053/j.gastro.2005.02.067

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  • Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet hyperplasia without hypoglycemia Reviewed

    XB Zhang, JP Gaspard, Y Mizukami, JN Li, F Graeme-Cook, DC Chung

    DIABETES   54 ( 3 )   712 - 719   2005.3

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    DOI: 10.2337/diabetes.54.3.712

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  • Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance Reviewed

    S Tanno, N Yanagawa, A Habiro, K Koizumi, Y Nakano, M Osanai, Y Mizukami, T Okumura, Testa, JR, Y Kohgo

    CANCER RESEARCH   64 ( 10 )   3486 - 3490   2004.5

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    DOI: 10.1158/0008-5472.CAN-03-1788

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  • Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer Reviewed

    Y Mizukami, JN Li, XB Zhang, MA Zimmer, O Iliopoulos, DC Chung

    CANCER RESEARCH   64 ( 5 )   1765 - 1772   2004.3

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  • Involvement of p38 mitogen-activated protein kinase in gemcitabine-induced apoptosis in human pancreatic cancer cells Reviewed

    A Habiro, S Tanno, K Koizumi, T Izawa, Y Nakano, M Osanai, Y Mizukami, T Okumura, Y Kohgo

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   316 ( 1 )   71 - 77   2004.3

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  • Oleylamine (Long-chain Fatty Amine)-induced Cell Death through MAP Kinase Pathways in Human Pancreatic Cancer Cells

    MIZUKAMI Yusuke

    The Hokkaido journal of medical science   77 ( 1 )   17 - 29   2002.1

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  • Clonality and field cancerization in intraductal papillary-mutinous tumors of the pancreas Reviewed

    T Izawa, T Obara, S Tanno, Y Mizukami, N Yanagawa, Y Kohgo

    CANCER   92 ( 7 )   1807 - 1817   2001.10

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    DOI: 10.1002/1097-0142(20011001)92:7<1807::AID-CNCR1697>3.0.CO;2-0

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  • Requirement of c-Jun N-terminal kinase for apoptotic cell death induced by farnesyltransferase inhibitor, farnesylamine, in human pancreatic cancer cells Reviewed

    Y Mizukami, H Ura, T Obara, A Habiro, T Izawa, M Osanai, N Yanagawa, S Tanno, Y Kohgo

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   288 ( 1 )   198 - 204   2001.10

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  • Temporary use of an accuflex stent for unextractable common bile duct stones Reviewed

    Y Mizukami, H Saito, T Obara, S Arisato, Y Nakano, Y Sakurai, T Izawa, Y Kohgo

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   15 ( 6 )   680 - 683   2000.6

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    DOI: 10.1046/j.1440-1746.2000.02200.x

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  • Pancreatic duct obstruction caused by malignant islet cell tumors of the pancreas Reviewed

    T Obara, R Shudo, T Fujii, S Tanno, Y Mizukami, T Izawa, Y Saitoh, S Satou, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   51 ( 5 )   604 - 607   2000.5

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  • Case report: Mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging Reviewed

    Y Mizukami, H Ohta, S Arisato, Y Nakano, M Murakami, Y Orii, H Saito, Y Sakurai, H Sakurai, T Sato, Y Uno, Y Nakanuma, M Ohhira, Y Kohgo

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   14 ( 12 )   1223 - 1226   1999.12

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    DOI: 10.1046/j.1440-1746.1999.02033.x

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  • Epithelial hyperplasia of the gallbladder in children with anomalous pancreaticobiliary ductal union Reviewed

    S Tanno, T Obara, T Fujii, Y Mizukami, N Yanagawa, T Izawa, H Ura, Y Kohgo

    HEPATO-GASTROENTEROLOGY   46 ( 30 )   3068 - 3073   1999.11

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  • alpha-fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation Reviewed

    S Tanno, T Obara, T Fujii, T Izawa, Y Mizukami, Y Saitoh, H Ura, Y Kohgo

    INTERNATIONAL JOURNAL OF PANCREATOLOGY   26 ( 1 )   43 - 47   1999.8

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  • Epithelial cell proliferation and gene mutation in the mucosa of gallbladder with pancreaticobiliary malunion and cancer Reviewed

    Takeshi Obara, Satoshi Tanno, Tsuneshi Fujii, Tsutomu Izawa, Yusuke Mizukami, Nobuyuki Yanagawa, Hitoshi Ura, Yutaka Kohgo

    Journal of Hepato-Biliary-Pancreatic Surgery   6 ( 3 )   229 - 236   1999

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    DOI: 10.1007/s005340050112

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  • Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union Reviewed

    S Tanno, T Obara, T Fujii, Y Mizukami, R Shudo, N Nishino, H Ura, AJP Klein-Szanto, Y Kohgo

    CANCER   83 ( 2 )   267 - 275   1998.7

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    DOI: 10.1002/(SICI)1097-0142(19980715)83:2<267::AID-CNCR10>3.0.CO;2-R

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  • Association between anomalous pancreaticobiliary ductal union and adenomyomatosis of the gall-bladder Reviewed

    S Tanno, T Obara, H Maguchi, T Fujii, Y Mizukami, R Shudo, K Takahashi, N Nishino, S Arisato, H Ura, Y Kohgo

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   13 ( 2 )   175 - 180   1998.2

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    DOI: 10.1111/j.1440-1746.1998.tb00634.x

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  • Report of an autopsy cases of hepatocellular carcinoma with marked pulmonary hypertension due to multiple pulmonary thrombus Reviewed

    Ohta, H., Matsumoto, A., Mizukami, Y., Nakano, Y., Ohta, T., Arisato, S., Murakami, M., Orii, Y., Sato, T.

    Japanese Journal of Gastroenterology   95 ( 8 )   900 - 904   1998

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    DOI: 10.11405/nisshoshi1964.95.900

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  • Thickened inner hypoechoic layer of the gallbladder wall in the diagnosis of anomalous pancreaticobiliary ductal union with endosonography Reviewed

    S Tanno, T Obara, H Maguchi, Y Mizukami, R Shudo, T Fujii, K Takahashi, N Nishino, S Arisato, Y Saitoh, H Ura, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   46 ( 6 )   520 - 526   1997.12

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    DOI: 10.1016/S0016-5107(97)70007-5

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  • A case of anaplastic carcinoma of the pancreas, disclosed a hemosuccus pancreaticus Reviewed

    Yusuke Mizukami, Satoshi Arisato, Kunihiko Satou, Yasuhiro Nakano, Tomoyuki Ohta, Hitoyoshi Ohta, Masanori Murakami, Yutaka Orii, Hiroya Saito, Yasuo Sakurai, Yuji Sawaguchi, Tomonori Hamada, Teiko Sato, Hiroyuki Maguchi

    Japanese Journal of Gastroenterology   94 ( 10 )   706 - 711   1997.10

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    DOI: 10.11405/nisshoshi1964.94.10_706

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  • A Case of Small Cholangiocellular Carcinoma, Diagnosed by Percutaneous Transhepatic Cholangioscopy.

    MIZUKAMI Yusuke, TAKAHASHI Kuniyuki, ARISATO Satoshi, WATARI Jiro, OHTA Hitoyoshi, MURAKAMI Masanori, ORII Yutaka, SAKURAI Yasuo, SAITO Hiroya, MAGUCHI Hiroyuki

    Gastroenterological Endoscopy   38 ( 7 )   1548 - 1554   1996.7

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  • Primary biliary cirrhosis associated with idiopathic thrombocytopenic purpura Reviewed

    Y Mizukami, M Ohhira, A Matsumoto, K Murazumi, H Ohta, M Ohhira, M Ono, T Miyake, Maekawa, I, Y Kohgo

    JOURNAL OF GASTROENTEROLOGY   31 ( 2 )   284 - 288   1996.4

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    DOI: 10.1007/BF02389532

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  • A case of metastatic gastric cancer simulating Borrmann type 4 gastric carcinoma Reviewed

    Tanabe, H., Watari, J., Nakano, Y., Waku, K., Mizukami, Y., Tanaka, K., Arisato, S., Ohta, H., Murakami, M., Orii, Y., Sakurai, K., Sato, T., Yokota, K., Kohgo, Y.

    Gastroenterological Endoscopy   38 ( 12 )   2865 - 2870   1996

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    DOI: 10.11280/gee1973b.38.2865

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  • Revaluation on detection of metastatic cancer of the colorectum with barium enema: Comparison with computed tomography and colonoscopy Reviewed

    Watari, J., Mizukami, Y., Tanabe, H., Nakano, Y., Tanaka, K., Arisato, S., Ohta, H., Murakami, M., Orii, Y., Saitoh, H., Saitoh, Y., Yokota, K.

    Japanese Journal of Clinical Radiology   41 ( 2 )   211 - 216   1996

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  • Evaluation of early colorectal cancer with submucosal invasion based on histological architecture

    WATARI Jiro, ORII Yutaka, SAITOH Yusuke, MURAKAMI Masanori, MIZUKAMI Yusuke, MURANAKA Shigeto, OHTA Tomoyuki, TAKAHASHI Kuniyuki, OHTA Hitoyoshi, YAMANO Miki, TOMARU Hisashi, MINEMOTO Hiromasa

    Nippon Shokakibyo Gakkai Zasshi   92 ( 9 )   1250 - 1257   1995.9

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    DOI: 10.11405/nisshoshi1964.92.1250

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  • A Case of Pedunclated Gastric Leiomyosarcoma Resected under Laparoscopic surgery.

    MIZUKAMI Yusuke, KATOH Kazuya, KOTANI Hiromi, SAITOH Takashige, HASEBE Chitomi, TORIMOTO Yoshihiro, YUKI Masamitsu, OKUYAMA Syuji, YOKOTA Kinichi, KOHDA Hironobu, YAZAKI Yasuyuki, SEKIYA Chihiro

    GASTROENTEROLOGICAL ENDOSCOPY   37 ( 2 )   308 - 315   1995

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    DOI: 10.11280/gee1973b.37.308

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MISC

  • リキッドバイオプシー解析から見た膵癌の分子多様性 Invited Reviewed

    小山一也, 高橋賢治, 小野裕介, 河端秀賢, 水上裕輔

    胆と膵   45 ( 7 )   681 - 688   2024.7

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  • 【新時代のKRAS変異〜診断の主役から治療の標的へ〜】IPMN発癌におけるKRAS変異 Reviewed

    小野裕介, 高橋賢治, 水上裕輔

    胆と膵   44 ( 7 )   665 - 671   2023.7

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  • Low-grade PanINは膵癌の前駆病変なのか? Low-grade PanINは胃型IPMNの前駆病変なのか? Reviewed

    大森優子, 水上裕輔, 古川徹

    胆と膵   44 ( 4 )   339 - 344   2023.4

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  • Molecular Phenotyping and the Combinatorial System by the Number of Accumulated Gene Alterations of Intraductal Papillary Mucinous Neoplasms Stratifies the Risk of Invasion and Outcome: New Insight for Management Strategy Reviewed

    Yuko Omori, Yusuke Ono, Takashi Kokumai, Fumiko Date, Ryota Higuchi, Goro Honda, Yusuke Mizukami, Takanori Morikawa, Michiaki Unno, Toru Furukawa

    LABORATORY INVESTIGATION   103 ( 3 )   S1520 - S1520   2023.3

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  • 【膵癌・胆道癌2023(上)膵癌編-基礎・臨床の最新研究動向-】上皮性腫瘍 嚢胞性膵腫瘍 膵管内乳頭粘液性腫瘍(IPMN) 診断 由来癌と併存癌 Invited Reviewed

    河端 秀賢, 高橋 賢治, 水上 裕輔

    日本臨床   81 ( 増刊2 膵癌・胆道癌2023(上)膵癌編 )   276 - 288   2023.2

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  • Molecular phenotyping and risk stratification of intraductal papillary mucinous neoplasms. Reviewed

    Yuko Omori, Yusuke Ono, Takashi Kokumai, Fumiko Date, Ryota Higuchi, Goro Honda, Yusuke Mizukami, Takanori Morikawa, Michiaki Unno, Toru Furukawa

    CANCER RESEARCH   82 ( 22 )   170 - 170   2022.11

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  • 【Liquid biopsyは膵癌の診断・治療をどう変えるか?】IPMNの悪性度評価とliquid biopsy Reviewed

    高橋 賢治, 大森 優子, 小野 裕介, 古川 徹, 水上 裕輔

    胆と膵   43 ( 1 )   33 - 42   2022.1

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  • Somatic mutations comparing between conventional colorectal adenoma and Familial adenomatous polyposis derived adenoma Reviewed

    Hiroki Tanabe, Yusuke Ono, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    CANCER SCIENCE   112   664 - 664   2021.2

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  • Potential Diagnostic and Therapeutic Applications of Exosomes in Pancreatic Cancer

    高橋賢治, 北野陽平, 水上裕輔, 藤谷幹浩, 奥村利勝

    胆と膵   42 ( 8 )   2021

  • Clinical application of ncRNA as a biomarker for liquid biopsy in pancreatic cancer

    高橋賢治, 北野陽平, 藤谷幹浩, 水上裕輔, 奥村利勝

    肝胆膵   83 ( 4 )   2021

  • Application of new diagnostic approach by liquid biopsy for pancreatic cancer.

    高橋賢治, 北野陽平, 藤谷幹浩, 水上裕輔, 奥村利勝

    月刊消化器・肝臓内科   10 ( 3 )   2021

  • Molecular biomarkers for progression of IPMNs focused on epithelial subtypes

    大森優子, 小野裕介, 小野裕介, 森川孝則, 伊達文子, 樋口亮太, 山本雅一, 唐崎秀則, 水上裕輔, 水上裕輔, 海野倫明, 古川徹

    日本病理学会会誌   110 ( 1 )   2021

  • STK11 Plays a Canonical Role in Malignant Progression of KRAS-mutant and GNAS-wild-type IPMNs

    大森優子, 小野裕介, 小野裕介, 森川孝則, 元井冬彦, 樋口亮太, 山本雅一, 唐崎秀則, 水上裕輔, 海野倫明, 古川徹

    日本病理学会会誌   110 ( 1 )   2021

  • IBD患者における新規バイオマーカーの検討

    伊藤貴博, 前本篤男, 水上裕輔

    日本消化器病学会雑誌(Web)   118   2021

  • 胆管内乳頭状腫瘍(IPNB)は臨床病理学的因子および分子異常と関連した2つのTypeに分けられる

    青木 泰孝, 水間 正道, 畠 達夫, 青木 豪, 大森 優子, 小野 裕介, 水上 裕輔, 海野 倫明, 古川 徹

    胆道   34 ( 3 )   498 - 498   2020.8

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  • PROBIOTIC-DERIVED POLYPHOSPHATE IMPROVES DAMAGED INTESTINAL EPITHELIA THROUGH INDUCING PLATELET-DERIVED CELL GROWTH MOLECULES

    Shotaro Isozaki, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Yuuki Murakami, Yuya Sugiyama, Yu Kobayashi, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Kazuyuki Tanaka, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Takuma Goto, Shuhei Takauji, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Toshikatsu Okumura

    GASTROENTEROLOGY   158 ( 6 )   S501 - S501   2020.5

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  • FEASIBILITY OF DIGITAL PCR-BASED QUANTIFICATION AND MUTATION ANALYSIS OF PLASMA CELL-FREE DNA FOR DIAGNOSIS AND SURVEILLANCE OF EARLY-STAGE PANCREATIC TUMORS

    Tetsuhiro Okada, Yusuke Mizukami, Kazuya Koizumi, Kuniyuki Takahashi, Hirotoshi Iwano, Shingo Asahara, Masaki Kuwatani, Toru Kawamoto, Hiroki Sato, Akihiro Hayashi, Hidemasa Kawabata, Takuma Goto, Junpei Sasajima, Mikihiro Fujiya, Yusuke Ono, Hidenori Karasaki, Toshikatsu Okumura

    GASTROENTEROLOGY   158 ( 6 )   S863 - S863   2020.5

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  • PROBIOTIC-DERIVED FERRICHROME INHIBITS THE GROWTH OF REFRACTORY PANCREATIC CANCER CELLS

    Akemi Kita, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Shin Kashima, Shotaro Isozaki, Yuya Sugiyama, Takehito Kunogi, Keitaro Takahashi, Takuya Iwama, Masami Ijiri, Yuuki Murakami, Shuhei Takauji, Takuma Goto, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Toshikatsu Okumura

    GASTROENTEROLOGY   158 ( 6 )   S766 - S766   2020.5

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  • 膵癌初期発生における膵腸相関

    小野 裕介, 中村 公則, 清水 由宇, 横井 友樹, 杉本 理菜, 早川 祐子, 佐藤 裕基, 水上 裕輔, 綾部 時芳, 奥村 利勝

    腸内細菌学雑誌   34 ( 2 )   141 - 141   2020.4

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  • 精神遅滞を有し免疫不全を伴わない患者に発症したWhipple病の一例

    久野木 健仁, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐藤 裕基, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 河端 秀賢, 林 明宏, 上野 伸展, 嘉島 伸, 後藤 拓磨, 盛一 健太郎, 田邊 裕貴, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   126回   70 - 70   2020.3

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  • IPMN組織亜型における遺伝子異常についての相互関係の分子病理学的解析

    小林 敏一, 大森 優子, 小野 裕介, 水上 裕輔, 牧野 直彦, 元井 冬彦, 海野 倫明, 上野 義之, 古川 徹

    日本病理学会会誌   109 ( 1 )   324 - 324   2020.3

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  • STK11 plays a canonical role in malignant progression of a subset of KRAS-mutant IPMNs(和訳中)

    大森 優子, 小野 裕介, 森川 孝則, 元井 冬彦, 樋口 亮太, 山本 雅一, 唐崎 秀則, 水上 裕輔, 海野 倫明, 古川 徹

    日本病理学会会誌   109 ( 1 )   324 - 324   2020.3

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  • 早期胃癌におけるマイクロサテライト不安定性の検討

    田邊 裕貴, 水上 裕輔, 小林 裕, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 藤谷 幹浩, 奥村 利勝

    日本内科学会雑誌   109 ( Suppl. )   228 - 228   2020.2

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  • リキッドバイオプシーによる膵癌の術前診断

    林明宏, 岡田哲弘, 佐藤裕基, 河端秀賢, 後藤拓磨, 小野裕介, 唐崎秀則, 水上裕輔, 藤谷幹浩, 奥村利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127th-121st   2020

  • 早期診断と予後評価を念頭においた膵癌ゲノム診療

    水上裕輔, 岡田哲弘, 岡田哲弘, 林明宏, 林明宏, 河端秀賢, 後藤拓磨, 河本徹, 唐崎秀則, 奥村利勝

    膵臓(Web)   35 ( 3 )   2020

  • 胆管上皮異型を合併し膵管内乳頭粘液性腫瘍関連膵癌との鑑別を要した浸潤性膵管癌の1例

    真口遼香, 佐藤裕基, 河端秀賢, 船山拓也, 梶浦麻未, 柳原弘明, 上原聡人, 林明宏, 後藤拓磨, 藤谷幹浩, 高橋裕之, 萩原正弘, 今井浩二, 横尾英樹, 松野直徒, 湯沢明夏, 谷野美智枝, 古川博之, 水上裕輔, 奥村利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127th-121st   2020

  • 胆管分流術後の肝内結石症に対し,ダブルバルーン小腸内視鏡と細径経鼻内視鏡を用いて結石除去を行った1例

    上原聡人, 林明宏, 佐藤裕基, 河端秀賢, 後藤拓磨, 水上裕輔, 藤谷幹浩, 奥村利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127th-121st   2020

  • サイズの大きな十二指腸乳頭部腫瘍に対する粘膜下局注の有用性

    柳原弘明, 河端賢秀, 梶浦麻未, 上原聡人, 佐藤裕基, 林明宏, 後藤拓磨, 水上裕輔, 藤谷幹浩, 奥村利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127th-121st   2020

  • Liquid biopsy of pancreatic tumors: Challenges for early detection and surveillance based on the molecular landscape during early carcinogenesis

    岡田哲弘, 岡田哲弘, 水上裕輔, 水上裕輔, 林明宏, 河端秀賢, 佐藤裕基, 河本徹, 後藤拓磨, 谷上賢瑞, 小野裕介, 小野裕介, 唐崎秀則, 奥村利勝

    膵臓(Web)   35 ( 4 )   2020

  • 早期胃癌におけるサブタイプ解析-Microsatellite instability and Epstein-Barr virus subtype-

    田邊裕貴, 水上裕輔, 小林裕, 久野木健仁, 高橋慶太郎, 安藤勝祥, 上野伸展, 嘉島伸, 盛一健太郎, 藤谷幹浩, 奥村利勝

    日本消化器病学会雑誌(Web)   117   2020

  • FNB検体を用いたデジタルPCR法による膵癌の新規診断法の開発;Cell-burst遺伝子解析法

    林明宏, 水上裕輔, 佐藤裕基, 岡田哲弘, 河端秀賢, 後藤拓磨, 唐崎秀則, 奥村利勝

    膵臓(Web)   35 ( 3 )   2020

  • 【肝胆膵領域のゲノム医療新時代-遺伝子パネルがやってきた!-】膵臓 IPMNのゲノム解析

    林 明宏, 水上 裕輔, 佐藤 裕基, 河端 秀賢, 岡田 哲弘, 後藤 拓磨, 河本 徹, 小野 裕介, 唐崎 秀則, 奥村 利勝

    肝・胆・膵   79 ( 6 )   1125 - 1133   2019.12

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  • The Temporal Order of KRAS and GNAS Mutations in Intraductal Papillary Mucinous Neoplasms of the Pancreas and Evolution to Invasive Carcinoma

    Y. Mizukami, H. Karasaki, Y. Ono, Y. Omori, A. Hayashi, S. Tachibana, Y. Sugiyama, H. Sato, H. Kawabata, T. Goto, M. Fujiya, K. Takahashi, A. Katanuma, H. Maguchi, T. Furukawa, T. Okumura

    PANCREAS   48 ( 10 )   1493 - 1493   2019.11

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  • 消化器病診療:内科と外科の対照と融合 遺伝子異常からみた膵管内乳頭粘液性腫瘍関連膵癌の発生経路

    水上 裕輔, 高橋 邦幸, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   125回   28 - 28   2019.9

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  • 消化器病診療:内科と外科の対照と融合 遺伝子異常からみた膵管内乳頭粘液性腫瘍関連膵癌の発生経路

    水上 裕輔, 高橋 邦幸, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   125回   28 - 28   2019.9

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  • 膵癌ドライバー変異はmRNA翻訳と蛋白質プレニル化を介しARF6が駆動する癌免疫回避を促進する(Pancreatic KRAS/TP53 mutations promote ARF6-based immune evasion via activating mRNA translation and protein prenylation)

    橋本 あり, 橋本 茂, 古川 聖太郎, 蔦保 暁生, 小野寺 康人, 半田 悠, 及川 司, 水上 裕輔, 西川 義浩, 児玉 裕三, 村上 正晃, 平野 聡, 佐邊 壽孝

    日本癌学会総会記事   78回   P - 3033   2019.9

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  • デジタルPCRによるBRAF遺伝子変異検査は甲状腺乳頭癌のFNA正診率を向上させる(BRAF mutation testing by dPCR improves the diagnosis accuracy of FNA for the papillary thyroid carcinoma)

    北崎 アリサ, 駒林 優樹, 小野 裕介, 木村 太一, 田中 伸哉, 長嶋 和郎, 水上 裕輔

    日本癌学会総会記事   78回   J - 1010   2019.9

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  • デジタルPCRを用いた血漿由来遊離核酸からの膵腫瘍の検出 早期診断への活用に向けて(Screening of mutations in circulating cell-free DNA for early-stage diagnosis and surveillance of pancreatic tumors)

    小野 裕介, 唐崎 秀則, 水上 裕輔

    日本癌学会総会記事   78回   J - 1036   2019.9

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  • Liquid biopsyの現状と将来展望 リキッドバイオプシーによる膵癌診断(Liquid biopsy: current status and future perspective Liquid biopsy in pancreatic tumors: Challenges for early detection and surveillance)

    水上 裕輔, 小野 裕介, 奥村 利勝

    日本癌学会総会記事   78回   S22 - 6   2019.9

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  • 血漿遊離核酸を用いた膵腫瘍診断

    岡田 哲弘, 水上 裕輔, 河本 徹, 林 明宏, 佐藤 裕基, 河端 秀賢, 後藤 拓磨, 笹島 順平, 小泉 一也, 高橋 邦幸, 岩野 博俊, 浅原 新吾, 桑谷 将城, 唐崎 秀則, 奥村 利勝

    膵臓   34 ( 3 )   A106 - A107   2019.6

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  • IPMNに関する課題克服に向けて IPMN関連膵癌の分子基盤と進展経路

    水上 裕輔, 大森 優子, 唐崎 秀則

    膵臓   34 ( 3 )   A54 - A54   2019.6

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  • 腸型IPMNはどのように発生するか? CDX2、MUC2、alcian blue三重染色による検討

    大森 優子, 水上 裕輔, 元井 冬彦, 海野 倫明, 古川 徹

    膵臓   34 ( 3 )   A169 - A169   2019.6

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  • 腸型IPMNはどのように発生するか? CDX2、MUC2、alcian blue三重染色による検討

    大森 優子, 水上 裕輔, 元井 冬彦, 海野 倫明, 古川 徹

    膵臓   34 ( 3 )   A169 - A169   2019.6

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  • 血漿遊離核酸を用いた膵腫瘍診断

    岡田 哲弘, 水上 裕輔, 河本 徹, 林 明宏, 佐藤 裕基, 河端 秀賢, 後藤 拓磨, 笹島 順平, 小泉 一也, 高橋 邦幸, 岩野 博俊, 浅原 新吾, 桑谷 将城, 唐崎 秀則, 奥村 利勝

    膵臓   34 ( 3 )   A106 - A107   2019.6

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  • IPMNに関する課題克服に向けて IPMN関連膵癌の分子基盤と進展経路

    水上 裕輔, 大森 優子, 唐崎 秀則

    膵臓   34 ( 3 )   A54 - A54   2019.6

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  • ABNORMAL ACTIVATION OF HNRNPA0 INHIBITS CANCER CELL APOPTOSIS AND PROMOTES EXCESSIVE MITOSIS IN CANCER CELLS

    Hiroaki Konishi, Mikihiro Fujiya, Akemi Kita, Hiroki Tanaka, Shin Kashima, Aki Sakatani, Tatsuya Dokoshi, Katsuyoshi Ando, Nobuhiro Ueno, Kentaro Moriichi, Takuya Iwama, Keitaro Takahashi, Yuuki Murakami, Katsuya Ikuta, Yusuke Mizukami, Takuma Goto, Toshikatsu Okumura

    GASTROENTEROLOGY   156 ( 6 )   S484 - S484   2019.5

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  • 膵癌と胆管癌の鑑別困難例に与える遺伝子解析の意義

    立花 史音, 杉山 雄哉, 岡田 哲弘, 笹島 順平, 富永 素矢, 坂本 淳, 木村 圭介, 小野 裕介, 唐崎 秀則, 水上 裕輔, 太田 智之

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   60 - 60   2019.3

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  • 早期発見が可能であったクローン病を背景としたColitic cancerの1例

    佐藤 允洋, 上野 伸展, 藤谷 幹浩, 奥村 利勝, 久野木 健仁, 佐々木 貴弘, 岩間 琢哉, 高橋 慶太郎, 村上 雄紀, 嘉島 伸, 盛一 健太郎, 安藤 勝祥, 田邊 裕貴, 水上 裕輔

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   78 - 78   2019.3

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  • EUS-FNAにより播種再発を来したと考えられた膵体部癌の1切除例

    河端 秀賢, 後藤 拓磨, 藤林 周吾, 笹島 順平, 今井 浩二, 谷野 美智枝, 佐藤 裕基, 岡田 哲弘, 林 明宏, 宮澤 佑貴, 河本 徹, 藤永 明裕, 小野 裕介, 唐崎 秀則, 高氏 修平, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   72 - 72   2019.3

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  • 胆管外に脱落のない胆管プラスチックステントによる腸管穿孔の1例

    林 明宏, 後藤 拓磨, 笹島 順平, 萩原 正弘, 今井 浩二, 佐藤 裕基, 岡田 哲弘, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   68 - 68   2019.3

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  • 膵癌と胆管癌の鑑別困難例に与える遺伝子解析の意義

    立花 史音, 杉山 雄哉, 岡田 哲弘, 笹島 順平, 富永 素矢, 坂本 淳, 木村 圭介, 小野 裕介, 唐崎 秀則, 水上 裕輔, 太田 智之

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   60 - 60   2019.3

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  • 早期発見が可能であったクローン病を背景としたColitic cancerの1例

    佐藤 允洋, 上野 伸展, 藤谷 幹浩, 奥村 利勝, 久野木 健仁, 佐々木 貴弘, 岩間 琢哉, 高橋 慶太郎, 村上 雄紀, 嘉島 伸, 盛一 健太郎, 安藤 勝祥, 田邊 裕貴, 水上 裕輔

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   78 - 78   2019.3

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  • EUS-FNAにより播種再発を来したと考えられた膵体部癌の1切除例

    河端 秀賢, 後藤 拓磨, 藤林 周吾, 笹島 順平, 今井 浩二, 谷野 美智枝, 佐藤 裕基, 岡田 哲弘, 林 明宏, 宮澤 佑貴, 河本 徹, 藤永 明裕, 小野 裕介, 唐崎 秀則, 高氏 修平, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   72 - 72   2019.3

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  • Omori Y, Ono Y, Tanino M et al : Pathways of progression from intraductal papillary mucinous neoplasm to pancreatic ductal adenocarcinoma based on molecular features. Gastroenterology 156 : 647-661. e2, 2019

    Science of Gastroenterology   3 ( 1 )   16,49 - 53   2019.3

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  • 胆管外に脱落のない胆管プラスチックステントによる腸管穿孔の1例

    林 明宏, 後藤 拓磨, 笹島 順平, 萩原 正弘, 今井 浩二, 佐藤 裕基, 岡田 哲弘, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   68 - 68   2019.3

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  • 血漿遊離核酸を用いた膵腫瘍診断

    岡田哲弘, 岡田哲弘, 水上裕輔, 水上裕輔, 河本徹, 林明宏, 佐藤裕基, 河端秀賢, 後藤拓磨, 笹島順平, 小泉一也, 高橋邦幸, 岩野博俊, 浅原新吾, 桑谷将城, 唐崎秀則, 奥村利勝

    膵臓(Web)   34 ( 3 )   2019

  • 膵嚢胞診療最前線―IPMN国際診療コンセンサスガイドライン改訂を踏まえて―IPMN国際診療コンセンサスガイドライン最新版(2017年)IPMNの分子基盤はどこまでわかったか Invited

    河端秀賢, 水上裕輔, 岡田哲弘, 佐藤裕基, 林明宏, 後藤拓磨, 上田潤, 小野裕介, 小野裕介, 唐崎秀則, 奥村利勝

    77 ( 5 )   1003‐1009 - 963   2018.11

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  • 血漿遊離核酸を用いた膵癌早期診断の可能性

    岡田 哲弘, 林 明宏, 佐藤 裕基, 河端 秀賢, 後藤 拓磨, 笹島 順平, 小泉 一也, 岩野 博俊, 山田 政孝, 高橋 邦幸, 潟沼 朗生, 小野 裕介, 唐崎 秀則, 水上 裕輔, 奥村 利勝

    日本消化器病学会雑誌   115 ( 臨増大会 )   A752 - A752   2018.10

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  • 膵癌ドライバー変異はARF6-AMAP1経路を活性化し悪性度と免疫回避能を促進する(Pancreatic KRAS and TP53 oncogenes cooperatively activate ARF6-AMAP1 pathway to drive malignancy and immune evasion)

    橋本 あり, 橋本 茂, 古川 聖太郎, 蔦保 暁生, 小野寺 康仁, 大塚 勇太郎, 半田 悠, 及川 司, 水上 裕輔, 村上 正晃, 平野 聡, 佐邊 壽孝

    日本癌学会総会記事   77回   2219 - 2219   2018.9

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  • デジタルPCRを用いた、血漿由来遊離核酸からのHER2増幅検出(Liquid biopsy monitoring HER2 amplification in plasma cfDNA using digital PCR system)

    小野 裕介, 唐崎 秀則, 水上 裕輔

    日本癌学会総会記事   77回   795 - 795   2018.9

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  • 変異型KRAS検出による腹腔洗浄細胞診診断の可能性が示唆された1例

    小野雅人, 中村透, 土川貴裕, 田中公貴, 中西喜嗣, 浅野賢道, 野路武寛, 岡村圭祐, 水上裕輔, 平野聡

    日本臨床外科学会雑誌   79 ( 6 )   1330 - 1330   2018.6

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  • 変異型KRAS検出による腹腔洗浄細胞診診断

    小野雅人, 中村透, 田中公貴, 中西喜嗣, 浅野賢道, 野路武寛, 倉島庸, 海老原裕磨, 村上壮一, 土川貴裕, 岡村圭祐, 七戸俊明, 水上裕輔, 平野聡

    膵臓   33 ( 3 )   503 - 503   2018.5

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  • ヒストンバリアントとがん~がん微小環境とエピゲノムを繋ぐもの~

    上田潤, 水上裕輔, 水上裕輔, 大栗敬幸

    月刊細胞   50 ( 5 )   278‐282   2018.5

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  • NEUROENDOCRINE CARCINOMA OF THE GALLBLADDER: PROGNOSTIC FACTORS AND OPTIMAL TREATMENT OPTIONS

    Hiroki Sato, Junpei Sasajima, Takuma Goto, Yusuke Mizukami, Takuya Iwama, Tetsuhiro Okada, Masami Ijiri, Keitaro Takahashi, Shugo Fujibayashi, Akihiro Hayashi, Hidemasa Kawabata, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Shuhei Takauji, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    GASTROENTEROLOGY   154 ( 6 )   S954 - S954   2018.5

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  • 変異型KRAS検出による腹腔洗浄細胞診診断

    小野 雅人, 中村 透, 田中 公貴, 中西 喜嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 土川 貴裕, 岡村 圭祐, 七戸 俊明, 水上 裕輔, 平野 聡

    膵臓   33 ( 3 )   503 - 503   2018.5

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  • IPMN併存膵癌の分子病理学的解析

    大森優子, 大森優子, 小野裕介, 唐崎秀則, 山口浩, 古川徹, 水上裕輔, 水上裕輔, 真口宏介

    膵臓   33 ( 3 )   546   2018.5

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  • IPMN関連膵癌におけるMolecular subtypeに基づいたクローン進化モデル

    大森優子, 大森優子, 小野裕介, 谷野美智枝, 唐崎秀則, 山口浩, 古川徹, 篠原敏也, 真口宏介, 水上裕輔, 水上裕輔, 田中伸哉

    日本病理学会会誌   107 ( 1 )   236   2018.4

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  • The Incidence and Risk Factors of Venous Thromboembolism in Japanese Inpatients With Inflammatory Bowel Disease: A Retrospective and Prospective Study

    Ando Katsuyoshi, Fujiya Mikihiro, Nomura Yoshiki, Ueno Nobuhiro, Inaba Yuhei, Sugiyama Yuya, Iwama Takuya, Ijiri Masami, Takahashi Keitaro, Tanaka Kazuyuki, Goto Takuma, Kashima Shin, Sasajima Junpei, Moriichi Kentaro, Mizukami Yusuke, Yamada Satoshi, Nakase Hiroshi, Okumura Toshikatsu

    AMERICAN JOURNAL OF GASTROENTEROLOGY   113   S12 - S12   2018.2

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    DOI: 10.14309/00000434-201802001-00047

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  • 内臓脂肪と腸腰筋筋肉量の変化からみたクローン病術後長期経過の検討

    安藤勝祥, 小林裕, 村上雄紀, 佐藤裕基, 岩間琢哉, 久野木健仁, 高橋慶太郎, 河端秀賢, 林明宏, 上野伸展, 後藤拓磨, 嘉島伸, 笹島順平, 盛一健太郎, 田邊裕貴, 藤谷幹浩, 水上裕輔, 奥村利勝

    日本消化器病学会雑誌(Web)   115   2018

  • 血漿遊離核酸を用いた膵癌早期診断の可能性

    岡田哲弘, 林明宏, 佐藤裕基, 河端秀賢, 後藤拓磨, 笹島順平, 小泉一也, 岩野博俊, 山田政孝, 高橋邦幸, 潟沼朗生, 小野裕介, 唐崎秀則, 水上裕輔, 奥村利勝

    日本消化器病学会雑誌(Web)   115   2018

  • 血漿遊離核酸を用いた膵腫瘍悪性度診断

    岡田 哲弘, 水上 裕輔, 小泉 一也, 山田 政孝, 高橋 邦幸, 浅原 進吾, 川久保 和道, 笹島 順平, 小野 裕介, 唐崎 秀則, 奥村 利勝

    日本消化器病学会雑誌   114 ( 臨増大会 )   A745 - A745   2017.9

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  • PROFILES OF SMALL INTESTINAL MICROBIOTA: POSSIBLE RELATIONSHIPS WITH IBD AND ABDOMINAL BLOATING

    Mitsue Nishiyama, Toru Kono, Yusuke Mizukami, Atsuo Maemoto, Shigeru Furukawa, Hidenori Karasaki, Taku Maejima, Masahiro Yamamoto

    GASTROENTEROLOGY   152 ( 5 )   S626 - S626   2017.4

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  • 今IPMNをどう診るか IPMN遺伝子解析の進歩 遺伝子異常からみたIPMN関連膵癌の特徴

    大森優子, 小野裕介, 谷野美智枝, 唐崎秀則, 高橋邦幸, 篠原敏也, 田中伸哉, 真口宏介, 水上裕輔

    肝胆膵   74 ( 4 )   541‐549   2017.4

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  • 今IPMNをどう診るか サーベイランスをめぐる諸問題 AGA腫瘍性膵嚢胞ガイドラインの概要,インパクト,問題点

    水上裕輔, 唐崎秀則, 真口宏介

    肝胆膵   74 ( 4 )   565‐571   2017.4

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  • Liquid biopsyによる早期発見,再発転移の評価システムの開発

    水上裕輔

    日本臨床腫瘍学会学術集会(CD-ROM)   15th   ROMBUNNO.SY25‐1   2017

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  • 切除不能膵癌における予後因子としてのサルコペニアの検討

    佐藤裕基, 笹島順平, 澤田康司, 岡田哲弘, 藤林周吾, 林明宏, 河端秀賢, 後藤拓磨, 高氏修平, 井尻学見, 高橋慶太郎, 田中一之, 安藤勝祥, 野村好紀, 上野伸展, 嘉島伸, 盛一健太郎, 水上裕輔, 藤谷幹浩, 奥村利勝

    日本消化器病学会大会(Web)   59th   2017

  • A Case Presentation of Distal Bile Duct Adenocarcinoma: Distinguishing Between Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma

    H. Karasaki, Y. Mizukami, Y. Ono, M. Ogata, D. Yoshikawa, T. Maejima, K. Nagashima, T. Kono

    PANCREAS   45 ( 10 )   1514 - 1514   2016.11

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  • Invasive Size Predicts Recurrence and Survival of Small Invasive Carcinoma Arising in Intraductal Papillary Mucinous Neoplasm of the Pancreas

    M. Mino-Kenudson, V. Morales-Oyarvide, K. Date, T. Ohtsuka, Y. Omori, M. Tanino, Y. Mizukami, S. -M. Hong, D. W. Hwang, S. C. Kim, G. Zamboni, P. Castelli, R. Higuchi, M. Yamamoto, K. Shimizu, M. Nakamura, H. Maguchi, C. Fernandez-Del Castillo, T. Furukawa

    PANCREAS   45 ( 10 )   1526 - 1526   2016.11

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  • Liquid Biopsy for Early Detection of Pancreatic Cancer

    Y. Mizukami, Y. Ono, H. Karasaki, M. Ogata, A. Sugitani, K. Koizumi, S. Asahara, K. Kawakubo, K. Takahashi, H. Maguchi, K. Nagashima

    PANCREAS   45 ( 10 )   1526 - 1526   2016.11

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  • 非小細胞肺癌を対象としたデジタルPCRによるliquid biopsy

    小野 裕介, 佐々木 高明, 吉田 遼平, 安藤 清宏, 大崎 能伸, 水上 裕輔

    日本癌学会総会記事   75回   P - 1332   2016.10

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  • Clinical Application of Liquid Biopsy in Lung Cancer Diagnosis

    Takaaki Sasaki, Yusuke Ono, Ryuuta Hukai, Kiyohiro Ando, Syunsuke Okumura, Sachie Tanno, Yoshinobu Ohsaki, Yusuke Mizukami

    ANNALS OF ONCOLOGY   27   2016.7

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  • IPMN関連浸潤癌におけるRNF43,βcatenin,SMAD4,p53の蛋白発現および遺伝子変異プロファイルの解析検討

    大森優子, 大森優子, 谷野美智枝, 水上裕輔, 小野裕介, 安保義恭, 真口宏介, 西原広史, 篠原敏也, 田中伸哉

    日本病理学会会誌   105 ( 1 )   368   2016.4

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  • Three Surgical Cases of Segmental Arterial Mediolysis

    Nobutaka Mukai, Hidenori Karasaki, Taku Maejima, Toru Kono, Yusuke Mizukami

    GASTROENTEROLOGY   150 ( 4 )   S1209 - S1209   2016.4

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  • Cell-free DNA genotyping using digital PCR for early detection of pancreatic neoplasm.

    Hidenori Karasaki, Yusuke Ono, Kazuya Koizumi, Kiyohiro Andoh, Shingo Asahara, Tomoki Yokochi, Kuniyuki Takahashi, Hiroyuki Maguchi, Masataka Yamada, Munehiko Ogata, Ayumu Sugitani, Toru Kono, Kazuo Nagashima, Yusuke Mizukami

    JOURNAL OF CLINICAL ONCOLOGY   34 ( 4 )   2016.2

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  • 液体生検による肺がん診断の臨床応用

    佐々木高明, 小野裕介, 深井隆太, 安藤清宏, 奥村俊介, 丹野幸恵, 大崎能伸, 水上裕輔

    日本臨床腫瘍学会学術集会(CD-ROM)   14th   ROMBUNNO.O3‐8‐4   2016

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  • A Surgical Approach to Extrahepatic Bile Duct Carcinoma With Intestinal Non-Rotation Presenting With Pre-Duodenal Portal Vein

    H. Karasaki, Y. Mizukami, T. Kono, T. Maejima, S. Fukahori, N. Mukai, S. Kasai, Y. Matsubara, H. Amizuka, K. Nagashima

    PANCREAS   44 ( 8 )   1385 - 1386   2015.11

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  • Plasma DNA Genotyping Using Digital PCR for Early Detection of Pancreatic Neoplasm

    Y. Mizukami, Y. Ono, H. Karasaki, M. Ogata, T. Kono, K. Nagashima

    PANCREAS   44 ( 8 )   1399 - 1399   2015.11

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  • Adenosquamous cell carcinoma derived from intraductal papillary mucinous neoplasm of the pancreas confirmed by genetic analysis.

    Hidenori Karasaki, Toru Kono, Yusuke Ono, Taku Maejima, Yusuke Mizukami

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 3 )   2015.1

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  • Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias.

    Yusuke Ono, Hidenori Karasaki, Koji Imai, Junpei Sasajima, Shin-ichi Chiba, Hiroshi Funakoshi, Miho Muraki, Hideki Hanaoka, Takahisa Furukawa, Hiroyuki Furukawa, Toru Kono, Kazuo Nagashima, Yusuke Mizukami

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 3 )   2015.1

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  • 民間病院におけるClinical Sequenceの取り組み;汎用性ある遺伝子診断システムの構築と運用を目指して

    水上裕輔

    日本臨床口腔病理学会総会・学術大会プログラム・抄録集(Web)   26th   40‐41 (WEB ONLY)   2015

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  • 液体生検による膵癌リスク評価

    水上裕輔, 真口宏介, 小泉一也

    日本消化器病学会大会(Web)   57th   SHOP‐258 (WEB ONLY)   2015

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  • 液体生検による膵管内乳頭粘液性腫瘍の悪性度評価

    水上裕輔

    日本膵臓病研究財団研究報告書   21st   27 - 35   2014.12

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  • Increased Angiogenic Property Of Human A Peripheral Blood Monocytes By ex Vivo Culture With c-Mpl Agonists In Hindlimb Ischemia Mouse Model

    Junpei Sasajima, Toru Kawamoto, Yoshiaki Sugiyama, Yusuke Mizukami, Yasuyuki Iuchi, Toshifumi Ashida, Hiroki Tanabe, Yoshihiro Torimoto, Yutaka Kohgo

    BLOOD   122 ( 21 )   2013.11

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  • single venous accessによる末梢血単核球分離とその効率

    蘆田知史, 奈田利恵, 井内康之, 千葉眞子, 加藤邦子, 福岡亜衣, 森木彩名, 永幡美鈴, 薄木亜也, 松原由佳, 原愛里, 八戸大輔, 山崎誠治, 水上裕輔

    再生医療   12   156   2013.2

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  • The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma

    佐藤 龍, 藤谷 幹浩, 渡 二郎, 上野 伸展, 盛一 健太郎, 嘉島 伸, 前田 重明, 安藤 勝祥, 河端 秀賢, 杉山 隆治, 野村 好紀, 奈田 利恵, 板橋 健太郎, 稲葉 勇平, 岡本 耕太郎, 水上 裕輔, 斉藤 裕輔, 高後 裕

    北海道醫學雜誌 = Acta medica Hokkaidonensia   87 ( 6 )   276 - 276   2012.11

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  • 高脂肪食投与による脂肪肝形成に伴う肝細胞Vanin‐1の発現亢進

    吉崎隆之, 本村亘, 高橋伸彦, 粂井志麻, 水上裕輔, JANG Seong‐Jae, 高後裕

    日本農芸化学会大会講演要旨集(Web)   2012   2J14P11 (WEB ONLY)   2012.3

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  • 消化器癌治療における新しい分子標的 バイパスシグナルの多様性からみて分子標的治療をどのように進めるか

    水上裕輔, 河本徹, 高後裕

    分子消化器病   9 ( 1 )   12 - 18   2012.3

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  • 自己免疫性膵炎における再燃抑制の観点からみたステロイド治療の意義

    小泉一也, 丹野誠志, 西川智哉, 河本徹, 杉山祥晃, 笹島順平, 藤永明裕, 後藤拓磨, 柳川伸幸, 中村和正, 千葉篤, 中野靖弘, 藤井常志, 水上裕輔, 高後裕

    日本消化器病学会雑誌   108   A905   2011.9

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  • 胆管扁平上皮癌の1例

    小泉一也, 河本徹, 杉山祥晃, 笹島順平, 水上裕輔, 今井浩二, 唐崎秀則, 徳差良彦, 丹野誠志, 三代川斉之, 古川博之, 高後裕

    胆道   25 ( 3 )   568   2011.8

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  • 新しい消化器疾患動物モデル 第2回 新たな膵発癌モデル

    水上裕輔, 河本徹, 高後裕

    分子消化器病   8 ( 2 )   167 - 171   2011.6

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  • 膵癌との比較からみた自己免疫性膵炎診断基準2006における血清学的診断項目の再評価

    小泉一也, 丹野誠志, 河本徹, 杉山祥晃, 笹島順平, 藤永明裕, 後藤拓磨, 柳川伸幸, 中村和正, 千葉篤, 西川智哉, 中野靖弘, 藤井常志, 水上裕輔, 高後裕

    膵臓   26 ( 3 )   348   2011.6

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  • 分枝型IPMN症例における進展例と不変例の検討

    羽広敦也, 丹野誠志, 小泉一也, 河本徹, 杉山祥晃, 水上裕輔, 高後裕

    膵臓   26 ( 3 )   416   2011.6

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  • The Paracrine Effect of Hedgehog on Bone Marrow-Derived Stromal Cells Occurs at Later Stages of Pancreatic Tumorigenesis

    Yoshiaki Sugiyama, Yusuke Mizukami, Toru Kawamoto, Junpei Sasajima, Kazuya Koizumi, Yoshiki Nomura, Kentaro Moriichi, Mikihiro Fujiya, Nabeel Bardeesy, Daniel C. Chung, Yutaka Kohgo

    GASTROENTEROLOGY   140 ( 5 )   S156 - S156   2011.5

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  • MicroRNA-146b Activates the NF-kB Pathway and Improves Intestinal Injury in a Mouse Enteritis Model

    Toshie Nata, Mikihiro Fujiya, Nobuhiro Ueno, Yuhei Inaba, Kentaro Moriichi, Yusuke Mizukami, Kazuya Sato, Yutaka Kohgo

    GASTROENTEROLOGY   140 ( 5 )   S520 - S520   2011.5

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  • 早期膵癌の病態解明 早期膵癌解明に向けた遺伝子解析 膵癌の間質形成制御に関連する遺伝子解析の動向

    水上裕輔, 杉山祥晃, 高後裕

    肝胆膵   62 ( 3 )   505 - 511   2011.3

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  • 自己免疫性膵炎における慢性炎症の持続と治療法の問題点

    小泉一也, 丹野誠志, 西川智哉, 河本徹, 杉山祥晃, 笹島順平, 藤永明裕, 後藤拓磨, 柳川伸幸, 河端秀賢, 中野靖弘, 藤井常志, 中村和正, 千葉篤, 水上裕輔, 高後裕

    日本消化器病学会雑誌   108   A268   2011.3

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  • 消化器癌のCancer Stem Cell,Cancer Initiating Cell 膵癌微小環境から癌幹細胞をみる

    水上裕輔, 笹島順平, 高後裕

    分子消化器病   8 ( 1 )   47 - 53   2011.3

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  • Effect of transplantation of pro-angiogenic monocytes to pancreatic cancer-bearing mice on resistance to chemotherapy/radiotherapy

    Y. Mizukami, T. Kawamoto, Y. Sugiyama, J. Sasajima, K. Koizumi, K. Moriichi, M. Fujiya, N. Bardeesy, D. C. Chung, Y. Kohgo

    JOURNAL OF CLINICAL ONCOLOGY   29 ( 4 )   2011.2

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    DOI: 10.1200/jco.2011.29.4_suppl.212

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  • トップランナーに聞く--最先端の医療に挑む若手研究者への直撃インタビュー(1)難治性がんの撲滅を目指して

    水上 裕輔

    最新医学   66 ( 1 )   120 - 122   2011.1

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  • 膵発癌の後期段階でのHedgehog過剰発現におけるHedgehog interacting protein(Hip)の役割

    杉山祥晃, 笹島順平, 河本徹, 小泉一也, 水上裕輔, 高後裕

    日本消化器癌発生学会総会プログラム・抄録集   22nd   77   2011

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  • 膵の漿液性嚢胞腫瘍(SCN)と粘液性嚢胞腫瘍(MCN)―最近の知見 von Hippel‐Lindau病に合併した膵SCNの1例

    唐崎秀則, 丹野誠志, 水上裕輔, 柳川伸幸, 齋藤博哉, 徳差良彦, 石崎彰, 笹島順平, 小泉一也, 三代川斉之, 今井浩二, 吉川大太郎, 紀野修一, 河野透, 高後裕, 古川博之

    肝胆膵画像   12 ( 6 )   737 - 742   2010.11

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  • 抗血管新生療法 1.腫瘍血管のリモデリングによる難治がん治療

    水上裕輔, 高後裕

    実験医学   28 ( 17 )   2885-2891,2716(7)   2010.11

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  • 自己免疫性膵炎の長期経過とステロイド治療による影響

    小泉一也, 水上裕輔, 高後裕

    日本消化器病学会雑誌   107   A582   2010.9

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  • 自己免疫性膵炎と膵癌の鑑別診断

    後藤拓磨, 柳川伸幸, 藤永昭裕, 坂谷慈, 佐藤智信, 後藤充, 井上充貴, 斎藤義徳, 折居裕, 柴田好, 伊藤巧, 河本徹, 杉山祥晃, 笹島順平, 小泉一也, 水上裕輔, 丹野誠志

    日本消化器病学会雑誌   107   A952   2010.9

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  • 腫瘍血管リモデリングは腫瘍低酸素を解除し,がん幹細胞様形質を軽減する

    水上裕輔, 笹島順平, 高後裕

    日本消化器病学会雑誌   107   A511   2010.9

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  • 膵癌におけるHedgehogのParacrine作用は発癌の後期段階で活性化する

    杉山祥晃, 笹島順平, 河本徹, 小泉一也, 佐藤一也, 水上裕輔, 高後裕

    日本消化器病学会雑誌   107   A944   2010.9

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  • 消化器癌の分子標的治療 膵癌に対する分子標的治療の現状と課題克服―遺伝子改変マウスモデルによるTarget Varidationの意義―

    笹島順平, 水上裕輔, 小泉一也, 河本徹, 杉山祥晃, 高後裕

    月刊消化器内科   51 ( 1 )   46 - 53   2010.7

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  • Molecular-targeted therapy in pancreatic cancer: target validation with genetic engineered mice model

    笹島 順平, 水上 裕輔, 小泉 一也

    Gastroenterology   51 ( 1 )   46 - 53   2010.7

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  • 分枝型IPMNの外科治療戦略 ムチン発現形質と壁在結節の有無からみたIPMNの切除適応

    唐崎秀則, 水上裕輔, 徳差良彦, 石崎彰, 今井浩二, 吉川大太郎, 小泉一也, 笹島順平, 丹野誠志, 松本学也, 三代川斉之, 紀野修一, 河野透, 高後裕, 古川博之

    胆とすい   31 ( 5 )   465 - 472   2010.5

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  • A case of pancreatic carcinoma presenting as pancreaticopleural fistula with pancreatic pleural effusion

    SUGIYAMA Yoshiaki, TANNO Satoshi, NISHIKAWA Tomoya, NAKAMURA Kazumasa, SASAJIMA Junpei, KOIZUMI Kazuya, MIZUKAMI Yusuke, KARASAKI Hidenori, KASAI Shinichi, YOSHIDA Yukinori, WATANABE Naomi, OKUMURA Toshikatsu, WATANABE Naomi

    Nippon Shokakibyo Gakkai Zasshi   107 ( 5 )   784 - 791   2010.5

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    DOI: 10.11405/nisshoshi.107.784

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  • Heat-Killed Body of Lactobacillus brevis Sbc8803 Contributes to Maintain Intestinal Homeostasis and Improve Intestinal Injury in a Murine Model of Colitis

    Nobuhiro Ueno, Mikihiro Fujiya, Shuichi Segawa, Toshie Nata, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Naoyuki Kobayashi, Kazutoshi Ito, Yutaka Kohgo

    GASTROENTEROLOGY   138 ( 5 )   S619 - S619   2010.5

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  • The Tumor Vasculature is a Paracrine Target of Hedgehog in Pancreatic Cancer

    Yoshiaki Sugiyama, Yusuke Mizukami, Junpei Sasajima, Kazumasa Nakamura, Toru Kawamoto, Kazuya Koizumi, Mikihiro Fujiya, Satoshi Tanno, Hidenori Karasaki, Toru Kono, Daniel C. Chung, Nabeel Bardeesy, Yutaka Kohgo

    GASTROENTEROLOGY   138 ( 5 )   S116 - S117   2010.5

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  • Competence and Sporulation Factor Derived From Bacillus Subtilis Improves Epithelial Cell Injury in Intestinal Inflammation via Immunomodulation and Cytoprotection

    Kotaro Okamoto, Mikihiro Fujiya, Toshie Nata, Nobuhiro Ueno, Yuhei Inaba, Chisato Ishikawa, Takahiro Ito, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Eugene B. Chang, Yutaka Kohgo

    GASTROENTEROLOGY   138 ( 5 )   S750 - S750   2010.5

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  • 【分枝型IPMNの外科治療戦略】 ムチン発現形質と壁在結節の有無からみたIPMNの切除適応

    唐崎 秀則, 水上 裕輔, 徳差 良彦, 石崎 彰, 今井 浩二, 吉川 大太郎, 小泉 一也, 笹島 順平, 丹野 誠志, 松本 学也, 三代川 斉之, 紀野 修一, 河野 透, 高後 裕, 古川 博之

    胆と膵   31 ( 5 )   465 - 472   2010.5

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    著者最終原稿版IPMNのムチン発現形質によるサブタイプ別予後、組織学的な異型度と壁在結節(MN)の関係に着目して、新たな切除適応の可能性について検討した。MUC2陽性型は最も予後が良好で、MNの有無と異型度に相関傾向を認めることから、MNが形成されるまでは経過観察が可能であると考えられた。MUC1陽性型もMNの有無と異型度に相関傾向を認めるものの、早期に浸潤を開始する可能性があるため、MNの有無にかかわらず切除適応と考えられた。一方、MUC1、2陰性型ではMNの有無と異型度に相関がなく、MNのないことが臨床的な安全性の高さを示すことにはならない。この型には経過観察が可能と思われる良性病変と、悪性度の高い病変が混在している可能性がある。MNの有無にかかわらず浸潤性管状腺癌の発生がみられることがあるため、経過観察において最も注意を要すると考えられた。

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  • 自己免疫性膵炎における膵外病変からみた疾患活動性に関する検討

    小泉一也, 丹野誠志, 藤井常志, 西川智哉, 河本徹, 杉山祥晃, 笹島順平, 水上裕輔, 後藤拓磨, 柳川伸幸, 中村和正, 千葉篤, 中野靖弘

    日本消化器病学会雑誌   107   A285   2010.3

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  • 腫瘍と血管新生【腫瘍血管新生における骨髄細胞の役割】

    水上裕輔, 笹島順平, 高後裕

    細胞   42 ( 2 )   52 - 55   2010.2

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  • 膵癌・胆道癌の前癌病変,リスクファクターを探る 長期経過からみた分枝型IPMNの悪性化リスクと通常型膵癌合併リスク

    丹野誠志, 小泉一也, 中野靖弘, 河本徹, 杉山祥晃, 笹島順平, 中村和正, 西川智哉, 水上裕輔, 千葉篤, 柳川伸幸, 藤井常志, 小原剛

    胆とすい   31 ( 2 )   155 - 159   2010.2

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  • 【膵癌・胆道癌の前癌病変、リスクファクターを探る】 長期経過からみた分枝型IPMNの悪性化リスクと通常型膵癌合併リスク

    丹野 誠志, 小泉 一也, 中野 靖弘, 河本 徹, 杉山 祥晃, 笹島 順平, 中村 和正, 西川 智哉, 水上 裕輔, 千葉 篤, 柳川 伸幸, 藤井 常志, 小原 剛

    胆と膵   31 ( 2 )   155 - 159   2010.2

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    著者最終原稿版画像診断機器の進歩によって、無症候性の分枝型IPMN病変が発見される機会は増加している。本稿では、分枝型IPMN症例におけるIPMN病変の悪性化リスクと通常型膵癌合併リスクについて最近の報告をもとに概説した。壁在結節のない症例に限定すれば、観察期間中央値32〜61ヵ月において、非浸潤癌へ進展した症例の頻度は0〜3.3%、浸潤癌への進展は0〜0.8%程度であり、壁在結節のない分枝型IPMN病変の悪性化リスクは低く、悪性化には長期間を要すると推測された。また、膵癌合併リスクについては、分枝型IPMN症例における通常型膵癌の合併頻度は2.5%〜9.2%であり、標準化死亡比は一般人口の15.8〜26倍と高率に通常型膵癌を合併する可能性のあることが示唆された。分枝型IPMN症例は、IPMN病変自体の悪性化リスクに加えて、通常型膵癌合併の高いリスクを有しており、これらのリスクを考慮した診療を行っていくことが必要である。

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  • Role of bone marrow-derived cells in tumor angiogenesis

    水上 裕輔, 笹島 順平, 高後 裕

    The Cell   42 ( 2 )   52 - 55   2010.2

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  • 膵癌の予防 分枝型IPMNにおける膵癌発生リスク:膵癌の早期発見は可能なのか?

    丹野誠志, 小泉一也, 中野靖弘, 杉山祥晃, 笹島順平, 西川智哉, 水上裕輔, 柳川伸幸, 藤井常志, 小原剛

    月刊消化器科   49 ( 6 )   512 - 516   2009.12

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  • Hedgehog Promotes Neovascularization through the Regulation of Bone-Marrow Derived Progenitors

    Yusuke Mizukami, Junpei Sasajima, Kazumasa Nakamura, Kazuya Sato, Yoshiaki Sugiyama, Madoka Yamazaki, Toru Kawamoto, Kazuya Koizumi, Katsunori Sasaki, Mikihiro Fujiya, Satoshi Tanno, Toshikatsu Okumura, Norihiko Shimizu, Jun-ichi Kawabe, Toru Kono, Yoshihiro Torimoto, Masaaki Ii, Nabeei Bardeesy, Daniel C. Chung, Yutaka Kohgo

    BLOOD   114 ( 22 )   1187 - 1187   2009.11

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  • A Crucial Cytotoxic Role of Anti-Idiotypic Antibody in Immunotherapy for B-Cell Neoplasms with Tumor Cell-Derived Heat Shock Protein 70.

    Kazuya Sato, Junko Jimbo, Naoka Okamura, Takaaki Hosoki, Motohiro Shindo, Katsuya Ikuta, Yusuke Mizukami, Mikihiro Fujiya, Yoshihiro Torimoto, Yutaka Kohgo

    BLOOD   114 ( 22 )   656 - 656   2009.11

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  • 胆・膵臓癌早期診断と検診の有効性 分枝型IPMNを膵癌高危険群として集約した検診体系の検討

    丹野誠志, 小泉一也, 西川智哉, 杉山祥晃, 笹島順平, 中野靖弘, 水上裕輔, 柳川伸幸, 藤井常志, 奥村利勝, 高後裕

    月刊消化器科   49 ( 4 )   353 - 357   2009.10

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  • 膵癌に対する分子標的治療の現状と課題克服~前臨床におけるターゲットバリデーション~

    笹島順平, 水上裕輔, 高後裕

    日本消化器病学会雑誌   106   A624   2009.9

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  • 切除不能進行膵癌に対するGEM+TS1/UFT併用療法と無効例における二次治療の検討

    笹島順平, 丹野誠志, 中村和正, 小泉一也, 羽廣敦也, 中野靖弘, 藤井常志, 千葉篤, 杉山祥晃, 西川智哉, 水上裕輔, 奥村利勝, 高後裕

    日本癌治療学会誌   44 ( 2 )   436   2009.9

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  • 自己免疫性膵炎の疾患活動性およびステロイドによる治療的診断に関する検討

    西川智哉, 丹野誠志, 藤井常志, 柳川伸幸, 中野靖弘, 中村和正, 杉山祥晃, 笹島順平, 小泉一也, 水上裕輔, 千葉篤, 奥村利勝, 高後裕

    膵臓   24 ( 3 )   369   2009.6

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  • 膵癌由来のSonic Hedgehogは骨髄由来細胞の制御により血管新生を誘導する

    笹島順平, 中村和正, 水上裕輔, 杉山祥晃, 西川智哉, 丹野誠志, 奥村利勝, 高後裕

    膵臓   24 ( 3 )   373   2009.6

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  • Hedgehog Signaling Regulates Angiogenesis in Pancreatic Cancer

    Yoshiaki Sugiyama, Yusuke Mizukami, Kazumasa Nakamura, Junpei Sasajima, Tomoya Nishikawa, Kazuya Koizumi, Mikihiro Fujiya, Satoshi Tanno, Toshikatsu Okumura, Toru Kono, Daniel Chung, Yutaka Kohgo

    GASTROENTEROLOGY   136 ( 5 )   A32 - A33   2009.5

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  • Effects of Helicobacter pylori Infection On Aberrant CpG Island Methylation Status and Cellular Phenotype in Columnar-Lined Esophagus in a Japanese Population

    Kentaro Moriichi, Jiro Watari, Kiron M. Das, Hiroki Tanabe, Mikihiro Fujiya, Toshie Nata, Yoshiki Nomura, Nobuhiro Ueno, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Ryu Sato, Kotaro Okamoto, Yusuke Mizukami, Yutaka Kohgo

    GASTROENTEROLOGY   136 ( 5 )   A599 - A599   2009.5

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  • Infliximab May Prevent Post-Operative Recurrences in Crohn&apos;s Disease

    Kotaro Okamoto, Mikihiro Fujiya, Toshie Nata, Yoshiki Nomura, Nobuhiro Ueno, Chisato Ishikawa, Yuhei Inaba, Takahiro Ito, Kentaro Moriichi, Hiroki Tanabe, Atsuo Maemoto, Yusuke Mizukami, Toshifumi Ashida, Toru Kono, Yutaka Kohgo

    GASTROENTEROLOGY   136 ( 5 )   A572 - A573   2009.5

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  • The tumor vasculature is a paracrine target of Hedgehog in pancreatic cancer

    Junpei Sasajima, Yusuke Mizukami, Kazumasa Nakamura, Yoshiaki Sugiyama, Madoka Yamazaki, Kazuya Sato, Mikihiro Fujiya, Jun-ichi Kawabe, Satoshi Tanno, Toshikatsu Okumura, Toru Kono, Masaaki Ii, Nabeel Bardeesy, Daniel Chung, Yutaka Kohgo

    CANCER RESEARCH   69   2009.5

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  • 15年間の経時的変化を観察し得た膵漿液性嚢胞腫瘍と分枝型IPMN合併の1例

    河本徹, 丹野誠志, 西川智哉, 杉山祥晃, 中村和正, 笹島順平, 小泉一也, 水上裕輔, 奥村利勝, 高後裕

    日本消化器病学会雑誌   106   A382   2009.3

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  • ゲムシタビン+TS1/UFT併用療法と無効例における二次治療の検討

    笹島順平, 丹野誠志, 小泉一也, 羽廣敦也, 藤井常志, 千葉篤, 杉山祥晃, 中村和正, 西川智哉, 水上裕輔, 奥村利勝, 高後裕

    日本消化器病学会雑誌   106   A158   2009.3

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  • 嚢胞径30mm以上の分枝型IPMN経過観察例の検討

    小泉一也, 丹野誠志, 柳川伸幸, 河本徹, 杉山祥晃, 中村和正, 笹島順平, 西川智哉, 水上裕輔, 千葉篤, 高後裕

    日本消化器病学会雑誌   106   A242   2009.3

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  • ステロイド投与による治療的診断を行った自己免疫性膵炎の2例

    杉山祥晃, 丹野誠志, 西川智哉, 河本徹, 中村和正, 笹島順平, 小泉一也, 水上裕輔, 奥村利勝, 高後裕

    日本消化器病学会雑誌   106   A440   2009.3

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  • 膵癌細胞が産生するSonic hedgehogは骨髄由来前駆細胞に対してParacrineに作用し,IGF‐1を介して腫瘍新生血管を安定化する

    水上裕輔, 笹島順平, 中村和正, 杉山祥晃, 佐藤一也, 伊井正明, 高後裕

    日本血管生物医学会   17th   66   2009

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  • Gemcitabine in combination with S-1 or UFT in patients with advanced pancreatic cancer

    Junpei Sasajima, Satoshi Tanno, Kazuya Koizumi, Yasuhiro Nakano, Atsuya Habiro, Atsushi Chiba, Tsuneshi Fujii, Yoshiaki Sugiyama, Kazumasa Nakamura, Tomoya Nishikawa, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    Japanese Journal of Cancer and Chemotherapy   36 ( 10 )   1657 - 1661   2009

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  • Sonic hedgehog(SHH)は骨髄細胞の動員と活性化を介して腫瘍血管新生を促進する

    笹島順平, 水上裕輔, 高後裕

    日本消化器病学会雑誌   105   A667   2008.9

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  • 自己免疫性膵炎の治療と予後

    西川智哉, 丹野誠志, 柳川伸幸, 藤井常志, 羽廣敦也, 中村和正, 笹島順平, 水上裕輔, 中野靖弘, 奥村利勝, 高後裕

    膵臓   23 ( 3 )   340   2008.6

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  • 切除不能進行膵癌に対するゲムシタビン+TS1,UFT併用療法の検討

    笹島順平, 丹野誠志, 小泉一也, 羽廣敦也, 藤井常志, 中村和正, 西川智哉, 水上裕輔, 奥村利勝, 高後裕

    膵臓   23 ( 3 )   391   2008.6

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  • 経過観察中に進展したIPMN(主膵管型と分枝型)の検討

    丹野誠志, 中村和正, 笹島順平, 小泉一也, 西川智哉, 水上裕輔, 奥村利勝, 高後裕

    膵臓   23 ( 3 )   281   2008.6

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  • Two cases of pancreatic tumor with von Hippel-Lindau disease

    KARASAKI Hidenori, ISHIZAKI Akira, YANAGAWA Nobuyuki, NAKANO Yasuhiro, SASAJIMA Jyunpei, MIZUKAMI Yusuke, TANNO Satoshi, TOKUSASHI Yoshihiko, MIYOKAWA Naoyuki, OBARA Mitsuhiro, GOTO Junichi, KINO Shuichi, KONO Toru, KASAI Shinichi

    Nippon Shokakibyo Gakkai Zasshi   105 ( 5 )   725 - 731   2008.5

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    DOI: 10.11405/nisshoshi.105.725

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  • HOXC6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth

    Kotoyo Fujiki, Eva-Maria Duerr, Hirotoshi Kikuchi, Aylwin Ng, Ramnik J. Xavier, Yusuke Mizukami, Takaaki Imamura, Matthew H. Kulke, Daniel Chung

    GASTROENTEROLOGY   134 ( 4 )   A297 - A297   2008.4

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  • Risk of pancreatic ductal adenocarcinomas in long-term followed-up patients with branch duct intraductal papillary-mucinous neoplasms

    Satoshi Tanno, Tomoya Nishikawa, Kazuya Koizumi, Junpei Sasajima, Kazumasa Nakamura, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    GASTROENTEROLOGY   134 ( 4 )   A698 - A699   2008.4

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  • Milk-of-calcium in a pseudocyst of the pancreas

    KOIZUMI Kazuya, TANNO Satoshi, YANAGAWA Nobuyuki, OSANAI Manabu, HABIRO Atsuya, NAKAMURA Kazumasa, MINOGUCHI Madoka, NAKANO Yasuhiro, MIZUKAMI Yusuke, OKUMURA Toshikatsu, KOHGO Yutaka

    Nippon Shokakibyo Gakkai Zasshi   105 ( 1 )   93 - 98   2008.1

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    DOI: 10.11405/nisshoshi.105.93

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  • ヒト血管内皮前駆細胞の可塑性に起因するがん微少環境の異常とその制御

    水上裕輔

    がん研究に係わる特定領域研究研究報告集録 平成19年度   221   2008

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  • 胆嚢壁内側低エコー層肥厚と胆嚢腺筋腫症に着目した腹部超音波検査による膵胆管合流異常の早期発見

    柳川伸幸, 丹野誠志, 中野靖弘, 笹島順平, 蓑口まどか, 水上裕輔, 小原剛, 高後裕

    旭川厚生病院医誌   17 ( 2 )   33 - 38   2007.12

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  • 胆嚢壁内側低エコー層肥厚と胆嚢腺筋腫症に着目した腹部超音波検査による膵胆管合流異常の早期発見

    柳川 伸幸, 丹野 誠志, 中野 靖弘, 笹島 順平, 簔口 まどか, 水上 裕輔, 小原 剛, 高後 裕

    旭川厚生病院医誌   17 ( 2 )   33 - 38   2007.12

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    雑誌掲載版合流異常合併胆嚢43例(非拡張型19例、拡張型24例)の超音波(US)所見と切除胆嚢の病理組織学的所見を比較し、合流異常の早期診断におけるUSの有用性について検討した。その結果、全体では胆嚢壁肥厚を60%、胆嚢壁内側低エコー層肥厚あるいは胆嚢腺筋腫症のいずれかを82.9%に認めた。また、非拡張型では4mm以上の胆嚢壁肥厚を88.2%、更に胆嚢壁内側肥厚と胆嚢腺筋腫症の両方、あるいはいずれかを94.1%に認めたのに対し、拡張型ではそれぞれ33.3%、66.7%であった。以上より、検診の腹部USで壁肥厚や内側低エコー層肥厚、胆嚢腺筋腫症を認めた場合には、合流異常の存在を疑うことが本症の早期発見につながると考えられた。尚、USを契機に発見された合流異常の検討から、検診対象者のうち腹部症状の現病歴・既往歴のある者や女性に対しては、胆嚢壁の所見に深く注意を払いながらUSを行う必要があると示唆された。

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  • 嚢胞壁の一部に微小浸潤癌を認めた分枝型IPMNの1例

    西川智哉, 丹野誠志, 中野靖弘, 中村和正, 笹島順平, 水上裕輔, 奥村利勝, 徳差良彦, 三代川斎之, 高後裕

    消化器画像   9 ( 6 )   603 - 608   2007.11

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  • 分枝型IPMNにおける膵内および膵外悪性腫瘍の検討

    西川智哉, 丹野誠志, 中村和正, 笹島順平, 水上裕輔, 奥村利勝, 高後裕

    日本消化器病学会雑誌   104   A745   2007.9

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  • A case of hypoplastic gallbladder

    KOIZUMI Kazuya, TANNO Satoshi, OSANAI Manabu, YANAGAWA Nobuyuki, KIMURA Keisuke, HABIRO Atsuya, NAKANO Yasuhiro, NAKAMURA Kazumasa, MINOGUCHI Madoka, NISHIKAWA Tomoya, MIZUKAMI Yusuke, KOHGO Yutaka

    胆道   21 ( 2 )   189 - 193   2007.5

  • 消化管腫瘍の分子診断と標的治療 消化器癌におけるHIF‐1阻害による血管新生の制御―血管新生阻害薬の獲得耐性の分子機構―

    水上裕輔, 山崎まどか, 中村和正, 笹島順平, 西川智哉, 丹野誠志, 奥村利勝, 高後裕

    月刊消化器科   44 ( 5 )   478 - 483   2007.5

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  • 自己免疫性膵炎のステロイド治療反応性と予後についての検討

    西川智哉, 丹野誠志, 柳川伸幸, 藤井常志, 中村和正, 中野靖弘, 水上裕輔, 笹島順平, 後藤拓磨, 奥村利勝, 高後裕

    膵臓   22 ( 3 )   266   2007.5

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  • 膵癌におけるゲムシタビン獲得耐性と治療抵抗性予測に関する検討

    中野靖弘, 丹野誠志, 中村和正, 西川智哉, 水上裕輔, 奥村利勝, 高後裕

    膵臓   22 ( 3 )   235   2007.5

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  • Significance of branch duct type intraductal papillary-mucinous neoplasms of the pancreas as a high risk factor for pancreatic cancer: Long-term follow-up results

    Satoshi Tanno, Takeshi Obara, Yasuhiro Nakano, Madoka Minoguchi, Tomoya Nishikawa, Kazumasa Nakamura, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    GASTROENTEROLOGY   132 ( 4 )   A531 - A531   2007.4

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  • 消化器癌浸潤・転移における間質・血管新生を探る 大腸癌における低酸素による血管新生促進の機序を探る

    水上裕輔

    分子消化器病   4 ( 1 )   20 - 24   2007.3

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  • ヒト血管内皮前駆細胞の可塑性に起因するがん微小環境の異常とその制御

    水上裕輔

    がん研究に係わる特定領域研究研究報告集録 平成18年度   221   2007

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  • The novel role of K-RAS signaling in the induction of VEGF during hypoxia in colon cancer

    Yusuke Mizukami, Yutaka Kohgo, Daniel C. Chung

    CLINICAL & EXPERIMENTAL METASTASIS   24 ( 4 )   232 - 233   2007

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  • 12年の経過観察後に切除した膵管内乳頭粘液性腺癌の一例

    中村和正, 中野靖弘, 簑口まどか, 水上裕輔, 高後裕, 丹野誠志, 奥村利勝

    日本消化器病学会雑誌   103   A1008   2006.9

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  • 膵癌におけるSonic hedgehogを介した腫瘍血管新生

    蓑口まどか, 中村和正, 水上裕輔, 中野靖弘, 佐藤一也, 丹野誠志, 奥村利勝, 蘆田知史, 高後裕

    日本消化器病学会雑誌   103   A980   2006.9

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  • 消化器癌におけるHIF‐1阻害による血管新生の制御

    水上裕輔, 高後裕

    日本消化器病学会雑誌   103   A410   2006.9

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  • ヒト大腸癌細胞において低酸素刺激はc‐Mycを介しHIF‐1非依存性にVEGFを誘導する

    水上裕輔, 高後裕

    日本癌学会学術総会記事   65th   31   2006.8

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  • ゲムシタビン耐性獲得過程における細胞内代謝関連遺伝子の検討

    中野靖弘, 丹野誠志, 中村和正, 蓑口まどか, 水上裕輔, 奥村利勝, 高後裕

    膵臓   21 ( 3 )   256   2006.6

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  • Role of Endoscopic Ultrasonography in Follow-Up of Branch Duct Type Intraductal Papillary-Mucinous Neoplasms of the Pancreas

    Satoshi Tanno, Yasuhiro Nakano, Kazumasa Nakamura, Madoka Minoguchi, Tsutomu Izawa, Yusuke Mizukami, Toshikatsu Okumura, Yutaka Kohgo

    GASTROINTESTINAL ENDOSCOPY   63 ( 5 )   AB278 - AB278   2006.4

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  • Natural History of Branch-Duct Type Intraductal Papillary-Mucinous Tumor (IPMT) of the Pancreas: &apos;Prospective&apos; Long-Term Follow-Up By MR Cholangiopancreatography (MRCP) and EUS

    Madoka Minoguchi, Yusuke Mizukami, Kazumasa Nakamura, Junpei Sasajima, Tsutomu Izawa, Yasuhiro Nakano, Nobuyuki Yanagawa, Satoshi Tanno, Tsuneshi Fujii, Toshikatsu Okumura, Takeshi Obara, Yutaka Kohgo

    GASTROINTESTINAL ENDOSCOPY   63 ( 5 )   AB256 - AB256   2006.4

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  • Gene expression profiles of pancreatic neuroendocrine tumors and gastrointestinal carcinoids

    Eva-Maria Duerr, Yusuke Mizukami, Andrew L. Warshaw, Matthew H. Kulke, Daniel C. Chung

    GASTROENTEROLOGY   130 ( 4 )   A278 - A278   2006.4

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  • Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells (vol 11, pg 992, 2005)

    Y Mizukami, WS Jo, EM Duerr, M Gala, J Li, Zhang, X, MA Zimmer, O Iliopoulos, LR Zukerberg, Y Kohgo, MP Lynch, BR Rueda, DC Chung

    NATURE MEDICINE   12 ( 2 )   253 - 253   2006.2

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  • EPC TSP-1 mediates diabetes induced delay in reendothelialization after arterial injury

    M Il, H Takenaka, J Asai, Y Mizukami, K Maruyama, YS Yoon, A Wecker, C Luedemann, E Eaton, T Thorne, DW Losordo

    CIRCULATION   112 ( 17 )   U48 - U49   2005.10

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  • すい癌におけるゲムシタビンの感受性と耐性化に関する基礎的検討

    中野靖弘, 丹野誠志, 中村和正, みの口まどか, 水上裕輔, 高後裕, 奥村利勝

    日本消化器病学会雑誌   102   A849   2005.9

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  • 新しいすい腫ようの概念:IPMT IPMTの治療方針―切除か経過観察か

    丹野誠志, 中野靖弘, 水上裕輔, 高後裕

    医学のあゆみ   214 ( 4 )   247 - 249   2005.7

  • Natural history of branch duct type intraductal papillary-mucinous neoplasms of the pancreas: A role of endoscopic ultrasonography in follow-up

    S Tanno, Y Nakano, T Izawa, Y Mizukami, T Okumura, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   61 ( 5 )   AB302 - AB302   2005.4

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  • Activation of NF-kappaB and preservation of the angiogenic response in HIF-1 deficient colon cancer cells

    Y Mizukami, WS Jo, M Gala, JN Li, XB Zhang, EM Duerr, M Zimmer, O Iliopoulos, MP Lynch, BR Rueda, DC Chung

    GASTROENTEROLOGY   128 ( 4 )   A480 - A481   2005.4

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  • Peroral cholangioscopy in combination with endoscopic transpapillary bile duct biopsy in the diagnosis of extrahepatic bile duct cancer

    Y Nakano, S Tanno, M Osanai, K Koizumi, Y Mizukami, T Okumura, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   59 ( 5 )   AB184 - AB184   2004.4

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  • K-ras and hypoxia induce VEGF through a novel cis-regulatory element in colon cancer

    Y Mizukami, JN Li, XB Zhang, DC Chung

    GASTROENTEROLOGY   126 ( 4 )   A66 - A66   2004.4

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  • K-ras can inhibit GSK-3 beta and stimulate the Wnt signaling pathway in colon cancer

    JN Li, Y Mizukami, XB Zhang, WS Jo, DC Chung

    GASTROENTEROLOGY   126 ( 4 )   A262 - A262   2004.4

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  • K-ras pathways regulate VEGF in hypoxia independent of HIF-1 in colon cancer

    Y Mizukami, JN Li, XB Zhang, DC Chung

    GASTROENTEROLOGY   124 ( 4 )   A34 - A34   2003.4

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  • EUS・IDUSの最近の進歩 造影IDUSによる胆道病変の質的診断

    藤井常志, 千葉篤, 斎藤博哉, 水上裕輔, 羽広敦也, 小山内学, 柳川伸幸, 丹野誠志, 高後裕

    消化器画像   4 ( 3 )   329 - 334   2002.5

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  • HIF-independent induction of VEGF by hypoxia in colon cancer cells

    XB Zhang, Y Mizukami, DC Chung

    GASTROENTEROLOGY   122 ( 4 )   A116 - A117   2002.4

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  • すい胆管合流異常(APBD)の診断におけるDIC‐CTの位置付け

    柳川伸幸, 丹野誠志, 小原剛, 羽広敦也, 水上裕輔, 小山内学, 木村圭介, 高後裕

    日本消化器病学会雑誌   99   A216   2002.3

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  • Oleylamine (Long-chain Fatty Amine)-induced Cell Death through MAP Kinase Pathways in Human Pancreatic Cancer Cells.

    水上裕輔

    北海道医学雑誌   77 ( 1 )   17-21,23-29   2002.1

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  • ヒト胆管癌組織における活性化型AKT発現と胆管癌細胞の放射線感受性におけるPI3K/AKT経路の役割

    柳川伸幸, 丹野誠志, 水上裕輔, 羽広敦也, 小山内学, 高後裕

    胆道   15 ( 3 )   259   2001.9

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  • 粘膜筋板由来の食道平滑筋腫の1例

    渡二郎, 斉藤裕輔, 田辺裕貴, 水上裕輔, 柳川伸幸, 綾部時芳, 小原剛, 高後裕

    超音波医学   28 ( 6 )   J949   2001.9

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  • Oleylamine, a long-chain fatty amine, induces autophagic degeneration in human pancreatic cancer cells

    Y Mizukami, S Tanno, H Ura, T Obara, N Yanagawa, A Habiro, Y Kohgo

    GASTROENTEROLOGY   120 ( 5 )   A618 - A618   2001.4

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  • Comparison of MR cholangiopancreatography (MRCP) with EUS and intraductal US (IDUS) in intraductal papillary-mucinous tumor (IPMT) of the pancreas

    N Yanagawa, Y Mizukami, S Tanno, A Habiro, K Kimura, T Obara, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   53 ( 5 )   AB175 - AB175   2001.4

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  • 術前十二指腸乳頭部癌と診断したすい管内乳頭腺癌に由来する浸潤癌の1症例

    山田理大, 小原充裕, 小野寺一彦, 葛西真一, 伊沢功, 水上裕輔, 高後裕, 徳差良彦, 三代川斉之

    北海道外科雑誌   45 ( 2 )   89   2000.12

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  • 早期胃癌の深達度診断における超音波細径プローブ検査の精度 内視鏡検査と比較したpilot study

    渡二郎, 斉藤裕輔, 田辺裕貴, 水上裕輔, 柳川伸幸, 綾部時芳, 小原剛, 高後裕

    超音波医学   27 ( 12 )   1489   2000.12

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  • 胃脂肪肉腫の一例

    田辺裕貴, 渡二郎, 水上裕輔, 柳川伸幸, 斉藤裕輔, 綾部時芳, 小原剛, 高後裕

    超音波医学   27 ( 12 )   1489 - 1490   2000.12

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  • K‐rasコドン12点突然変異とX染色体不活化現象を用いたすい管内乳頭腫ようにおける腫よう内heterogeneity及びclonalityの検討

    伊沢功, 小原剛, 丹野誠志, 水上裕輔, 柳川伸幸, 浦等, 高後裕

    Japanese Journal of Cancer Research   91 ( Supplement (Sept) )   170   2000.9

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  • Long‐chain fatty amine(LFA)はすい癌細胞にapoptosisとtype‐2 cell deathを誘導する

    水上裕輔, 浦等, 小原剛, 柳川伸幸, 伊沢功, 丹野誠志, 高後裕

    Jpn J Cancer Res   91 ( Supplement (Sept) )   582   2000.9

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  • MRCPによるすい管内乳頭腫ようの診断 EUS/IDUSとの比較

    水上裕輔, 柳川伸幸, 小原剛

    日本消化器病学会雑誌   97   A499   2000.9

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  • MRCPによるすい管内乳頭腫ようの診断 EUS/IDUSとの比較

    水上裕輔, 柳川伸幸, 小原剛

    すい臓   15 ( 4 )   352   2000.9

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  • MRCPによるすい管内乳頭腫ようの診断 EUS/IDUSとの比較

    水上裕輔, 柳川伸幸, 小原剛

    胆道   14 ( 3 )   267   2000.9

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  • 続発性硬化性胆管炎の1例

    千里直之, 石崎彰, 紀野修一, 水上裕輔, 柳川伸幸, 小原剛, 尾島英知, 徳差良彦, 三代川斉之

    北海道外科雑誌   45 ( 1 )   76   2000.6

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  • 内視鏡手技とっておきのコツ すい管狭窄鑑別のための内視鏡的すい生検

    藤井常志, 小原剛, 水上裕輔, 柳川伸幸, 伊沢功, 中野靖弘, 高後裕

    消化器内視鏡   12 ( 6 )   824 - 825   2000.6

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  • Heterogeneity of K-ras mutations and clonality in ductal hyperplasia and intraductal papillary-mucinous tumor of the pancreas.

    T Izawa, T Obara, S Tanno, Y Mizukami, K Kimura, N Yanagawa, Y Kohgo

    GASTROENTEROLOGY   118 ( 4 )   A651 - A651   2000.4

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  • The apoptotic effect of isoprenoids linked with amine and long-chain fatty amines on human pancreatic cancer cells.

    Y Mizukami, H Ura, T Obara, T Izawa, N Yanagawa, K Kimura, S Tanno, Y Kohgo

    GASTROENTEROLOGY   118 ( 4 )   A523 - A523   2000.4

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  • すい管内乳頭腫ようにおけるK‐ras codon 12 point mutationはheterogeneityを示す

    伊沢功, 小原剛, 丹野誠志, 水上裕輔, 柳川伸行, 藤井常志, 西野徳之, 浦等, 高後裕

    日本癌学会総会記事   58th   402   1999.8

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  • Glucagonoma.

    小原剛, 西野徳之, 藤井常志, 丹野誠志, 水上裕輔, 伊沢功, 浦等, 高後裕

    肝胆膵   38 ( 6 )   981 - 985   1999.6

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  • Intratumoral heterogeneity of K-ras codon 12 mutations in intraductal papillary-mucinous tumor of the pancreas

    T Izawa, T Obara, S Tanno, Y Mizukami, T Fujii, N Nishino, H Ura, Y Kohgo

    GASTROENTEROLOGY   116 ( 4 )   A1135 - A1135   1999.4

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  • Diagnosis of longitudinal extent of biliary malignancies: The role of contrast-enhanced intraductal ultrasonography with carbon dioxide microbubbles

    Y Mizukami, T Obara, H Saito, T Fujii, Y Nakano, S Arisato, T Izawa, N Nishino, S Tanno, Y Kogho

    GASTROINTESTINAL ENDOSCOPY   49 ( 4 )   AB156 - AB156   1999.4

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  • Magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of neoplastic cysts of the pancreas: Comparison with endoscopic retrograde cholangiopancreatography (ERCP)

    T Fujii, T Obara, N Nishino, T Izawa, Y Mizukami, S Tanno, Y Kohgo

    GASTROINTESTINAL ENDOSCOPY   49 ( 4 )   AB55 - AB55   1999.4

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  • Epithelial hyperplasia of the gallbladder: Prevalence and fate in patients with anomalous pancreaticobiliary ductal union

    T Obara, S Tanno, T Fujii, Y Mizukami, T Izawa, N Nishino, H Ura, Y Kohgo

    GASTROENTEROLOGY   116 ( 4 )   A25 - A25   1999.4

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  • Advances of clinical medicine New diagnostic imaging series 29. Bile duct cavity ultrasonography of hepatobiliary diseases Progress level diagnosis of bile duct cancer.

    水上裕輔, 藤井常志, 小原剛, 中野靖弘, 有里智志, 斎藤博哉, 高後裕

    臨床科学   35 ( 3 )   359 - 368   1999.3

  • Report of an autopsy cases of hepatocellular carcinoma with marked pulmonary hypertension due to multiple pulmonary thrombus

    OHTA Hitoyoshi, MATSUMOTO Akinori, MIZUKAMI Yusuke, NAKANO Yasuhiro, OHTA Tomoyuki, ARISATO Satoshi, MURAKAMI Masanori, ORII Yutaka, SATO Teiko

    Nippon Shokakibyo Gakkai Zasshi   95 ( 8 )   900 - 904   1998.8

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    DOI: 10.11405/nisshoshi1964.95.900

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  • New Information of Pancreatobiliary Carcinoma Inspection. Preoperative diagnosis of pancreatic neoplasm by endoscopic ultrasonography and intraductal ultrasonography.

    水上裕輔, 中野靖弘, 有里智志, 藤井常志, 伊沢功, 丹野誠志, 西野徳之, 斎藤博哉, 真口宏介

    月刊消化器科   27 ( 2 )   181 - 189   1998.8

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  • A early bile duct cancer extend to papilla of Vater diagnosed by intraductal ultrasonography ; Case report

    MIZUKAMI Yusuke, ARISATO Satoshi, SAITO Hiroya, NAKANO Yasuhiro, OHTA Hitoyoshi, ORII Yutaka, SAKURAI Yasuo, MAGUCHI Hiroyuki

    胆道 = Journal of Japan Biliary Association   12 ( 3 )   258 - 264   1998.7

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  • A early bile duct cancer extend to papilla of Vater diagnosed by intraductal ultrasonography; Case report.

    水上裕輔, 有里智志, 斎藤博哉, 中野靖弘, 大田人可, 折居裕, 桜井康雄, 真口宏介

    胆道   12 ( 3 )   258 - 264   1998.7

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  • A case of anaplastic carcinoma of the pancreas, disclosed a hemosuccus pancreaticus.

    MIZUKAMI Yusuke, ARISATO Satoshi, SATOU Kunihiko, NAKANO Yasuhiro, OHTA Tomoyuki, OHTA Hitoyoshi, MURAKAMI Masanori, ORII Yutaka, SAITO Hiroya, SAKURAI Yasuo, SAWAGUCHI Yuji, HAMADA Tomonori, SATO Teiko, MAGUCHI Hiroyuki

    Nippon Shokakibyo Gakkai Zasshi   94 ( 10 )   706 - 711   1997.10

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    DOI: 10.11405/nisshoshi1964.94.10_706

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  • Intraductal ultrasonographic angiography for evaluation of biliary disease

    MIZUKAMI Yusuke

    Nippon Shokakibyo Gakkai Zasshi   94 ( 7 )   514 - 514   1997.7

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    DOI: 10.11405/nisshoshi1964.94.7_514

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  • Intraductal ultrasonographic angiography for evaluation of biliary disease

    MIZUKAMI Yusuke

    Nippon Shokakibyo Gakkai Zasshi   94 ( 7 )   1997.7

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    Language:Japanese   Publisher:The Japanese Society of Gastroenterology  

    DOI: 10.11405/nisshoshi1964.94.7_514

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  • 大腸表面陥凹型sm癌の臨床病理的特徴及び深達度診断の検討

    太田 智之, 折居 裕, 村上 雅則, 佐川 美穂, 伊澤 功, 中野 靖弘, 水上 裕輔, 有里 智志, 松本 昭範, 大田 人可, 澤口 裕二, 里 悌子

    旭川厚生病院医誌   7 ( 1 )   3 - 7   1997.6

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    Language:Japanese  

    雑誌掲載版大腸表面陥凹型sm癌20病変の臨床病理学的特徴を明らかにし,注腸X線及び大腸内視鏡所見による深達度診断の指標について検討した.20病変の各肉眼型はII a+ II c 14病変,II c 4病変,II c+ II a 2病変で全sm癌に占める割合は17.4%であった.平均腫瘍径はII a+ II c 13.9mm,II c 7.3mmでいずれも小さなうちから深部浸潤傾向が強かった.組織型では高分化型腺癌13病変,中分化型7病変であったが中分化型では85.7%がsm 2以深であった.組織構築像はNPG型が89.4%を占め,de novo癌と考えられる病変が多く,更にその70.6%がsm 2以深であった.注腸X線所見で辺縁が類円形のものと内視鏡所見で腫瘍の立ち上がりが正常粘膜からなるものは高率にNPG型であり,また注腸X線所見で陥凹が描出される病変やひだ集中がみられる病変はsm 2以深であることが多かった

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    Other Link: http://search.jamas.or.jp/link/ui/1998253615

  • A CASE OF METASTATIC GASTRIC CANCER SIMULATING BORRMANN TYPE 4 GASTRIC CARCINOMA

    TANABE Hiroki, WATARI Jiro, NAKANO Yasuhiro, WAKU Katsuaki, MIZUKAMI Yusuke, TANAKA Kohji, ARISATO Satoshi, OHTA Hitoyoshi, MURAKAMI Masanori, ORII Yutaka, SAKURAI Kohji, SATO Teiko, YOKOTA Kinichi, KOHGO Yutaka

    Gastroenterol Endosc   38 ( 12 )   2865 - 2870   1996.12

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  • Biliary tract diseases in this hospital multiphasic health screening.

    有里智志, 今田英樹, 佐藤邦彦, 中野靖弘, 水上裕輔, 太田智之, 折居裕, 松尾弘文, 杉村厳

    日本農村医学会雑誌   45 ( 3 )   264   1996.9

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    Language:Japanese  

    J-GLOBAL

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  • A Case of Small Cholangiocellular Carcinoma, Diagnosed by Percutaneous Transhepatic Cholangioscopy.

    水上裕輔, 高橋邦幸, 有里智志, 渡二郎, 大田人可, 村上雅則, 折居裕, 桜井康雄, 真口宏介

    Gastroenterol Endosc   38 ( 7 )   1548 - 1555   1996.7

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  • クローン病に合併したdiversion colitisの1例

    村上 雅則, 中野 靖弘, 水上 裕輔, 太田 智之, 有里 智志, 大田 人可, 折居 裕, 峯本 博正

    旭川厚生病院医誌   6 ( 1 )   39 - 43   1996.6

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    雑誌掲載版29歳女.上行結腸狭窄と回腸穿孔の為,2回の腸管切除手術が行われ,回腸瘻増設により残存大腸は横行結腸中部で盲端となった.残存大腸には,リンパ過形成やアフタがみられ,管腔の狭小化と腸管の長軸方向の短縮を伴い,内視鏡検査では送気操作によって縦走性潰瘍を生じた.組織学的には,粘膜上皮細胞の萎縮と粘膜下組織におけるリンパ濾胞の腫大が認められた.回腸瘻造設から1年3ヵ月後に回腸-横行結腸吻合術が行われた.吻合後,約1ヵ月で縦走性潰瘍はみられなくなり,4ヵ月後には腸管の伸展性も完全に回復していた

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    Other Link: http://search.jamas.or.jp/link/ui/1997159243

  • 当科において最近経験した肝細胞癌症例の臨床的検討

    大田 人可, 高橋 伸彦, 水上 裕輔, 中野 靖弘, 田邉 裕貴, 田中 浩二, 有里 智志, 渡 二郎, 村上 雅則, 折居 裕, 桜井 康雄, 齋藤 博哉

    旭川厚生病院医誌   6 ( 1 )   9 - 12   1996.6

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    雑誌掲載版最近18ヵ月間に入院した初発の肝細胞癌症例40例を調査した.ウイルス別では,C型が22例,B型が11例,B, Cとも陽性が1例,B, Cとも陰性が6例と,B型の占める割合が全国平均より高かった.基盤の肝病変は正常肝1例,非特異的変化2例,慢性肝炎4例,肝硬変33例であった.発見のきっかけは,当科でfollow up中が8例,当科に初診が4例,他院からの紹介が26例で全体の65%と多くを占めた.発見のきっかけと腫瘍径の関係は,当科でfollow up中の8例は全例5cm以下だったが,紹介例の腫瘍径は様々であった.尚,他院から肝腫瘍で紹介された24例をみると,前医でfollow upを受けていて腫瘍がみつかったのは8例でそのうち7例は5cm以下だった.逆に前医でも初診だった場合は16例中12例が5cm以上という結果であった

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    Other Link: http://search.jamas.or.jp/link/ui/1997148683

  • Revaluation on detection of metastatic cancer of the coloretum with barium enema; comparison with computed tomography and colonoscopy.

    渡二郎, 水上裕輔, 田辺裕貴, 中野靖弘, 田中浩二, 折居裕, 斎藤博哉, 斉藤裕輔, 横田欽一

    臨床放射線   41 ( 2 )   211 - 216   1996.2

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    J-GLOBAL

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  • 経過観察中に増大した肝細胞癌境界病変の一例

    中野 靖弘, 大田 人可, 田邊 裕貴, 水上 裕輔, 田中 浩二, 有里 智志, 渡 二郎, 村上 雅則, 都丸 久, 折居 裕, 豊島 經康, 桜井 康雄, 齋藤 博哉, 里 悌子

    旭川厚生病院医誌   5 ( 2 )   140 - 144   1995.12

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    雑誌掲載版64歳女.平成元年5月よりB型肝硬変で外来通院していた.平成3年7月に施行した腹部CT検査で肝右葉後上区域(S7)に径12mmの低吸収域を認めた.肝細胞癌境界病変(境界病変)として定期的にUS, CT, MRIを施行したが,平成7年2月に施行したCTで径27mmと腫瘍が増大した為,3月に精査目的で入院した.CT-APでは病変部に一致して門脈血流の低下を認め,肝腫瘍生検では僅かに細胞密度の増加を伴う脂肪沈着の強い境界病変と考えられる.径が27mmと大きい点,増大傾向にある点,及びCT-APの所見を総合すると高分化肝癌の合併も否定できず治療の適応とし

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    Other Link: http://search.jamas.or.jp/link/ui/1997024819

  • 消化器癌患者に対する病名告知 (Truth Telling) の現状について : 2症例の検討を中心に

    大田 人可, 田中 浩二, 水上 裕輔, 有里 智志, 渡 二郎, 村上 雅則, 都丸 久, 折居 裕

    日本農村医学会雑誌   44 ( 3 )   399 - 399   1995.9

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    CiNii Books

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  • 人間ドックで発見された胆のう隆起性病変の2手術例

    田中 浩二, 水上 裕輔, 渡 二郎, 大田 人可, 中野 靖弘, 田邉 裕貴, 有里 智志, 村上 雅則, 都丸 久, 折居 裕

    日本農村医学会雑誌   44 ( 3 )   331 - 331   1995.9

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    CiNii Books

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  • 同一亜区域内に発生した多中心性発生と考えられる肝細胞癌の一例

    大田 人可, 村中 茂人, 水上 裕輔, 高橋 邦幸, 渡 二郎, 山野 三紀, 村上 雅則, 都丸 久, 折居 裕, 峯本 博正, 桜井 康雄, 齋藤 博哉, 桜井 宏治, 里 悌子

    旭川厚生病院医誌   4 ( 2 )   133 - 138   1994.12

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    雑誌掲載版59歳男.肝機能異常の為,入院,C型肝硬変と共に肝腫瘤所見を認めた.腹部超音波検査(US)で肝右葉後下区に径32mmのモザイク状と径12mmの低エコーの2個の腫瘤を認めた.腹部CT,血管造影(DSA),リピオドールCTでは大きい方の腫瘤しか描出されなかった.US下肝腫瘍生検を施行し,大きい方は中-低分化型肝癌,小さい方は高分化型肝癌の所見であった

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    Other Link: http://search.jamas.or.jp/link/ui/1996147751

  • 内視鏡的乳頭括約筋切開術を施行した総胆管結石症例の検討

    高橋 邦幸, 山野 三紀, 水上 裕輔, 村中 茂人, 渡 二郎, 大田 人可, 村上 雅則, 都丸 久, 折居 裕, 峯本 博正, 真口 宏介

    旭川厚生病院医誌   4 ( 1 )   25 - 28   1994.6

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    雑誌掲載版1)早期合併症は158例中12例に認められたが,何れも保存的に軽快した. 2)後期合併症は147例中18例に認められた. 3)胆管炎例では何れも傍乳頭憩室を伴っていた. 4)有胆嚢無石例では逆行性感染による無石胆嚢炎は認めなかった. 5)有胆嚢有石例では81.4%はEST後無症状で合併症も認めず,特に外科的リスクの高い例に対してESTは積極的に行うべき治療法と考えられた. 6)総胆管結石再発例では完全排石を確認していない例が多く,遺残結石の可能性が示唆され,完全排石の確認が重要である

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    Other Link: http://search.jamas.or.jp/link/ui/1996157034

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Research Projects

  • Early Diagnosis of Pancreatic Cancer Based on the Mechanism of Development of Precancerous Lesions and the Emergence of Invasive Buds during Carcinogenesis

    Grant number:24K02431  2024.4 - 2027.3

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

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    Grant amount:\18,590,000 ( Direct Cost: \14,300,000 、 Indirect Cost:\4,290,000 )

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  • Strategy for an early diagnosis by modeling the developmental and evolutionary paths of human pancreatic cancer

    Grant number:22KK0125  2022.10 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))  Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

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    Grant amount:\20,150,000 ( Direct Cost: \15,500,000 、 Indirect Cost:\4,650,000 )

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  • Early diagnosis of pancreatic cancer based on diversity of field defect and molecular genetic approach

    Grant number:20H03655  2020.4 - 2023.3

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

    Mizukami Yusuke

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    Grant amount:\17,810,000 ( Direct Cost: \13,700,000 、 Indirect Cost:\4,110,000 )

    Our goal was to create detailed maps of multiple lesions found in surgically removed pancreatic specimens, with a focus on pancreatic cancer related to IPMN. We discovered a variety of genetic mutations in precursor lesions located in the pancreas. We also extracted a portion of the tumor cells from the removed material and conducted RNA-Seq analysis and long-read sequencing using nanopores. With the results, we attempted to assess the clonal affinity by analyzing the genetic abnormalities accumulation pattern from low-grade to high-grade lesions, and we reconstructed the evolution timeline within the lesion. Moreover, we are analyzing the same region's spatial transcriptome and comparing it with the mutation distribution. We are currently working on the manuscript, and the data analysis is underway.

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  • Diversity of molecular paths during pancreatic carcinogenesis

    Grant number:17K09472  2017.4 - 2020.3

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

    Mizukami Yusuke

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

    We aimed to clarify the role of two driver genes, KRAS and GNAS, on the pancreatic carcinogenesis using surgically resected pancreatic cancers associated with intraductal papillary mucinous neoplasm (IPMN). By molecular pathological analysis, new subtypes leading to the development of pancreatic cancer were found. We also clarified pancreatobiliary-type IPMN with wild-type GNAS is prone to residual pancreatic recurrence.
    We also sought to clarify the downstream pathway of mutant GNAS and the effect on tumor phenotype using genetically engineered mouse models and genome-editing experiments using primary cells derived from human IPMN-related pancreatic cancer with mutant GNAS. The driver gene plays a role in tumor progression and maintenance by regulating mucin traits and tumor metabolic paths.
    These findings are useful for stratifying the progression path of pancreatic carcinogenesis in IPMN patients and predicting the risk for developing malignant progression.

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  • Non-invasive modality for diagnosis of pancreatic neoplasm

    Grant number:25461029  2013.4 - 2016.3

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

    Mizukami Yusuke, ASHIDA Toshifumi, MORIICHI Kentaro

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5,070,000 ( Direct Cost: \3,900,000 、 Indirect Cost:\1,170,000 )

    Recent technologies are emerging to allow genotyping of plasma cell-free DNA (cfDNA) shed from tumors into the general circulation. There are two main types of pathologically distinct precursors for PDA, pancreatic intraepithelial neoplasias and intraductal papillary mucinous cystic neoplasias (IPMNs), and the mutations in KRAS and/or GNAS mediate key signaling during early development of the tumors. The clinical viability of cfDNA genotyping using digital PCR targeting mutations in KRAS and GNAS were examined. Ten PDA and 21 IPMN patients were recruited. The primary endpoint of this study was to evaluate whether such an approach can appropriately monitor the risk IPMN progression and detect localized early-stage PDA non-invasively. The major technical challenge of widespread implementation of this clinical test is the coverage for uncommon forms of KRAS mutation, as well as sensitivity for early stages cancer where the amount of cfDNA may be limited.

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  • Role of bone marrow-derived cells during pancreatic tumorigenesis

    Grant number:22590754  2010 - 2012

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

    MIZUKAMI Yusuke, II Masaaki

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4,420,000 ( Direct Cost: \3,400,000 、 Indirect Cost:\1,020,000 )

    Tumor-derived factors affect the stroma of cancer tissue. One of the key components of this response is the mobilization of the progenitors from the bone marrow (BM), which contribute toward the development of desmoplastic stroma. These BM-derived cells are involved in normal physiological processes such as tissue repair and wound healing; however, in cancer bearing hosts, these cells actively contribute toward the chaotic microenvironment. Using genetically engineered mice models for pancreatic cancer, we found that BM-progenitors are passively activated by even early stage tumors. We have identified the signaling pathways by which BM-derived cells are recruited and activated to establish malignant stroma in later stages of tumor development.

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  • 腫瘍血管リモデリング誘導による新規難治がん克服技術の研究開発

    2007.8 - 2011.6

    新エネルギー・産業技術総合開発機構(NEDO)  先導的産業技術創出事業(若手研究グラント) 

    水上 裕輔

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    Authorship:Principal investigator  Grant type:Competitive

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  • 胆道癌の精密診断を目的とした胆汁中核酸サンプリングの標準化

    Grant number:24K18961  2024.4 - 2029.3

    日本学術振興会  科学研究費助成事業  若手研究

    岡田 哲弘, 水上裕輔

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

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  • GNAS・KRASのクロストークによる膵癌進展機序解明と治療標的の探索

    Grant number:24K18932  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  若手研究

    河端 秀賢, 水上裕輔

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

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  • 膵癌分子サブタイプに関わるncRNAの探索と分子診断および創薬への応用

    Grant number:24K11058  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高橋 賢治, 水上裕輔

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    Grant amount:\4,550,000 ( Direct Cost: \3,500,000 、 Indirect Cost:\1,050,000 )

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  • Prediction of postoperative recurrence of pancreatic cancer by monitoring genomic abnormalities in the whole pancreas

    Grant number:23K08164  2023.4 - 2026.3

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

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

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  • 血漿遊離核酸マルチレイヤー解析の自己免疫性膵炎診断・活動性評価への応用

    Grant number:23K07389  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岩本 英孝, 高橋 賢治, 水上 裕輔, 小野 裕介

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

    自己免疫性膵炎(AIP)の病態・病勢悪化の機序は未解明な点が多く、炎症性腫瘤を形成する場合には膵癌との鑑別困難例が存在し、発癌サーベイランスも重要課題である。我々はノンコーディングRNA(ncRNA)の膵発癌・進展に及ぼす役割、リキッドバイオプシー標的としての知見を発信してきたが、発癌の初期段階たる慢性炎症におけるncRNA発現の生物学的意義の検証が十分ではなかった。本研究では、複数の体液検体(血液と膵液)におけるncRNA発現とAIP臨床像との関連を明らかとする。また、AIPの病態理解や病勢評価に寄与するRNA情報を得て、精密診断やステロイド抵抗性、膵の内外分泌機能の廃絶といった患者予後の推定が可能かを検証する。さらに体液中に検出される、DNA変異を統合したマルチレイヤー核酸検出によって、膵癌との鑑別や発癌リスクの臨床的指標の基盤となる情報を得るとともに、病態機序解明へつなげることを目的としている。
    現在、AIP及び慢性膵炎患者検体を収集しているが、未だ目標症例数に到達しておらず、引き続き研究への参加登録・検体採取を継続する。これまでの検討において、膵液・十二指腸液を用いたDNA変異解析の、組織における変異との一致率はそれぞれ約90%、50%という結果を得ている。特に膵液の組織変異一致率が高く、組織診を補完するためのリキッドバイオプシー標的としての有用性が期待できる結果となっている。また、膵癌患者の組織検体を用いたDNA変異解析の情報から、TP53遺伝子変異頻度が予後因子になり得る証左を得ている。現在、AIP及び慢性膵炎患者の膵液および組織検体を用いたncRNA発現・DNA発現解析を準備中であり、疾患活動性との関連や、膵癌との鑑別に関わる因子等について検証していく。

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  • Liquid Biopsy using Multi-Nucleic Acid for the early diagnosis of PDAC

    Grant number:23K06759  2023.4 - 2026.3

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

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    Authorship:Coinvestigator(s) 

    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

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  • 肺がん背景肺に潜むゲノム・エピゲノム異常の徹底的マッピングによる発がん機序の解明

    Grant number:22K06935  2022.4 - 2025.3

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

    谷野 美智枝, 湯澤 明夏, 小山 恭平, 水上 裕輔

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    Grant amount:\4,160,000 ( Direct Cost: \3,200,000 、 Indirect Cost:\960,000 )

    2018年から2023年に対象の期間を拡大し、計28症例の肺原発扁平上皮癌 (背景肺別の内訳は特発性肺線維症:9症例、肺気腫のみ:8症例、喫煙関連間質性線維症:11症例)を解析対象として選定した。全対象症例のホルマリン固定パラフィン包埋検体から、腫瘍部・腫瘍から近傍の背景肺・腫瘍から遠隔の背景肺について、肺癌の診断や予後予測において有用性が報告されているCDH13、CDKN2A、RASSF1のメチル化解析と免疫組織化学染色を実施した。背景肺のメチル化解析では、既報よりも詳細な病理組織学的評価のもとに病的変化のある組織や癌の由来となる上皮細胞を多く含む領域をマクロダイゼクションした。
    さらに、肺癌を始めとする悪性腫瘍の予後指標として報告のある病理組織学的所見(Tumor budding、腫瘍の核直径)や免疫組織化学染色の結果を半定量的に評価し、メチル化率や臨床病理学的因子との関係性も解析した。結果として、CDKN2A exon2のメチル化は、肺の線維化や肺気腫を背景にした扁平上皮癌の独立した診断マーカーとして有用である可能性が示唆された。
    肺扁平上皮癌におけるCDKN2A exon2のメチル化の意義や特発性肺線維症などの発癌素地のエピゲノム異常をさらに解明するため、従来から肺癌の診断・予後予測マーカーとして比較的多くの報告があるCDKN2A promoterのメチル化解析なども進めている。

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  • TP53-RAS/RAF経路のクロストークに基づく局所進行直腸癌の術前治療戦略

    Grant number:22K08814  2022.4 - 2025.3

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

    庄中 達也, 水上 裕輔, 小野 裕介, 西川 祐司, 谷野 美智枝

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    Grant amount:\4,290,000 ( Direct Cost: \3,300,000 、 Indirect Cost:\990,000 )

    本研究の目的は局所進行直腸癌の予後改善を目的として、分子特性の評価で治療法選択や効果予測を行うことができないか?という研究である。術前治療を加えた局所進行直腸癌の中で治療効果の高い群を見出し、分子特性との関連性を明らかにしたいと考えている。特にTP53異常に伴うRAS/RAFシグナルの増幅に着目し変異(バリアント)の組み合わせでみた術前加療への効果や、術前加療での分子特性に着目することで新たな治療戦略が描けると考えている。これに付随して免疫染色による遺伝子発言の早期予測法も検討している。
    現時点では、化学療法の有効性の高い症例ほど予後を改善する、というデータが得られた。これらの症例のTP53とRAS遺伝子の変異事での予後との相関が見られなかった。このため、Big dataを使用し遺伝子変異の有無による予後解析を追加で行っている。これらの他にもAPC,SMAD4などを追加で検討している。
    また、遺伝子検索について局所進行直腸癌のみではなく、転移のメカニズムにも検討対象を伸ばしている。現在、我々は大腸癌肝転移でも病理像と遺伝子変異についての検討を追加で行っている。

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  • Study on the mechanism of oncogene activation by structural variants in cancer genome

    Grant number:21K08171  2021.4 - 2024.3

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

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    Grant amount:\3,900,000 ( Direct Cost: \3,000,000 、 Indirect Cost:\900,000 )

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  • The clinical applications of long non-coding RNA and extracellular vesicles to diagnosis and therapy for pancreatic cancer

    Grant number:21K07954  2021.4 - 2024.3

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

    TAKAHASHI Kenji

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    Grant amount:\4,160,000 ( Direct Cost: \3,200,000 、 Indirect Cost:\960,000 )

    There is a strong need for reliable biomarkers for early diagnosis for pancreatic ductal adenocarcinoma (PDAC). Some RNAs are carried within extracellular vesicles (EVs), and EV-encapsulated RNAs in blood have been utilized as a biomarker. We identified highly expressed lncRNAs (LINC02280, HEVEPA) in EVs derived from patients with PDAC. In vitro and vivo studies, LINC02280 could promote tumor cell invasion and migration through induction of epithelial-mesenchymal transition (EMT) pathway whereas HEVEPA could inhibit apoptosis in PDAC cells. In serum EVs, the expression levels of LINC02280 and HEVEPA were highly expressed in PDAC patients compared to healthy individuals and intraductal papillary mucinous neoplasms (IPMNs) patients. A combination of EV lncRNAs showed good performance in predicting PDAC diagnosis. Detecting those candidate RNAs and establishing EV RNA panel would have a potential to improve the diagnostic accuracy for early stage of PDAC.

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  • Study for novel biomarker in liquid biopsy on on carcinogenic pathways induced by driver mutations

    Grant number:20K07671  2020.4 - 2023.3

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

    Ono Yusuke

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    Grant amount:\4,290,000 ( Direct Cost: \3,300,000 、 Indirect Cost:\990,000 )

    In this study, we searched for new biomarkers targeting RNAs linked to driver genes using pancreatic cancer as a model. We generated KRAS mutant, GNAS mutant, KRAS/GNAS mutant, and wild-type strains of these genes in two different pancreatic ductal epithelial cell lines (HPDE, HPNE) and analyzed their expression patterns by RNA-seq. Furthermore, an effective method for collecting and purifying unstable plasma cell-free mRNA was validated, and a highly sensitive expression detection system using digital PCR was constructed. cfRNA was extracted from 35 PDA patient samples, and the amounts present were compared after quantification.

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  • Distribution and clonality of multiple intraductal neoplasms of the pancreas evaluated by morphology

    Grant number:20K09070  2020.4 - 2023.3

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

    Karasaki Hidenori

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    Grant amount:\4,290,000 ( Direct Cost: \3,300,000 、 Indirect Cost:\990,000 )

    The liquid biopsy, promising clinical application for early detection of pancreatic neoplasms consist of many molecular alterations about not only the index tumor but also the background. For better understanding of the genetic alterations occurring throughout the pancreas, mutation analysis of multiple sites, including normal pancreatic ducts, in two cases with high-grade IPMN and double pancreatic cancer as index lesions, respectively. Approximately 40% of the patients had some kind of gene mutation. The majority of these mutations were low-grade intraductal lesions, but mutations were also found in some normal pancreatic ducts. There was no significant difference in the number of samples examined between the two cases, the distribution of grades, and the rate of concordance in KRAS mutation type between index lesions and background pancreatic sites, but individual differences were observed in the number of KRAS mutations.

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  • Elucidation of the molecular mechanisms responsible for IPMNs progression

    Grant number:20K09025  2020.4 - 2023.3

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

    IMAI KOJI

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    Grant amount:\4,290,000 ( Direct Cost: \3,300,000 、 Indirect Cost:\990,000 )

    We conducted a precise pathological mapping and multiregional sequencing analysis on a surgically resected pancreas to identify characteristics of IPMN that may lead to invasive cancer. We marked the specimens into different components with varying histological grades and epithelial subtypes. Each region, including microscopic lesions in the normal-looking pancreas, underwent targeted sequencing, enabling us to estimate clonal relatedness and spatial distribution in each area using minimal mutation markers. Our goal is to investigate the mechanisms behind malignant transformation by increasing the histological grade of neoplastic lesions and performing spatial expression analysis to identify any factors that cannot be explained by a few driver mutations.

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  • Genetic alterations in early-onset pancreatic cancer

    Grant number:17K09451  2017.4 - 2020.3

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

    Sasajima Junpei

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

    This study aimed to examine novel genetic alterations that are useful for predicting the onset of pancreatic cancer. Fifty-two early-onset Japanese pancreatic cancer patients who developed the disease under the age of 50 were enrolled, and exome sequencing was performed to identify pathogenic germline variants. Three potential susceptibility genes were found. A reanalysis of publicly available somatic mutation data, including 109 cases from UT Southwestern Medical Center, identified a significant number of copy number mutations in young-onset cases. Using tumor-normal tissue pair from our Japanese cohort, we validated the abnormality was more frequently observed in the early onset cases relative to average aged patients. Our findings will support the algorithm's basis to predict subjects who are at high risk of developing pancreatic cancer.

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  • Monitoring of Emerging Resistance of Lung Cancer using Liquid Biopsy

    Grant number:15K09239  2015.4 - 2018.3

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

    TANNO Sachie, YOSHIDA Ryouhei

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    Grant amount:\4,810,000 ( Direct Cost: \3,700,000 、 Indirect Cost:\1,110,000 )

    Pre and Post surgical Lung adenocarcinoma samples were analyzed by ddPCR. 5 cases of EGFR or KRAS were analyzed. Because of the low amount of circulating tumor DNA, some of the samples were not detected any mutation.
    We had collected 103 samples from 74 patients. T790M and C797S mutations were successfully analyzed.

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  • Pancreatic-Intestinal Crosstalk: a novel approach to elucidate the tumorigenic process of PDAC

    Grant number:15K14716  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    ONO Yusuke

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    Grant amount:\3,900,000 ( Direct Cost: \3,000,000 、 Indirect Cost:\900,000 )

    The tumorigenic process of pancreatic ductal carcinoma (PDA) may be closely associated with homeostasis of the intestinal tract, e.g., innate immune system. To elucidate the "Pancreatic-Intestinal Crosstalk" during the tumor initiation, we analyzed the alterations in an intestinal environment using a mouse strain which spontaneously develops acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasias (PanINs), offering a model of the early-stage of the pancreatic tumorigenesis.
    16S rRNA gene-based metagenomics assay of stool DNA provided a specific microflora profile during pancreatitis-induced progression from ADM into PanIN. Besides, the morphological study demonstrated the close link between the tumorigenic process in the pancreas and the intestinal tract where Paneth cells may play an essential role.

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  • Endoscopic ultrasound-guided through-the-needle-biopsy for the diagnosis of pancreatic cystic neoplasms

    Grant number:15K19301  2015.4 - 2017.3

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

    Kawakubo Kazumichi, MITSUHASHI Tomoko, MIZUKAMI Yusuke, ONO Yusuke, KUWATANI Masaki

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    Grant amount:\3,900,000 ( Direct Cost: \3,000,000 、 Indirect Cost:\900,000 )

    Endoscopic ultrasonography-guided through-the-needle cyst wall biopsy (EUS-TNCB) was performed in two patients. A 71-year-old female had 32mm cystic lesion in the head of the pancreas. EUS-TNCB revealed fragmented epithelial cells with small nucleus with interstitial fibrotic tissue. A 48-year-old male had 20mm cystic lesion in the body of the pancreas. EUS-TNCB revealed no epithelial cells but interstitial fibrotic tissue. Gene mutation analysis by next-generation sequencer could not detect any mutation in both samples.

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  • Cryo-immunology; booster effects of cryotherapy on the anti-tumor immune response

    Grant number:26670305  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Saito Hiroya, Nabeel Bardeesy

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    Grant amount:\3,770,000 ( Direct Cost: \2,900,000 、 Indirect Cost:\870,000 )

    Cryotherapy (also called cryosurgery) is a treatment that uses extremely cold temperature to freeze and destroy cancer tissue. Although mainly employed in cases of prostate cancer, the therapeutic option can be used to treat a number of different types of cancer. Curiously, distant and untreated sites of disease can also be regressed after freezing a primary lesion, suggesting cryotherapy may stimulate an anti-tumor immune response. Given the tremendous potential of the local therapy that could also have systemic benefits, we sought to validate the ability of cryotherapy to stimulate a tumor recognition using allograft mouse pancreatic cancer system as a pre-clinical model. The tumor bearing animals treated by cryotherapy decreased growth of either primary or secondary tumor (an imaginary metastasis) relative to the controls. Cryotherapy offers an option for treating cancers that do not respond to standard treatments, and more studies are needed to determine the long-term effects.

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  • Development of novel therapy based on epigenetic alterations in Barrett's esophagus

    Grant number:25460923  2013.4 - 2017.3

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

    Moriichi Kentaro

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    Grant amount:\5,070,000 ( Direct Cost: \3,900,000 、 Indirect Cost:\1,170,000 )

    We successfully established primary cell culture of patient-derived Barrett's esophageal cancer (BE ca) using conditioning reprogramming method. To investigate the carcinogenic mechanisms of BE ca, the primary cells were exposed to low pH bile acids. The exposures of low pH bile acid decreased mRNA expressions of p63 and CK5. It was speculated that the post-transcriptional regulations such as abnormal gene methylations or histone acetylations were involved in the altered expressions of these genes. However, treatments of demethylation or deacetylation did not change the expressions of these mRNA, indicating the other mechanisms are associated with the effects of the exposures of low pH bile acid. We are continuously analyzing the mechanisms. In parallel, our transcriptome analysis identified novel alterations of nine gene expressions which were epigenetically regulated in the process to develop BE ca. We are analyzing the roles of these gene alterations in the cancer development.

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  • Primary tumor culture for personalized medicine

    Grant number:25460966  2013.4 - 2016.3

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

    Ashida Toshifumi, MIZUKAMI Yusuke

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    Grant amount:\5,070,000 ( Direct Cost: \3,900,000 、 Indirect Cost:\1,170,000 )

    The application of primary cultures preserving intrinsic property of cancers holds promise for serving human resources to uncover core pathway guiding novel therapy and to provide patient-specific tumor antigens. In the current study, we sought to develop a culture system that can allow pancreatic neoplasia at various stages to adapt in vitro microenvironment without losing tumor forming capability in vivo. The primary culture by combining tumor oraganoid isolation and conditional reprogramming facilitated to rebuild physiological tumor structure by transplanting to immunodeficient mice, whereas most commercially available cell lines did not. Sequencing data of the primary culture indicated these tumor cells include heterogeneity of the primary tumors, providing useful model to learn clonal evolution of the precursors. These studies demonstrate the general utility of a tractable tumor culture for human cancer modeling and therapeutic strategy against pancreatic neoplasms.

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  • Non-invasive identification and monitoring of cancer using hair follicle gene expression profiling

    Grant number:25670086  2013.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    CHIBA Masako, SASAKI Katsunori, MIZUKAMI Yusuke

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    Grant amount:\3,770,000 ( Direct Cost: \2,900,000 、 Indirect Cost:\870,000 )

    The involvement of primary tumors on the host systemic environment and resulting tumor-supportive role for host-derived stromal cells are of particular interest. Non-invasive monitoring such stromal activation may encourage technological innovation in cancer screening for high-risk patient. We obtained gene expression profiles of the hair follicles, including stem-like cells that has self-renewal capability and can differentiate to hair and skin. Colon cancer patients have significantly different expression profiles in subset of genes involved in cell-differentiation and metabolic regulation relative to healthy individuals. Qualitative evaluation of the gene expressions in hair follicle cells in larger scale patients will be required to establish effective approach for cancer screening.

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  • Overcome to avoidance from the anti-leukemia immunity by using combination therapy with HSP and dendritic cells targeted to both tumor and tumor angiogenesis

    Grant number:20591143  2008 - 2010

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

    SATO Kazuya, MIZUKAMI Yuusuke, OHTAKE Takaaki, IKUTA Katsuya

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    Grant amount:\4,550,000 ( Direct Cost: \3,500,000 、 Indirect Cost:\1,050,000 )

    In this study, we tried induction of the anti-leukemia immunity by using heat shock protein (HSP) targeted to both tumor and tumor angiogenesis. We demonstrated the presence of tumor angiogenesis in the A20-bearing mouse by endothelium cell (EC)-marker CD31 immunostaining. It was difficult to obtain the enough amount of EC by MACS with anti-CD31 antibody (Ab). We therefore originated GFP transduced A20-cells, and then GFP-negative fraction was sorted from A20-tumor tissue. Now we tried to separate the A20-tumor-associated EC (A20-EC) by using sorted GFP-negative fraction. To increase the number of EC, a vector containing immortalizing gene teromerase reverse transcriptase (TERT) was constructed. After successful A20-EC separation, transduction of TERT gene to A20-ESs and expansion of them will be performed, and then purification of A20-EC-derived HSP will be planed. To obtain the useful information of tumor endotherial antigen in the B-cell neoplasms, the specimen of solitary plasmacytoma in POEMS syndrome, which is known as one of the angiogenic B-cell neoplasms, was immunostained with angiogenic factors, and we demonstrated that the expression levels of VEGF and IGF were very high in the tumor. In addition, we showed the possibility that anti-idiotype Ab of mouse B-cell neoplasm may inhibit the angiogenesis in the microenvironment of the B-cell tumor through humoral immunity by the CDC. These findings enable the approach by novel immunotherapy against tumor ECs with unique motifs, such as HSPs derived from B-cell neoplasm associated ECs or anti-idiotype Ab.

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  • 血管内皮前駆細胞を用いた細胞遺伝子治療の開発〜がん治療への応用〜

    Grant number:18790439  2006 - 2007

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

    水上 裕輔

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3,300,000 ( Direct Cost: \3,300,000 )

    血管内皮前駆細胞(endothelial progenitor cell;EPC)の虚血領域への血管選択的な局在能に着目し、これらを用いたdrug delivery system(DDS)を念頭においた基礎実験を行った。マウス骨髄由来EPCに対してレンチウイルスを用いた導入実験を行い、良好な導入効率が得られることを確認した。次に、担癌ヌードマウスに対してTie2/LacZトランスジェニックマウスないしGFPマウスの骨髄単核球より分化誘導したEPCの移植を行い、腫瘍血管へのEPCの分布を組織学的に解析した。移植(経静脈投与)されたEPCは腫瘍血管に局在し、その一部は血管内皮紹胞へと分化することが確認された。しかし、その割合はこれまでの骨髄置換モデルにおける報告と比較して著しく低く、腫瘍内に分布した移植細胞の数%に留まり、その多くが血管周囲に分布していた。さらに、当初はEPC移植による腫瘍の増大を危惧していたが、逆に10^5〜10^6個を移植した際には腫瘍の縮小を認めた。組織学的に内腔の拡大を伴う腫瘍血管の増生と腫瘍内低酸素域の縮小がみられたことから、分化誘導処理が施されたEPCが腫瘍組織内に動員されることによって、がん微少環境が修飾される可能性が示された。この現象は、難治がん治療へと応用可能と考え(特許出願済み)、遺伝子修飾を施したEPCの移植を行うという当初の方向性を修正し、現在EPCによって誘導されるがん微少環境の変化の詳細とその分子メカニズムの解明を試みている。

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  • ヒト血管内皮前駆細胞の可塑性に起因するがん微小環境の異常とその制御

    Grant number:18013004  2006 - 2007

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    水上 裕輔, 前本 篤男, 佐藤 一也, 伊井 正明

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\11,600,000 ( Direct Cost: \11,600,000 )

    成人末梢血から分化誘導培養によって得た血管内皮前駆細胞(EPC)を用いて、がん細胞とEPCの相互作用の分子機構を解析した。膵がん細胞はEPCにおけるPTCH1の発現を促し、腫瘍血管新生におけるHedgehog(Hh)経路の関与が示唆された。Sonichedgehog(SHH)を過剰発現させた293細胞のconditioned medium(CM)はEPCにおけるVEGFやAng-1などの血管新生因子の発現を顕著に増強した。さらに、SHHを高発現するヒト膵がん細胞株由来のCMもEPCにおけるVEGFを誘導し、これは中和抗体ならびにcyclopamineなどHh経路の阻害により抑制された。同時に、CM刺激を施したEPCとHUVECとのco-cultureによる管腔形成の促進効果もHh阻害によって抑制された(Cancer Sci2008)。一方、ヌードマウス皮下腫瘍モデルをcyclopamine処理することで、腫瘍縮小のみならず血管新生が著しく抑制された。GFPマウスをドナーとした骨髄移植ヌードマウスを用いて同様の実験を行い、腫瘍内へのEPCをはじめとする骨髄由来細胞の動員が減少することも確認された。また、Hh阻害により腫瘍血管の狭小化・断片化がみられ、SHHはEPCを介して腫瘍血管の成熟過程に関与することが示唆された(投稿準備中)。ヒト膵癌では、癌細胞のみならず腫瘍血管内皮細においてもPTCH1の発現が認められることから、SHHは重要な治療標的となると考えられる。
    腫瘍血管を含むがん微少環境の形成には骨髄が深く関与しており、これらの適切な制御にはその成り立ちの理解が鍵となる。現在、異なる癌腫間でみられるEPCの活性化機構の違いを網羅的な解析を進めると共に、がんと骨髄とのクロストークの分子機構の解明するモデルを構築している。

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  • Therapeutic targeting of tumor angiogenesis

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    Grant type:Competitive

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  • 血管新生を標的とした癌治療の開発

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    Grant type:Competitive

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Other

  • 膵臓がん、血液で早期発見

    2019.10

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    日本経済新聞 9面 10月28日

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  • 膵囊胞からの発症経路解明

    2019.3

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    北海道新聞 14面 3月20日

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Social Activities

  • 膵がんの早期診断について

    Role(s): Appearance, Panelist

    難治性がん啓発キャンペーン実行委員会  難治性がん啓発キャンペーン2025 ~治療の進歩と挑戦そして未来への展望~  2025.6

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    Type:Citizen’s meeting/Assembly

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