Updated on 2024/07/03

写真a

 
YASHIRO Masakazu
 
Organization
Graduate School of Medicine Department of Clinical Medical Science Associate Professor
School of Medicine Department of Medical Science
Title
Associate Professor
Affiliation
Institute of Medicine
Profile
1988 M.D. Osaka City University Medical School. 1995 Ph.D. Osaka City University. 1996-1997 Research Fellow, UCSD, School of Medicine. 1997-Present Department of Surgical Oncology. 2007-present Associate Professor Molecular Oncology and Therapeutics/

Position

  • Graduate School of Medicine Department of Clinical Medical Science 

    Associate Professor  2022.04 - Now

  • School of Medicine Department of Medical Science 

    Associate Professor  2022.04 - Now

Degree

  • Doctor of Medicine ( Others )

Research Areas

  • Life Science / Digestive surgery  / Gastroenterol Surgery

  • Life Science / Pathological biochemistry  / Oncology

  • Life Science / General surgery and pediatric surgery

  • Life Science / Digestive surgery

  • Life Science / General surgery and pediatric surgery

Research Interests

  • Cancer,Molecular biology, Targetting therapy

  • Oncology」

  • Gastroenterol Surgery

Research subject summary

  • We aim at the development of the novel molecular target therapy based on cancer molecular mechanism.

Research Career

Professional Memberships

  • AACR

      Overseas

  • 遺伝性腫瘍学会

      Domestic

  • 日本癌学会

  • 日本消化器外科学会

  • 日本乳癌学会

      Domestic

  • 日本外科学会

  • 日本消化器内視鏡学会

      Domestic

  • 日本消化器病学会

      Domestic

  • 日本大腸肛門病学会

      Domestic

  • 日本消化器癌発生学会

  • 日本胃癌学会

  • 米国癌学会

  • 日本胃癌学会

  • 日本癌学会

  • 日本消化器癌発生学会

  • 日本消化器病学会

  • 日本消化器外科学会

  • 日本消化器内視鏡学会

  • 日本大腸肛門病学会

  • 日本外科学会

  • 日本乳癌学会

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Awards

  • 日本消化器癌発生学会奨励賞

    2007  

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    Country:Japan

  • 日本消化器癌発生学会奨励賞

    2007  

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    Country:Japan

  • The SUBSIDY Award for Cancer Research (The 5th International Symposium on Cancer Research

    2006  

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    Country:Japan

  • 癌研究奨励賞

    2006  

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    Country:Japan

  • 平成18年度大阪市医学会市長賞

    2005  

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    Country:Japan

  • 平成18年度大阪市医学会市長賞

    2005  

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    Country:Japan

  • 大阪市医学会市長賞

    1998  

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    Country:Japan

  • 大阪市医学会市長賞

    1997  

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    Country:Japan

  • 国際胃癌学会ポスター賞(Poster Prize)

    1995  

  • 消化器癌発生研究会(Young Researchers Award)

    1995  

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    Country:Japan

  • 日本消化器外科学会研究者賞(Young Researchers Award)

    1993  

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    Country:Japan

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Job Career (off-campus)

  • 大阪市立住吉市民病院・研究医   研究医

    1990.06 - 1991.05

Education

  • Osaka City University   Doctor's Course  

    - 1995

  • Osaka City University    

    - 1988

Papers

  • Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan's National Database. Reviewed

    Kawabata K, Nishikubo H, Kanei S, Aoyama R, Tsukada Y, Sano T, Imanishi D, Sakuma T, Maruo K, Yamamoto Y, Wang Q, Zhu Z, Fan C, Yashiro M

    Genes   15 ( 6 )   2024.06

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/genes15060792

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  • Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey Reviewed

    Miyamoto T.

    Arthritis and Rheumatology   76 ( 6 )   949 - 962   2024.06( ISSN:23265191

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/art.42808

  • Prognostic significance of connective tissue growth factor expression in stromal cells in patients with diffuse‑type gastric cancer. Reviewed

    Miki Y, Yoshii M, Miyauchi R, Kasashima H, Fukuoka T, Tamura T, Shibutani M, Toyokawa T, Lee S, Yashiro M, Maeda K

    Oncology letters   27 ( 6 )   241   2024.06( ISSN:1792-1074

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3892/ol.2024.14374

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  • Bioinformatics Analysis and Validation of Potential Markers Associated with Prediction and Prognosis of Gastric Cancer. Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    International journal of molecular sciences   25 ( 11 )   2024.05( ISSN:16616596

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of the disease, and current anticancer drug advancements are still lacking. Therefore, it is crucial to find relevant biomarkers with the accurate prediction of prognoses and good predictive accuracy to select appropriate patients with GC. Recent advances in molecular profiling technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have enabled the approach of GC biology at multiple levels of omics interaction networks. Systemic biological analyses, such as computational inference of "big data" and advanced bioinformatic approaches, are emerging to identify the key molecular biomarkers of GC, which would benefit targeted therapies. This review summarizes the current status of how bioinformatics analysis contributes to biomarker discovery for prognosis and prediction of therapeutic efficacy in GC based on a search of the medical literature. We highlight emerging individual multi-omics datasets, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics, for validating putative markers. Finally, we discuss the current challenges and future perspectives to integrate multi-omics analysis for improving biomarker implementation. The practical integration of bioinformatics analysis and multi-omics datasets under complementary computational analysis is having a great impact on the search for predictive and prognostic biomarkers and may lead to an important revolution in treatment.

    DOI: 10.3390/ijms25115880

    PubMed

  • Epithelial aPKC deficiency leads to stem cell loss preceding metaplasia in colorectal cancer initiation. Reviewed

    Kinoshita H, Martinez-Ordoñez A, Cid-Diaz T, Han Q, Duran A, Muta Y, Zhang X, Linares JF, Nakanishi Y, Kasashima H, Yashiro M, Maeda K, Albaladejo-Gonzalez A, Torres-Moreno D, García-Solano J, Conesa-Zamora P, Inghirami G, Diaz-Meco MT, Moscat J

    Developmental cell   2024.05( ISSN:1534-5807

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.devcel.2024.05.001

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  • Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2. Reviewed

    Kikuchi Y, Shimada H, Yamasaki F, Yamashita T, Araki K, Horimoto K, Yajima S, Yashiro M, Yokoi K, Cho H, Ehira T, Nakahara K, Yasuda H, Isobe K, Hayashida T, Hatakeyama S, Akakura K, Aoki D, Nomura H, Tada Y, Yoshimatsu Y, Miyachi H, Takebayashi C, Hanamura I, Takahashi H

    International journal of clinical oncology   29 ( 5 )   512 - 534   2024.05( ISSN:1341-9625

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s10147-024-02497-0

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  • C-CAT's triumph in gastroenterology: the wisdom of cats is infinitely superior. Reviewed

    Enomoto M, Odagiri N, Rinka K, Maruyama H, Shimamoto Y, Ishikawa-Kakiya Y, Fujiwara Y, Kawada N, Yashiro M

    Journal of gastroenterology   59 ( 2 )   157 - 158   2024.02( ISSN:0944-1174

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00535-023-02061-z

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  • Exosomes secreted by ST3GAL5(high) cancer cells promote peritoneal dissemination by establishing a premetastatic microenvironment. Reviewed

    Horie M, Takagane K, Itoh G, Kuriyama S, Yanagihara K, Yashiro M, Umakoshi M, Goto A, Arita J, Tanaka M

    Molecular oncology   18 ( 1 )   21 - 43   2024.01( ISSN:1574-7891

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/1878-0261.13524

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  • Clinical Significance of Multi-Cancer Genome Profiling: Data from a Single Hospital in Japan. Reviewed

    Aoyama R, Nishikubo H, Kawabata K, Kanei S, Yamamoto Y, Nishimura S, Yashiro M

    Cancer genomics & proteomics   21 ( 1 )   79 - 87   2024.01( ISSN:1109-6535

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.21873/cgp.20431

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  • Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey Reviewed

    Korematsu S.

    Clinical and Translational Allergy   14 ( 1 )   2024.01

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/clt2.12330

  • Current status and perspectives of genetic testing in gastrointestinal cancer (Review). Reviewed

    Matsuoka T, Yashiro M

    Oncology letters   27 ( 1 )   21   2024.01( ISSN:1792-1074

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3892/ol.2023.14155

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  • Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma. Reviewed

    Tagami M, Kasashima H, Kakehashi A, Yoshikawa A, Nishio M, Misawa N, Sakai A, Wanibuchi H, Yashiro M, Azumi A, Honda S

    Frontiers in oncology   14   1277749   2024( ISSN:2234-943X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3389/fonc.2024.1277749

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  • Two families with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): case reports and literature review. Reviewed

    Sakuma T, Sera T, Aoyama R, Sawada A, Kasashima H, Ogisawa K, Bamba H, Yashiro M

    Journal of gastrointestinal oncology   14 ( 6 )   2650 - 2657   2023.12( ISSN:2078-6891

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.21037/jgo-23-564

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  • Molecular Insight into Gastric Cancer Invasion-Current Status and Future Directions. Reviewed

    Matsuoka T, Yashiro M

    Cancers   16 ( 1 )   2023.12( ISSN:2072-6694

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/cancers16010054

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  • Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis. Reviewed

    Muta Y, Linares JF, Martinez-Ordoñez A, Duran A, Cid-Diaz T, Kinoshita H, Zhang X, Han Q, Nakanishi Y, Nakanishi N, Cordes T, Arora GK, Ruiz-Martinez M, Reina-Campos M, Kasashima H, Yashiro M, Maeda K, Albaladejo-Gonzalez A, Torres-Moreno D, García-Solano J, Conesa-Zamora P, Inghirami G, Metallo CM, Osborne TF, Diaz-Meco MT, Moscat J

    Nature communications   14 ( 1 )   8075   2023.12

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-023-43690-5

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  • The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers. Reviewed

    Matsuoka T, Yashiro M

    Biomolecules   13 ( 10 )   2023.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/biom13101551

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  • Impact of SMAD2 and MET Expression on Lymph Node Metastasis of HER2-positive Gastric Cancer Cells. Reviewed

    Tsujio G, Yashiro M, Sakuma T, Aoyama R, Maruo K, Yamamoto Y, Maeda K

    Anticancer research   43 ( 10 )   4359 - 4364   2023.10( ISSN:0250-7005

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.21873/anticanres.16631

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  • RBM17 Expression Is Associated With the Efficacy of ICI Monotherapy in NSCLC With Low PD-L1 Expression. Reviewed

    Nagamine H, Yashiro M, Yoshimoto N, Izumi M, Sugimoto A, Nakahama K, Ogawa K, Matsumoto Y, Sawa K, Tani Y, Kaneda H, Mitsuoka S, Yamada K, Watanabe T, Aasai K, Fukumura K, Mayeda A, Kawaguchi T

    Anticancer research   43 ( 10 )   4663 - 4672   2023.10( ISSN:0250-7005

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.21873/anticanres.16662

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  • THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer Reviewed

    Omatsu Mayuki, Nakanishi Yuki, Iwane Kosuke, Aoyama Naoki, Duran Angeles, Muta Yu, Martinez-Ordoñez Anxo, Han Qixiu, Agatsuma Nobukazu, Mizukoshi Kenta, Kawai Munenori, Yamakawa Go, Namikawa Mio, Hamada Kensuke, Fukunaga Yuichi, Utsumi Takahiro, Sono Makoto, Masuda Tomonori, Hata Akitaka, Araki Osamu, Nagao Munemasa, Yoshikawa Takaaki, Ogawa Satoshi, Hiramatsu Yukiko, Tsuda Motoyuki, Maruno Takahisa, Kogame Toshiaki, Kasashima Hiroaki, Kakiuchi Nobuyuki, Nakagawa Masahiro M., Kawada Kenji, Yashiro Masakazu, Maeda Kiyoshi, Saito Yasuyuki, Matozaki Takashi, Fukuda Akihisa, Kabashima Kenji, Obama Kazutaka, Ogawa Seishi, Sheibani Nader, Diaz-Meco Maria T., Moscat Jorge, Seno Hiroshi

    Nature Communications   14   2023.09

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    Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.

  • THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer. Reviewed

    Omatsu M, Nakanishi Y, Iwane K, Aoyama N, Duran A, Muta Y, Martinez-Ordoñez A, Han Q, Agatsuma N, Mizukoshi K, Kawai M, Yamakawa G, Namikawa M, Hamada K, Fukunaga Y, Utsumi T, Sono M, Masuda T, Hata A, Araki O, Nagao M, Yoshikawa T, Ogawa S, Hiramatsu Y, Tsuda M, Maruno T, Kogame T, Kasashima H, Kakiuchi N, Nakagawa MM, Kawada K, Yashiro M, Maeda K, Saito Y, Matozaki T, Fukuda A, Kabashima K, Obama K, Ogawa S, Sheibani N, Diaz-Meco MT, Moscat J, Seno H

    Nature communications   14 ( 1 )   5534   2023.09

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-023-41095-y

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  • [The Role of Cancer-Associated Fibroblasts in Modulating Tumor Immunity in Colorectal Cancer]. Reviewed

    Kasashima H, Fukui Y, Kitayama K, Miki Y, Yoshii M, Fukuoka T, Tamura T, Shibutani M, Toyokawa T, Ree S, Tanaka H, Yashiro M, Maeda K

    Gan to kagaku ryoho. Cancer & chemotherapy   50 ( 9 )   958 - 959   2023.09( ISSN:0385-0684

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  • 大腸癌微小環境における抗原提示性癌関連線維芽細胞が腫瘍進展に及ぼす影響の解析(The effect of antigen-presenting cancer-associated fibroblast in TME for tumor progression of colon cancer) Reviewed

    笠島 裕明, 福井 康裕, 中西 祐貴, 北山 紀州, 三木 友一朗, 吉井 真美, 福岡 達成, 田村 達郎, 渋谷 雅常, 豊川 貴弘, 田中 浩明, 李 栄柱, 八代 正和, 前田 清

    日本癌学会総会記事   82回   838 - 838   2023.09( ISSN:0546-0476

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  • Trophoblast cell surface antigen-2 phosphorylation triggered by binding of galectin-3 drives metastasis through down-regulation of E-cadherin. Reviewed

    Iwamoto S, Mori Y, Yamashita T, Ojima K, Akita K, Togano S, Kushiyama S, Yashiro M, Yatera Y, Yamaguchi T, Komiyama A, Sago Y, Itano N, Nakada H

    The Journal of biological chemistry   299 ( 8 )   104971   2023.08( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jbc.2023.104971

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  • Novel biomarkers for early detection of gastric cancer. Reviewed

    Matsuoka T, Yashiro M

    World journal of gastroenterology   29 ( 17 )   2515 - 2533   2023.05( ISSN:1007-9327

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3748/wjg.v29.i17.2515

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  • Establishment of a gastric cancer cell line with high microsatellite instability, OCUM-13, derived from Borrmann type-2 primary tumor. Reviewed

    Yamamoto Y, Masuda G, Kushiyama S, Maruo K, Tsujio G, Sera T, Sugimoto A, Nishimura S, Kuroda K, Togano S, Okuno T, Ohira M, Yashiro M

    Cancer medicine   12 ( 5 )   6016 - 6022   2023.03

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/cam4.5403

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  • IL-1β derived from mixed-polarized macrophages activates fibroblasts and synergistically forms a cancer-promoting microenvironment. Reviewed

    Zhang J, Fu L, Yasuda-Yoshihara N, Yonemura A, Wei F, Bu L, Hu X, Akiyama T, Kitamura F, Yasuda T, Semba T, Uchihara T, Itoyama R, Yamashita K, Eto K, Iwagami S, Yashiro M, Komohara Y, Baba H, Ishimoto T

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   26 ( 2 )   187 - 202   2023.03( ISSN:1436-3291

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s10120-022-01352-3

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  • GLUT1 and PKM2 may be useful prognostic predictors in patients with non‑small cell lung cancer following curative R0 resection. Reviewed

    Ito R, Yashiro M, Tsukioka T, Izumi N, Komatsu H, Inoue H, Yamamoto Y, Nishiyama N

    Oncology letters   25 ( 3 )   129   2023.03( ISSN:1792-1074

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3892/ol.2023.13715

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  • 混合分極化マクロファージ由来のIL-1βは線維芽細胞を活性化し、相乗的に癌促進性微小環境を形成する(IL-1β derived from mixed-polarized macrophages activates fibroblasts and synergistically forms a cancer-promoting microenvironment) Reviewed

    Zhang Jun, Fu Lingfeng, Yasuda-Yoshihara Noriko, Yonemura Atsuko, Wei Feng, Bu Luke, Hu Xichen, Akiyama Takahiko, Kitamura Fumimasa, Yasuda Tadahito, Semba Takashi, Uchihara Tomoyuki, Itoyama Rumi, Yamashita Kohei, Eto Kojiro, Iwagami Shiro, Yashiro Masakazu, Komohara Yoshihiro, Baba Hideo, Ishimoto Takatsugu

    Gastric Cancer   26 ( 2 )   187 - 202   2023.03( ISSN:1436-3291

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    びまん型胃癌(DGC)進行における腫瘍微小環境でのマクロファージ、線維芽細胞、DGC細胞の相互活性化メカニズムについて検討した。マクロファージ、非癌性線維芽細胞(NF)、DGC細胞を共培養し、マスサイトメトリー分析を実施した。NFとマクロファージはDGC細胞と相互作用し、DGC組織の浸潤先進部に細胞クラスターを形成した。共培養下でM1/M2型細胞表面マーカーを有する混合分極化マクロファージを認めた。混合分極化マクロファージが産生したIL-1βは、NFの癌関連線維芽細胞様細胞変換を誘導し、IL-6やIL-24、白血病阻害因子の分泌が増加し、DGC細胞の悪性表現型を促進した。混合分極化マクロファージの安定性はIL-6とGM-CSFにより維持されていた。混合極性化マクロファージはDGC組織で多く検出された。

  • Hyaluronan driven by epithelial aPKC deficiency remodels the microenvironment and creates a vulnerability in mesenchymal colorectal cancer. Reviewed

    Martinez-Ordoñez A, Duran A, Ruiz-Martinez M, Cid-Diaz T, Zhang X, Han Q, Kinoshita H, Muta Y, Linares JF, Kasashima H, Nakanishi Y, Omar M, Nishimura S, Avila L, Yashiro M, Maeda K, Pannellini T, Pigazzi A, Inghirami G, Marchionni L, Sigal D, Diaz-Meco MT, Moscat J

    Cancer cell   41 ( 2 )   252 - 271.e9   2023.02( ISSN:1535-6108

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ccell.2022.11.016

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  • Usefulness of pyruvate dehydrogenase-E1α expression to determine SUVmax cut-off value of [(18)F]FDG-PET for predicting lymph node metastasis in lung cancer. Reviewed

    Ito R, Yashiro M, Tsukioka T, Izumi N, Komatsu H, Inoue H, Nishiyama N

    Scientific reports   13 ( 1 )   1565   2023.01

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-023-28805-8

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  • CD9-positive Exosomes Derived from Cancer-associated Fibroblasts Might Inhibit the Proliferation of Malignant Melanoma Cells. Reviewed

    Fujii N, Yashiro M, Hatano T, Fujikawa H, Motomura H

    Anticancer research   43 ( 1 )   25 - 33   2023.01( ISSN:0250-7005

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.21873/anticanres.16130

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  • The heterogeneity of cancer-associated fibroblast subpopulations: Their origins, biomarkers, and roles in the tumor microenvironment. Reviewed

    Yamamoto Y, Kasashima H, Fukui Y, Tsujio G, Yashiro M, Maeda K

    Cancer science   114 ( 1 )   16 - 24   2023.01( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.15609

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  • CCDC85A is regulated by miR-224-3p and augments cancer cell resistance to endoplasmic reticulum stress. Reviewed

    Takahashi S, Takagane K, Itoh G, Kuriyama S, Umakoshi M, Goto A, Yanagihara K, Yashiro M, Iijima K, Tanaka M

    Frontiers in oncology   13   1196546   2023( ISSN:2234-943X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3389/fonc.2023.1196546

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  • Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer. Reviewed

    Tanaka R, Eguchi S, Kimura K, Ohira G, Tanaka S, Amano R, Tanaka H, Yashiro M, Ohira M, Kubo S

    PloS one   18 ( 1 )   e0280348   2023

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0280348

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  • The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy. Reviewed

    Sakurai K, Kubo N, Hasegawa T, Nishimura J, Iseki Y, Nishii T, Inoue T, Yashiro M, Nishiguchi Y, Maeda K

    Annals of nutrition & metabolism   79 ( 6 )   511 - 521   2023( ISSN:0250-6807

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1159/000534244

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  • The safe removal of a superior mediastinal foreign body by mediastinoscopy: a case report. Reviewed

    Sakuma T, Tamura T, Nambara M, Gyobu K, Yoshii M, Toyokawa T, Lee S, Tanaka H, Muguruma K, Yashiro M, Ohira M, Maeda K

    Surgical case reports   8 ( 1 )   174   2022.09( ISSN:2198-7793

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s40792-022-01525-3

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  • Lipocalin-2 negatively regulates epithelial-mesenchymal transition through matrix metalloprotease-2 downregulation in gastric cancer. Reviewed

    Nishimura S, Yamamoto Y, Sugimoto A, Kushiyama S, Togano S, Kuroda K, Okuno T, Kasashima H, Ohira M, Maeda K, Yashiro M

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   25 ( 5 )   850 - 861   2022.09( ISSN:1436-3291

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    DOI: 10.1007/s10120-022-01305-w

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  • リポカリン-2は胃癌におけるマトリックスメタロプロテアーゼ-2の発現抑制を通じて上皮間葉転換を負に調節する(Lipocalin-2 negatively regulates epithelial-mesenchymal transition through matrix metalloprotease-2 downregulation in gastric cancer) Reviewed

    Nishimura Sadaaki, Yamamoto Yurie, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Okuno Tomohisa, Kasashima Hiroaki, Ohira Masaichi, Maeda Kiyoshi, Yashiro Masakazu

    Gastric Cancer   25 ( 5 )   850 - 861   2022.09( ISSN:1436-3291

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    リポカリン-2(LCN2)は生体内で炎症反応の調節や抗菌作用など多様な機能を有する分泌性糖タンパク質である。本研究では、LCN2の胃癌における関与とそのメカニズムを検討した。LCN2は、拡散型胃癌と上皮間葉転換型胃癌で発現が低下していた。LCN2の発現抑制は、胃癌細胞の増殖、浸潤、遊走を有意に促進した。その分子メカニズムとして、LCN2の発現抑制は、胃癌細胞におけるEMTシグナルを促進するマトリックスメタロプロテイナーゼ-2(MMP2)刺激に寄与していた。GSEA(gene set enrichment analysis)の発現解析より、ヒト試料におけるLCN2の発現抑制がEMTシグナルに関与していた。LCN2タンパク質およびmRNAの低レベルは、胃癌患者の予後不良と有意に関連しており、LCN2 mRNAレベルは患者の全生存に対する独立した予後因子であった。以上より、LCN2は、胃癌の進行においてMMP2活性を介したEMTシグナルに重要な役割を担っていた。

  • 縦隔鏡を用いて行った上縦隔の異物の安全な除去 症例報告(The safe removal of a superior mediastinal foreign body by mediastinoscopy: a case report) Reviewed

    Sakuma Takashi, Tamura Tatsuro, Nambara Mikio, Gyobu Ken, Yoshii Mami, Toyokawa Takahiro, Lee Shigeru, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi, Maeda Kiyoshi

    Surgical Case Reports   8   1 of 5 - 5 of 5   2022.09

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    症例は74歳男性。庭で剪定作業を行っている際に梯子から転落し、アザレアの枝が左側の胸鎖乳突筋に刺さる事故を起こした。直ちに近医へ搬送され、当日のうちにその除去手術を受けた。以後は無症状であったが、4ヵ月後に嗄声を自覚し始めたため再受診した。精査の結果、刺さった枝が残存していることが疑われたため、上縦隔内の異物の外科的管理を目的に当科へ紹介された。上部消化管内視鏡検査では胸部上部食道の前壁に隆起病変を認め、造影CTでは上縦隔の気管と食道の間に当たる位置に直線形状で約10×45mm大の異物が描出された。異物除去手術を実施し、圧を5~8cmH2Oかける気縦隔下でビデオ縦隔鏡を挿入した。その結果、広い術視野が得られ、瘢痕組織を切開して4cm長のアザレアの枝を注意深く安全に除去することに成功した。処置中に他の縦隔臓器を損傷することは無かった。手術時間は166分、出血量は45mlであった。手術から5日目に合併症のみられない状態で退院した。以降、4ヵ月毎に行った経過観察では創傷治癒が良好であることが確認されたが患者は嗄声を依然として自覚しており、そのため音声リハビリテーションが実施された。

  • Interleukin-8 produced from cancer-associated fibroblasts suppresses proliferation of the OCUCh-LM1 cancer cell line. Reviewed

    Tanaka R, Kimura K, Eguchi S, Ohira G, Tanaka S, Amano R, Tanaka H, Yashiro M, Ohira M, Kubo S

    BMC cancer   22 ( 1 )   748   2022.07

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    DOI: 10.1186/s12885-022-09847-z

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  • Significance of tumor heterogeneity of p-Smad2 and c-Met in HER2-positive gastric carcinoma with lymph node metastasis. Reviewed

    Tsujio G, Maruo K, Yamamoto Y, Sera T, Sugimoto A, Kasashima H, Miki Y, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M, Yashiro M

    BMC cancer   22 ( 1 )   598   2022.06

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    DOI: 10.1186/s12885-022-09681-3

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  • Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success. Reviewed

    Eguchi S, Kimura K, Kageyama K, Tani N, Tanaka R, Nishio K, Shinkawa H, Ohira GO, Amano R, Tanaka S, Yamamoto A, Takemura S, Yashiro M, Kubo S

    Anticancer research   42 ( 5 )   2395 - 2404   2022.05( ISSN:0250-7005

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    DOI: 10.21873/anticanres.15718

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  • Transferrin receptor 1 promotes the fibroblast growth factor receptor-mediated oncogenic potential of diffused-type gastric cancer. Reviewed

    Shirakihara T, Yamaguchi H, Kondo T, Yashiro M, Sakai R

    Oncogene   41 ( 18 )   2587 - 2596   2022.04( ISSN:0950-9232

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    DOI: 10.1038/s41388-022-02270-5

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  • Prognostic impact of postoperative systemic inflammatory response in patients with stage II/III gastric cancer. Reviewed

    Kuroda K, Toyokawa T, Miki Y, Yoshii M, Tamura T, Tanaka H, Lee S, Muguruma K, Yashiro M, Ohira M

    Scientific reports   12 ( 1 )   3025   2022.02

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    DOI: 10.1038/s41598-022-07098-3

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  • Integrin α5 mediates cancer cell-fibroblast adhesion and peritoneal dissemination of diffuse-type gastric carcinoma. Reviewed

    Miyamoto S, Nagano Y, Miyazaki M, Nagamura Y, Sasaki K, Kawamura T, Yanagihara K, Imai T, Ohki R, Yashiro M, Tanaka M, Sakai R, Yamaguchi H

    Cancer letters   526   335 - 345   2022.02( ISSN:0304-3835

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    DOI: 10.1016/j.canlet.2021.11.008

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  • Cancer-associated fibroblasts educate normal fibroblasts to facilitate cancer cell spreading and T-cell suppression. Reviewed

    Itoh G, Takagane K, Fukushi Y, Kuriyama S, Umakoshi M, Goto A, Yanagihara K, Yashiro M, Tanaka M

    Molecular oncology   16 ( 1 )   166 - 187   2022.01( ISSN:1574-7891

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    DOI: 10.1002/1878-0261.13077

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  • Dipeptidyl Peptidase-4 from Cancer-associated Fibroblasts Stimulates the Proliferation of Scirrhous-type Gastric Cancer Cells. Reviewed

    Kushiyama S, Yashiro M, Yamamoto Y, Sera T, Sugimoto A, Nishimura S, Togano S, Kuroda K, Okuno T, Miki Y, Ohira M

    Anticancer research   42 ( 1 )   501 - 509   2022.01( ISSN:0250-7005

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    DOI: 10.21873/anticanres.15508

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  • CXCL1 might be a useful predictive prognostic marker in patients with gastric cancer Reviewed

    Yamamoto Yurie, Maruo Koji, Tsujio Gen, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Syuhei, Nishimura Sadaaki, Kasashima Hiroaki, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   37 ( 0 )   29 - 30   2022

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    DOI: 10.11241/jsmtmr.37.29

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  • Identification of Characteristic Genes of Scirrhous-type Gastric Cancer Cells By RNA-Seq Reviewed

    Sera Tomohiro, Maruo Koji, Tsujio Gen, Yamamoto Yurie, Sugimoto Atsushi, Kushiyama Syuhei, Togano Shingo, Kuroda Kenji, Kasashima Hiroaki, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   37 ( 0 )   21 - 22   2022

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    DOI: 10.11241/jsmtmr.37.21

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  • CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma. Reviewed

    Yamamoto Y, Sugimoto A, Maruo K, Tsujio G, Sera T, Kushiyama S, Nishimura S, Kuroda K, Togano S, Eguchi S, Tanaka R, Kimura K, Amano R, Ohira M, Yashiro M

    PloS one   17 ( 4 )   e0266027   2022

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    DOI: 10.1371/journal.pone.0266027

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  • Analysis of Protein and Gene Expression in Gastric Cancers Related to Lymph Node Metastasis and Prognosis with Clustering Analysis Reviewed

    Tsujio Gen, Maruo Koji, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Kasashima Hiroaki, Miki Yuichiro, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   38 ( 0 )   33 - 33   2022

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    DOI: 10.11241/jsmtmr.38.33

  • Clinical significance of the cancer gene panel Reviewed

    Aoyama Rika, Sakuma Takashi, Maruo Koji, Yamamoto Yurie, Sera Tomohiro, Tsujio Gen, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   38 ( 0 )   16 - 16   2022

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    DOI: 10.11241/jsmtmr.38.16

  • Intratumoral Heterogeneity of Protein and Gene Level in Gastric Cancer Reviewed

    Tsujio Gen, Maruo Koji, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Syuhei, Nishimura Sadaaki, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Kasashima Hiroaki, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   37 ( 0 )   31 - 31   2022

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    DOI: 10.11241/jsmtmr.37.31

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  • Search for driver gene of scirrhous-type gastric cancer by RNA-seq using Next-Generation Sequencer Reviewed

    Sera Tomohiro, Aoyama Rika, Sakuma Takashi, Maruo Koji, Tsujio Gen, Yamamoto Yurie, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Kasashima Hiroaki, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   38 ( 0 )   46 - 46   2022

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    DOI: 10.11241/jsmtmr.38.46

  • mFOLFOX6+Panitumumab療法中に高アンモニア血症を来した直腸癌の1例 Reviewed

    辻尾 元, 六車 一哉, 江口 真平, 井関 康仁, 三木 友一朗, 吉井 真美, 福岡 達成, 田村 達郎, 渋谷 雅常, 永原 央, 豊川 貴弘, 田中 浩明, 李 栄柱, 八代 正和, 大平 雅一

    癌と化学療法   48 ( 13 )   2073 - 2075   2021.12( ISSN:0385-0684

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    症例は80歳、男性。直腸S状部癌および腹膜播種に対し腹腔鏡下直腸高位前方切除術を施行した。直腸S状部癌、muc、pT4a、N3(14/15)、M1c、P1、pStage IVc、RAS/BRAF野生型の診断にて、入院の上mFOLFOX6+panitumumab(Pmab)療法を開始した。化学療法開始時の血液検査ではCr 1.45mg/dLと軽度腎機能障害を認めた。化学療法開始3日目朝より徐々に意識レベルの低下を認めた(JCSIII-200)。血液検査にて血漿アンモニア濃度338μg/dLと高値を認め、5-FUに伴う高アンモニア血症と診断し、5-FU持続静注の中止および分枝鎖アミノ酸製剤の投与を行った。意識レベルは翌朝には改善を認め、血漿アンモニア濃度も78μg/dLまで低下し、その後も意識障害は認めず退院となった。second-lineとしてCPT-11+Pmab療法へ変更し化学療法を開始したが、患者希望に1コースで投与終了とし化学療法を終了とした。今回われわれは、5-FUに起因する高アンモニア血症というまれな症例を経験したため若干の文献的考察を加えて報告する。(著者抄録)

  • 80歳以上の切除不能進行・再発胃癌に対する化学療法初回減量の経験 Reviewed

    瀬良 知央, 田村 達郎, 田中 浩明, 楠 由希奈, 辻尾 元, 岡崎 由季, 杉本 敦史, 三木 友一朗, 吉井 真美, 豊川 貴弘, 六車 一哉, 八代 正和, 大平 雅一

    癌と化学療法   48 ( 13 )   1619 - 1621   2021.12( ISSN:0385-0684

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    高齢患者を対象とした化学療法はリスクが高く、治療マネジメントに工夫が必要である。今回われわれは、80歳以上の切除不能進行・再発胃癌患者に対する化学療法の初回減量効果について検討した。2020年1月~2021年1月の間に教室にて80歳以上の切除不能進行・再発胃癌患者にS-1+L-OHP療法(SOX)を施行した6例を対象とした。初回減量群(U群:4例)のうちGrade 3以上の有害事象を来した症例は認めなかったが、通常量群(N群:2例)では1例に認めた。U群では全例が4コース以上を継続し得たが、N群は2例とも1コースで終了となっていた。治療効果としてPRを得たのは3例であり、すべてU群であった。second-lineに移行した症例はU群/N群=2例/0例であり、second-line治療を行った2例ともthird-lineまで移行し得た。80歳以上の高齢患者でも初回より減量することで有害事象の発生率を低減でき、長期の化学療法の継続が可能となることが示唆された。(著者抄録)

  • [Effect of Upfront Dose Reduction in the First Cycle of Chemotherapy for Unresectable/Recurrent Gastric Cancers in Patients Aged Over 80 Years]. Reviewed

    Sera T, Tamura T, Tanaka H, Kusunoki Y, Tsujio G, Okazaki Y, Sugimoto A, Miki Y, Yoshii M, Toyokawa T, Muguruma K, Yashiro M, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   48 ( 13 )   1619 - 1621   2021.12( ISSN:0385-0684

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  • [A Case of Hyperammonemic Encephalopathy following mFOLFOX6 plus Panitumumab Therapy for Rectal Cancer]. Reviewed

    Tsujio G, Muguruma K, Eguchi S, Iseki Y, Miki Y, Yoshii M, Fukuoka T, Tamura T, Shibutani M, Nagahara H, Toyokawa T, Tanaka H, Lee S, Yashiro M, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   48 ( 13 )   2073 - 2075   2021.12( ISSN:0385-0684

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  • PKCλ/ι inhibition activates an ULK2-mediated interferon response to repress tumorigenesis. Reviewed

    Linares JF, Zhang X, Martinez-Ordoñez A, Duran A, Kinoshita H, Kasashima H, Nakanishi N, Nakanishi Y, Carelli R, Cappelli L, Arias E, Yashiro M, Ohira M, Patel S, Inghirami G, Loda M, Cuervo AM, Diaz-Meco MT, Moscat J

    Molecular cell   81 ( 21 )   4509 - 4526.e10   2021.11( ISSN:1097-2765

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    DOI: 10.1016/j.molcel.2021.08.039

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  • Telmisartan Exerts Cytotoxicity in Scirrhous Gastric Cancer Cells by Inducing G(0)/G(1) Cell Cycle Arrest. Reviewed

    Tsujiya Y, Yamamori M, Hasegawa AI, Yamamoto Y, Yashiro M, Okamura N

    Anticancer research   41 ( 11 )   5461 - 5468   2021.11( ISSN:0250-7005

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    DOI: 10.21873/anticanres.15358

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  • Gastric cancer stem cells survive in stress environments via their autophagy system. Reviewed

    Togano S, Yashiro M, Masuda G, Sugimoto A, Miki Y, Yamamoto Y, Sera T, Kushiyama S, Nishimura S, Kuroda K, Okuno T, Ohira M

    Scientific reports   11 ( 1 )   20664   2021.10

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    DOI: 10.1038/s41598-021-00155-3

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  • Pyruvate dehydrogenase E1α represents a reliable prognostic predictor for patients with non-small cell lung cancer resected via curative operation. Reviewed

    Ito R, Yashiro M, Tsukioka T, Izumi N, Komatsu H, Inoue H, Yamamoto Y, Nishiyama N

    Journal of thoracic disease   13 ( 10 )   5691 - 5700   2021.10( ISSN:2072-1439

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    DOI: 10.21037/jtd-21-1463

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  • Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study. Reviewed

    Sugimoto A, Toyokawa T, Miki Y, Yoshii M, Tamura T, Sakurai K, Kubo N, Tanaka H, Lee S, Muguruma K, Yashiro M, Ohira M

    BMC surgery   21 ( 1 )   348   2021.09

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    DOI: 10.1186/s12893-021-01344-7

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  • Asporinによる癌細胞の代謝リプログラムは酸化ストレス抵抗性を獲得させる Reviewed

    田中 正光, 高金 くらら, 伊藤 剛, 栗山 正, 山田 聡, 八代 正和

    日本癌学会総会記事   80回   [J8 - 4]   2021.09( ISSN:0546-0476

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  • オルガノイドが駆動するがん研究 PKCζ欠失により誘導されるSOX2-SFRP1/2陽性癌関連線維芽細胞集団の同定と機能解析 Reviewed

    笠島 裕明, Moscat Jorge, Diazmeco Maria T., 中西 祐貴, 工藤 洋太郎, 八代 正和, 大平 雅一

    日本癌学会総会記事   80回   [CS4 - 6]   2021.09( ISSN:0546-0476

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  • オルガノイドが駆動するがん研究 PKCζ欠失により誘導されるSOX2-SFRP1/2陽性癌関連線維芽細胞集団の同定と機能解析 Reviewed

    笠島 裕明, Moscat Jorge, Diazmeco Maria T., 中西 祐貴, 工藤 洋太郎, 八代 正和, 大平 雅一

    日本癌学会総会記事   80回   [CS4 - 6]   2021.09( ISSN:0546-0476

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  • EMMPRIN in extracellular vesicles from peritoneal mesothelial cells stimulates the invasion activity of diffuse-type gastric cancer cells. Reviewed

    Sugimoto A, Okuno T, Miki Y, Tsujio G, Sera T, Yamamoto Y, Kushiyama S, Nishimura S, Kuroda K, Togano S, Maruo K, Kasashima H, Ohira M, Yashiro M

    Cancer letters   521   169 - 177   2021.08( ISSN:0304-3835

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    DOI: 10.1016/j.canlet.2021.08.031

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  • Cancer-associated Fibroblast-derived Spondin-2 Promotes Motility of Gastric Cancer Cells. Reviewed

    Kuramitsu S, Masuda T, Hu Q, Tobo T, Yashiro M, Fujii A, Kitagawa A, Abe T, Otsu H, Ito S, Oki E, Mori M, Mimori K

    Cancer genomics & proteomics   18 ( 4 )   521 - 529   2021.07( ISSN:1109-6535

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    DOI: 10.21873/cgp.20277

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  • The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma. Reviewed

    Kubo N, Sakurai K, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Yashiro M, Maeda K, Ohira M

    Esophagus : official journal of the Japan Esophageal Society   18 ( 3 )   548 - 558   2021.07( ISSN:1612-9059

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    DOI: 10.1007/s10388-021-00821-5

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  • 全身性炎症反応症候群の期間は、食道扁平上皮癌に対する根治的食道切除後の長期生存に関連する信頼し得る因子である(The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma) Reviewed

    Kubo Naoshi, Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi

    Esophagus   18 ( 3 )   548 - 558   2021.07( ISSN:1612-9059

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    2005年から2015年の間に局在性食道扁平上皮癌(ESCC)に対して根治的食道切除術を行った222例(男性179例、女性43例、平均年齢63.7歳)を検討対象とした。(a)体温>38℃または<36℃、(b)心拍数>90回/分、(c)呼吸回数>20回/分、(d)白血球数>12000または<4000/mm3、の4項目中2項目以上を満たす場合を、全身性炎症反応症候群(SIRS)と定義した。SIRS期間は術後7日までのうちSIRSの診断基準を満たした日数と定義した。5年全生存率をエンドポイントとして描いた受信者操作特性曲線解析の結果、SIRS期間のカットオフ値は5.0日であった。222症例のうち、165例(74.4%)および57例(25.6%)がそれぞれ短期(<5.0)および長期(≧5.0)SIRSに分類された。ロジスティック回帰分析の結果、長期SIRSは、術後肺炎、術中大量出血、術後高CRP値および術後低アルブミン血症と有意に関連していた。多変量Cox比例ハザード分析の結果、長期SIRSは全生存率(OS)および癌特異的生存率(CSS)に関する有意な増悪因子であった。術後肺炎および術後高CRP値はいずれもOS、CSSの増悪因子ではなかった。

  • Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges. Reviewed

    Matsuoka T, Yashiro M

    World journal of gastrointestinal oncology   13 ( 5 )   366 - 390   2021.05( ISSN:1948-5204

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    DOI: 10.4251/wjgo.v13.i5.366

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  • Clinicopathologic significance of TROP2 and phospho-TROP2 in gastric cancer Reviewed

    Kushiyama Shuhei, Yashiro Masakazu, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Nakada Hiroshi, Ohira Masaichi

    MOLECULAR AND CLINICAL ONCOLOGY   14 ( 5 )   105   2021.05( ISSN:2049-9450

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    DOI: 10.3892/mco.2021.2267

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  • Clinicopathologic significance of TROP2 and phospho-TROP2 in gastric cancer. Reviewed

    Kushiyama S, Yashiro M, Yamamoto Y, Sera T, Sugimoto A, Nishimura S, Togano S, Kuroda K, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Nakada H, Ohira M

    Molecular and clinical oncology   14 ( 5 )   105   2021.05( ISSN:2049-9450

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    DOI: 10.3892/mco.2021.2267

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  • Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress Reviewed

    Sasaki Yuto, Takagane Kurara, Konno Takumi, Itoh Go, Kuriyama Sei, Yanagihara Kazuyoshi, Yashiro Masakazu, Yamada Satoru, Murakami Shinya, Tanaka Masamitsu

    CANCER SCIENCE   112 ( 3 )   1251 - 1261   2021.03( ISSN:1347-9032

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    DOI: 10.1111/cas.14794

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  • Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress. Reviewed

    Sasaki Y, Takagane K, Konno T, Itoh G, Kuriyama S, Yanagihara K, Yashiro M, Yamada S, Murakami S, Tanaka M

    Cancer science   112 ( 3 )   1251 - 1261   2021.03( ISSN:1347-9032

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    DOI: 10.1111/cas.14794

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  • アスポリンの発現は癌細胞をリプログラミングし、酸化ストレスに対する耐性を獲得させる(Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress) Reviewed

    Sasaki Yuto, Takagane Kurara, Konno Takumi, Itoh Go, Kuriyama Sei, Yanagihara Kazuyoshi, Yashiro Masakazu, Yamada Satoru, Murakami Shinya, Tanaka Masamitsu

    Cancer Science   112 ( 3 )   1251 - 1261   2021.03( ISSN:1347-9032

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    変形性関節症の感受性遺伝子として知られるアスポリンの胃癌における関与を検討した。アスポリンを胃癌細胞株(HSC-43細胞と44As3細胞)で過剰発現させると、CD44の発現誘導とRac1とMMP9の活性化を伴って、遊走能と浸潤能が亢進した。アスポリンの発現は、ミトコンドリアの活性酸素種を減少させることにより、胃癌細胞株の酸化ストレスに対する耐性を高めた。アスポリンは、転写因子HIF1αの発現を誘導し、乳酸脱水素酵素AおよびPDH-E1αの発現を亢進させた。それにより、アスポリンがHSC-43細胞を嫌気的な解糖に再プログラムし、ミトコンドリアでの活性酸素の生成を抑制していると考えられた。対照的に、44As3細胞は酸化ストレスに反応して高レベルのHIF1αを発現し、アスポリンの発現にかかわらずアポトーシスを免れた。アスポリンノックアウトマウスの胃壁に移植された異種移植片を調べたところ、微小血管密度が増加したHSC-43腫瘍の増殖はアスポリンによって著しく促進され、アスポリンはHSC-43腫瘍と44As3腫瘍の両方の浸潤の深さを増加させた。以上より、アスポリンは、グルコース代謝の再プログラムを介したHIF1αによる酸化ストレスへの耐性およびCD44-Rac1とMMP9の活性化による細胞の遊走と浸潤の促進という2つの異なる作用を持つことが示唆された。

  • Clinical benefit for clinical sequencing using cancer panel testing Reviewed

    Nishimura Sadaaki, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Yamamoto Yurie, Yamauchi Makoto, Sumi Toshiyuki, Kaneda Hiroyasu, Kawaguchi Tomoya, Kato Minoru, Tagami Mizuki, Oebisu Naoto, Hoshi Manabu, Kimura Kenjiro, Kubo Shoji, Muguruma Kazuya, Takashima Tsutomu, Ohira Masaichi, Yashiro Masakazu

    PLOS ONE   16 ( 2 )   e0247090   2021.02( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0247090

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  • Clinical difference between fibroblast growth factor receptor 2 subclass, type IIIb and type IIIc, in gastric cancer Reviewed

    Yashiro Masakazu, Kuroda Kenji, Masuda Go, Okuno Tomohisa, Miki Yuichiro, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Shuhei, Nishimura Sadaaki, Togano Shingo, Ohira Masaichi

    SCIENTIFIC REPORTS   11 ( 1 )   4698   2021.02( ISSN:2045-2322

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    DOI: 10.1038/s41598-021-84107-x

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  • Clinical difference between fibroblast growth factor receptor 2 subclass, type IIIb and type IIIc, in gastric cancer. Reviewed

    Yashiro M, Kuroda K, Masuda G, Okuno T, Miki Y, Yamamoto Y, Sera T, Sugimoto A, Kushiyama S, Nishimura S, Togano S, Ohira M

    Scientific reports   11 ( 1 )   4698   2021.02

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    DOI: 10.1038/s41598-021-84107-x

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  • The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma Reviewed

    Kubo Naoshi, Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi

    ESOPHAGUS   2021.02( ISSN:1612-9059

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    DOI: 10.1007/s10388-021-00821-5

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  • Analysis of clinicopathologic factors associated with false negative of lymph node metastasis by FDG-PET in lung cancer Reviewed

    Ito Ryuichi, Yashiro Masakazu, Inoue Hidetoshi

    CANCER SCIENCE   112   498 - 498   2021.02( ISSN:1347-9032

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  • The clinicopathological significance of CXCR2 ligand family in gastric carcinoma Reviewed

    Yamamoto Yurie, Yashiro Masakazu, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Shuhei, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Okuno Tomohisa, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi

    CANCER SCIENCE   112   422 - 422   2021.02( ISSN:1347-9032

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  • Spondin2 secreted from cancer-associated fibroblasts (CAF) facilitates gastric cancer motility Reviewed

    Saito Hideyuki, Masuda Takaaki, Kuramitsu Shotaro, Yashiro Masakazu, Koike Kensuke, Kobayashi Yuta, Takahashi Junichi, Takao Seiichiro, Motomura Yushi, Otsu Hajime, Takeishi Kazuki, Yonemura Yusuke, Saeki Hiroshi, Mimori Koshi

    CANCER SCIENCE   112   358 - 358   2021.02( ISSN:1347-9032

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  • Significance of Circulating Tumor Cells with Fibroblast growth factor receptor 2 Expression in Gastric Cancer Reviewed

    Kuroda Kenji, Yashiro Masakazu, Miki Yuichiro, Sera Tomohiro, Yamamoto Yurie, Sugimoto Atsushi, Nishimura Sadaaki, Kushiyama Shuhei, Togano Shingo, Okuno Tomohisa, Ohira Masaichi

    CANCER SCIENCE   112   475 - 475   2021.02( ISSN:1347-9032

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  • Scirrhous gastric cancer extracellular vesicles cells might stimulate the proliferation of cancer-associated fibroblasts Reviewed

    Sugimoto Atsushi, Yashiro Masakazu, Okuno Tomohisa, Miki Yuichiro, Yamamoto Yurie, Sera Tomohiro, Kushiyama Shuhei, Nishimura Sadaaki, Kuroda Kenji, Togano Shingo, Ohira Masaichi

    CANCER SCIENCE   112   712 - 712   2021.02( ISSN:1347-9032

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  • Is Cancer Panel Testing useful for cancer treatment? Reviewed

    Nishimura Sadaaki, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Yamauchi Makoto, Sumi Toshiyuki, Sawa Kenji, Kawaguchi Tomoya, Kimura Kenjiro, Nagahara Hisashi, Muguruma Kazuya, Takashima Tsutomu, Ohira Masaichi, Yashiro Masakazu

    CANCER SCIENCE   112   325 - 325   2021.02( ISSN:1347-9032

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  • Dynamics of giant cancer cells cooperating with cancer associated fibroblasts Reviewed

    Itoh Go, Yashiro Masakazu, Tanaka Masamitsu

    CANCER SCIENCE   112   307 - 307   2021.02( ISSN:1347-9032

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  • Distance from tumor to serosa might be a useful predictive factor for dissemination after operation of T3-gastric cancer Reviewed

    Togano Shingo, Yashiro Masakazu, Miki Yuichiro, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Shuhei, Nishimura Sadaaki, Kuroda Kenji, Okuno Tomohisa, Tanaka Hiroaki, Muguruma Kazuya, Tanaka Sayaka, Ohira Masaichi

    CANCER SCIENCE   112   782 - 782   2021.02( ISSN:1347-9032

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  • Clinicopathological significance of TROP-2 and pTROP-2 in gastric cancer Reviewed

    Kushiyama Shuhei, Yashiro Masakazu, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Sugimoto Atsushi, Sera Tomohiro, Yamamoto Yurie, Okuno Tomohisa, Miki Yuichiro, Nakada Hiroshi, Ohira Masaichi

    CANCER SCIENCE   112   780 - 780   2021.02( ISSN:1347-9032

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  • Clinical significance of BRACAnalysis and PARP inhibitors at Osaka City University Hospital Reviewed

    Sera Tomohiro, Takashima Tsutomu, Yamamoto Yurie, Sugimoto Atsushi, Kushiyama Shuhei, Nishimura Sadaaki, Kashiwagi Shinichiro, Ohira Masaichi, Yashiro Masakazu

    CANCER SCIENCE   112   825 - 825   2021.02( ISSN:1347-9032

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  • CEA positive circulating tumor cells and its clinical significance Reviewed

    Miki Yuichiro, Yashiro Masakazu, Kuroda Kenji, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Lee Shigeru, Muguruma Kazuya, Ohira Masaichi

    CANCER SCIENCE   112   425 - 425   2021.02( ISSN:1347-9032

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  • Cancer-associated fibroblasts educate normal fibroblasts to facilitate gastric cancer dissemination Reviewed

    Tanaka Masamitsu, Itoh Go, Takagane Kurara, Kuriyama Sei, Yashiro Masakazu

    CANCER SCIENCE   112   356 - 356   2021.02( ISSN:1347-9032

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  • Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population Reviewed

    Kasashima Hiroaki, Duran Angeles, Martinez-Ordonez Anxo, Nakanishi Yuki, Kinoshita Hiroto, Linares Juan F., Reina-Campos Miguel, Kudo Yotaro, L'Hermitte Antoine, Yashiro Masakazu, Ohira Masaichi, Bao Fei, Tauriello Daniele V. F., Batlle Eduard, Diaz-Meco Maria T., Moscat Jorge

    DEVELOPMENTAL CELL   56 ( 1 )   95 - +   2021.01( ISSN:1534-5807

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    DOI: 10.1016/j.devcel.2020.10.014

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  • Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population. Reviewed

    Kasashima H, Duran A, Martinez-Ordoñez A, Nakanishi Y, Kinoshita H, Linares JF, Reina-Campos M, Kudo Y, L'Hermitte A, Yashiro M, Ohira M, Bao F, Tauriello DVF, Batlle E, Diaz-Meco MT, Moscat J

    Developmental cell   56 ( 1 )   95 - 110.e10   2021.01( ISSN:1534-5807

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    DOI: 10.1016/j.devcel.2020.10.014

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  • Circulating CEA-positive and EpCAM-negative tumor cells might be a predictive biomarker for recurrence in patients with gastric cancer Reviewed

    Miki Yuichiro, Yashiro Masakazu, Kuroda Kenji, Okuno Tomohisa, Togano Shingo, Masuda Go, Kasashima Hiroaki, Ohira Masaichi

    CANCER MEDICINE   10 ( 2 )   521 - 528   2021.01( ISSN:2045-7634

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    DOI: 10.1002/cam4.3616

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  • SDF1 alpha/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment Reviewed

    Yashiro Masakazu, Kinoshita Haruhito, Tsujio Gen, Fukuoka Tatsunari, Yamamoto Yurie, Sera Tomohiro, Sugimoto Atsushi, Nishimura Sadaaki, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Toyokawa Takahiro, Ohira Masaichi

    ONCOLOGY LETTERS   21 ( 1 )   38   2021.01( ISSN:1792-1074

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    DOI: 10.3892/ol.2020.12299

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  • Combination of p53 and Ki67 as a Promising Predictor of Postoperative Recurrence of Meningioma Reviewed

    Nagahama Atsufumi, Yashiro Masakazu, Kawashima Toshiyuki, Nakajo Kosuke, Morisako Hiroki, Uda Takehiro, Naito Kentaro, Ichinose Tsutomu, Ohata Kenji, Goto Takeo

    ANTICANCER RESEARCH   41 ( 1 )   203 - 210   2021.01( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14766

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  • Circulating CEA-positive and EpCAM-negative tumor cells might be a predictive biomarker for recurrence in patients with gastric cancer. Reviewed

    Miki Y, Yashiro M, Kuroda K, Okuno T, Togano S, Masuda G, Kasashima H, Ohira M

    Cancer medicine   10 ( 2 )   521 - 528   2021.01

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    DOI: 10.1002/cam4.3616

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  • SDF1α/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment. Reviewed

    Yashiro M, Kinoshita H, Tsujio G, Fukuoka T, Yamamoto Y, Sera T, Sugimoto A, Nishimura S, Kushiyama S, Togano S, Kuroda K, Toyokawa T, Ohira M

    Oncology letters   21 ( 1 )   38   2021.01( ISSN:1792-1074

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    DOI: 10.3892/ol.2020.12299

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  • Combination of p53 and Ki67 as a Promising Predictor of Postoperative Recurrence of Meningioma. Reviewed

    Nagahama A, Yashiro M, Kawashima T, Nakajo K, Morisako H, Uda T, Naito K, Ichinose T, Ohata K, Goto T

    Anticancer research   41 ( 1 )   203 - 210   2021.01( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14766

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  • Does clinical sequencing bridge to clinical benefit in cancer treatment? Reviewed

    Nishimura Sadaaki, Kato Minoru, Kimura Kenjiro, Nagahara Hisashi, Muguruma Kazuya, Lee Shigeru, Takashima Tsutomu, Kubo Shoji, Ohira Masaichi, Yashiro Masakazu, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Yamauchi Makoto, Sumi Toshiyuki, Kaneda Hiroyasu, Kawaguchi Tomoya

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   36 ( 0 )   5 - 6   2021

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    DOI: 10.11241/jsmtmr.36.5

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  • Asporin Expression on Stromal Cells and/or Cancer Cells Might Be A Useful Prognostic Marker in Patients with Diffuse-Type Gastric Cancer. Reviewed

    Yashiro M, Hasegawa T, Yamamoto Y, Tsujio G, Nishimura S, Sera T, Sugimoto A, Kushiyama S, Kasashima H, Fukuoka T, Sakurai K, Toyokawa T, Kubo N, Ohira M

    European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes   62 ( 1 )   53 - 60   2021( ISSN:0014-312X

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    DOI: 10.1159/000515458

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  • The clinicopathologic significance of Tks5 expression of peritoneal mesothelial cells in gastric cancer patients. Reviewed

    Sugimoto A, Okuno T, Tsujio G, Sera T, Yamamoto Y, Maruo K, Kushiyama S, Nishimura S, Kuroda K, Togano S, Miki Y, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M, Yashiro M

    PloS one   16 ( 7 )   e0253702   2021

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    DOI: 10.1371/journal.pone.0253702

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  • Clinical benefit for clinical sequencing using cancer panel testing. Reviewed

    Nishimura S, Sugimoto A, Kushiyama S, Togano S, Kuroda K, Yamamoto Y, Yamauchi M, Sumi T, Kaneda H, Kawaguchi T, Kato M, Tagami M, Oebisu N, Hoshi M, Kimura K, Kubo S, Muguruma K, Takashima T, Ohira M, Yashiro M

    PloS one   16 ( 2 )   e0247090   2021

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  • Does clinical sequencing bridge to clinical benefit in cancer treatment? Reviewed

    Nishimura Sadaaki, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Yamauchi Makoto, Sumi Toshiyuki, Kaneda Hiroyasu, Kawaguchi Tomoya, Kato Minoru, Kimura Kenjiro, Nagahara Hisashi, Muguruma Kazuya, Lee Shigeru, Takashima Tsutomu, Kubo Shoji, Ohira Masaichi, Yashiro Masakazu

    Japan Journal of Molecular Tumor Marker Research   36 ( 0 )   5 - 6   2021

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    DOI: 10.11241/jsmtmr.36.5

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  • Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor Reviewed

    Kuroda Kenji, Yashiro Masakazu, Miki Yuichiro, Sera Tomohiro, Yamamoto Yurie, Sugimoto Atsushi, Nishimura Sadaaki, Kushiyama Shuhei, Togano Shingo, Okuno Tomohisa, Ohira Masaichi

    CANCER SCIENCE   111 ( 12 )   4500 - 4509   2020.12( ISSN:1347-9032

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    DOI: 10.1111/cas.14654

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  • Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor(和訳中) Reviewed

    Kuroda Kenji, Yashiro Masakazu, Miki Yuichiro, Sera Tomohiro, Yamamoto Yurie, Sugimoto Atsushi, Nishimura Sadaaki, Kushiyama Shuhei, Togano Shingo, Okuno Tomohisa, Ohira Masaichi

    John Wiley & Sons Australia, Ltd Cancer Science   111 ( 12 )   4500 - 4509   2020.12( ISSN:1347-9032

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  • FGFR2発現を伴う循環腫瘍細胞は既存FGFR2過剰発現腫瘍患者の同定に有用である(Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor) Reviewed

    Kuroda Kenji, Yashiro Masakazu, Miki Yuichiro, Sera Tomohiro, Yamamoto Yurie, Sugimoto Atsushi, Nishimura Sadaaki, Kushiyama Shuhei, Togano Shingo, Okuno Tomohisa, Ohira Masaichi

    Cancer Science   111 ( 12 )   4500 - 4509   2020.12( ISSN:1347-9032

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    血液中に循環するFGFR2の過剰発現を伴う循環腫瘍細胞(CTC)の同定が、FGFR2過剰発現の胃癌患者の検出に有用性かどうかについて検討した。胃切除術を受けた胃癌患者100例を対象として、胃切除術の直前に各患者から総量8mLの末梢血を採取し、フィコール密度勾配遠心法により単核細胞を濃縮した。各細胞検体でFGFR2を発現しているCTC数をフローサイトメーターで測定した。切除した原発腫瘍のFGFR2発現レベルは免疫組織化学検査で評価した。その結果、胃癌患者の末梢血中のFGFR2陽性CTC数は、原発性胃癌のFGFR2発現レベルと有意に相関していた。FGFR2陽性CTCを持つ患者(≧5細胞/10mL血液)の無再発生存率は、FGFR2陽性CTCを持たない患者(<5細胞/10mL血液)よりも有意に低かった。FGFR2陽性CTCを判定することにより、FGFR2を過剰発現する胃癌を特定できる可能性が示唆された。

  • Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor. Reviewed

    Kuroda K, Yashiro M, Miki Y, Sera T, Yamamoto Y, Sugimoto A, Nishimura S, Kushiyama S, Togano S, Okuno T, Ohira M

    Cancer science   111 ( 12 )   4500 - 4509   2020.12( ISSN:1347-9032

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  • Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Reviewed

    Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H, Otsuki S, Funabashi K, Yashiro M, Matsuo K, Yonekura K, Hirai H

    Cancer research   80 ( 22 )   4986 - 4997   2020.11( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-19-2568

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  • Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells. Reviewed

    Nishimura S, Yashiro M, Sera T, Yamamoto Y, Kushitani Y, Sugimoto A, Kushiyama S, Togano S, Kuroda K, Okuno T, Murakami Y, Ohira M

    Carcinogenesis   41 ( 11 )   1616 - 1623   2020.11( ISSN:0143-3334

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    DOI: 10.1093/carcin/bgaa031

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  • Clinical update with plasma and tumour-based genomic analyses in expansion part of phase I study of selective FGFR inhibitor E7090 Reviewed

    Morizane C., Ueno M., Ioka T., Tajika M., Ikeda M., Yamaguchi K., Hara H., Yabusaki H., Miyamoto A., Iwasa S., Muto M., Takashima T., Minashi K., Komatsu Y., Nishina T., Nakajima T., Sahara T., Funasaka S., Yashiro M., Furuse J.

    ANNALS OF ONCOLOGY   31   S1292 - S1293   2020.11( ISSN:0923-7534

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    DOI: 10.1016/j.annonc.2020.10.149

  • Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells Reviewed

    Nishimura Sadaaki, Yashiro Masakazu, Sera Tomohiro, Yamamoto Yurie, Kushitani Yukako, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Okuno Tomohisa, Murakami Yoshiki, Ohira Masaichi

    CARCINOGENESIS   41 ( 11 )   1616 - 1623   2020.11( ISSN:0143-3334

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    DOI: 10.1093/carcin/bgaa031

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  • Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors Reviewed

    Sootome Hiroshi, Fujita Hidenori, Ito Kenjiro, Ochiiwa Hiroaki, Fujioka Yayoi, Ito Kimihiro, Miura Akihiro, Sagara Takeshi, Ito Satoru, Ohsawa Hirokazu, Otsuki Sachie, Funabashi Kaoru, Yashiro Masakazu, Matsuo Kenichi, Yonekura Kazuhiko, Hirai Hiroshi

    CANCER RESEARCH   80 ( 22 )   4986 - 4997   2020.11( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-19-2568

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  • Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer Reviewed

    Miki Yuichiro, Yashiro Masakazu, Moyano-Galceran Lidia, Sugimoto Atsushi, Ohira Masaichi, Lehti Kaisa

    FRONTIERS IN ONCOLOGY   10   568557   2020.10( ISSN:2234-943X

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    DOI: 10.3389/fonc.2020.568557

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  • CXCR2リガンドファミリーの胃癌における臨床病理学的因子への関与 Reviewed

    山本 百合恵, 八代 正和, 瀬良 知央, 杉本 敦史, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 吉井 真美, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本癌学会総会記事   79回   OJ13 - 2   2020.10( ISSN:0546-0476

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  • 腫瘍先進部-漿膜間距離の測定は治癒切除したT3胃癌の腹膜播種再発の予測に有用である Reviewed

    栂野 真吾, 八代 正和, 三木 友一朗, 山本 百合恵, 瀬良 知央, 杉本 敦史, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 奥野 倫久, 田中 浩明, 六車 一哉, 田中 さやか, 大平 雅一

    日本癌学会総会記事   79回   PJ14 - 3   2020.10( ISSN:0546-0476

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  • 胃癌のFGFR2発現の診断にCirculating Tumor Cells測定を用いた検討 Reviewed

    黒田 顕慈, 八代 正和, 三木 友一朗, 瀬良 知央, 山本 百合恵, 杉本 敦史, 西村 貞徳, 櫛山 周平, 栂野 真吾, 奥野 倫久, 大平 雅一

    日本癌学会総会記事   79回   OJ14 - 3   2020.10( ISSN:0546-0476

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  • 癌パネル検査は癌治療においてはたして有用か? Reviewed

    西村 貞徳, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 山内 真, 角 俊幸, 澤 兼二, 川口 知哉, 木村 健二郎, 永原 央, 六車 一哉, 高島 勉, 大平 雅一, 八代 正和

    日本癌学会総会記事   79回   OJ7 - 9   2020.10( ISSN:0546-0476

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  • 癌パネル検査は癌治療においてはたして有用か? Reviewed

    西村 貞徳, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 山内 真, 角 俊幸, 澤 兼二, 川口 知哉, 木村 健二郎, 永原 央, 六車 一哉, 高島 勉, 大平 雅一, 八代 正和

    日本癌学会総会記事   79回   OJ7 - 9   2020.10( ISSN:0546-0476

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  • 大阪市立大学病院におけるBRACAnalysisとPARP阻害薬の臨床的意義 Reviewed

    瀬良 知央, 高島 勉, 山本 百合恵, 杉本 敦史, 櫛山 周平, 西村 貞徳, 柏木 伸一郎, 大平 雅一, 八代 正和

    日本癌学会総会記事   79回   PJ14 - 10   2020.10( ISSN:0546-0476

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  • スキルス胃癌細胞由来細胞外小胞は癌関連線維芽細胞の増殖を促進する Reviewed

    杉本 敦史, 八代 正和, 奥野 倫久, 三木 友一朗, 山本 百合恵, 瀬良 知央, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 栂野 真吾, 大平 雅一

    日本癌学会総会記事   79回   PJ11 - 2   2020.10( ISSN:0546-0476

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  • スキルス胃癌細胞の変異遺伝子STK11/LKB1の同定 Reviewed

    西村 貞徳, 八代 正和, 瀬良 知央, 山本 百合恵, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 村上 善基, 大平 雅一

    日本癌治療学会学術集会抄録集   58回   O86 - 4   2020.10

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  • がん遺伝子パネル検査を用いたクリニカルシーケンスの課題と現状 Reviewed

    西村 貞徳, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 山内 真, 角 俊幸, 金田 裕靖, 川口 知哉, 加藤 実, 木村 健二郎, 永原 央, 六車 一哉, 李 栄柱, 高島 勉, 久保 正二, 大平 雅一, 八代 正和

    日本分子腫瘍マーカー研究会プログラム・講演抄録   40回   42 - 43   2020.09

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  • Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing beta 1 Integrin, Enhancing Drug Resistance Reviewed

    Uchihara Tomoyuki, Miyake Keisuke, Yonemura Atsuko, Komohara Yoshihiro, Itoyama Rumi, Koiwa Mayu, Yasuda Tadahito, Arima Kota, Harada Kazuto, Eto Kojiro, Hayashi Hiromitsu, Iwatsuki Masaaki, Iwagami Shiro, Baba Yoshifumi, Yoshida Naoya, Yashiro Masakazu, Masuda Mari, Ajani Jaffer A., Tan Patrick, Baba Hideo, Ishimoto Takatsugu

    CANCER RESEARCH   80 ( 16 )   3222 - 3235   2020.08( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-19-3803

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  • Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance. Reviewed

    Uchihara T, Miyake K, Yonemura A, Komohara Y, Itoyama R, Koiwa M, Yasuda T, Arima K, Harada K, Eto K, Hayashi H, Iwatsuki M, Iwagami S, Baba Y, Yoshida N, Yashiro M, Masuda M, Ajani JA, Tan P, Baba H, Ishimoto T

    Cancer research   80 ( 16 )   3222 - 3235   2020.08( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-19-3803

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  • Association between FGFR4 Gly388Arg polymorphism rs351855 or the IDH1 rs11554137 and Japanese gastric cancer Reviewed

    Sera Tomohiro, Yashiro Masakazu, Yamamoto Yurie, Kushitani Yukako, Sugimoto Atsushi, Kushiyama Syuhei, Kuroda Kenji, Togano Shingo, Okuno Tomohisa, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi

    CANCER RESEARCH   80 ( 16 )   2020.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2020-5856

  • Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells Reviewed

    Nishimura Sadaaki, Yashiro Masakazu, Sera Tomohiro, Yamamoto Yurie, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Kuroda Kenji, Okuno Tomohisa, Ohira Masaichi

    CANCER RESEARCH   80 ( 16 )   2020.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2020-1217A

  • Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia Reviewed

    Yashiro Masakazu, Kasashima Hiroaki, Yamamoto Yurie, Kuroda Kenji, Sera Tomohiro, Sugimoto Atsushi, Kushiyama Shuhei, Togano Shingo, Okuno Tomohisa, Miki Yuichiro, Ohira Masaichi

    CANCER RESEARCH   80 ( 16 )   2020.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2020-3566

  • Clinicopathological features of TROP-2 and pTROP-2 in gastric cancer Reviewed

    Kushiyama Syuhei, Yashiro Masakazu, Nishimura Sadaaki, Togano Shingo, Kuroda Kanji, Sugimoto Atsushi, Sera Tomohiro, Yamamoto Yurie, Okuno Tomohisa, Miki Yuichiro, Nakada Hiroshi, Ohira Masaichi

    CANCER RESEARCH   80 ( 16 )   2020.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2020-6465

  • スキルス胃癌におけるSTK11/LKB1遺伝子の意義 Reviewed

    西村 貞徳, 八代 正和, 瀬良 知央, 山本 百合恵, 櫛谷 友佳子, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 三木 友一朗, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   SF - 2   2020.08

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  • 胃癌患者におけるFGFR2をマーカーにしたCirculating Tumor Cells測定の意義 Reviewed

    黒田 顕慈, 八代 正和, 三木 友一朗, 杉本 敦史, 瀬良 知央, 山本 百合恵, 櫛山 周平, 西村 貞徳, 栂野 真吾, 奥野 倫久, 吉井 真美, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   SF - 5   2020.08

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  • 胃癌幹細胞のオートファジーの意義 Reviewed

    栂野 真吾, 八代 正和, 三木 友一朗, 山本 百合恵, 瀬良 知央, 櫛谷 友佳子, 杉本 敦史, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 奥野 倫久, 吉井 真美, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   DP - 7   2020.08

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  • 胃癌におけるCXCケモカインファミリー発現の臨床学的意義 Reviewed

    山本 百合恵, 八代 正和, 瀬良 知央, 櫛谷 友佳子, 杉本 敦史, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 栂野 真吾, 奥野 倫久, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   RS - 3   2020.08

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  • スキルス胃癌細胞由来のエクソソームは癌関連線維芽細胞の増殖を促進する Reviewed

    杉本 敦史, 八代 正和, 山本 百合恵, 瀬良 知央, 櫛谷 友佳子, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 田中 涼太, 栂野 真吾, 奥野 倫久, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   DP - 3   2020.08

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  • スキルス胃癌細胞に対する癌関連線維芽細胞由来の新規増殖促進因子の検討 Reviewed

    櫛山 周平, 八代 正和, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 杉本 敦史, 瀬良 知央, 山本 百合恵, 奥野 倫久, 三木 友一朗, 大平 雅一

    日本外科学会定期学術集会抄録集   120回   DP - 6   2020.08

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  • Cancer cells with high-metastatic potential promote a glycolytic shift in activated fibroblasts Reviewed

    Kogure Akiko, Naito Yutaka, Yamamoto Yusuke, Yashiro Masakazu, Kiyono Tohru, Yanagihara Kazuyoshi, Hirakawa Kosei, Ochiya Takahiro

    PLOS ONE   15 ( 6 )   e0234613   2020.06( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0234613

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  • Clinical significance of prognostic inflammation-based and/or nutritional markers in patients with stage III gastric cancer Reviewed

    Toyokawa Takahiro, Muguruma Kazuya, Yoshii Mami, Tamura Tatsuro, Sakurai Katsunobu, Kubo Naoshi, Tanaka Hiroaki, Lee Shigeru, Yashiro Masakazu, Ohira Masaichi

    BMC CANCER   20 ( 1 )   517   2020.06

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    DOI: 10.1186/s12885-020-07010-0

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  • Clinical significance of prognostic inflammation-based and/or nutritional markers in patients with stage III gastric cancer. Reviewed

    Toyokawa T, Muguruma K, Yoshii M, Tamura T, Sakurai K, Kubo N, Tanaka H, Lee S, Yashiro M, Ohira M

    BMC cancer   20 ( 1 )   517   2020.06

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    DOI: 10.1186/s12885-020-07010-0

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  • Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma Reviewed

    Tanaka Ryota, Kageyama Ken, Kimura Kenjiro, Eguchi Shinpei, Tauchi Jun, Shinkawa Hiroji, Ohira Go, Yamazoe Sadaaki, Yamamoto Akira, Tanaka Shogo, Amano Ryosuke, Tanaka Hiroaki, Yashiro Masakazu, Kubo Shoji, Ohira Masaichi

    ANTICANCER RESEARCH   40 ( 5 )   2637 - 2644   2020.05( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14234

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  • Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8(+) T Cells in Biliary Tract Cancer Reviewed

    Tanaka Ryota, Kimura Kenjiro, Eguchi Shinpei, Tauchi Jun, Shibutani Masatune, Shinkawa Hiroji, Ohira Go, Yamazoe Sadaaki, Tanaka Shogo, Amano Ryosuke, Tanaka Hiroaki, Yashiro Masakazu, Kubo Shoji, Ohira Masaichi

    ANTICANCER RESEARCH   40 ( 5 )   2881 - 2887   2020.05( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14264

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  • Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma. Reviewed

    Tanaka R, Kageyama K, Kimura K, Eguchi S, Tauchi J, Shinkawa H, Ohira GO, Yamazoe S, Yamamoto A, Tanaka S, Amano R, Tanaka H, Yashiro M, Kubo S, Ohira M

    Anticancer research   40 ( 5 )   2637 - 2644   2020.05( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14234

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  • Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8(+) T Cells in Biliary Tract Cancer. Reviewed

    Tanaka R, Kimura K, Eguchi S, Tauchi J, Shibutani M, Shinkawa H, Ohira GO, Yamazoe S, Tanaka S, Amano R, Tanaka H, Yashiro M, Kubo S, Ohira M

    Anticancer research   40 ( 5 )   2881 - 2887   2020.05( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14264

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  • Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer. Reviewed

    Moyano-Galceran L, Pietilä EA, Turunen SP, Corvigno S, Hjerpe E, Bulanova D, Joneborg U, Alkasalias T, Miki Y, Yashiro M, Chernenko A, Jukonen J, Singh M, Dahlstrand H, Carlson JW, Lehti K

    EMBO molecular medicine   12 ( 4 )   e11177   2020.04( ISSN:1757-4676

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    DOI: 10.15252/emmm.201911177

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  • 症例 横行結腸癌術後Sister Mary Josephʼs noduleの1例 Reviewed

    伊藤 厳太郎, 大澤 尚志, 永原 央, 八代 正和, 大平 雅一

    外科   82 ( 4 )   376 - 380   2020.04( ISSN:0016593X

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    DOI: 10.15106/j_geka82_376

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  • 横行結腸癌術後Sister Mary Joseph&#700;s noduleの1例 Reviewed

    伊藤 厳太郎, 大澤 尚志, 永原 央, 八代 正和, 大平 雅一

    (株)南江堂 外科   82 ( 4 )   376 - 380   2020.04( ISSN:0016-593X

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    79歳女性。横行結腸癌術後10ヵ月目に臍部痛と臍部腫瘍が触知され、精査加療目的で入院となった。所見ではCEAの上昇が認められ、腹部超音波検査では低エコーを示す腫瘍がみられ、転移が疑われた。また、腹部造影CTでは造影効果を示す臍部に皮下組織から腹膜に至る33×32mmの辺縁不整な腫瘍が確認され、PET/CTでは臍部に強い集積が認められた。以上より、本症例は横行結腸癌術後の異時性孤立臍転移と診断され、臍腫瘍切除術が施行された。その結果、臍部痛は消失し、病理組織学的には横行結腸癌術後のSister Mary Joseph's noduleと確定診断された。退院後はUFT/UZELによる化学療法が行われたが、術後7ヵ月より肝転移が出現し、best supportive careへ移行されたものの、肝転移の増大や癌性腹水、悪液質の進行を認め、臍転移切除術後24ヵ月目に死亡となった。

  • 横行結腸癌術後Sister Mary Joseph&#700;s noduleの1例 Reviewed

    伊藤 厳太郎, 大澤 尚志, 永原 央, 八代 正和, 大平 雅一

    外科   82 ( 4 )   376 - 380   2020.04( ISSN:0016-593X

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    79歳女性。横行結腸癌術後10ヵ月目に臍部痛と臍部腫瘍が触知され、精査加療目的で入院となった。所見ではCEAの上昇が認められ、腹部超音波検査では低エコーを示す腫瘍がみられ、転移が疑われた。また、腹部造影CTでは造影効果を示す臍部に皮下組織から腹膜に至る33×32mmの辺縁不整な腫瘍が確認され、PET/CTでは臍部に強い集積が認められた。以上より、本症例は横行結腸癌術後の異時性孤立臍転移と診断され、臍腫瘍切除術が施行された。その結果、臍部痛は消失し、病理組織学的には横行結腸癌術後のSister Mary Joseph's noduleと確定診断された。退院後はUFT/UZELによる化学療法が行われたが、術後7ヵ月より肝転移が出現し、best supportive careへ移行されたものの、肝転移の増大や癌性腹水、悪液質の進行を認め、臍転移切除術後24ヵ月目に死亡となった。

  • Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer. Reviewed

    Moyano-Galceran L, Pietilä EA, Turunen SP, Corvigno S, Hjerpe E, Bulanova D, Joneborg U, Alkasalias T, Miki Y, Yashiro M, Chernenko A, Jukonen J, Singh M, Dahlstrand H, Carlson JW, Lehti K

    EMBO molecular medicine   e11177   2020.03( ISSN:1757-4676

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    DOI: 10.15252/emmm.201911177

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  • スキルス胃癌細胞由来の細胞外小胞は癌関連線維芽細胞の増殖を促進する(Exosomes from Scirrhous Gastric Cancer Cells promote proliferation of Cancer-associated Fibroblasts) Reviewed

    杉本 敦史, 八代 正和, 奥野 倫久, 三木 友一郎, 山本 百合恵, 瀬良 知央, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 田中 涼太, 栂野 真吾, 大平 雅一

    日本胃癌学会総会記事   92回   270 - 270   2020.03

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  • 胃癌におけるCXCR2リガンドファミリー発現の臨床学的意義(The Clinicopathological Significance of CXCR2 Ligands in Gastric Cancer) Reviewed

    山本 百合恵, 八代 正和, 瀬良 知央, 櫛谷 友佳子, 杉本 敦史, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 栂野 真吾, 奥野 倫久, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本胃癌学会総会記事   92回   269 - 269   2020.03

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  • Expansion part of phase I study of E7090 in patients with cholangiocarcinoma harboring FGFR2 gene fusion and with gastric cancer harboring FGFR2 gene amplification or FGFR2 protein high expression Reviewed

    Morizane Chigusa, Ueno Makoto, Ioka Tatsuya, Tajika Masahiro, Ikeda Masafumi, Yamaguchi Kensei, Hara Hiroki, Yabusaki Hiroshi, Miyamoto Atsushi, Iwasa Satoru, Muto Manabu, Takashima Tsutomu, Minashi Keiko, Komatsu Yoshito, Nishina Tomohiro, Nakajima Takako Eguchi, Sahara Takatoshi, Funasaka Setsuo, Yashiro Masakazu, Furuse Junji

    JOURNAL OF CLINICAL ONCOLOGY   38 ( 4 )   2020.02( ISSN:0732-183X

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  • A Giant Gastric Gastrointestinal Stromal Tumor Successfully Resected Following Neoadjuvant Treatment With Imatinib Mesylate. Reviewed

    Takahashi R, Toyokawa T, Yoshii M, Tamura T, Tanaka H, Lee S, Muguruma K, Yashiro M, Ohira M

    Anticancer research   40 ( 2 )   1147 - 1152   2020.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14056

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  • Generation of Rat Monoclonal Antibodies Specific for Human Stromal Cell-Derived Factor-2. Reviewed

    Tanaka M, Shiota M, Koyama M, Nakayama J, Yashiro M, Semba K, Goda N

    Monoclonal antibodies in immunodiagnosis and immunotherapy   39 ( 1 )   23 - 26   2020.02

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    DOI: 10.1089/mab.2019.0043

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  • Generation of Rat Monoclonal Antibodies Specific for Human Stromal Cell-Derived Factor-2. Reviewed

    Tanaka M, Shiota M, Koyama M, Nakayama J, Yashiro M, Semba K, Goda N

    Monoclonal antibodies in immunodiagnosis and immunotherapy   39 ( 1 )   23 - 26   2020.02

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    DOI: 10.1089/mab.2019.0043

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  • A Giant Gastric Gastrointestinal Stromal Tumor Successfully Resected Following Neoadjuvant Treatment With Imatinib Mesylate. Reviewed

    Takahashi R, Toyokawa T, Yoshii M, Tamura T, Tanaka H, Lee S, Muguruma K, Yashiro M, Ohira M

    Anticancer research   40 ( 2 )   1147 - 1152   2020.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.14056

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  • Precision medicine for gastrointestinal cancer: Recent progress and future perspective. Reviewed

    Matsuoka T, Yashiro M

    World journal of gastrointestinal oncology   12 ( 1 )   1 - 20   2020.01

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    DOI: 10.4251/wjgo.v12.i1.1

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  • Precision medicine for gastrointestinal cancer: Recent progress and future perspective. Reviewed

    Matsuoka T, Yashiro M

    World journal of gastrointestinal oncology   12 ( 1 )   1 - 20   2020.01( ISSN:1948-5204

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    DOI: 10.4251/wjgo.v12.i1.1

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  • Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways Reviewed

    Moro Hiroshi, Hattori Naoko, Nakamura Yoshiaki, Kimura Kana, Imai Toshio, Maeda Masahiro, Yashiro Masakazu, Ushijima Toshikazu

    GASTRIC CANCER   23 ( 1 )   105 - 115   2020.01( ISSN:1436-3291

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    DOI: 10.1007/s10120-019-01010-1

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  • Gastric cancer cells alter the immunosuppressive function of neutrophils Reviewed

    Hiramatsu Soichiro, Tanaka Hiroaki, Nishimura Junya, Yamakoshi Yoshihito, Sakimura Chie, Tamura Tatsuro, Toyokawa Takahiro, Muguruma Kazuya, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    ONCOLOGY REPORTS   43 ( 1 )   251 - 259   2020.01( ISSN:1021-335X

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    DOI: 10.3892/or.2019.7410

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  • Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways(和訳中) Reviewed

    Moro Hiroshi, Hattori Naoko, Nakamura Yoshiaki, Kimura Kana, Imai Toshio, Maeda Masahiro, Yashiro Masakazu, Ushijima Toshikazu

    シュプリンガー・ジャパン(株) Gastric Cancer   23 ( 1 )   105 - 115   2020.01( ISSN:1436-3291

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  • Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways (vol 12, pg 289, 2019) Reviewed

    Moro Hiroshi, Hattori Naoko, Nakamura Yoshiaki, Kimura Kana, Imai Toshio, Maeda Masahiro, Yashiro Masakazu, Ushijima Toshikazu

    GASTRIC CANCER   23 ( 1 )   116 - 117   2020.01( ISSN:1436-3291

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    DOI: 10.1007/s10120-019-01013-y

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  • Gastric cancer cells alter the immunosuppressive function of neutrophils. Reviewed

    Hiramatsu S, Tanaka H, Nishimura J, Yamakoshi Y, Sakimura C, Tamura T, Toyokawa T, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Oncology reports   43 ( 1 )   251 - 259   2020.01( ISSN:1021-335X

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    DOI: 10.3892/or.2019.7410

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  • Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways. Reviewed

    Moro H, Hattori N, Nakamura Y, Kimura K, Imai T, Maeda M, Yashiro M, Ushijima T

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   23 ( 1 )   105 - 115   2020.01( ISSN:1436-3291

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    DOI: 10.1007/s10120-019-01010-1

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  • Correction to: Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways. Reviewed

    Moro H, Hattori N, Nakamura Y, Kimura K, Imai T, Maeda M, Yashiro M, Ushijima T

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   23 ( 1 )   116 - 117   2020.01( ISSN:1436-3291

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    DOI: 10.1007/s10120-019-01013-y

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  • エピジェネティックなプライミングにより胃癌細胞は複数の経路を回復させそのことでイリノテカンおよびシスプラチンに対し感受性を示すようになる(Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways) Reviewed

    Moro Hiroshi, Hattori Naoko, Nakamura Yoshiaki, Kimura Kana, Imai Toshio, Maeda Masahiro, Yashiro Masakazu, Ushijima Toshikazu

    Gastric Cancer   23 ( 1 )   105 - 115   2020.01( ISSN:1436-3291

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    DNA脱メチル化剤である5-アザ-2'-デオキシシチジン(5-aza-dC)を胃癌細胞に作用させることで、臨床的に用いられている細胞毒性剤に対する感受性が付与されるか解析した。各種の胃癌細胞株を対象に、感受性試験を行った結果、SN38(イリノテカンの活性型代謝産物)、シスプラチン、パクリタキセル、5-FUのそれぞれに耐性を示す胃癌細胞株を同定した。それらの耐性細胞株を5-aza-dCで72時間処理してその増殖を評価したところ、SN38耐性株とシスプラチン耐性株では50%阻害濃度(IC50)が低下したが、パクリタキセル耐性株と5-FU耐性株では低下しなかった。5-aza-dCでの前処理によってアポトーシス関連遺伝子類が再活性化され、そのうちの2種の遺伝子ではプロモーター領域のCpGアイランドのDNAが脱メチル化されたことが確かめられた。SN38耐性胃癌細胞株を皮下異種移植したマウスモデルをイリノテカンで治療する実験系において、イリノテカン治療前に5-aza-dCを腹腔内投与したところ腫瘍抑制効果は著明に亢進した。5-aza-dCを用いてエピジェネティックにプライミングを行えば、胃癌細胞のSN38およびシスプラチンへの感受性を向上させられることが明らかになった。

  • Microscopic distance from tumor invasion front to serosa might be a useful predictive factor for peritoneal recurrence after curative resection of T3-gastric cancer. Reviewed

    Togano S, Yashiro M, Miki Y, Yamamato Y, Sera T, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Kuroda K, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Tanaka S, Ohira M

    PloS one   15 ( 1 )   e0225958   2020

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    DOI: 10.1371/journal.pone.0225958

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  • Correction: Microscopic distance from tumor invasion front to serosa might be a useful predictive factor for peritoneal recurrence after curative resection of T3-gastric cancer. Reviewed

    Togano S, Yashiro M, Miki Y, Yamamoto Y, Sera T, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Kuroda K, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Tanaka S, Ohira M

    PloS one   15 ( 5 )   e0233743   2020

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    DOI: 10.1371/journal.pone.0233743

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  • Microscopic distance from tumor invasion front to serosa might be a useful predictive factor for peritoneal recurrence after curative resection of T3-gastric cancer. Reviewed

    Togano S, Yashiro M, Miki Y, Yamamoto Y, Sera T, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Kuroda K, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Tanaka S, Ohira M

    PloS one   15 ( 1 )   e0225958   2020

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    DOI: 10.1371/journal.pone.0225958

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  • Cancer cells with high-metastatic potential promote a glycolytic shift in activated fibroblasts. Reviewed

    Kogure A, Naito Y, Yamamoto Y, Yashiro M, Kiyono T, Yanagihara K, Hirakawa K, Ochiya T

    PloS one   15 ( 6 )   e0234613   2020

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    DOI: 10.1371/journal.pone.0234613

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  • Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer. Reviewed

    Miki Y, Yashiro M, Moyano-Galceran L, Sugimoto A, Ohira M, Lehti K

    Frontiers in oncology   10   568557   2020( ISSN:2234-943X

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    DOI: 10.3389/fonc.2020.568557

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  • Correction: Microscopic distance from tumor invasion front to serosa might be a useful predictive factor for peritoneal recurrence after curative resection of T3-gastric cancer. Reviewed

    Shingo Togano, Masakazu Yashiro, Yuichiro Miki, Yurie Yamamoto, Tomohiro Sera, Yukako Kushitani, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Kenji Kuroda, Tomohisa Okuno, Mami Yoshii, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Sayaka Tanaka, Masaichi Ohira

    PloS one   15 ( 5 )   e0233743   2020

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    [This corrects the article DOI: 10.1371/journal.pone.0225958.].

    DOI: 10.1371/journal.pone.0233743

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  • The Clinicopathological Significance of the CXCR2 Ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in Gastric Cancer. Reviewed

    Yamamoto Y, Kuroda K, Sera T, Sugimoto A, Kushiyama S, Nishimura S, Togano S, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M, Yashiro M

    Anticancer research   39 ( 12 )   6645 - 6652   2019.12( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13879

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  • The Clinicopathological Significance of the CXCR2 Ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in Gastric Cancer. Reviewed

    Yamamoto Y, Kuroda K, Sera T, Sugimoto A, Kushiyama S, Nishimura S, Togano S, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M, Yashiro M

    Anticancer research   39 ( 12 )   6645 - 6652   2019.12( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13879

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  • High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 Reviewed

    Kasurinen Aaro, Gramolelli Silvia, Hagstrom Jaana, Laitinen Alli, Kokkola Arto, Miki Yuichiro, Lehti Kaisa, Yashiro Masakazu, Ojala Paivi M., Bockelman Camilla, Haglund Caj

    CANCER MEDICINE   8 ( 16 )   6995 - 7005   2019.11( ISSN:2045-7634

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    DOI: 10.1002/cam4.2576

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  • High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1. Reviewed

    Kasurinen A, Gramolelli S, Hagström J, Laitinen A, Kokkola A, Miki Y, Lehti K, Yashiro M, Ojala PM, Böckelman C, Haglund C

    Cancer medicine   8 ( 16 )   6995 - 7005   2019.11

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    DOI: 10.1002/cam4.2576

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  • T3胃癌におけるE-cadherinおよび癌先進部漿膜間距離と腹膜播種再発との関連性 Reviewed

    栂野 真吾, 八代 正和, 黒田 顕慈, 奥野 倫久, 西村 貞徳, 櫛山 周平, 三木 友一朗, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本癌治療学会学術集会抄録集   57回   P11 - 7   2019.10

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  • 胃癌におけるFibroblast Growth Factor Receptor 2発現の臨床病理学的意義 Reviewed

    黒田 顕慈, 八代 正和, 増田 剛, 杉本 敦史, 瀬良 知央, 櫛谷 友佳子, 櫛山 周平, 西村 貞徳, 栂野 真吾, 奥野 倫久, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本癌治療学会学術集会抄録集   57回   O6 - 4   2019.10

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  • Feasibility of Identifying Patients at High Risk of Hereditary Gastric Cancer Based on Clinicopathological Variables Reviewed

    Nishimura Sadaaki, Yashiro Masakazu, Sera Tomohiro, Yamamoto Yurie, Kushitani Yukako, Sugimoto Atsushi, Kushiyama Shuhei, Kuroda Kenji, Togano Shingo, Okuno Tomohisa, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    ANTICANCER RESEARCH   39 ( 9 )   5057 - 5064   2019.09( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13698

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  • Feasibility of Identifying Patients at High Risk of Hereditary Gastric Cancer Based on Clinicopathological Variables. Reviewed

    Nishimura S, Yashiro M, Sera T, Yamamoto Y, Kushitani Y, Sugimoto A, Kushiyama S, Kuroda K, Togano S, Okuno T, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Hirakawa K, Ohira M

    Anticancer research   39 ( 9 )   5057 - 5064   2019.09( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13698

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  • スキルス胃癌と癌関連線維芽細胞の相互作用(Heterogeneous interactions between scirrhous gastric cancer cells and cancer-associated fibroblasts) Reviewed

    櫛山 周平, 八代 正和, 山本 百合恵, 黒田 顕慈, 栂野 真吾, 西村 貞徳, 櫛谷 友佳子, 杉本 敦史, 瀬良 知央, 大平 雅一

    日本癌学会総会記事   78回   P - 2286   2019.09( ISSN:0546-0476

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  • 胃癌間質におけるThrombospondin 4発現の臨床病理学的検討(Clinicopathological Significance of Thrombospondin 4 Expression in Gastric Cancer Stroma) Reviewed

    黒田 顕慈, 八代 正和, 栂野 真吾, 櫛山 周平, 西村 貞徳, 杉本 敦史, 瀬良 知央, 櫛谷 友佳子, 山本 百合恵, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本癌学会総会記事   78回   P - 1113   2019.09( ISSN:0546-0476

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  • ストレス下における胃癌幹細胞とオートファジーの関連性(The correlation between gastric cancer stem cells under stress and autophagy system) Reviewed

    栂野 真吾, 八代 正和, 増田 剛, 山本 百合恵, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 奥野 倫久, 三木 友一朗, 平川 弘聖, 大平 雅一

    日本癌学会総会記事   78回   P - 3262   2019.09( ISSN:0546-0476

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  • スキルス胃癌におけるマルチプレックス遺伝子パネル検査の有用性(Feasibility of multiplex gene panel testing to scirrhous gastric cancer) Reviewed

    西村 貞徳, 八代 正和, 瀬良 知央, 櫛谷 友佳子, 杉本 敦史, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 大平 雅一

    日本癌学会総会記事   78回   J - 2030   2019.09( ISSN:0546-0476

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  • Induction of Trop-2 expression through the binding of galectin-3 to MUC1 Reviewed

    Yamashita Tomoko, Mori Yugo, Alzaaqi Shouq M., Yashiro Masakazu, Sawada Tetsuji, Hirakawa Kosei, Nakada Hiroshi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   516 ( 1 )   44 - 49   2019.08( ISSN:0006-291X

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    DOI: 10.1016/j.bbrc.2019.06.003

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  • Induction of Trop-2 expression through the binding of galectin-3 to MUC1. Reviewed

    Yamashita T, Mori Y, Alzaaqi SM, Yashiro M, Sawada T, Hirakawa K, Nakada H

    Biochemical and biophysical research communications   516 ( 1 )   44 - 49   2019.08( ISSN:0006-291X

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    DOI: 10.1016/j.bbrc.2019.06.003

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  • 症例 腹腔鏡下胆囊摘出術中に胆囊底部に認めた異所性肝の1例 Reviewed

    伊藤 厳太郎, 八代 正和, 山添 定明, 木村 健二郎, 天野 良亮, 大平 雅一

    外科   81 ( 9 )   999 - 1002   2019.08( ISSN:0016593X

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    DOI: 10.15106/j_geka81_999

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  • [A Case of Lymph Node Recurrence Seven Years after Curative Esophagectomy for T1a(LPM)Upper Thoracic Esophageal Cancer]. Reviewed

    Sasaki M, Tamura T, Toyokawa T, Sakurai K, Amano R, Kubo N, Tanaka H, Muguruma K, Yashiro M, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 8 )   1295 - 1297   2019.08( ISSN:0385-0684

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    PubMed

  • Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines Reviewed

    Sai Eirin, Miwa Yoshiyuki, Takeyama Reina, Kojima Shinya, Ueno Toshihide, Yashiro Masakazu, Seto Yasuyuki, Mano Hiroyuki

    CANCER SCIENCE   110 ( 8 )   2643 - 2651   2019.08( ISSN:1347-9032

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    DOI: 10.1111/cas.14111

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  • スキルス胃癌細胞株における発癌ドライバー遺伝子の候補の同定(Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines) Reviewed

    Sai Eirin, Miwa Yoshiyuki, Takeyama Reina, Kojima Shinya, Ueno Toshihide, Yashiro Masakazu, Seto Yasuyuki, Mano Hiroyuki

    John Wiley & Sons Australia, Ltd Cancer Science   110 ( 8 )   2643 - 2651   2019.08( ISSN:1347-9032

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    確立したスキルス胃癌細胞株2種に対し全エクソーム配列解析とRNA配列解析とを施行することでスキルス胃癌の発癌ドライバー遺伝子の新規候補を検索することを試みた。両細胞株で発見された突然変異の大部分は未報告のものであった。片方の細胞株ではCD44遺伝子とIGF1R遺伝子の新規融合遺伝子が発見され、ゲノム内でCD44遺伝子とIGF1R遺伝子とが著明に増幅され豊富に発現していた。さらに同融合遺伝子は形質転換能を有することが細胞株を用いたフォーカス形成アッセイとマウスでの腫瘍形成アッセイで示された。もう片方の細胞株はゲノム中に複数の発癌イベントを所有していると思われる所見が得られ、中でも新規に見出されたBORCS5-ETV6融合遺伝子は発癌活性を有することが明らかになった。これらの新規融合遺伝子が実際のスキルス胃癌でも出現しているのかはこれから検討する必要があるものの、スキルス胃癌の詳細なゲノム解析を行うための被検物として細胞株は重要であることが確認された。

  • 腹腔鏡下胆嚢摘出術中に胆嚢底部に認めた異所性肝の1例 Reviewed

    伊藤 厳太郎, 八代 正和, 山添 定明, 木村 健二郎, 天野 良亮, 大平 雅一

    (株)南江堂 外科   81 ( 9 )   999 - 1002   2019.08( ISSN:0016-593X

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    69歳女性。近医より心窩部痛の精査目的で当院へ紹介となった。腹部CTおよび超音波所見より胆嚢結石と診断され、腹腔鏡下胆嚢摘出術を施行したところ、胆嚢底部に付着する約15mmの結節を認めたため胆嚢とともに切除した。病理組織学的に胆嚢底部に生じた異所性肝と診断され、術後は経過良好で術後7日目に退院となった。

  • 根治術後7年目に左鎖骨上リンパ節再発を来した胸部食道T1a(LPM)癌の1例 Reviewed

    佐々木 麻帆, 田村 達郎, 豊川 貴弘, 櫻井 克宣, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 八代 正和, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   46 ( 8 )   1295 - 1297   2019.08( ISSN:0385-0684

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    食道癌根治手術後の再発は28〜47%、その約85%が2年以内の早期に認められ、再発診断時からの生存期間中央値は5〜10ヵ月と極めて不良である。一方、壁深達度T1a(MM)、T1b(SM1)の症例でのリンパ節転移は10〜20%であることが知られており多くは手術治療が行われるが、T1a(LPM)ではリンパ節転移の頻度は極めてまれである。今回われわれは、pT1a(LPM)の食道癌根治術後7年という長期経過後に左鎖骨上リンパ節(No.104L)に再発したまれな症例を経験したので文献的考察を加えて報告する。(著者抄録)

  • Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines. Reviewed

    Sai E, Miwa Y, Takeyama R, Kojima S, Ueno T, Yashiro M, Seto Y, Mano H

    Cancer science   110 ( 8 )   2643 - 2651   2019.08( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.14111

    PubMed

  • [A Case of Lymph Node Recurrence Seven Years after Curative Esophagectomy for T1a(LPM)Upper Thoracic Esophageal Cancer]. Reviewed

    Sasaki M, Tamura T, Toyokawa T, Sakurai K, Amano R, Kubo N, Tanaka H, Muguruma K, Yashiro M, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 8 )   1295 - 1297   2019.08( ISSN:0385-0684

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • スキルス胃癌細胞株における発癌ドライバー遺伝子の候補の同定(Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines) Reviewed

    Sai Eirin, Miwa Yoshiyuki, Takeyama Reina, Kojima Shinya, Ueno Toshihide, Yashiro Masakazu, Seto Yasuyuki, Mano Hiroyuki

    Cancer Science   110 ( 8 )   2643 - 2651   2019.08( ISSN:1347-9032

     More details

    Publishing type:Research paper (scientific journal)  

    確立したスキルス胃癌細胞株2種に対し全エクソーム配列解析とRNA配列解析とを施行することでスキルス胃癌の発癌ドライバー遺伝子の新規候補を検索することを試みた。両細胞株で発見された突然変異の大部分は未報告のものであった。片方の細胞株ではCD44遺伝子とIGF1R遺伝子の新規融合遺伝子が発見され、ゲノム内でCD44遺伝子とIGF1R遺伝子とが著明に増幅され豊富に発現していた。さらに同融合遺伝子は形質転換能を有することが細胞株を用いたフォーカス形成アッセイとマウスでの腫瘍形成アッセイで示された。もう片方の細胞株はゲノム中に複数の発癌イベントを所有していると思われる所見が得られ、中でも新規に見出されたBORCS5-ETV6融合遺伝子は発癌活性を有することが明らかになった。これらの新規融合遺伝子が実際のスキルス胃癌でも出現しているのかはこれから検討する必要があるものの、スキルス胃癌の詳細なゲノム解析を行うための被検物として細胞株は重要であることが確認された。

  • 腹腔鏡下胆嚢摘出術中に胆嚢底部に認めた異所性肝の1例 Reviewed

    伊藤 厳太郎, 八代 正和, 山添 定明, 木村 健二郎, 天野 良亮, 大平 雅一

    外科   81 ( 9 )   999 - 1002   2019.08( ISSN:0016-593X

     More details

    Publishing type:Research paper (scientific journal)  

    69歳女性。近医より心窩部痛の精査目的で当院へ紹介となった。腹部CTおよび超音波所見より胆嚢結石と診断され、腹腔鏡下胆嚢摘出術を施行したところ、胆嚢底部に付着する約15mmの結節を認めたため胆嚢とともに切除した。病理組織学的に胆嚢底部に生じた異所性肝と診断され、術後は経過良好で術後7日目に退院となった。

  • 根治術後7年目に左鎖骨上リンパ節再発を来した胸部食道T1a(LPM)癌の1例 Reviewed

    佐々木 麻帆, 田村 達郎, 豊川 貴弘, 櫻井 克宣, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 八代 正和, 大平 雅一

    癌と化学療法   46 ( 8 )   1295 - 1297   2019.08( ISSN:0385-0684

     More details

    Publishing type:Research paper (scientific journal)  

    食道癌根治手術後の再発は28~47%、その約85%が2年以内の早期に認められ、再発診断時からの生存期間中央値は5~10ヵ月と極めて不良である。一方、壁深達度T1a(MM)、T1b(SM1)の症例でのリンパ節転移は10~20%であることが知られており多くは手術治療が行われるが、T1a(LPM)ではリンパ節転移の頻度は極めてまれである。今回われわれは、pT1a(LPM)の食道癌根治術後7年という長期経過後に左鎖骨上リンパ節(No.104L)に再発したまれな症例を経験したので文献的考察を加えて報告する。(著者抄録)

  • Cancer extracellular vesicles contribute to stromal heterogeneity by inducing chemokines in cancer-associated fibroblasts Reviewed

    Naito Yutaka, Yamamoto Yusuke, Sakamoto Naoya, Shimomura Iwao, Kogure Akiko, Kumazaki Minami, Yokoi Akira, Yashiro Masakazu, Kiyono Tohru, Yanagihara Kazuyoshi, Takahashi Ryou-u, Hirakawa Kosei, Yasui Wataru, Ochiya Takahiro

    ONCOGENE   38 ( 28 )   5566 - 5579   2019.07( ISSN:0950-9232

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    DOI: 10.1038/s41388-019-0832-4

    PubMed

  • Bone marrow-derived stromal cells in the tumor microenvironment might be associated with the progression of gastric cancer Reviewed

    Yashiro Masakazu, Kasashima Hiroaki, Kushiyama Syuhei, Nishimura Sadaaki, Kuroda Kenji, Togano Shingo, Okuno Tomohisa, Miki Yuichiro, Fukuoka Tatsunari, Nakamae Hirohisa, Hino Masayuki, Ohira Masaichi

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2019-2742

  • A factor (> MR 30 kDa) from cancer-associated fibroblasts may stimulate the progression of schirrous gastric cancer without FGFR2 overexpression Reviewed

    Kushiyama Syuhei, Yashiro Masakazu, Okuno Tomohisa, Kuroda Kenji, Tanaka Ryota, Togano Shingo, Nishimura Sadaaki, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2019-2045

  • Effect of cancer-associated fibroblasts on lymphatic vessel formation in malignant melanoma Reviewed

    Maeda Shusaku, Yashiro Masakazu, Motomura Hisashi, Hatano Takaharu, Fujikawa Heishiro

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2019-3763

  • Extracellular vesicles from scirrhous gastric cancer cells induce premetastatic niche formation for peritoneal metastasis Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Kushiyama Shuhei, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.SABCS18-5160

  • p53 expression is a useful predictive marker for recurrence of meningioma Reviewed

    Nagahama Atsufumi, Yashiro Masakazu, Miki Yuichiro, Morisako Hiroki, Uda Takehiro, Goto Takeo, Takami Takehiro, Ohata Kenji

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2019-4901

  • Macrophage Inflammatory Protein-3 beta (MIP-3 beta) from cancer-associated fibroblasts promote the proliferation of melanoma cells Reviewed

    Fujikawa Heishiro, Yashiro Masakazu, Hatano Takaharu, Maeda Shusaku, Motomura Hisashi

    CANCER RESEARCH   79 ( 13 )   2019.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2019-2037

  • Long-term survival estimates in older patients with pathological stage I gastric cancer undergoing gastrectomy: Duocentric analysis of simplified scoring system Reviewed

    Sakurai Katsunobu, Kubo Naoshi, Tamamori Yutaka, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Nishiguchi Yukio, Hirakawa Kosei, Ohira Masaichi

    JOURNAL OF GERIATRIC ONCOLOGY   10 ( 4 )   604 - 609   2019.07( ISSN:1879-4068

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    DOI: 10.1016/j.jgo.2019.01.003

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  • Long-term survival estimates in older patients with pathological stage I gastric cancer undergoing gastrectomy: Duocentric analysis of simplified scoring system. Reviewed

    Sakurai K, Kubo N, Tamamori Y, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Yashiro M, Maeda K, Nishiguchi Y, Hirakawa K, Ohira M

    Journal of geriatric oncology   10 ( 4 )   604 - 609   2019.07( ISSN:1879-4068

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    DOI: 10.1016/j.jgo.2019.01.003

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  • Cancer extracellular vesicles contribute to stromal heterogeneity by inducing chemokines in cancer-associated fibroblasts. Reviewed

    Naito Y, Yamamoto Y, Sakamoto N, Shimomura I, Kogure A, Kumazaki M, Yokoi A, Yashiro M, Kiyono T, Yanagihara K, Takahashi RU, Hirakawa K, Yasui W, Ochiya T

    Oncogene   38 ( 28 )   5566 - 5579   2019.07( ISSN:0950-9232

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    DOI: 10.1038/s41388-019-0832-4

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  • スキルス胃癌の増殖進展における癌細胞-間質線維芽細胞の相互作用に関わる新規シグナルの解析 Reviewed

    櫛山 周平, 八代 正和, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 福岡 達成, 大平 雅一

    日本消化器外科学会総会   74回   RS20 - 2   2019.07

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  • 胆道癌および膵癌における癌関連線維芽細胞の癌進展に及ぼす影響について Reviewed

    田中 涼太, 木村 健二郎, 天野 良亮, 山添 定明, 大平 豪, 田内 潤, 西村 貞徳, 田中 浩明, 八代 正和, 大平 雅一

    日本消化器外科学会総会   74回   P200 - 2   2019.07

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  • 胃癌におけるFGFR2陽性循環癌細胞(CTCs)測定の意義 Reviewed

    黒田 顕慈, 八代 正和, 三木 友一朗, 櫛山 周平, 西村 貞徳, 栂野 真吾, 奥野 倫久, 田中 浩明, 六車 一哉, 大平 雅一

    日本消化器外科学会総会   74回   P66 - 5   2019.07

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  • 癌ゲノム医療の二次的所見を推察する家族性胃癌の臨床病理学的特徴の検討 Reviewed

    西村 貞徳, 八代 正和, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本消化器外科学会総会   74回   P68 - 7   2019.07

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  • 潜在型TGF-βは、胃癌患者における有望な予後良好のバイオマーカーとなりうる Reviewed

    栂野 真吾, 八代 正和, 櫛山 周平, 西村 貞徳, 黒田 顕慈, 奥野 倫久, 三木 友一朗, 村上 善基, 大平 雅一

    日本消化器外科学会総会   74回   P68 - 5   2019.07

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  • スキルス胃癌細胞の産生するextracellular vesiclesは腹膜中皮細胞の形態を制御し腹膜転移に関与する Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 大平 雅一

    日本消化器外科学会総会   74回   O48 - 8   2019.07

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  • Postoperative Inflammation Is an Independent Prognostic Factor in Patients With Thoracic Esophageal Squamous Cell Carcinoma Reviewed

    Toyokawa Takahiro, Tamura Tatsuro, Sakurai Katsunobu, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi

    ANTICANCER RESEARCH   39 ( 6 )   2777 - 2784   2019.06( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13404

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  • Postoperative Inflammation Is an Independent Prognostic Factor in Patients With Thoracic Esophageal Squamous Cell Carcinoma. Reviewed

    Toyokawa T, Tamura T, Sakurai K, Kubo N, Tanaka H, Muguruma K, Yashiro M, Ohira M

    Anticancer research   39 ( 6 )   2777 - 2784   2019.06( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13404

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  • [Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer]. Reviewed

    Tsujio G, Toyokawa T, Fukuoka T, Tamura T, Ohira G, Shibutani M, Yamazoe S, Nagahara H, Kimura K, Amano R, Tanaka H, Muguruma K, Yashiro M, Maeda K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 5 )   895 - 899   2019.05( ISSN:0385-0684

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    PubMed

  • 切除不能進行・再発胃癌に対するPaclitaxel+Ramucirumab療法の治療成績 Reviewed

    辻尾 元, 豊川 貴弘, 福岡 達成, 田村 達郎, 大平 豪, 渋谷 雅常, 山添 定明, 永原 央, 木村 健二郎, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 前田 清, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   46 ( 5 )   895 - 899   2019.05( ISSN:0385-0684

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    進行・再発胃癌に対する二次以降の化学療法として施行したpaclitaxel(PTX)+ramucirumab(RAM)療法(PTX 80mg/m2、day 1、8、15、RAM 8mg/kg、day 1、15)の安全性および有効性について検討した。対象は当科でPTX+RAM療法を施行した進行・再発胃癌33例で、年齢中央値は68歳、PS2以上の症例は5例であった。投与コース数の中央値は4コースで、Grade 3以上の有害事象は28例(85%)[白血球・好中球減少21例(64%)、末梢神経障害3例(9%)など]に認められた。抗腫瘍効果は奏効率14.8%、病勢コントロール率66.7%であり、全生存期間および無増悪生存期間中央値はそれぞれ9.3ヵ月、4.7ヵ月であった。切除不能進行・再発胃癌に対するPTX+RAM療法は一定の効果が期待できるが、実地臨床においては高齢かつPSの悪い症例に対して使用することも多く、慎重なマネージメントが必要である。(著者抄録)

  • [Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer]. Reviewed

    Tsujio G, Toyokawa T, Fukuoka T, Tamura T, Ohira G, Shibutani M, Yamazoe S, Nagahara H, Kimura K, Amano R, Tanaka H, Muguruma K, Yashiro M, Maeda K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 5 )   895 - 899   2019.05( ISSN:0385-0684

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    PubMed

  • 切除不能進行・再発胃癌に対するPaclitaxel+Ramucirumab療法の治療成績 Reviewed

    辻尾 元, 豊川 貴弘, 福岡 達成, 田村 達郎, 大平 豪, 渋谷 雅常, 山添 定明, 永原 央, 木村 健二郎, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 前田 清, 平川 弘聖, 大平 雅一

    癌と化学療法   46 ( 5 )   895 - 899   2019.05( ISSN:0385-0684

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    進行・再発胃癌に対する二次以降の化学療法として施行したpaclitaxel(PTX)+ramucirumab(RAM)療法(PTX 80mg/m2、day 1、8、15、RAM 8mg/kg、day 1、15)の安全性および有効性について検討した。対象は当科でPTX+RAM療法を施行した進行・再発胃癌33例で、年齢中央値は68歳、PS2以上の症例は5例であった。投与コース数の中央値は4コースで、Grade 3以上の有害事象は28例(85%)[白血球・好中球減少21例(64%)、末梢神経障害3例(9%)など]に認められた。抗腫瘍効果は奏効率14.8%、病勢コントロール率66.7%であり、全生存期間および無増悪生存期間中央値はそれぞれ9.3ヵ月、4.7ヵ月であった。切除不能進行・再発胃癌に対するPTX+RAM療法は一定の効果が期待できるが、実地臨床においては高齢かつPSの悪い症例に対して使用することも多く、慎重なマネージメントが必要である。(著者抄録)

  • 食道癌患者の食道切除後の手術成績に対するGeriatric Nutritional Risk Indexの影響(The impact of geriatric nutritional risk index on surgical outcomes after esophagectomy in patients with esophageal cancer) Reviewed

    Kubo Naoshi, Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi

    シュプリンガー・ジャパン(株) Esophagus   16 ( 2 )   147 - 154   2019.04( ISSN:1612-9059

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    食道扁平上皮癌(ESCC)患者におけるGeriatric Nutritional Risk Index(GNRI)と短期・長期手術成績との関連を調査した。2000〜2012年に当施設で外科的切除後に組織学的にESCCを確認した患者240例(男性196例、女性44例、平均63.4歳)を後ろ向きに調査した。全例が2〜3領域リンパ節郭清と併用して根治的食道切除術を受けた。GNRIのカットオフ値を92として、GNRI<92の低GNRI群44例とGNRI≧92の高GNRI群196例に分けた。リンパ節転移率と病理学的病期は高GNRI群よりも低GNRI群の方が有意に高かった。肺合併症の割合は高GNRI群よりも低GNRI群の方が有意に高かったが、多変量解析ではGNRIは肺合併症発症に対する独立危険因子ではなかった。5年全生存率は高GNRI群よりも低GNRI群の方が有意に低かった。GNRIは全生存率に対する独立予後因子であったが、癌特異的生存率(CSS)は予後因子ではなかった。腫瘍病期の階層化による解析では、全生存率、CSSともに病期III ESCC患者で高GNRI群よりも低GNRI群の方が悪化した。病期III ESCCでは原発腫瘍サイズは高GNRI群よりも低GNRI群の方が大きい傾向にあり、術前嚥下障害の発生率は高GNRI群よりも低GNRI群の方が有意に高かった。

  • Establishment of a New Scirrhous Gastric Cancer Cell Line with FGFR2 Overexpression, OCUM-14 Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Masuda Go, Togano Shingo, Kuroda Kenji, Miki Yuichiro, Hirakawa Kosei, Ohsawa Masahiko, Wanibuchi Hideki, Ohira Masaichi

    ANNALS OF SURGICAL ONCOLOGY   26 ( 4 )   1093 - 1102   2019.04( ISSN:1068-9265

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    DOI: 10.1245/s10434-018-07145-2

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  • The impact of geriatric nutritional risk index on surgical outcomes after esophagectomy in patients with esophageal cancer Reviewed

    Kubo Naoshi, Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi

    ESOPHAGUS   16 ( 2 )   147 - 154   2019.04( ISSN:1612-9059

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    DOI: 10.1007/s10388-018-0644-6

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  • Establishment of a New Scirrhous Gastric Cancer Cell Line with FGFR2 Overexpression, OCUM-14. Reviewed

    Okuno T, Yashiro M, Masuda G, Togano S, Kuroda K, Miki Y, Hirakawa K, Ohsawa M, Wanibuchi H, Ohira M

    Annals of surgical oncology   26 ( 4 )   1093 - 1102   2019.04( ISSN:1068-9265

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    DOI: 10.1245/s10434-018-07145-2

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  • The impact of geriatric nutritional risk index on surgical outcomes after esophagectomy in patients with esophageal cancer. Reviewed

    Kubo N, Sakurai K, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Yashiro M, Ohira M

    Esophagus : official journal of the Japan Esophageal Society   16 ( 2 )   147 - 154   2019.04( ISSN:1612-9059

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    DOI: 10.1007/s10388-018-0644-6

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  • 食道癌患者の食道切除後の手術成績に対するGeriatric Nutritional Risk Indexの影響(The impact of geriatric nutritional risk index on surgical outcomes after esophagectomy in patients with esophageal cancer) Reviewed

    Kubo Naoshi, Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi

    Esophagus   16 ( 2 )   147 - 154   2019.04( ISSN:1612-9059

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    食道扁平上皮癌(ESCC)患者におけるGeriatric Nutritional Risk Index(GNRI)と短期・長期手術成績との関連を調査した。2000~2012年に当施設で外科的切除後に組織学的にESCCを確認した患者240例(男性196例、女性44例、平均63.4歳)を後ろ向きに調査した。全例が2~3領域リンパ節郭清と併用して根治的食道切除術を受けた。GNRIのカットオフ値を92として、GNRI<92の低GNRI群44例とGNRI≧92の高GNRI群196例に分けた。リンパ節転移率と病理学的病期は高GNRI群よりも低GNRI群の方が有意に高かった。肺合併症の割合は高GNRI群よりも低GNRI群の方が有意に高かったが、多変量解析ではGNRIは肺合併症発症に対する独立危険因子ではなかった。5年全生存率は高GNRI群よりも低GNRI群の方が有意に低かった。GNRIは全生存率に対する独立予後因子であったが、癌特異的生存率(CSS)は予後因子ではなかった。腫瘍病期の階層化による解析では、全生存率、CSSともに病期III ESCC患者で高GNRI群よりも低GNRI群の方が悪化した。病期III ESCCでは原発腫瘍サイズは高GNRI群よりも低GNRI群の方が大きい傾向にあり、術前嚥下障害の発生率は高GNRI群よりも低GNRI群の方が有意に高かった。

  • 胆道癌の癌局所免疫における癌関連線維芽細胞の働き Reviewed

    田中 涼太, 木村 健二郎, 天野 良亮, 山添 定明, 大平 豪, 田内 潤, 西村 貞徳, 田中 浩明, 八代 正和, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   PS - 8   2019.04

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  • 胃癌間質におけるThrombospondin4発現の検討 Reviewed

    黒田 顕慈, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 奥野 倫久, 三木 友一朗, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   SF - 6   2019.04

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  • 家族性胃癌の臨床病理学的検討 Reviewed

    西村 貞徳, 八代 正和, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 田村 達郎, 豊川 貴弘, 木村 健二郎, 天野 良亮, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   PS - 2   2019.04

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  • トラニラスト、シスプラチン併用療法によるスキルス胃癌への治療効果の検討 Reviewed

    櫛山 周平, 八代 正和, 村橋 邦康, 奥野 倫久, 黒田 顕慈, 田中 涼太, 栂野 真吾, 西村 貞徳, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   PS - 6   2019.04

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  • スキルス胃癌細胞由来EVsの腹膜中皮細胞への影響の違い Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   SF - 7   2019.04

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  • 飢餓ストレスにおける胃癌幹細胞のオートファジーの意義 Reviewed

    栂野 真吾, 八代 正和, 増田 剛, 黒田 顕慈, 奥野 倫久, 西村 貞徳, 櫛山 周平, 三木 友一朗, 平川 弘聖, 大平 雅一

    日本外科学会定期学術集会抄録集   119回   SF - 8   2019.04

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  • Macrophage-mediated transfer of cancer-derived components to stromal cells contributes to establishment of a pro-tumor microenvironment Reviewed

    Umakoshi Michinobu, Takahashi So, Itoh Go, Kuriyama Sei, Sasaki Yuto, Yanagihara Kazuyoshi, Yashiro Masakazu, Maeda Daichi, Goto Akiteru, Tanaka Masamitsu

    ONCOGENE   38 ( 12 )   2162 - 2176   2019.03( ISSN:0950-9232

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    DOI: 10.1038/s41388-018-0564-x

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  • Clinicopathological Significance of Autophagy-related Proteins and its Association With Genetic Alterations in Gliomas Reviewed

    Tamrakar Samantha, Yashiro Masakazu, Kawashima Toshiyuki, Uda Takehiro, Terakawa Yuzo, Kuwae Yuko, Ohsawa Masahiko, Ohata Kenji

    ANTICANCER RESEARCH   39 ( 3 )   1233 - 1242   2019.03( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13233

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  • Macrophage-mediated transfer of cancer-derived components to stromal cells contributes to establishment of a pro-tumor microenvironment. Reviewed

    Umakoshi M, Takahashi S, Itoh G, Kuriyama S, Sasaki Y, Yanagihara K, Yashiro M, Maeda D, Goto A, Tanaka M

    Oncogene   38 ( 12 )   2162 - 2176   2019.03( ISSN:0950-9232

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    DOI: 10.1038/s41388-018-0564-x

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  • Clinicopathological Significance of Autophagy-related Proteins and its Association With Genetic Alterations in Gliomas. Reviewed

    Tamrakar S, Yashiro M, Kawashima T, Uda T, Terakawa Y, Kuwae Y, Ohsawa M, Ohata K

    Anticancer research   39 ( 3 )   1233 - 1242   2019.03( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13233

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  • A Pretreatment-Free, Polymer-Based Platform Prepared by Molecular Imprinting and Post-Imprinting Modifications for Sensing Intact Exosomes Reviewed

    Mori Kisho, Hirase Mitsuhiro, Morishige Takahiro, Takano Eri, Sunayama Hirobumi, Kitayama Yukiya, Inubushi Sachiko, Sasaki Ryohei, Yashiro Masakazu, Takeuchi Toshifumi

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   58 ( 6 )   1612 - 1615   2019.02( ISSN:1433-7851

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    DOI: 10.1002/anie.201811142

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  • A Pretreatment-Free, Polymer-Based Platform Prepared by Molecular Imprinting and Post-Imprinting Modifications for Sensing Intact Exosomes. Reviewed

    Mori K, Hirase M, Morishige T, Takano E, Sunayama H, Kitayama Y, Inubushi S, Sasaki R, Yashiro M, Takeuchi T

    Angewandte Chemie (International ed. in English)   58 ( 6 )   1612 - 1615   2019.02( ISSN:1433-7851

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    DOI: 10.1002/anie.201811142

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  • Adverse Effects of Preoperative Sarcopenia on Postoperative Complications of Patients With Gastric Cancer Reviewed

    Tamura Tatsuro, Sakurai Katsunobu, Nambara Mikio, Miki Yuichiro, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Ohira Masaichi

    ANTICANCER RESEARCH   39 ( 2 )   987 - 992   2019.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13203

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  • Oligodendrocytes Up-regulate the Invasive Activity of Glioblastoma Cells via the Angiopoietin-2 Signaling Pathway Reviewed

    Kawashima Toshiyuki, Yashiro Masakazu, Kasashima Hiroaki, Terakawa Yuzo, Uda Takehiro, Nakajo Kosuke, Umaba Ryoko, Tanoue Yuta, Tamrakar Samantha, Ohata Kenji

    ANTICANCER RESEARCH   39 ( 2 )   577 - 584   2019.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13150

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  • Adverse Effects of Preoperative Sarcopenia on Postoperative Complications of Patients With Gastric Cancer. Reviewed

    Tamura T, Sakurai K, Nambara M, Miki Y, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Yashiro M, Ohira M

    Anticancer research   39 ( 2 )   987 - 992   2019.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13203

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  • Oligodendrocytes Up-regulate the Invasive Activity of Glioblastoma Cells via the Angiopoietin-2 Signaling Pathway. Reviewed

    Kawashima T, Yashiro M, Kasashima H, Terakawa Y, Uda T, Nakajo K, Umaba R, Tanoue Y, Tamrakar S, Ohata K

    Anticancer research   39 ( 2 )   577 - 584   2019.02( ISSN:0250-7005

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    DOI: 10.21873/anticanres.13150

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  • スキルス胃癌細胞由来EVsは腹膜中皮細胞にmesenchymal transitionを引き起こす Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本胃癌学会総会記事   91回   490 - 490   2019.02

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  • 家族性胃癌の臨床病学的因子の検討 Reviewed

    西村 貞徳, 八代 正和, 櫛山 周平, 栂野 真吾, 黒田 顕慈, 奥野 倫久, 平川 弘聖, 大平 雅一

    日本胃癌学会総会記事   91回   538 - 538   2019.02

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  • 特集 スキルス胃癌のすべて I. 基礎 3.スキルス胃癌腹膜播種形成の分子機構と分子標的治療 Reviewed

    八代 正和, 大平 雅一

    外科   81 ( 1 )   12 - 15   2019.01( ISSN:0016593X

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    DOI: 10.15106/j_geka81_12

  • スキルス胃癌細胞株由来Exosomeは腹膜中皮細胞のmesothelial-mesenchymal transitionを引き起こし腹膜転移に関与する Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本分子腫瘍マーカー研究会 日本分子腫瘍マーカー研究会誌   34   23 - 25   2019.01

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    スキルス胃癌(SGC)細胞由来Exosomeの腹膜への分布とその影響を検討した。In vitroにおけるlive imagingと蛍光顕微鏡による検討の結果、SGC細胞由来Exosomeは腹膜中皮細胞に取り込まれやすく、腹膜中皮細胞を敷石状から紡錘形に形態変化させた。SGC由来のPKH26標識Exosomeをヌードマウスに3週間尾静脈投与を行った結果、腹膜に指向性に集積した。また胃癌切除組織症例における腹膜のExosomeマーカー(CD9、CD63)の発現は遠隔転移と有意に相関していたことから、CD9およびCD63は腹膜転移の予測因子であることが示唆された。

  • スキルス胃癌細胞株由来Exosomeは腹膜中皮細胞のmesothelial-mesenchymal transitionを引き起こし腹膜転移に関与する Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本分子腫瘍マーカー研究会誌   34   23 - 25   2019.01

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    スキルス胃癌(SGC)細胞由来Exosomeの腹膜への分布とその影響を検討した。In vitroにおけるlive imagingと蛍光顕微鏡による検討の結果、SGC細胞由来Exosomeは腹膜中皮細胞に取り込まれやすく、腹膜中皮細胞を敷石状から紡錘形に形態変化させた。SGC由来のPKH26標識Exosomeをヌードマウスに3週間尾静脈投与を行った結果、腹膜に指向性に集積した。また胃癌切除組織症例における腹膜のExosomeマーカー(CD9、CD63)の発現は遠隔転移と有意に相関していたことから、CD9およびCD63は腹膜転移の予測因子であることが示唆された。

  • スキルス胃癌細胞株由来Exosomeは腹膜中皮細胞のmesothelial-mesenchymal transitionを引き起こし腹膜転移に関与する Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本分子腫瘍マーカー研究会誌   34   23 - 25   2019.01

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    スキルス胃癌(SGC)細胞由来Exosomeの腹膜への分布とその影響を検討した。In vitroにおけるlive imagingと蛍光顕微鏡による検討の結果、SGC細胞由来Exosomeは腹膜中皮細胞に取り込まれやすく、腹膜中皮細胞を敷石状から紡錘形に形態変化させた。SGC由来のPKH26標識Exosomeをヌードマウスに3週間尾静脈投与を行った結果、腹膜に指向性に集積した。また胃癌切除組織症例における腹膜のExosomeマーカー(CD9、CD63)の発現は遠隔転移と有意に相関していたことから、CD9およびCD63は腹膜転移の予測因子であることが示唆された。

    Other URL: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04910&link_issn=&doc_id=20191118260011&doc_link_id=10.11241%2Fjsmtmr.34.23&url=https%3A%2F%2Fdoi.org%2F10.11241%2Fjsmtmr.34.23&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer. Reviewed

    Kuroda K, Yashiro M, Sera T, Yamamoto Y, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Togano S, Okuno T, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M

    PloS one   14 ( 11 )   e0224727   2019

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    DOI: 10.1371/journal.pone.0224727

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  • Exosomes from scirrhous gastric cancer cells might affect on the morphology of peritoneal mesothelial cells and induce peritoneal metastasis Reviewed

    Okuno Tomohisa, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi, Yashiro Masakazu, Kushiyama Shuhei, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   34 ( 0 )   23 - 25   2019

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    DOI: 10.11241/jsmtmr.34.23

    CiNii Article

  • The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer. Reviewed

    Kuroda K, Yashiro M, Sera T, Yamamoto Y, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Togano S, Okuno T, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Ohira M

    PloS one   14 ( 11 )   e0224727   2019

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    DOI: 10.1371/journal.pone.0224727

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  • Exosomes from scirrhous gastric cancer cells might affect on the morphology of peritoneal mesothelial cells and induce peritoneal metastasis Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Kushiyama Shuhei, Nishimura Sadaaki, Togano Shingo, Kuroda Kenji, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    Japan Journal of Molecular Tumor Marker Research   34 ( 0 )   23 - 25   2019

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    DOI: 10.11241/jsmtmr.34.23

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  • [A Case of Appendiceal Cancer Wherein the Abdominal Abscess Ruptured into the Urinary Bladder Owing to Obstructive Appendicitis]. Reviewed

    Tsujio G, Nagahara H, Shibutani M, Fukuoka T, Matsutani S, Kusunoki C, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   2458 - 2460   2018.12( ISSN:0385-0684

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  • Clinical significance of diffuse-type histologic type coexistence in gastric cancer Reviewed

    Tanaka Hiroaki, Muguruma Kazuya, Tamura Tatsuro, Toyokawa Takahiro, Shibutani Masatsune, Nagahara Hisashi, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    CANCER SCIENCE   109   479 - 479   2018.12( ISSN:1349-7006

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  • The significance of autophagy of gastric cancer stem cells Reviewed

    Togano Shingo, Yashiro Masakazu, Masuda Go, Kuroda Kenji, Okuno Tomohisa, Miki Yuichiro, Tamura Tatsuro, Toyokawa Takahiro, Amano Ryosuke, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    CANCER SCIENCE   109   1253 - 1253   2018.12( ISSN:1349-7006

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  • Functional Heterogeneity in Activated Fibroblasts Created by Extracellular Vesicles Reviewed

    Naito Yutaka, Yamamoto Yusuke, Yashiro Masakazu, Kiyono Tohru, Hirakawa Kosei, Yanagihara Kazuyoshi, Yasui Wataru, Ochiya Takahiro

    CANCER SCIENCE   109   266 - 266   2018.12( ISSN:1349-7006

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  • Extracellular vesicles from gastric carcinoma induce mesothelial-mesenchymal transition of peritoneal mesothelial cells Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Togano Shingo, Kuroda Kenji, Miki Yuichiro, Kasashima Hiroaki, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    CANCER SCIENCE   109   475 - 475   2018.12( ISSN:1349-7006

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  • Macrophages transmit tumor-derived extracellular vesicles to stromal cells and create pro-tumor microenvironment Reviewed

    Tanaka Masamitsu, Umakoshi Michinobu, Takahashi So, Itoh Go, Kuriyama Sei, Yashiro Masakazu, Goto Akiteru

    CANCER SCIENCE   109   281 - 281   2018.12( ISSN:1349-7006

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  • 閉塞性虫垂炎による腹腔内膿瘍膀胱穿通を来した虫垂癌の1例 Reviewed

    辻尾 元, 永原 央, 渋谷 雅常, 福岡 達成, 松谷 慎治, 楠 誓子, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   45 ( 13 )   2458 - 2460   2018.12( ISSN:0385-0684

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    症例は73歳、女性。下腹部痛、腹部膨満感を主訴に近医を受診、下腹部に腫瘍性病変を認め当院紹介となった。造影CT検査で、膀胱右前壁に壁肥厚および虫垂先端に連続する約6cm大の内部に壊死性変化を疑う腫瘤を認めた。虫垂腫瘍膀胱浸潤や膀胱腫瘍虫垂浸潤が疑われ手術の方針とした。約1ヵ月後の入院時に施行した造影CT検査にて虫垂先端の腫瘤は著明に縮小していたが膀胱の壁肥厚は残存しており、虫垂に造影効果を受ける腫瘤を認め、虫垂癌もしくは膀胱癌と考え手術を施行した。術中所見では虫垂先端が膀胱壁と一塊になっており、膀胱壁を含めた虫垂切除を行い、虫垂中部に約1cm大の腫瘍を認めた。迅速病理検査にて虫垂癌と診断されたため、回盲部切除+D2リンパ節郭清を追加した。病理組織学的検査で虫垂癌、pT2N0M0、pStage Iの診断、虫垂癌による閉塞性虫垂炎で虫垂が穿破し、腹腔内膿瘍を形成、膀胱に穿通したものと考えた。(著者抄録)

  • [A Case of Appendiceal Cancer Wherein the Abdominal Abscess Ruptured into the Urinary Bladder Owing to Obstructive Appendicitis]. Reviewed

    Tsujio G, Nagahara H, Shibutani M, Fukuoka T, Matsutani S, Kusunoki C, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   2458 - 2460   2018.12( ISSN:0385-0684

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    PubMed

  • 閉塞性虫垂炎による腹腔内膿瘍膀胱穿通を来した虫垂癌の1例 Reviewed

    辻尾 元, 永原 央, 渋谷 雅常, 福岡 達成, 松谷 慎治, 楠 誓子, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    癌と化学療法   45 ( 13 )   2458 - 2460   2018.12( ISSN:0385-0684

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    症例は73歳、女性。下腹部痛、腹部膨満感を主訴に近医を受診、下腹部に腫瘍性病変を認め当院紹介となった。造影CT検査で、膀胱右前壁に壁肥厚および虫垂先端に連続する約6cm大の内部に壊死性変化を疑う腫瘤を認めた。虫垂腫瘍膀胱浸潤や膀胱腫瘍虫垂浸潤が疑われ手術の方針とした。約1ヵ月後の入院時に施行した造影CT検査にて虫垂先端の腫瘤は著明に縮小していたが膀胱の壁肥厚は残存しており、虫垂に造影効果を受ける腫瘤を認め、虫垂癌もしくは膀胱癌と考え手術を施行した。術中所見では虫垂先端が膀胱壁と一塊になっており、膀胱壁を含めた虫垂切除を行い、虫垂中部に約1cm大の腫瘍を認めた。迅速病理検査にて虫垂癌と診断されたため、回盲部切除+D2リンパ節郭清を追加した。病理組織学的検査で虫垂癌、pT2N0M0、pStage Iの診断、虫垂癌による閉塞性虫垂炎で虫垂が穿破し、腹腔内膿瘍を形成、膀胱に穿通したものと考えた。(著者抄録)

  • High stromaltransforming growth factor -induced expression is a novel marker of progression and poor prognosis in gastric cancer Reviewed

    Suzuki Masaki, Yokobori Takehiko, Gombodorj Navchaa, Yashiro Masakazu, Turtoi Andrei, Handa Tadashi, Ogata Kyoichi, Oyama Tetsunari, Shirabe Ken, Kuwano Hiroyuki

    JOURNAL OF SURGICAL ONCOLOGY   118 ( 6 )   966 - 974   2018.11( ISSN:0022-4790

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    DOI: 10.1002/jso.25217

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  • High stromal transforming growth factor β-induced expression is a novel marker of progression and poor prognosis in gastric cancer. Reviewed

    Suzuki M, Yokobori T, Gombodorj N, Yashiro M, Turtoi A, Handa T, Ogata K, Oyama T, Shirabe K, Kuwano H

    Journal of surgical oncology   118 ( 6 )   966 - 974   2018.11( ISSN:0022-4790

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    DOI: 10.1002/jso.25217

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  • The significance of scirrhous gastric cancer cell lines: the molecular characterization using cell lines and mouse models Reviewed

    Yashiro Masakazu, Matsuoka Tasuku, Ohira Masaichi

    HUMAN CELL   31 ( 4 )   271 - 281   2018.10( ISSN:1749-0774

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    DOI: 10.1007/s13577-018-0211-4

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  • The significance of scirrhous gastric cancer cell lines: the molecular characterization using cell lines and mouse models Reviewed

    Masakazu Yashiro, Tasuku Matsuoka, Masaichi Ohira

    Human Cell   31 ( 4 )   271 - 281   2018.10( ISSN:0914-7470

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    Scirrhous gastric cancer (SGC) exhibits aggressiveness of the rapid infiltrating tumor cells with abundant fibroblasts. Experimental studies using SGC cell lines have obtained useful information about this cancer. Our literature search divulged a total of 18 SGC cell lines
    two cell lines were established from primary SGC and the other lines were established from a metastatic lesion of SGC. Fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor-beta receptor (TβR) are linked to the rapid development of SGC. Cross-talk between the cancer cells and cancer-associated fibroblasts (CAFs) has been shown to contribute to the progression of SGC. Chemokine (C-X-C motif) receptor 1 (CXCR1) from SGC cells might be associated with the abundant CAFs in cancer microenvironments. The in vivo models established using SGC cell lines are expected to serve as a useful tool for the development of drugs such as FGFR2 inhibitors, TβR inhibitors, and CXCR1 inhibitors, which might be promising as SGC treatments. However, the number of available SGC cell lines is insufficient for the clarification of the entire biologic behavior of SGC. Since the mechanisms responsible for the characteristic aggressiveness of SGC are not fully elucidated, the establishment of new SGC cell lines could help clarify the biological behavior of SGC and contribute to its treatment.

    DOI: 10.1007/s13577-018-0211-4

    PubMed

  • 膵頭十二指腸切除術後における膵液瘻発症の危険因子の検討 Reviewed

    田内 潤, 木村 健二郎, 天野 良亮, 山添 定明, 大平 豪, 田中 涼太, 西村 貞徳, 田村 達郎, 渋谷 雅常, 永原 央, 豊川 貴弘, 田中 浩明, 六車 一哉, 八代 正和, 大平 雅一

    日本臨床外科学会雑誌   79 ( 増刊 )   801 - 801   2018.10( ISSN:1345-2843

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  • 同時性遠隔転移あるいは術後再発を生じた浸潤性膵癌における外科的介入の意義 Reviewed

    木村 健二郎, 天野 良亮, 山添 定明, 大平 豪, 田中 涼太, 田内 潤, 西村 貞徳, 柏原 伸一郎, 渋谷 雅常, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    日本癌治療学会学術集会抄録集   56回   P92 - 5   2018.10

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  • 膵癌に対するGemcitabine+nab-paclitaxel療法の当院での治療成績 Reviewed

    田中 涼太, 木村 健二郎, 天野 良亮, 山添 定明, 大平 豪, 田内 潤, 西村 貞徳, 永原 央, 豊川 貴弘, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    日本癌治療学会学術集会抄録集   56回   O18 - 4   2018.10

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  • Clinico-pathological significance of exosome marker CD63 expression on cancer cells and stromal cells in gastric cancer Reviewed

    Miki Yuichiro, Yashiro Masakazu, Okuno Tomohisa, Kuroda Kenji, Togano Shingo, Hirakawa Kosei, Ohira Masaichi

    PLOS ONE   13 ( 9 )   e0202956   2018.09( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0202956

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  • スキルス胃癌由来細胞外小胞顆粒によるCAFの機能的不均一性(Functional Heterogeneity in Activated Fibroblasts Created by Extracellular Vesicles) Reviewed

    内藤 寛, 山本 雄介, 八代 正和, 清野 透, 平川 弘聖, 柳原 五吉, 安井 弥, 落谷 孝広

    日本癌学会総会記事   77回   349 - 349   2018.09( ISSN:0546-0476

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  • スキルス胃癌細胞株由来Exosomeは腹膜中皮細胞のmesothelial-mesenchymal transitionを引き起こし腹膜転移に関与する Reviewed

    奥野 倫久, 八代 正和, 櫛山 周平, 西村 貞徳, 栂野 真吾, 黒田 顕慈, 田村 達郎, 豊川 貴弘, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    日本分子腫瘍マーカー研究会プログラム・講演抄録   38回   40 - 42   2018.09

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  • C-X-C Motif Ligand 1 (CXCL1) from melanoma cells down-regulates the invasion of their metastatic melanoma cells. Reviewed

    Hatano T, Yashiro M, Fujikawa H, Motomura H

    Oncotarget   9 ( 57 )   31090 - 31097   2018.07

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    DOI: 10.18632/oncotarget.25783

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  • C-X-C Motif Ligand 1 (CXCL1) from melanoma cells down-regulates the invasion of their metastatic melanoma cells. Reviewed

    Hatano T, Yashiro M, Fujikawa H, Motomura H

    Oncotarget   9 ( 57 )   31090 - 31097   2018.07

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    DOI: 10.18632/oncotarget.25783

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  • Biomarkers of gastric cancer: Current topics and future perspective Reviewed

    Matsuoka Tasuku, Yashiro Masakazu

    WORLD JOURNAL OF GASTROENTEROLOGY   24 ( 26 )   2818 - 2832   2018.07( ISSN:1007-9327

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    DOI: 10.3748/wjg.v24.i26.2818

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  • Biomarkers of gastric cancer: Current topics and future perspective. Reviewed

    Matsuoka T, Yashiro M

    World journal of gastroenterology   24 ( 26 )   2818 - 2832   2018.07( ISSN:1007-9327

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    DOI: 10.3748/wjg.v24.i26.2818

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  • C-X-C motif ligand 1 from melanoma cells downregulates the invasion of their metastatic melanoma cells Reviewed

    Hatano Takaharu, Yashiro Masakazu, Motomura Hisashi, Fujikawa Heishiro, Maeda Shusaku

    CANCER RESEARCH   78 ( 13 )   2018.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2018-4507

  • Pyruvate kinase isozymes M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer Reviewed

    Yashiro Masakazu, Kitayama Kishu

    CANCER RESEARCH   78 ( 13 )   2018.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2018-5484

  • Loss of E-cadherin expression is a critical step for peritoneal metastasis of gastric cancer with sub-serosal invasion Reviewed

    Togano Shingo, Yashiro Masakazu, Kuroda Kenji, Okuno Tomohisa, Miki Yuichiro, Hirakawa Kosei, Ohira Masaichi

    CANCER RESEARCH   78 ( 13 )   2018.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2018-4030

  • Effect of extracellular vesicles from gastric cancer cells on the morphologic and genetic changes of peritoneal mesothelial cells Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Togano Shingo, Kuroda Kenji, Miki Yuichiro, Kasashima Hiroaki, Hirakawa Kosei, Ohira Masaichi

    CANCER RESEARCH   78 ( 13 )   2018.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2018-5219

  • Effect of cancer-associated fibroblasts on the progression of malignant melanoma cells Reviewed

    Fujikawa Heishiro, Yashiro Masakazu, Hatano Takaharu, Maeda Shusaku, Motomura Hisashi

    CANCER RESEARCH   78 ( 13 )   2018.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2018-4489

  • Comparison of the prognostic impact and combination of preoperative inflammation-based and/or nutritional markers in patients with stage II gastric cancer. Reviewed

    Toyokawa T, Muguruma K, Tamura T, Sakurai K, Amano R, Kubo N, Tanaka H, Yashiro M, Hirakawa K, Ohira M

    Oncotarget   9 ( 50 )   29351 - 29364   2018.06

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    DOI: 10.18632/oncotarget.25486

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  • Comparison of the prognostic impact and combination of preoperative inflammation-based and/or nutritional markers in patients with stage II gastric cancer. Reviewed

    Toyokawa T, Muguruma K, Tamura T, Sakurai K, Amano R, Kubo N, Tanaka H, Yashiro M, Hirakawa K, Ohira M

    Oncotarget   9 ( 50 )   29351 - 29364   2018.06

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    DOI: 10.18632/oncotarget.25486

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  • Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response Reviewed

    Hiramatsu Soichiro, Tanaka Hiroaki, Nishimura Junya, Sakimura Chie, Tamura Tatsuro, Toyokawa Takahiro, Muguruma Kazuya, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    BMC IMMUNOLOGY   19 ( 1 )   13   2018.04

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    DOI: 10.1186/s12865-018-0251-2

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  • Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response Reviewed

    Soichiro Hiramatsu, Hiroaki Tanaka, Junya Nishimura, Chie Sakimura, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Masakazu Yashiro, Kosei Hirakawa, Masaichi Ohira

    BMC Immunology   19 ( 1 )   13   2018.04( ISSN:1471-2172

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    Background: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15+neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer. Results: Immunohistochemical staining showed that the median number of CD15+TANs was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs, respectively. Patients were divided into high and low infiltration groups based on the median number. A high number of infiltrating CD15+TANs in the primary tumors and in the TDLNs were associated with depth of invasion and lymph node metastasis. Kaplan-Meier analysis revealed that a poor overall survival was associated with high numbers of CD15+TANs, and the multivariate analyses revealed that a high number of CD15+TANs in the TDLNs was an independent prognostic factor. The numbers of CD15+TANs in the primary tumors and TDLNs showed weak positive correlation. The number of CD15+TANs in the primary tumors was positively correlated with the preoperative NLR, (P=0.001, R=0.327) and immunohistochemical staining revealed that C-X-C motif chemokine receptor 2 (CXCR2) +neutrophils might be the origin of the CD15+TANs. Flow cytometry analysis indicated that infiltrating neutrophils increased in the tumor and TDLN compared to non-cancerous tissue. Neutrophils treated with cancer supernatant upregulated TWIST and IL-6 genes in vitro. Conclusion: Our findings suggested that local infiltration of CD15+TANs may be correlated with inflammation in TDLNs and systemic response to cause metastasis in gastric carcinoma.

    DOI: 10.1186/s12865-018-0251-2

    PubMed

  • 腫瘍炎症環境において間質に依存する胃癌進展の分子メカニズム Reviewed

    石本 崇胤, 三宅 慧輔, 八代 正和, 内原 智幸, 有馬 浩太, 泉 大輔, 岩槻 政晃, 馬場 祥史, 渡邊 雅之, Tan Patrick, 馬場 秀夫

    日本外科学会定期学術集会抄録集   118回   961 - 961   2018.04

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  • CD9-positive exosomes from cancer-associated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells Reviewed

    Miki Yuichiro, Yashiro Masakazu, Okuno Tomohisa, Kitayama Kishu, Masuda Go, Hirakawa Kosei, Ohira Masaichi

    BRITISH JOURNAL OF CANCER   118 ( 6 )   867 - 877   2018.03( ISSN:0007-0920

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    DOI: 10.1038/bjc.2017.487

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  • CD9-positive exosomes from cancerassociated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells Reviewed

    Yuichiro Miki, Masakazu Yashiro, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Kosei Hirakawa, Masaichi Ohira

    British Journal of Cancer   118 ( 6 )   867 - 877   2018.03( ISSN:0007-0920

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    Background: Crosstalk between cancer cells and fibroblasts is crucial for tumour progression. It has been reported that exosomes derived from cancer cells play an important role in the intracellular communications involved in the development of carcinoma. However, the role of exosomes from fibroblasts remains unclear. This study aimed to clarify the effect of exosomes from fibroblasts on the motility of gastric cancer cells. Methods: 5 gastric cancer cell lines were used: OCUM-12, NUGC-3, MKN45, FU97 and MKN74. 2 cancer-associated fibroblasts (CAFs) were used. CD9 expression of exosomes from fibroblasts was examined by western blot. The effect of exosomes on the motility of cancer cells was analysed by migration assays. MMP2 was examined by RT-PCR or gelatin zymography. Then, CD9 and MMP2 expressions of 619 gastric cancers were analysed by immunohistochemistry. Results: Exosomes from CAFs were taken into scirrhous-type gastric cancer cells, namely OCUM-12 cells and NUGC-3 cells, but not into other types of gastric cancer cells. Exosomes from CAFs were positive for CD9. Exosomes from CAFs significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells, which was inhibited by anti-CD9 antibody or CD9-siRNA. MMP2 expression of OCUM-12 and NUGC-3 cells was significantly decreased by CD9-siRNA. 116 CD9-positive cases were significantly correlated with scirrhous-type gastric cancer, lymph node metastasis and venous invasion. The 5-year survival rate of patients with CD9-positive tumours was significantly lower (Po0.001) than in those with CD9-negative tumours. Conclusions: CD9-positive exosomes from CAFs might stimulate the migration ability of scirrhous-type gastric cancer cells.

    DOI: 10.1038/bjc.2017.487

    PubMed

  • 胃癌の微小環境からみた腫瘍免疫の基礎 Reviewed

    田中 浩明, 田村 達郎, 吉井 真美, 大北 仁裕, 徳本 真央, 呉 幸枝, 崎村 千恵, 平松 宗一郎, 西村 潤也, 山越 義仁, 三木 友一朗, 豊川 貴弘, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    日本胃癌学会総会記事   90回   205 - 205   2018.03

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  • Significance of immune-cell infiltration in gastric Reviewed

    Hiroaki Tanaka, Tatsuro Tamura, Yoshihiro Okita, Mami Yoshii, Mao Tokumoto, Yukie Go, Chie Sakimura, Soichiro Hiramatsu, Junya Nishimura, Yoshihito Yamagoe, Masakazu Yashiro, Yuichiro Miki, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira

    Japanese Journal of Cancer and Chemotherapy   45 ( 2 )   217 - 221   2018.02( ISSN:0385-0684

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    There are many reports on the association between infiltrating immune cells and cancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associated with tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells (MDSC), and neutrophils. These immunosuppressive cells enhance the production of TGF-β and IL-10 and the expression of PDL-1 by cytokines produced by stromal cells such as cancer cells and fibroblasts, thereby inducing cytotoxic T cells lymphocytes (CTL). On the other hand, it has been proved that CD8+ T cells react in an antigen-specific manner even in advanced gastric cancer, suggesting the possibility that memory T cells, NK cells and NKT cells in gastric cancer tissues correlate with good prognosis. Recently, it has been reported that the presence of follicular lymphoid structure called tertiary lymphoid structure (TLS) in gastric cancer tissue is associated with favorable prognosis. Although immune responses are suppressed in gastric cancer tissues, the effectiveness of an immune checkpoint inhibitor (anti-PD-1 antibody) has been proved in 2017. The tumor-infiltrating immune cells is known as a predictive effect biomarker. As cancer genome research progresses, which type of immune response is induced is gradually being elucidated in near future. Thus, assessing the invasive morphology and function of various tumorinfiltrating immune cells is considered to be extremely important in Precision Medicine for gastric cancer.

    PubMed

  • [Significance of Immune-Cell Infiltration in Gastric]. Reviewed

    Tanaka H, Tamura T, Okita Y, Yoshii M, Tokumoto M, Go Y, Sakimura C, Hiramatsu S, Nishimura J, Yamagoe Y, Yashiro M, Miki Y, Toyokawa T, Muguruma K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 2 )   217 - 221   2018.02( ISSN:0385-0684

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  • [Significance of Immune-Cell Infiltration in Gastric]. Reviewed

    Tanaka H, Tamura T, Okita Y, Yoshii M, Tokumoto M, Go Y, Sakimura C, Hiramatsu S, Nishimura J, Yamagoe Y, Yashiro M, Miki Y, Toyokawa T, Muguruma K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 2 )   217 - 221   2018.02( ISSN:0385-0684

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  • CD9-positive Exosomes from CaF Stimulate the Migration Ability of Scirrhous-type Gastric Cancer Cells Reviewed

    Miki Yuichiro, Yashiro Masakazu, Okuno Tomohisa, Tamura Tatsuro, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kesei, Ohira Masaichi

    CANCER SCIENCE   109   875 - 875   2018.01( ISSN:1349-7006

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  • Extracellular vesicle-driven crosstalk between cancer and stromal cells orchestrates the microenvironment for metastasis Reviewed

    Naito Yutaka, Yamamoto Yusuke, Yoshioka Yusuke, Yashiro Masakazu, Kiyono Tohru, Hirakawa Kosei, Yanagihara Kazuyoshi, Yasui Wataru, Ochiya Takahiro

    CANCER SCIENCE   109   486 - 486   2018.01( ISSN:1349-7006

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  • Establishment of a new scirrhous gastric cancer cell line with FGFR2 overexpression, OCUM-14. Reviewed

    Okuno Tomohisa, Yashiro Masakazu, Masuda Go, Kitayama Kishu, Hirakawa Kosei, Ohira Masaichi

    CANCER SCIENCE   109   644 - 644   2018.01( ISSN:1349-7006

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  • Protection of SDF-2 by Hsp72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells Reviewed

    Shiota Masayuki, Takahashi Katsuyuki, Yashiro Masakazu, Tanaka Masako

    CANCER SCIENCE   109   64 - 64   2018.01( ISSN:1349-7006

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  • Possibility of inducing tumor infiltrating lymphocytes by B cells in tertiary lymphoid structures in gastric cancer Reviewed

    Tanaka Hiroaki, Sakimura Chie, Kazuya Muguruma, Tamura Tatsuro, Shibutani Masatsune, Kimura Kenjiro, Nagahara Hisashi, Toyokawa Takahiro, Amano Ryosuke, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    CANCER SCIENCE   109   837 - 837   2018.01( ISSN:1349-7006

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  • 【Borderline resectable膵癌に対する集学的治療】技術的切除可能な主要動脈浸潤局所進行膵癌に対するR0を目指した集学的治療 Reviewed

    天野 良亮, 木村 健二郎, 山添 定明, 西尾 康平, 大平 豪, 渋谷 雅常, 永原 央, 豊川 貴弘, 田中 浩明, 六車 一哉, 八代 正和, 前田 清, 平川 弘聖, 大平 雅一

    (株)篠原出版新社 癌の臨床   63 ( 5 )   447 - 453   2018.01( ISSN:0021-4949

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    肝動脈浸潤・接触、上腸間膜動脈接触を認める局所進行膵癌42例中、膵切除を行った30例を対象とした。術前化学放射線療法の完遂率は97.6%、外科切除率は71.4%であった。NCCNガイドラインにおけるBorderline resectable(BR)が14例、Unresectable(UR)が16例で、術前治療により腫瘍径、腫瘍マーカーともに有意な低下を認めた。PD-CARやPD-CHAR、TP-CARなどの肝動脈合併膵切除症例が14例で、10例に肝動脈再建を要した。門脈合併切除は70%に行い、術中輸血率は60%であった。grade 3a以上の術後合併症発症率は36.7%であった。胃排出遅延は16.7%に認め、1例が在院死亡に至った。病理所見では、リンパ節転移例は33.3%、膵頭神経叢浸潤は43.3%、門脈浸潤率は30%であった。病理学的な90%以上の腫瘍壊死効果は43.3%に認め、R0切除率は93.3%であった。S-1による術後補助化学療法導入率は82.6%であった。2年生存率は56.1%であった。

  • 【Borderline resectable膵癌に対する集学的治療】技術的切除可能な主要動脈浸潤局所進行膵癌に対するR0を目指した集学的治療 Reviewed

    天野 良亮, 木村 健二郎, 山添 定明, 西尾 康平, 大平 豪, 渋谷 雅常, 永原 央, 豊川 貴弘, 田中 浩明, 六車 一哉, 八代 正和, 前田 清, 平川 弘聖, 大平 雅一

    癌の臨床   63 ( 5 )   447 - 453   2018.01( ISSN:0021-4949

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    肝動脈浸潤・接触、上腸間膜動脈接触を認める局所進行膵癌42例中、膵切除を行った30例を対象とした。術前化学放射線療法の完遂率は97.6%、外科切除率は71.4%であった。NCCNガイドラインにおけるBorderline resectable(BR)が14例、Unresectable(UR)が16例で、術前治療により腫瘍径、腫瘍マーカーともに有意な低下を認めた。PD-CARやPD-CHAR、TP-CARなどの肝動脈合併膵切除症例が14例で、10例に肝動脈再建を要した。門脈合併切除は70%に行い、術中輸血率は60%であった。grade 3a以上の術後合併症発症率は36.7%であった。胃排出遅延は16.7%に認め、1例が在院死亡に至った。病理所見では、リンパ節転移例は33.3%、膵頭神経叢浸潤は43.3%、門脈浸潤率は30%であった。病理学的な90%以上の腫瘍壊死効果は43.3%に認め、R0切除率は93.3%であった。S-1による術後補助化学療法導入率は82.6%であった。2年生存率は56.1%であった。

  • Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Okuno Tomohisa, Miki Yuichiro, Kitayama Kisyu, Masuda Go, Kinoshita Haruhito, Morisaki Tamami, Fukuoka Tatsunari, Hasegawa Tsuyoshi, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    DIGESTION   98 ( 4 )   238 - 248   2018( ISSN:0012-2823

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    DOI: 10.1159/000489558

    PubMed

  • Clinico-pathological significance of exosome marker CD63 expression on cancer cells and stromal cells in gastric cancer. Reviewed

    Miki Y, Yashiro M, Okuno T, Kuroda K, Togano S, Hirakawa K, Ohira M

    PloS one   13 ( 9 )   e0202956   2018

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    DOI: 10.1371/journal.pone.0202956

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  • Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer. Reviewed

    Kasashima H, Yashiro M, Okuno T, Miki Y, Kitayama K, Masuda G, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Hirakawa K, Ohira M

    Digestion   98 ( 4 )   238 - 248   2018( ISSN:0012-2823

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    DOI: 10.1159/000489558

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  • Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer Reviewed

    Kitayama Kishu, Yashiro Masakazu, Morisaki Tamami, Miki Yuichiro, Okuno Tomohisa, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Hasegawa Tsuyoshi, Sakurai Katsunobu, Kubo Naoshi, Hirakawa Kosei, Ohira Masaichi

    CANCER SCIENCE   108 ( 12 )   2462 - 2469   2017.12( ISSN:1349-7006

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    DOI: 10.1111/cas.13421

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  • Examination of cancer cells exposed to gastric serosa by serosal stamp cytology plus RT-PCR is useful for the identification of gastric cancer patients at high risk of peritoneal recurrence Reviewed

    Miki Yuichiro, Yashiro Masakazu, Ando Kanae, Okuno Tomohisa, Kitayama Kishu, Masuda Go, Tamura Tatsuro, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Osawa Masahiko, Hirakawa Kosei, Ohira Masaichi

    SURGICAL ONCOLOGY-OXFORD   26 ( 4 )   352 - 358   2017.12( ISSN:0960-7404

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    DOI: 10.1016/j.suronc.2017.07.008

    PubMed

  • ピルビン酸キナーゼアイソザイムM2およびグルタミナーゼは胃癌の治療に対する有望な分子標的となる可能性がある(Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer) Reviewed

    Kitayama Kishu, Yashiro Masakazu, Morisaki Tamami, Miki Yuichiro, Okuno Tomohisa, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Hasegawa Tsuyoshi, Sakurai Katsunobu, Kubo Naoshi, Hirakawa Kosei, Ohira Masaichi

    John Wiley & Sons Australia, Ltd Cancer Science   108 ( 12 )   2462 - 2469   2017.12( ISSN:1347-9032

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    低酸素環境下の胃癌細胞の増殖に対する反応における解糖系およびグルタミン代謝に対する酵素の重要性を評価した。4種の低酸素耐性胃癌細胞株と患者細胞株を用い、代謝に関連した酵素のmRNA発現解析および、これらの酵素が細胞増殖に及ぼす影響について調べた。全ての低酸素耐性胃癌細胞株において、解糖系酵素ピルビン酸キナーゼのアイソザイムM2(PKM2)およびグルタミナーゼ(GLS)mRNAは患者細胞と比較して高値を示した。siRNAによるノックダウンにより低酸素耐性胃癌細胞株の増殖は減少した。また、siRNAによるノックダウンまたはPKM2阻害剤シコニンとGLS阻害剤BPTES処置では、それぞれ単体よりも併用により有意に細胞増殖が減少した。in vivoにおいても併用処置により腫瘍サイズが減少した。以上より、PKM2とGLSは低酸素胃癌細胞の増殖に重要な役割を果たし、これら阻害剤の併用が胃癌治療に有用と考えられた。

  • Examination of cancer cells exposed to gastric serosa by serosal stamp cytology plus RT-PCR is useful for the identification of gastric cancer patients at high risk of peritoneal recurrence Reviewed

    Yuichiro Miki, Masakazu Yashiro, Kanae Ando, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Tatsuro Tamura, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masahiko Osawa, Kosei Hirakawa, Masaichi Ohira

    SURGICAL ONCOLOGY-OXFORD   26 ( 4 )   352 - 358   2017.12( ISSN:0960-7404

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    Background: We sought to clarify the clinical value of the examination of cancer cells exposed to gastric serosa by our novel method of serosal stamp cytology and a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis.
    Method: A total of 70 patients who underwent gastrectomy were enrolled. Stamp cytology specimens were obtained by stamping the gastric serosa at the primary gastric tumor lesion, followed by Papanicolaou's staining. Samples obtained by brushing the serosa at the primary gastric tumor were analyzed by our RT-PCR of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20).
    Results: Among the 70 patients, 11 patients were diagnosed as stamp cytology-positive. Eight and five patients were found to be CEA-positive and CK20-positive, respectively. Since 21 of the 70 patients were either stamp cytology-positive or RT-PCR analysis-positive, these 21 patients were considered to be positive for cancer cells exposed to serosa of primary gastric tumor. The 3-year recurrence-free survival rate of the patients with a single positive result by our method (41.7%) was significantly (log rank p = 0.0002) worse than that of the patients with both negative results (81.0%). Our method showed 58.8% sensitivity and 79.2% specificity. A multivariate analysis revealed that a stamp cytology and/or RT-PCR result was an independent prognostic factor for recurrence.
    Conclusion: The examination of cancer cells exposed to gastric serosa by our serosal stamp cytology and RT-PCR system will be useful for the identification of patients at high risk for peritoneal recurrence after curative surgery for gastric cancer. (C) 2017 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.suronc.2017.07.008

    PubMed

  • Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer Reviewed

    Kishu Kitayama, Masakazu Yashiro, Tamami Morisaki, Yuichiro Miki, Tomohisa Okuno, Haruhito Kinoshita, Tatsunari Fukuoka, Hiroaki Kasashima, Go Masuda, Tsuyoshi Hasegawa, Katsunobu Sakurai, Naoshi Kubo, Kosei Hirakawa, Masaichi Ohira

    Cancer Science   108 ( 12 )   2462 - 2469   2017.12( ISSN:1347-9032

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    The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription–PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were significantly high in all hypoxia-resistant cell lines, compared with those of their parent cells. Knockdown of PKM2 and GLS significantly decreased the proliferation of all hypoxia-resistant cells. The combination of siPKM2 and siGLS significantly decreased proliferation compared with treatment by siPKM2 or siGLS alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation of all hypoxia-resistant cells. Combination treatment using shikonin and BPTES inhibited the proliferation of all hypoxia-resistant cancer cells more than that by either agent alone. The in vivo study indicated that the tumor size treated by the combination of shikonin and BPTES was significantly smaller than that of vehicle-treated group. These findings suggested that PKM2 and GLS might play important roles in the proliferation of hypoxic gastric cancer cells. A combination of PKM2 and GLS inhibitors could be therapeutically promising for the treatment of gastric cancer.

    DOI: 10.1111/cas.13421

    PubMed

  • ピルビン酸キナーゼアイソザイムM2およびグルタミナーゼは胃癌の治療に対する有望な分子標的となる可能性がある(Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer) Reviewed

    Kitayama Kishu, Yashiro Masakazu, Morisaki Tamami, Miki Yuichiro, Okuno Tomohisa, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Hasegawa Tsuyoshi, Sakurai Katsunobu, Kubo Naoshi, Hirakawa Kosei, Ohira Masaichi

    Cancer Science   108 ( 12 )   2462 - 2469   2017.12( ISSN:1347-9032

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    低酸素環境下の胃癌細胞の増殖に対する反応における解糖系およびグルタミン代謝に対する酵素の重要性を評価した。4種の低酸素耐性胃癌細胞株と患者細胞株を用い、代謝に関連した酵素のmRNA発現解析および、これらの酵素が細胞増殖に及ぼす影響について調べた。全ての低酸素耐性胃癌細胞株において、解糖系酵素ピルビン酸キナーゼのアイソザイムM2(PKM2)およびグルタミナーゼ(GLS)mRNAは患者細胞と比較して高値を示した。siRNAによるノックダウンにより低酸素耐性胃癌細胞株の増殖は減少した。また、siRNAによるノックダウンまたはPKM2阻害剤シコニンとGLS阻害剤BPTES処置では、それぞれ単体よりも併用により有意に細胞増殖が減少した。in vivoにおいても併用処置により腫瘍サイズが減少した。以上より、PKM2とGLSは低酸素胃癌細胞の増殖に重要な役割を果たし、これら阻害剤の併用が胃癌治療に有用と考えられた。

  • [A Case of Small Intestinal Metastasis with Intussusception Due to Barium]. Reviewed

    Tsujio G, Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1973 - 1975   2017.11( ISSN:0385-0684

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  • [A Case of Laparoscopic Surgery Performed for Locally Advanced Rectal Cancer Suspected of Invasion to Prostate]. Reviewed

    Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Doi Y, Ohtani H, Yamazaki T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1523 - 1525   2017.11( ISSN:0385-0684

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  • バリウム内服を契機に発症した小腸重積により診断された転移性小腸腫瘍の1例 Reviewed

    辻尾 元, 永原 央, 中尾 重富, 福岡 達成, 渋谷 雅常, 前田 清, 松谷 慎治, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   44 ( 12 )   1973 - 1975   2017.11( ISSN:0385-0684

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    症例は48歳、男性。受診2日前より嘔気を自覚、翌日に健康診断を受診し、胸部X線検査および食道・胃・十二指腸造影検査を施行した。胸部に異常陰影を指摘されたため当院に紹介受診となった。胸部〜骨盤部CT検査にて左肺門部に約4cm大の腫瘤を認め、小腸にtarget signを認めた。小腸重積の診断となり緊急手術の方針となった。開腹にて腹腔内を観察したところ、Treitz靱帯より約20cm、130cm肛門側の小腸に重積を認め、Hutchinson手技にて重積を解除し得た。口側の重積部では先進部に腫瘍を認めたが、肛門側の重積部では先進部に明らかな腫瘍性病変は認めずバリウム内服による蠕動亢進が原因と考えた。検索を進めたところ小腸に3ヶ所腫瘍性病変を認め、1ヶ所は口側腸重積の先進部となっていた。腫瘍を有する部位の小腸計3ヶ所を部分切除・再建し手術を終了した。病理組織検査では肺多型癌小腸転移の診断となり、現在外来で加療中である。(著者抄録)

  • 前立腺浸潤が疑われた局所進行直腸癌に対し腹腔鏡下に手術を施行した1例 Reviewed

    永原 央, 中尾 重富, 福岡 達成, 渋谷 雅常, 前田 清, 松谷 慎治, 土井 洋輔, 大谷 博, 山崎 健史, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   44 ( 12 )   1523 - 1525   2017.11( ISSN:0385-0684

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    症例は58歳、男性。肛門痛、血便を主訴に他院を受診し、前立腺浸潤を伴う直腸癌と診断、人工肛門造設術を施行され、術前化学療法としてmFOLFOX6を6コース施行後、手術目的に当院を紹介受診となった。術前評価はPRであったが前立腺の浸潤は残存していると判断し、腹腔鏡下に腹会陰式直腸切断術、前立腺合併切除、尿道膀胱吻合による尿路再建を行い、術後第10病日に軽快退院となった。術後2年を経過した現在、明らかな排尿障害、残尿は認めず無再発生存中である。本術式は良好な術野が得られ、確実な切除が得られる点で非常に有用な術式であると思われた。(著者抄録)

  • [A Case of Laparoscopic Surgery Performed for Locally Advanced Rectal Cancer Suspected of Invasion to Prostate]. Reviewed

    Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Doi Y, Ohtani H, Yamazaki T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1523 - 1525   2017.11( ISSN:0385-0684

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  • [A Case of Small Intestinal Metastasis with Intussusception Due to Barium]. Reviewed

    Tsujio G, Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1973 - 1975   2017.11( ISSN:0385-0684

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  • [A Case of Small Intestinal Metastasis with Intussusception Due to Barium]. Reviewed

    Tsujio G, Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1973 - 1975   2017.11( ISSN:0385-0684

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  • [A Case of Laparoscopic Surgery Performed for Locally Advanced Rectal Cancer Suspected of Invasion to Prostate]. Reviewed

    Nagahara H, Nakao S, Fukuoka T, Shibutani M, Maeda K, Matsutani S, Doi Y, Ohtani H, Yamazaki T, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1523 - 1525   2017.11( ISSN:0385-0684

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  • バリウム内服を契機に発症した小腸重積により診断された転移性小腸腫瘍の1例 Reviewed

    辻尾 元, 永原 央, 中尾 重富, 福岡 達成, 渋谷 雅常, 前田 清, 松谷 慎治, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    癌と化学療法   44 ( 12 )   1973 - 1975   2017.11( ISSN:0385-0684

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    症例は48歳、男性。受診2日前より嘔気を自覚、翌日に健康診断を受診し、胸部X線検査および食道・胃・十二指腸造影検査を施行した。胸部に異常陰影を指摘されたため当院に紹介受診となった。胸部~骨盤部CT検査にて左肺門部に約4cm大の腫瘤を認め、小腸にtarget signを認めた。小腸重積の診断となり緊急手術の方針となった。開腹にて腹腔内を観察したところ、Treitz靱帯より約20cm、130cm肛門側の小腸に重積を認め、Hutchinson手技にて重積を解除し得た。口側の重積部では先進部に腫瘍を認めたが、肛門側の重積部では先進部に明らかな腫瘍性病変は認めずバリウム内服による蠕動亢進が原因と考えた。検索を進めたところ小腸に3ヶ所腫瘍性病変を認め、1ヶ所は口側腸重積の先進部となっていた。腫瘍を有する部位の小腸計3ヶ所を部分切除・再建し手術を終了した。病理組織検査では肺多型癌小腸転移の診断となり、現在外来で加療中である。(著者抄録)

  • 前立腺浸潤が疑われた局所進行直腸癌に対し腹腔鏡下に手術を施行した1例 Reviewed

    永原 央, 中尾 重富, 福岡 達成, 渋谷 雅常, 前田 清, 松谷 慎治, 土井 洋輔, 大谷 博, 山崎 健史, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    癌と化学療法   44 ( 12 )   1523 - 1525   2017.11( ISSN:0385-0684

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    症例は58歳、男性。肛門痛、血便を主訴に他院を受診し、前立腺浸潤を伴う直腸癌と診断、人工肛門造設術を施行され、術前化学療法としてmFOLFOX6を6コース施行後、手術目的に当院を紹介受診となった。術前評価はPRであったが前立腺の浸潤は残存していると判断し、腹腔鏡下に腹会陰式直腸切断術、前立腺合併切除、尿道膀胱吻合による尿路再建を行い、術後第10病日に軽快退院となった。術後2年を経過した現在、明らかな排尿障害、残尿は認めず無再発生存中である。本術式は良好な術野が得られ、確実な切除が得られる点で非常に有用な術式であると思われた。(著者抄録)

  • Adverse Effects of Low Preoperative Skeletal Muscle Mass in Patients Undergoing Gastrectomy for Gastric Cancer Reviewed

    Sakurai Katsunobu, Kubo Naoshi, Tamura Tatsuro, Toyokawa Takahiro, Amano Ryosuke, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei, Ohira Masaichi

    ANNALS OF SURGICAL ONCOLOGY   24 ( 9 )   2712 - 2719   2017.09( ISSN:1068-9265

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    DOI: 10.1245/s10434-017-5875-6

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  • Adverse Effects of Low Preoperative Skeletal Muscle Mass in Patients Undergoing Gastrectomy for Gastric Cancer Reviewed

    Katsunobu Sakurai, Naoshi Kubo, Tatsuro Tamura, Takahiro Toyokawa, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira

    ANNALS OF SURGICAL ONCOLOGY   24 ( 9 )   2712 - 2719   2017.09( ISSN:1068-9265

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    Objective. The aim of this study was to determine the impact of preoperative skeletal muscle mass on short- and long-term outcomes of patients with gastric cancer (GC) who undergo gastrectomy.
    Methods. A total of 569 patients subjected to gastrectomy for GC at our institution between January 2007 and December 2013 were reviewed and skeletal muscle index (SMI) was measured via cross-sectional, image-based muscle assessment. Computed tomography (CT) and the volume analyzer SYNAPSE VINCENT were required. Patients were divided into two groups, with the first quartile serving as the cut-point for both men and women. Clinicopathologic features and short- and long-term outcomes were compared.
    Results. In multivariate analysis, SMI emerged as an independent predictor of 5 year overall survival (OS) and cancer-specific survival (CSS) in patients with GC. In subgroup analysis, by stage, patients with stage I disease and low (vs. high) SMI demonstrated significantly worse 5 year OS. The incidence of postoperative complications did not differ significantly by group.
    Conclusions. Preoperative SMI, measured in cross-section using CT, is a useful nutritional determinant that may predict OS and CSS in patients with GC who undergo gastrectomy. In our view, nutritional support for sarcopenic patients with stage I GC, aimed at retaining or adding skeletal muscle mass, may improve survival. Our analysis showed no relationship between preoperative SMI and postoperative complications.

    DOI: 10.1245/s10434-017-5875-6

    PubMed

  • Cancer-associated fibroblasts induce cancer cell apoptosis that regulates invasion mode of tumours Reviewed

    Itoh G., Chida S., Yanagihara K., Yashiro M., Aiba N., Tanaka M.

    ONCOGENE   36 ( 31 )   4434 - 4444   2017.08( ISSN:0950-9232

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    DOI: 10.1038/onc.2017.49

  • Cancer-associated fibroblasts induce cancer cell apoptosis that regulates invasion mode of tumours. Reviewed

    Itoh G, Chida S, Yanagihara K, Yashiro M, Aiba N, Tanaka M

    Oncogene   36 ( 31 )   4434 - 4444   2017.08( ISSN:0950-9232

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    DOI: 10.1038/onc.2017.49

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  • Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells Reviewed

    Ishimoto Takatsugu, Miyake Keisuke, Nandi Tannistha, Yashiro Masakazu, Onishi Nobuyuki, Huang Kie Kyon, Lin Suling Joyce, Kalpana Ramnarayanan, Tay Su Ting, Suzuki Yuka, Cho Byoung Chul, Kuroda Daisuke, Arima Kota, Izumi Daisuke, Iwatsuki Masaaki, Baba Yoshifumi, Oki Eiji, Watanabe Masayuki, Saya Hideyuki, Hirakawa Kosei, Baba Hideo, Tan Patrick

    GASTROENTEROLOGY   153 ( 1 )   191 - +   2017.07( ISSN:0016-5085

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    DOI: 10.1053/j.gastro.2017.03.046

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  • Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells Reviewed

    Takatsugu Ishimoto, Keisuke Miyake, Tannistha Nandi, Masakazu Yashiro, Nobuyuki Onishi, Kie Kyon Huang, Suling Joyce Lin, Ramnarayanan Kalpana, Su Ting Tay, Yuka Suzuki, Byoung Chul Cho, Daisuke Kuroda, Kota Arima, Daisuke Izumi, Masaaki Iwatsuki, Yoshifumi Baba, Eiji Oki, Masayuki Watanabe, Hideyuki Saya, Kosei Hirakawa, Hideo Baba, Patrick Tan

    GASTROENTEROLOGY   153 ( 1 )   191 - 204.e16   2017.07( ISSN:0016-5085

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    BACKGROUND & AIMS: Fibroblasts that interact with cancer cells are called cancer-associated fibroblasts (CAFs), which promote progression of different tumor types. We investigated the characteristics and functions of CAFs in diffuse-type gastric cancers (DGCs) by analyzing features of their genome and gene expression patterns. METHODS: We isolated CAFs and adjacent non-cancer fibroblasts (NFs) from 110 gastric cancer (GC) tissues from patients who underwent gastrectomy in Japan from 2008 through 2016. Cells were identified using specific markers of various cell types by immunoblot and flow cytometry. We selected pairs of CAFs and NFs for whole-exome and RNA sequencing analyses, and compared expression of specific genes using quantitative reverse transcription PCR. Protein levels and phosphorylation were compared by immunoblot and immunofluorescence analyses. Rhomboid 5 homolog 2 (RHBDF2) was overexpressed from a transgene in fibroblasts or knocked down using small interfering RNAs. Motility and invasiveness of isolated fibroblasts and GC cell lines (AGS, KATOIII, MKN45, NUGC3, NUGC4, OCUM-2MD3 and OCUM-12 cell lines) were quantified by real-time imaging analyses. We analyzed 7 independent sets of DNA microarray data from patients with GC and associated expression levels of specific genes with patient survival times. Nude mice were given injections of OCUM-2MD3 in the stomach wall; tumors and metastases were collected and analyzed by immunohistochemistry. RESULTS: Many of the genes with increased expression in CAFs compared with NFs were associated with transforming growth factor beta 1 (TGFB1) activity. When CAFs were cultured in extracellular matrix, they became more motile than NFs; DGC cells incubated with CAFs were also more motile and invasive in vitro than DGC cells not incubated with CAFs. When injected into nude mice, CAF-incubated DGC cells invaded a greater number of lymphatic vessels than NF-incubated DGC cells. We identified RHBDF2 as a gene overexpressed in CAFs compared with NFs. Knockdown of RHBDF2 in CAFs reduced their elongation and motility in response to TGFB1, whereas overexpression of RHBDF2 in NFs increased their motility in extracellular matrix. RHBDF2 appeared to regulate oncogenic and non-canonical TGFB1 signaling. Knockdown of RHBDF2 in CAFs reduced cleavage of the TGFB receptor 1 (TGFBR1) by ADAM metallopeptidase domain 17 (ADAM17 or TACE) and reduced expression of genes that regulate motility. Incubation of NFs with in interleukin 1 alpha (IL1A), IL1B or tumor necrosis factor, secreted by DGCs, increased fibroblast expression of RHBDF2. Simultaneous high expression of these cytokines in GC samples was associated with shorter survival times of patients. CONCLUSIONS: In CAFs isolated from human DGCs, we observed increased expression of RHBDF2, which regulates TGFB1 signaling. Expression of RHBDF2 in fibroblasts is induced by inflammatory cytokines (such as IL1A, IL1B, and tumor necrosis factor) secreted by DGCs. RHBDF2 promotes cleavage of TGFBR1 by activating TACE and motility of CAFs in response to TGFB1. These highly motile CAFs induce DGCs to invade extracellular matrix and lymphatic vessels in nude mice.

    DOI: 10.1053/j.gastro.2017.03.046

    PubMed

  • Interaction between the malignant melanoma cell of the primary lesion and the metastatic lesion Reviewed

    Hatano Takaharu, Motomura HIsashi, Fujikawa Heishiro, Yashiro Masakazu, Kitayama Kishu

    CANCER RESEARCH   77   2017.07( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2017-2985

  • Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Nakamae Hirohisa, Masuda Go, Kinoshita Haruhito, Morisaki Tamami, Fukuoka Tatsunari, Hasegawa Tsuyoshi, Nakane Takahiko, Hino Masayuki, Hirakawa Kosei, Ohira Masaichi

    PLOS ONE   12 ( 6 )   e0178635   2017.06( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0178635

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  • Immunoregulatory Function of Lymphatic Endothelial Cells in Tumor-draining Lymph Nodes of Human Gastric Cancer Reviewed

    Tokumoto Mao, Tanaka Hiroaki, Tauchi Yukie, Tamura Tatsuro, Toyokawa Takahiro, Kimura Kenjiro, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei, Ohira Masaichi

    ANTICANCER RESEARCH   37 ( 6 )   2875 - 2883   2017.06( ISSN:0250-7005

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    DOI: 10.21873/anticanres.11640

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  • Immunoregulatory Function of Lymphatic Endothelial Cells in Tumor-draining Lymph Nodes of Human Gastric Cancer Reviewed

    Mao Tokumoto, Hiroaki Tanaka, Yukie Tauchi, Tatsuro Tamura, Takahiro Toyokawa, Kenjiro Kimura, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira

    ANTICANCER RESEARCH   37 ( 6 )   2875 - 2883   2017.06( ISSN:0250-7005

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    Background/Aim: Lymph node metastasis is the most important prognostic factor for patients with gastric cancer. Increasing evidence suggests that lymphatic endothelial cells (LECs) regulate immune responses. The aim of this study was to examine the effect of LECs on the activation of CD4(+) T cells. Materials and Methods: We examined the impact of cancer cells on the phenotype and production of cytokines of LECs derived from tumor-draining lymph nodes. Results: We showed that LECs inhibited CD4(+) T cell production of cytokines, such as IL-2, IL-10, and INF-gamma. The mRNA expression of programmed death-ligand 1 (PD-L1) and indoleamine 2, 3-dioxygenase (IDO) by LECs were significantly up-regulated when the LECs and CD4(+) T cells were co-cultured with cells of the gastric cancer cell line, OCUM12. Conclusion: Intranodal LECs may be a key player in the induction of immune tolerance against cancer and in facilitating metastasis through lymphatic vessels in gastric cancer.

    DOI: 10.21873/anticanres.11640

    PubMed

  • Clinical experience of S-1 and oxaliplatin (SOX) as the first-line chemotherapy for metastatic/recurrent gastric cancer Reviewed

    Takahiro Toyokawa, Tatsuro Tamura, Masatsune Shibutani, Goh Ohira, Sadaaki Yamazoe, Kenjiro Kimura, Hisashi Nagahara, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kosei Hirakawa, Masaichi Ohira

    Japanese Journal of Cancer and Chemotherapy   44 ( 5 )   405 - 408   2017.05( ISSN:0385-0684

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    We retrospectively investigated the efficacy and safety of S-1 and oxaliplatin (SOX) as the first-line chemotherapy in patients with metastatic/recurrent gastric cancer. A total of 27 patients who received SOX as the first-line chemotherapy in our hospital were considered for the study. The SOX chemotherapy schedule consisted of 1 course every 3 weeks. S-1 was administered orally, at 80-120 mg-body, every day for 14 days. Oxaliplatin was infused at 100mg/m2 on day 1 of each course. The median number of treatment courses was 7. The response rate and disease control rate were 47.6% and 76.2%, respectively. The observed adverse events of Grade 3 or more included neutropenia (33.3%)
    peripheral neuropathy and anorexia (11.1%)
    thrombocytopenia (7.4%)
    and anemia, diarrhea, fatigue, and hypercalcemia (3.7%). The median overall survival was not achieved, and the 1-year survival rate was 63.2%. Therefore, SOX is an effective and feasible first-line chemotherapy that is easily available for ambulatory treatment of patients with metastatic/recurrent gastric cancer.

    PubMed

  • [Clinical Experience of S-1 and Oxaliplatin(SOX)as the First-Line Chemotherapy for Metastatic/Recurrent Gastric Cancer]. Reviewed

    Toyokawa T, Tamura T, Shibutani M, Ohira G, Yamazoe S, Kimura K, Nagahara H, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 5 )   405 - 408   2017.05( ISSN:0385-0684

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  • 進行再発胃癌に対するSOX療法の治療成績 Reviewed

    豊川 貴弘, 田村 達郎, 渋谷 雅常, 大平 豪, 山添 定明, 木村 健二郎, 永原 央, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   44 ( 5 )   405 - 408   2017.05( ISSN:0385-0684

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    進行再発胃癌に対する一次治療としてのS-1+oxaliplatin(SOX)療法の有効性と安全性について検討した。対象は当科でSOX療法を施行した進行再発胃癌27例である。投与方法はoxaliplatin 100mg/m2を第1日目に点滴静注、S-1 80〜120mg/bodyを2週投与1週休薬で投与し、3週1コースとした。投与コース中央値は7コースで、奏効率47.6%、病勢コントロール率は76.2%であった。Grade 3以上の有害事象は、好中球減少33.3%、末梢神経障害、食欲不振11.1%、血小板減少7.4%、貧血、下痢、疲労、高カルシウム血症を3.7%に認めた。生存期間中央値には到達せず、1年生存率は63.2%であった。実地臨床においてもSOX療法の治療効果は良好で、外来で安全に施行可能であった。(著者抄録)

  • [Clinical Experience of S-1 and Oxaliplatin(SOX)as the First-Line Chemotherapy for Metastatic/Recurrent Gastric Cancer]. Reviewed

    Toyokawa T, Tamura T, Shibutani M, Ohira G, Yamazoe S, Kimura K, Nagahara H, Amano R, Tanaka H, Muguruma K, Yashiro M, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 5 )   405 - 408   2017.05( ISSN:0385-0684

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  • 進行再発胃癌に対するSOX療法の治療成績 Reviewed

    豊川 貴弘, 田村 達郎, 渋谷 雅常, 大平 豪, 山添 定明, 木村 健二郎, 永原 央, 天野 良亮, 田中 浩明, 六車 一哉, 八代 正和, 平川 弘聖, 大平 雅一

    癌と化学療法   44 ( 5 )   405 - 408   2017.05( ISSN:0385-0684

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    進行再発胃癌に対する一次治療としてのS-1+oxaliplatin(SOX)療法の有効性と安全性について検討した。対象は当科でSOX療法を施行した進行再発胃癌27例である。投与方法はoxaliplatin 100mg/m2を第1日目に点滴静注、S-1 80~120mg/bodyを2週投与1週休薬で投与し、3週1コースとした。投与コース中央値は7コースで、奏効率47.6%、病勢コントロール率は76.2%であった。Grade 3以上の有害事象は、好中球減少33.3%、末梢神経障害、食欲不振11.1%、血小板減少7.4%、貧血、下痢、疲労、高カルシウム血症を3.7%に認めた。生存期間中央値には到達せず、1年生存率は63.2%であった。実地臨床においてもSOX療法の治療効果は良好で、外来で安全に施行可能であった。(著者抄録)

  • C-Reactive Protein Indicates Early Stage of Postoperative Infectious Complications in Patients Following Minimally Invasive Esophagectomy Reviewed

    Miki Yuichiro, Toyokawa Takahiro, Kubo Naoshi, Tamura Tatsuro, Sakurai Katsunobu, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    WORLD JOURNAL OF SURGERY   41 ( 3 )   796 - 803   2017.03( ISSN:0364-2313

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    DOI: 10.1007/s00268-016-3803-8

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  • C-Reactive Protein Indicates Early Stage of Postoperative Infectious Complications in Patients Following Minimally Invasive Esophagectomy Reviewed

    Yuichiro Miki, Takahiro Toyokawa, Naoshi Kubo, Tatsuro Tamura, Katsunobu Sakurai, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kosei Hirakawa, Masaichi Ohira

    WORLD JOURNAL OF SURGERY   41 ( 3 )   796 - 803   2017.03( ISSN:0364-2313

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    Esophagectomy for patients with esophageal cancer is associated with high rate of postoperative infectious complications (PICs). Although minimally invasive esophagectomy (MIE) could reduce the rate of PICs, its incidence cannot be ignored. Early detection of PICs may be beneficial in clinical settings. We investigated whether systemic inflammation markers, such as C-reactive protein (CRP) and white blood cell count (WBC), are useful for the early detection of PICs.
    We reviewed 158 patients who underwent MIE from 2000 to 2015 and assessed PIC incidence and severity. The value of CRP and WBC in the early detection of PICs was evaluated by receiver operating characteristics analyses. Univariate and multivariate analyses were performed to identify severe PICs risk factors (Clavien-Dindo classification, grade IIIa or higher).
    Thirty patients developed PICs: grades III, IV, and V in 19 (12.0%), 9 (5.7%), and 2 (1.3%) patients, respectively. CRP on 4POD showed the highest value for detection of PICs (AUC = 072). Cutoff value of CRP on 4POD was determined as 11.1 (mg/dL), in which the sensitivity and specificity were the maximum value. The univariate analysis revealed that sex (male), operation time (&gt;= 597 min), and CRP on 4POD (&gt;= 11.1 mg/dL) were significant factors for detecting PICs. Multivariate analyses showed that operation time (&gt;= 597) and CRP on 4POD (&gt;= 11.1 mg/dL) were independent significant factors for detecting PICs.
    CRP on 4POD &gt;= 11.1 mg/dL was an independent PICs risk factor in patients who underwent MIE. It will be beneficial for the early detection of PICs following MIE.

    DOI: 10.1007/s00268-016-3803-8

    PubMed

  • Cervical chylous leakage following esophagectomy treated by intranodal lipiodol lymphangiography: a case report Reviewed

    Tamura Tatsuro, Kubo Naoshi, Yamamoto Akira, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei, Ohira Masaichi

    BMC SURGERY   17 ( 1 )   20   2017.02( ISSN:1471-2482

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    DOI: 10.1186/s12893-017-0218-x

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  • Cervical chylous leakage following esophagectomy treated by intranodal lipiodol lymphangiography: a case report Reviewed

    Tatsuro Tamura, Naoshi Kubo, Akira Yamamoto, Katsunobu Sakurai, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira

    BMC SURGERY   17 ( 1 )   20   2017.02( ISSN:1471-2482

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    Background: Chylous leakage is a well-known complication after esophagectomy, but cervical chylous leakage is relatively rare, and considerable controversy remains regarding the appropriate management strategies. We herein report a case of cervical chylous leakage treated successfully by lipiodol lymphangiography.
    Case presentation: The patient, a 70-year-old man with middle thoracic esophageal cancer, underwent radical esophagectomy with 3-field lymph node dissection and subsequently developed cervical chylous leakage. From the second postoperative day (POD2), the amount of fluid in the cervical drainage tube increased by 200-300 ml/day. We started octreotide (300 mu g/day) on POD5 and etilefrine (120 mg/day) on the POD6. However, the amount of cervical discharge did not decrease. We performed lipiodol lymphangiography on POD8. Thereafter, the amount of cervical discharge finally began to decrease. We removed the drainage tube on POD13, and the patient was discharged from the hospital on POD23.
    Conclusions: Our case suggests the clinical efficacy of lipiodol lymphangiography for cervical chylous leakage after esophagectomy.

    DOI: 10.1186/s12893-017-0218-x

    PubMed

  • Mesothelial Cells Create a Novel Tissue Niche That Facilitates Gastric Cancer Invasion Reviewed

    Tanaka Masamitsu, Kuriyama Sei, Itoh Go, Maeda Daichi, Goto Akiteru, Tamiya Yutaro, Yanagihara Kazuyoshi, Yashiro Masakazu, Aiba Namiko

    CANCER RESEARCH   77 ( 3 )   684 - 695   2017.02( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-16-0964

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  • Mesothelial Cells Create a Novel Tissue Niche That Facilitates Gastric Cancer Invasion Reviewed

    Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba

    CANCER RESEARCH   77 ( 3 )   684 - 695   2017.02( ISSN:0008-5472

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    Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that the PMCs guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMCs covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles. Infiltrated PMCs in turn promoted subserosal invasion of cancer cells. Mutual attraction between cancer cells and PMCs accelerated tumor invasion in the gastric wall, and PMC-led cancer cell invasion in disseminated tumors within the abdominal wall and diaphragm. Addition of the carboxyl terminus of Dickkopf-1 attenuated directional invasion of PMCs toward cancer cells both in vitro and in the gastric wall in vivo. PMCs were sensitive to the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF), as ALDH activity is elevated in PMCs. Wnt3a upregulated ALDH, and addition of DSF inhibited the invasive properties of PMCs, whereas DSF pretreatment suppressed gastric infiltration of PMCs and subserosal invasion by cancer cells. Our results suggest that stabilization of PMCs may become an effective therapy for the prevention of local invasion and metastasis of gastric cancer. (C) 2016 AACR.

    DOI: 10.1158/0008-5472.CAN-16-0964

    PubMed

  • Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy Reviewed

    Kubo Naoshi, Ohira Masaichi, Tamura Tatsuro, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Yashiro Masakazu, Yamashita Yoshito, Hirakawa Kosei

    ESOPHAGUS   14 ( 1 )   84 - 90   2017.01( ISSN:1612-9059

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    DOI: 10.1007/s10388-016-0548-2

  • 根治的食道切除後の食道扁平上皮癌患者における術前の予後指標としての栄養指数の意義(Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy) Reviewed

    Kubo Naoshi, Ohira Masaichi, Tamura Tatsuro, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Yashiro Masakazu, Yamashita Yoshito, Hirakawa Kosei

    シュプリンガー・ジャパン(株) Esophagus   14 ( 1 )   84 - 90   2017.01( ISSN:1612-9059

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    食道扁平上皮癌(ESCC)に対する根治的食道切除後の短期および長期成績に、術前のprognostic nutritional index(PNI)がどのような影響を及ぼすか後ろ向きに検討した。対象はESCC患者202例(男性162例、女性40例、年齢43〜87歳)で、PNIは10×血清アルブミン値(g/dL)+0.005×総リンパ球計数(per mm3)で計算した。平均PNIは48.9±4.6で、多重ロジスティック回帰分析における受信者動作特性曲線下面積は0.5367であった。予測5年生存率はPNIが44.1の場合に最適であったためカットオフ値を44とし、患者をPNI 44以上の高PNI群(173例)と44未満の低PNI群(29例)に分類した。全生存率(OS)および無再発生存率(RFS)は高PNI群に比して低PNI群で有意に不良で、5年OSとRFSは高PNI群で67.2%と61.5%、低PNI群で41.2%と38.8%であった。術後合併症は両群で差は認められなかった。OSおよびRFSに対するCox比例ハザードモデルを用いた単変量および多変量解析では、PNIが両者に対する重要な予後因子であることが明らかとなった。PNIは根治手術を予定されているESCC患者に対する実践的予後マーカーであり、低PNIのESCC患者に対する術後の腫瘍再発に対する注意深いフォローアップが必要であることが示唆された。

  • 根治的食道切除後の食道扁平上皮癌患者における術前の予後指標としての栄養指数の意義(Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy) Reviewed

    Kubo Naoshi, Ohira Masaichi, Tamura Tatsuro, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Yashiro Masakazu, Yamashita Yoshito, Hirakawa Kosei

    Esophagus   14 ( 1 )   84 - 90   2017.01( ISSN:1612-9059

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    食道扁平上皮癌(ESCC)に対する根治的食道切除後の短期および長期成績に、術前のprognostic nutritional index(PNI)がどのような影響を及ぼすか後ろ向きに検討した。対象はESCC患者202例(男性162例、女性40例、年齢43~87歳)で、PNIは10×血清アルブミン値(g/dL)+0.005×総リンパ球計数(per mm3)で計算した。平均PNIは48.9±4.6で、多重ロジスティック回帰分析における受信者動作特性曲線下面積は0.5367であった。予測5年生存率はPNIが44.1の場合に最適であったためカットオフ値を44とし、患者をPNI 44以上の高PNI群(173例)と44未満の低PNI群(29例)に分類した。全生存率(OS)および無再発生存率(RFS)は高PNI群に比して低PNI群で有意に不良で、5年OSとRFSは高PNI群で67.2%と61.5%、低PNI群で41.2%と38.8%であった。術後合併症は両群で差は認められなかった。OSおよびRFSに対するCox比例ハザードモデルを用いた単変量および多変量解析では、PNIが両者に対する重要な予後因子であることが明らかとなった。PNIは根治手術を予定されているESCC患者に対する実践的予後マーカーであり、低PNIのESCC患者に対する術後の腫瘍再発に対する注意深いフォローアップが必要であることが示唆された。

  • Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy Reviewed

    Naoshi Kubo, Masaichi Ohira, Tatsuro Tamura, Katsunobu Sakurai, Takahiro Toyokawa, Hiroaki Tanaka, Masakazu Yashiro, Yoshito Yamashita, Kosei Hirakawa

    ESOPHAGUS   14 ( 1 )   84 - 90   2017.01( ISSN:1612-9059

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    Background Radical esophagectomy is the cornerstone of curative treatment for patients with resectable esophageal squamous cell carcinoma (ESCC). Patient survival after surgery for ESCC is mainly associated with pathological tumor progression. Recently, the impact of baseline immune-nutritional status of various types of patients with cancer on survival has been highlighted. The purpose of the present study was to investigate the association between the baseline prognostic nutritional index (PNI) and postoperative short-and long-term results after esophagectomy for patients with ESCC. Methods In total, 202 patients with ESCC who underwent radical esophagectomy at our institution between 2002 and 2010 were enrolled. PNI was calculated as 10x serum albumin (g/dL) + 0.005 x total lymphocyte counts (per mm3). Receiver operating characteristic (ROC) curves were generated for multiple logistic regression analysis using 5-year overall survival as the endpoint to determine an optimal PNI cutoff value, in which patients were classified into two groups: high PNI and low PNI. We evaluated the significance of PNI on postoperative morbidity and long-term survival using univariate and multivariate analyses. Results The mean PNI was 48.9 +/- 4.6 (range 37.2-64.0). The area under the ROC curve in multiple logistic regression analysis was 0.5367. The projected 5-year survival rate was optimal at a PNI of 44.1. Hence, the PNI cutoff point was set at 44, with subjects classified by PNI level into the low (PNI &lt; 44) or high (PNI = 44) PNI groups. Of 202 patients, 173 (85.7 %) and 29 (14.3 %) were classified as having high and low PNI, respectively. No significant differences were noted between the two groups regarding patient background, including age, sex, pT, pN, and pStage, or postoperative complications. However, overall survival (OS) and relapse-free survival (RFS) were significantly worse in the low PNI group than in the high PNI group. The 5-year OS and RFS rates in the high PNI vs. low PNI groups were 67.2 vs. 41.2 % (P = 0.007) and 61.5 vs. 38.8 % (P = 0.008), respectively. Multivariate analysis revealed that PNI was a significant prognostic factor for both OS (hazard ratio, 1.826; 95 % confidence interval, 1.015-3.285; P = 0.044) and RFS (hazard ratio, 1.862; 95 % confidence interval, 1.121-3.095; P = 0.016). Conclusion Preoperative PNI is an independent prognostic marker of both OS and RFS for patients with potentially curative ESCC. A careful follow-up for tumor recurrence after surgery is required for ESCC patients with low PNI.

    DOI: 10.1007/s10388-016-0548-2

  • Effect of glucose metabolism-related enzymes on the proliferation of gastric cancer cells in hypoxic microenvironment Reviewed

    Kitayama Kishu, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi, Yashiro Masakazu, Morisaki Tamami, Okuno Tomohisa, Miki Yuichiro, Kasashima Hiroaki, Masuda Go, Toyokawa Takahiro, Tanaka Hiroaki

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   32 ( 0 )   2017

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    DOI: 10.11241/jsmtmr.32.55

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  • 胃癌診療における腫瘍マーカー Reviewed

    八代 正和

    日本分子腫瘍マーカー研究会 日本分子腫瘍マーカー研究会誌   32 ( 0 )   2017

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    DOI: 10.11241/jsmtmr.32.10

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  • Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma Reviewed

    Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira

    PLOS ONE   12 ( 6 )   e0178635   2017( ISSN:1932-6203

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    Purpose
    It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer.
    Methods
    The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro.
    Results
    The expression of CXCL1 in cancer cells was correlated with T invasion (T2-T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2-T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients.
    Conclusion
    The expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.

    DOI: 10.1371/journal.pone.0178635

    PubMed

  • Effect of glucose metabolism-related enzymes on the proliferation of gastric cancer cells in hypoxic microenvironment Reviewed

    Kitayama Kishu, Yashiro Masakazu, Morisaki Tamami, Okuno Tomohisa, Miki Yuichiro, Kasashima Hiroaki, Masuda Go, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Hirakawa Kosei, Ohira Masaichi

    Japan Journal of Molecular Tumor Marker Research   32 ( 0 )   55   2017

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    DOI: 10.11241/jsmtmr.32.55

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  • 胃癌診療における腫瘍マーカー Reviewed

    八代 正和

    日本分子腫瘍マーカー研究会誌   32 ( 0 )   10   2017

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    DOI: 10.11241/jsmtmr.32.10

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  • Identification of the novel molecules mediating gastric cancer invasion based on genomic analysis of cancer-associated fibroblasts Reviewed

    Ishimoto T., Miyake K., Nandi T., Yashiro M., Huang K. K., Arima K., Izumi D., Baba Y., Baba H., Tan P.

    ANNALS OF ONCOLOGY   27   2016.12( ISSN:0923-7534

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  • 癌宿主因子における予後および効果予測 Reviewed

    後藤 航, 柏木 伸一郎, 浅野 有香, 渋谷 雅常, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 高島 勉, 八代 正和, 小野田 尚佳, 前田 清, 平川 弘聖, 大平 雅一

    大道学館出版部 臨牀と研究   93 ( 12 )   1614 - 1615   2016.12( ISSN:0021-4965

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    癌宿主因子における炎症指標の有用性について検証した。グラスゴー予後予測スコアはCRP値とアルブミン値によって算出されるが、その他の指標はそれぞれの因子の絶対値の組み合わせで求められる。カットオフ値はROC解析で求めることが多く、評価項目は全生存期間または無病生存期間に関連して測定されることが多い。すべての指標において基準とされる数値は存在しない。末梢血から求められる炎症反応や栄養状態、免疫環境などの宿主因子は、有用な予後および治療効果予測因子である可能性が示唆された。

  • 癌宿主因子における予後および効果予測 Reviewed

    後藤 航, 柏木 伸一郎, 浅野 有香, 渋谷 雅常, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 高島 勉, 八代 正和, 小野田 尚佳, 前田 清, 平川 弘聖, 大平 雅一

    臨牀と研究   93 ( 12 )   1614 - 1615   2016.12( ISSN:0021-4965

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    癌宿主因子における炎症指標の有用性について検証した。グラスゴー予後予測スコアはCRP値とアルブミン値によって算出されるが、その他の指標はそれぞれの因子の絶対値の組み合わせで求められる。カットオフ値はROC解析で求めることが多く、評価項目は全生存期間または無病生存期間に関連して測定されることが多い。すべての指標において基準とされる数値は存在しない。末梢血から求められる炎症反応や栄養状態、免疫環境などの宿主因子は、有用な予後および治療効果予測因子である可能性が示唆された。

  • [A Case of Metastatic Lung Cancer from Colon Cancer with a Long Partial Response with Regorafenib Treatment]. Reviewed

    Iseki Y, Yashiro M, Shibutani M, Nagahara H, Maeda K, Matsutani S, Tamura T, Ohira G, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2338 - 2340   2016.11( ISSN:0385-0684

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  • CXCL1-Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow-Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Nakamae Hirohisa, Kitayama Kisyu, Masuda Go, Kinoshita Haruhito, Fukuoka Tatsunari, Hasegawa Tsuyoshi, Nakane Takahiko, Hino Masayuki, Hirakawa Kosei, Ohira Masaichi

    AMERICAN JOURNAL OF PATHOLOGY   186 ( 11 )   3028 - 3039   2016.11( ISSN:0002-9440

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    DOI: 10.1016/j.ajpath.2016.07.024

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  • Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin Reviewed

    Ohbatake Yoshinao, Fushida Sachio, Tsukada Tomoya, Kinoshita Jun, Oyama Katsunobu, Hayashi Hironori, Miyashita Tomoharu, Tajima Hidehiro, Takamura Hiroyuki, Ninomiya Itasu, Yashiro Masakazu, Hirakawa Kousei, Ohta Tetsuo

    CLINICAL AND EXPERIMENTAL MEDICINE   16 ( 4 )   585 - 592   2016.11( ISSN:1591-8890

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    DOI: 10.1007/s10238-015-0387-9

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  • レゴラフェニブにて18ヵ月間の長期PRが得られた大腸癌肺転移の1例 Reviewed

    井関 康仁, 八代 正和, 渋谷 雅常, 永原 央, 前田 清, 松谷 慎治, 田村 達郎, 大平 豪, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    (株)癌と化学療法社 癌と化学療法   43 ( 12 )   2338 - 2340   2016.11( ISSN:0385-0684

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    症例は66歳、女性。2005年12月、当科にてS状結腸癌に対してS状結腸切除術を施行。病理結果にてpT2N0M0、fStage Iであり、術後補助化学療法は施行せず経過観察していた。2011年11月にCEA 9.7ng/mLと上昇を認め、精査にて転移性肺癌を認めた。FOLFOX+bevacizumab(BV)療法を21コース、FOLFIRI+BV療法を6コース、XELOX+BV療法を13コース施行した。いずれのレジメンもprogressive disease(PD)となったため、fourth-lineとしてレゴラフェニブ療法を開始した。レゴラフェニブ開始前のレジメンにて手足症候群がみられたため、80mg/dayで開始した、Grade 2以上の副作用はでることなく投与開始後18ヵ月経過し、長期間partial response(PR)が持続し現在22コース施行中である。大腸癌肺転移再発症例に対してレゴラフェニブ投与により長期にわたるPRを得ることができた1例を経験した。(著者抄録)

  • Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin Reviewed

    Yoshinao Ohbatake, Sachio Fushida, Tomoya Tsukada, Jun Kinoshita, Katsunobu Oyama, Hironori Hayashi, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Masakazu Yashiro, Kousei Hirakawa, Tetsuo Ohta

    CLINICAL AND EXPERIMENTAL MEDICINE   16 ( 4 )   585 - 592   2016.11( ISSN:1591-8890

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    Paclitaxel (PTX) which easily elutes into ascites is widely used to treat gastric cancer patients with peritoneal carcinomatosis (PC), but clinical outcomes are suboptimal. Increased concentrations of alpha 1-acid glycoprotein (AGP), an important drug-binding protein, have been reported in the plasma and ascites of cancer patients. This study sought to clarify whether AGP binds to PTX and alters its anticancer effects. AGP concentrations were measured in the serum and ascites of gastric cancer patients with PC and in the serum of healthy volunteers. The in vitro effects of AGP and AGP plus erythromycin (EM) on PTX were evaluated by MTT assays in the gastric cancer cell lines. We also measured AGP concentrations in the ascites of PC model mice and examined the effects of EM plus PTX on PC. The mean AGP concentrations in the serum and ascites of gastric cancer patients with PC were 1524 and 834 mu g/mL, respectively, higher than the mean AGP concentration of 650 mu g/mL observed in the sera of healthy volunteers. AGP &gt; 400 mu g/mL significantly suppressed the cell growth inhibitory effect of PTX in vitro, but the co-administration of EM restored it. Elevated AGP concentrations were observed in the ascites of PC model mice. Administration of PTX alone did not markedly diminish PC, whereas co-administration of PTX and EM significantly reduced PC (p = 0.011). AGP is an important regulatory factor modulating the anticancer activity of intraperitoneal PTX. The co-administration of PTX and EM may be effective in treating gastric cancer patients with PC.

    DOI: 10.1007/s10238-015-0387-9

    PubMed

  • [A Case of Metastatic Lung Cancer from Colon Cancer with a Long Partial Response with Regorafenib Treatment]. Reviewed

    Iseki Y, Yashiro M, Shibutani M, Nagahara H, Maeda K, Matsutani S, Tamura T, Ohira G, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2338 - 2340   2016.11( ISSN:0385-0684

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    PubMed

  • CXCL1-Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow-Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma Reviewed

    Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira

    AMERICAN JOURNAL OF PATHOLOGY   186 ( 11 )   3028 - 3039   2016.11( ISSN:0002-9440

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    Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stomal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken beta-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs). The influences of chemokine (C-X-C motif) receptor 2 (CXCR2) inhibitor on the migration of BM-MCs were examined both in vitro and in vivo. BM-MCs frequently migrated into stroma of DGC in vivo. The number of migrating BM-MCs was increased by conditioned medium from DGC cells. CXCL1 from DGC cells stimulated the chemoattractant ability of BM-MCs. Both anti-CXCL1 antibody and CXCR2 inhibitor decreased the migration of BM-MCs, stimulated by DGC cells. A CXCR2 inhibitor, SB225002, reduced the recruitment of BM-MCs into the tumor microenvironment in vivo, decreasing tumor size and lymph node metastasis, and prolonging the survival of gastric tumor-bearing mice. These findings suggested that most tumor stromal cells in DGC might originate from BM-MCs. CXCL1 from DGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs. Inhibition of BM-MC recruitment via the CXCL1-CXCR2 axis appears a promising therapy for DGC.

    DOI: 10.1016/j.ajpath.2016.07.024

    PubMed

  • [A Case of Metastatic Lung Cancer from Colon Cancer with a Long Partial Response with Regorafenib Treatment]. Reviewed

    Iseki Y, Yashiro M, Shibutani M, Nagahara H, Maeda K, Matsutani S, Tamura T, Ohira G, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, Muguruma K, Hirakawa K, Ohira M

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2338 - 2340   2016.11( ISSN:0385-0684

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    PubMed

  • レゴラフェニブにて18ヵ月間の長期PRが得られた大腸癌肺転移の1例 Reviewed

    井関 康仁, 八代 正和, 渋谷 雅常, 永原 央, 前田 清, 松谷 慎治, 田村 達郎, 大平 豪, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 田中 浩明, 六車 一哉, 平川 弘聖, 大平 雅一

    癌と化学療法   43 ( 12 )   2338 - 2340   2016.11( ISSN:0385-0684

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    症例は66歳、女性。2005年12月、当科にてS状結腸癌に対してS状結腸切除術を施行。病理結果にてpT2N0M0、fStage Iであり、術後補助化学療法は施行せず経過観察していた。2011年11月にCEA 9.7ng/mLと上昇を認め、精査にて転移性肺癌を認めた。FOLFOX+bevacizumab(BV)療法を21コース、FOLFIRI+BV療法を6コース、XELOX+BV療法を13コース施行した。いずれのレジメンもprogressive disease(PD)となったため、fourth-lineとしてレゴラフェニブ療法を開始した。レゴラフェニブ開始前のレジメンにて手足症候群がみられたため、80mg/dayで開始した、Grade 2以上の副作用はでることなく投与開始後18ヵ月経過し、長期間partial response(PR)が持続し現在22コース施行中である。大腸癌肺転移再発症例に対してレゴラフェニブ投与により長期にわたるPRを得ることができた1例を経験した。(著者抄録)

  • Low Preoperative Prognostic Nutritional Index Predicts Poor Survival Post-gastrectomy in Elderly Patients with Gastric Cancer Reviewed

    Sakurai Katsunobu, Tamura Tatsuro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    ANNALS OF SURGICAL ONCOLOGY   23 ( 11 )   3669 - 3676   2016.10( ISSN:1068-9265

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    DOI: 10.1245/s10434-016-5272-6

    PubMed

  • Low Preoperative Prognostic Nutritional Index Predicts Poor Survival Post-gastrectomy in Elderly Patients with Gastric Cancer Reviewed

    Katsunobu Sakurai, Tatsuro Tamura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    ANNALS OF SURGICAL ONCOLOGY   23 ( 11 )   3669 - 3676   2016.10( ISSN:1068-9265

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    Preoperative nutritional status may predict short- and long-term outcomes of patients with cancer.
    The aim of this study was to clarify the impact of preoperative nutritional status on outcomes of elderly patients who have undergone gastrectomy for gastric cancer (GC).
    A review examining 147 patients treated for GC by gastrectomy at our institution between January 2004 and December 2011 was conducted. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cutpoint to stratify patients by high (PNI &gt; 43.8; n = 84) or low (PNI aecurrency sign 43.8; n = 63) nutritional status. Clinicopathologic features and short- and long-term outcomes, including the cause of death, were compared.
    In multivariate analysis, low PNI was identified as an independent correlate of poor 5-year overall survival (OS). In subgroup analysis, 5-year OS rates for patients with stage 1 GC were significantly worse in the low PNI (vs. high PNI) patient subset, which also posed a significantly higher risk of death from other disease; however, 5-year cancer-specific survival and PNI were unrelated. Deaths from recurrence in both groups were statistically similar, and morbidity rates did not differ significantly by group.
    PNI is useful in predicting long-term outcomes of elderly patients surgically treated for GC, helping to identify those at high risk of death from other disease. In an effort to improve patient outcomes, nutritional status and oncologic staging merit attention.

    DOI: 10.1245/s10434-016-5272-6

    PubMed

  • The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study Reviewed

    Toyokawa Takahiro, Kubo Naoshi, Tamura Tatsuro, Sakurai Katsunobu, Amano Ryosuke, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Hirakawa Kosei, Ohira Masaichi

    BMC CANCER   16   722   2016.09( ISSN:1471-2407

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    DOI: 10.1186/s12885-016-2696-0

    PubMed

  • The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study Reviewed

    Takahiro Toyokawa, Naoshi Kubo, Tatsuro Tamura, Katsunobu Sakurai, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kosei Hirakawa, Masaichi Ohira

    BMC CANCER   16 ( 1 )   722   2016.09( ISSN:1471-2407

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    Background: The purpose of this study was to investigate the impact of the Controlling Nutritional Status (CONUT) score on survival compared with the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) in patients with resectable thoracic esophageal squamous cell carcinoma (ESCC).
    Methods: One hundred eighty-five consecutive patients who underwent subtotal esophagectomy with curative intent for resectable thoracic ESCC were retrospectively reviewed. Time-dependent receiver operating characteristic curve analyses for 3-year overall survival (OS) as the endpoint were performed, and the maximal Youden indices were calculated to assess discrimination ability and to determine the appropriate cut-off values of CONUT, PLR, and NLR. The patients were then classified into high and low groups based on these cut-off values. Correlations between CONUT and other clinicopathological characteristics were analyzed. Prognostic factors predicting overall survival (OS) and relapse-free survival (RFS) were analyzed using Cox proportional hazards models.
    Results: The areas under the curve predicting 3-year OS were 0.603 for CONUT, 0.561 for PLR, 0.564 for NLR, and 0.563 for GPS. The optimal cut-off values were two for the CONUT score, 193 for PLR, and 3.612 for NLR. The high-CONUT group was significantly associated with lower BMI, high-PLR, high-NLR, and GPS1/2 groups. On univariate analysis, high-CONUT, high-PLR, high-NLR, and GPS 1/2 groups were significantly associated with poorer OS and RFS. Of these factors, multivariate analysis revealed that only the CONUT score was an independent prognostic factor for OS (HR 2.303, 95 % CI 1.191-4.455; p = 0.013) and RFS (HR 2.163, 95 % CI 1.139-4.109; p = 0.018).
    Conclusions: The CONUT score was an independent predictor of OS and RFS before treatment and was superior to PLR, NLR, and GPS in terms of predictive ability for prognosis in patients with resectable thoracic ESCC.

    DOI: 10.1186/s12885-016-2696-0

    PubMed

  • Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia Reviewed

    Hirakawa Toshiki, Yashiro Masakazu, Doi Yosuke, Kinoshita Haruhito, Morisaki Tamami, Fukuoka Tatsunari, Hasegawa Tsuyoshi, Kimura Kenjiro, Amano Ryosuke, Hirakawa Kosei

    PLOS ONE   11 ( 8 )   e0159912   2016.08( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0159912

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  • Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells Reviewed

    Takahashi Katsuyuki, Tanaka Masako, Yashiro Masakazu, Matsumoto Masaki, Ohtsuka Asuka, Nakayama Keiichi I., Izumi Yasukatsu, Nagayama Katsuya, Miura Katsuyuki, Iwao Hiroshi, Shiota Masayuki

    CANCER LETTERS   378 ( 1 )   8 - 15   2016.08( ISSN:0304-3835

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    DOI: 10.1016/j.canlet.2016.05.002

    PubMed

  • Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells Reviewed

    Katsuyuki Takahashi, Masako Tanaka, Masakazu Yashiro, Masaki Matsumoto, Asuka Ohtsuka, Keiichi I. Nakayama, Yasukatsu Izumi, Katsuya Nagayama, Katsuyuki Miura, Hiroshi Iwao, Masayuki Shiota

    CANCER LETTERS   378 ( 1 )   8 - 15   2016.08( ISSN:0304-3835

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    Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is constitutively expressed at elevated levels, which can result in enhanced stress tolerance. Similarly, following treatment with anticancer drugs, Hsp72 binds to denatured proteins that may be essential for survival. We therefore hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Here, we aimed to identify proteins that are critical for oxaliplatin (OXA) resistance by analyzing human gastric cancer cell lines, as well as OXA-resistant cells via a mass spectrometry-based proteomic approach combined with affinity purification using anti-Hsp72 antibodies. Stromal cell-derived factor 2 (SDF-2) was identified as an Hsp72 client protein unique to OCUM-2M/OXA cells. SDF-2 was overexpressed in OXA-resistant cells and SDF-2 silencing promoted the apoptotic effects of OXA. Furthermore, Hsp72 prevented SDF-2 degradation in a chaperone activity-dependent manner. Together, our data demonstrate that Hsp72 protected SDF-2 to avoid OXA-induced cell death. We propose that inhibition of SDF-2 may comprise a novel therapeutic strategy to counteract OXA-resistant cancers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.canlet.2016.05.002

    PubMed

  • Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer Reviewed

    Tauchi Yukie, Tanaka Hiroaki, Kumamoto Kanako, Tokumoto Mao, Sakimura Chie, Sakurai Katsunobu, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER SCIENCE   107 ( 8 )   1101 - 1109   2016.08( ISSN:1347-9032

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    DOI: 10.1111/cas.12977

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  • 腫瘍関連マクロファージはヒト胃癌由来リンパ管内皮細胞の毛細管形成を誘導する(Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer) Reviewed

    Tauchi Yukie, Tanaka Hiroaki, Kumamoto Kanako, Tokumoto Mao, Sakimura Chie, Sakurai Katsunobu, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    John Wiley & Sons Australia, Ltd Cancer Science   107 ( 8 )   1101 - 1109   2016.08( ISSN:1347-9032

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    胃癌の予後指標である腫瘍リンパ管形成におけるマクロファージの役割について検討するため、当院で胃癌の外科的処置が施行された患者の転移リンパ節(LN)由来リンパ管内皮細胞(LEC)と腫瘍関連マクロファージ間の相互作用について評価した。LECをマクロファージと直接的または間接的に、胃癌細胞系OCUM-12の培養上清の有無の条件下で共培養を行い、LECにおよぼすマクロファージの影響を解析し、共培養したLECの形態学的変化およびマクロファージとLECのリンパ管形成遺伝子発現について検討した。その結果、LECの管形成は接触培養時にのみ観察され、OCUM-12はマクロファージ誘導性の管形成を促進した。また、毛細管形成中のLECおよび共培養マクロファージの双方で、MMPと接着分子の遺伝子発現が有意にアップレギュレートされ、癌で前処理されたマクロファージにおいて、炎症性サイトカイン、MMP、接着分子、VEGF-Cなどのリンパ管形成因子のアップレギュレーションが示され、ICAM-1とマクロファージ活性化を阻害するとLECの管形成が抑制され、免疫組織化学から、リンパ管周囲に局在するマクロファージが検出された。以上の所見から、LECとマクロファージ間の相互作用が、LN転移を発症する腫瘍リンパ管形成の初期段階で重要なことが示唆された。

  • Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer Reviewed

    Yukie Tauchi, Hiroaki Tanaka, Kanako Kumamoto, Mao Tokumoto, Chie Sakimura, Katsunobu Sakurai, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    CANCER SCIENCE   107 ( 8 )   1101 - 9   2016.08( ISSN:1347-9032

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    Tumor lymphangiogenesis is a major prognostic indicator of gastric cancer. Tumor-induced inflammation has been shown to attract tumor-associated macrophages that affect lymphangiogenesis. However, detailed mechanisms of macrophage-induced lymphangiogenesis have not been elucidated. Here, we evaluated the interaction between tumor-associated macrophages and lymphatic endothelial cells (LECs) derived from lymph nodes (LNs) of human gastric cancer. Lymphatic endothelial cells were directly or indirectly cocultured with macrophages from healthy human blood, with or without the supernatant of the gastric cancer cell line, OCUM-12. We analyzed the effect of cancer pretreated macrophages and of macrophages from metastatic LNs of gastric cancer on LECs. We observed morphological changes of LECs in coculture and assessed the gene expression of possible lymphangiogenic molecules of macrophages and LECs after contact coculture, and of cancer pretreated macrophages, by quantitative RT-PCR. Specimens of metastatic LN of gastric cancer were immunofluorescently stained. We found that tubulogenesis of LECs was observed only in the contact coculture model. OCUM-12 cells promoted macrophage-induced tubulogenesis of LECs. Relative gene expression of MMP and adhesion molecules was significantly upregulated in both capillary-forming LECs and cocultured macrophages. Cancer pretreated macrophages upregulated lymphangiogenic factors including inflammatory cytokines, MMPs, adhesion molecules, and vascular endothelial growth factor-C. Blocking of intercellular adhesion molecule-1 and macrophage activation suppressed tubulogenesis of LECs. Immunohistochemistry showed macrophages localized around lymphatic vessels. Our results suggested that interaction between LECs and macrophages may be an important initial step of tumor lymphangiogenesis developing LN metastasis. Understanding of its mechanisms could be useful for future therapeutics of gastric cancer.

    DOI: 10.1111/cas.12977

    PubMed

  • 腫瘍関連マクロファージはヒト胃癌由来リンパ管内皮細胞の毛細管形成を誘導する(Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer) Reviewed

    Tauchi Yukie, Tanaka Hiroaki, Kumamoto Kanako, Tokumoto Mao, Sakimura Chie, Sakurai Katsunobu, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    Cancer Science   107 ( 8 )   1101 - 1109   2016.08( ISSN:1347-9032

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    胃癌の予後指標である腫瘍リンパ管形成におけるマクロファージの役割について検討するため、当院で胃癌の外科的処置が施行された患者の転移リンパ節(LN)由来リンパ管内皮細胞(LEC)と腫瘍関連マクロファージ間の相互作用について評価した。LECをマクロファージと直接的または間接的に、胃癌細胞系OCUM-12の培養上清の有無の条件下で共培養を行い、LECにおよぼすマクロファージの影響を解析し、共培養したLECの形態学的変化およびマクロファージとLECのリンパ管形成遺伝子発現について検討した。その結果、LECの管形成は接触培養時にのみ観察され、OCUM-12はマクロファージ誘導性の管形成を促進した。また、毛細管形成中のLECおよび共培養マクロファージの双方で、MMPと接着分子の遺伝子発現が有意にアップレギュレートされ、癌で前処理されたマクロファージにおいて、炎症性サイトカイン、MMP、接着分子、VEGF-Cなどのリンパ管形成因子のアップレギュレーションが示され、ICAM-1とマクロファージ活性化を阻害するとLECの管形成が抑制され、免疫組織化学から、リンパ管周囲に局在するマクロファージが検出された。以上の所見から、LECとマクロファージ間の相互作用が、LN転移を発症する腫瘍リンパ管形成の初期段階で重要なことが示唆された。

  • Identification of anti-cancer chemical compounds using Xenopus embryos Reviewed

    Tanaka Masamitsu, Kuriyama Sei, Itoh Go, Kohyama Aki, Iwabuchi Yoshiharu, Shibata Hiroyuki, Yashiro Masakazu, Aiba Namiko

    CANCER SCIENCE   107 ( 6 )   803 - 811   2016.06( ISSN:1347-9032

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    DOI: 10.1111/cas.12940

    PubMed

  • Xenopus胚を用いた抗癌化合物の同定(Identification of anti-cancer chemical compounds using Xenopus embryos) Reviewed

    Tanaka Masamitsu, Kuriyama Sei, Itoh Go, Kohyama Aki, Iwabuchi Yoshiharu, Shibata Hiroyuki, Yashiro Masakazu, Aiba Namiko

    John Wiley & Sons Australia, Ltd Cancer Science   107 ( 6 )   803 - 811   2016.06( ISSN:1347-9032

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    Xenopus胚の原腸形成または頭部神経冠細胞(CNCC)移動の阻害を指標として、癌浸潤を抑制する抗癌化合物をスクリーニングする手法について検討した。原腸形成に及ぼす効果は、ステージ10(原腸形成開始時)に達した胚を化合物で処理し、対照胚のステージ12 1/2およびステージ14到達時に原口閉鎖の状態を評価した。また、CNCCに及ぼす効果は、原腸形成後の胚を化合物で処理し、ホールマウントin situハイブリダイゼーションによりCNCCの移動の評価を行った。その結果、AMD3100およびパクリタキセルは、原口閉鎖を阻害し、CNCC移動に影響を及ぼした。さらに、100の合成化合物を盲検的にスクリーニングし、胚致死性を示さず、原腸形成または神経冠発生に重篤な欠損を認めた9つの化合物を候補化合物としたところ、候補化合物中、ポドフィロトキシンアナログであるC-157およびインドールアルカロイドであるD-572は、間期微小管の破壊を通して癌細胞浸潤を阻害し、SAS細胞のアポトーシスを誘導し、マウスに異種移植された腫瘍増殖および浸潤を抑制した。以上の所見から、Xenopus胚は、腫瘍増殖および浸潤に影響を及ぼす化合物のスクリーニングに有用と考えられた。

  • Identification of anti-cancer chemical compounds using Xenopus embryos Reviewed

    Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Aki Kohyama, Yoshiharu Iwabuchi, Hiroyuki Shibata, Masakazu Yashiro, Namiko Aiba

    CANCER SCIENCE   107 ( 6 )   803 - 11   2016.06( ISSN:1347-9032

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    Cancer tissues have biological characteristics similar to those observed in embryos during development. Many types of cancer cells acquire pro-invasive ability through epithelial-mesenchymal transition (EMT). Similar processes (gastrulation and migration of cranial neural crest cells [CNCC]) are observed in the early stages of embryonic development in Xenopus during which cells that originate from epithelial sheets through EMT migrate to their final destinations. The present study examined Xenopus embryonic tissues to identify anti-cancer compounds that prevent cancer invasion. From the initial test of known anti-cancer drugs, AMD3100 (an inhibitor of CXCR4) and paclitaxel (a cytoskeletal drug targeting microtubules) effectively prevented migration during gastrulation or CNCC development. Blind-screening of 100 synthesized chemical compounds was performed, and nine candidates that inhibited migration of these embryonic tissues without embryonic lethality were selected. Of these, C-157 (an analog of podophyllotoxin) and D-572 (which is an indole alkaroid) prevented cancer cell invasion through disruption of interphase microtubules. In addition, these compounds affected progression of mitotic phase and induced apoptosis of SAS oral cancer cells. SAS tumors were reduced in size after intratumoral injection of C-157, and peritoneal dissemination of melanoma cells and intracranial invasion of glioma cells were inhibited by C-157 and D-572. When the other analogues of these chemicals were compared, those with subtle effect on embryos were not tumor suppressive. These results suggest that a novel chemical-screening approach based on Xenopus embryos is an effective method for isolating anti-cancer drugs and, in particular, targeting cancer cell invasion and proliferation.

    DOI: 10.1111/cas.12940

    PubMed

  • Xenopus胚を用いた抗癌化合物の同定(Identification of anti-cancer chemical compounds using Xenopus embryos) Reviewed

    Tanaka Masamitsu, Kuriyama Sei, Itoh Go, Kohyama Aki, Iwabuchi Yoshiharu, Shibata Hiroyuki, Yashiro Masakazu, Aiba Namiko

    Cancer Science   107 ( 6 )   803 - 811   2016.06( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

    Xenopus胚の原腸形成または頭部神経冠細胞(CNCC)移動の阻害を指標として、癌浸潤を抑制する抗癌化合物をスクリーニングする手法について検討した。原腸形成に及ぼす効果は、ステージ10(原腸形成開始時)に達した胚を化合物で処理し、対照胚のステージ12 1/2およびステージ14到達時に原口閉鎖の状態を評価した。また、CNCCに及ぼす効果は、原腸形成後の胚を化合物で処理し、ホールマウントin situハイブリダイゼーションによりCNCCの移動の評価を行った。その結果、AMD3100およびパクリタキセルは、原口閉鎖を阻害し、CNCC移動に影響を及ぼした。さらに、100の合成化合物を盲検的にスクリーニングし、胚致死性を示さず、原腸形成または神経冠発生に重篤な欠損を認めた9つの化合物を候補化合物としたところ、候補化合物中、ポドフィロトキシンアナログであるC-157およびインドールアルカロイドであるD-572は、間期微小管の破壊を通して癌細胞浸潤を阻害し、SAS細胞のアポトーシスを誘導し、マウスに異種移植された腫瘍増殖および浸潤を抑制した。以上の所見から、Xenopus胚は、腫瘍増殖および浸潤に影響を及ぼす化合物のスクリーニングに有用と考えられた。

  • Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging Reviewed

    Murakami Takashi, Zhang Yong, Wang Xiaoen, Hiroshima Yukihiko, Kasashima Hiroaki, Yashiro Masakazu, Hirakawa Kosei, Miwa Atsushi, Kiyuna Tasuku, Matsuyama Ryusei, Tanaka Kuniya, Bouvet Michael, Endo Itaru, Hoffman Robert M.

    ANTICANCER RESEARCH   36 ( 5 )   2125 - 2130   2016.05( ISSN:0250-7005

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  • Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging. Reviewed

    Murakami T, Zhang Y, Wang X, Hiroshima Y, Kasashima H, Yashiro M, Hirakawa K, Miwa A, Kiyuna T, Matsuyama R, Tanaka K, Bouvet M, Endo I, Hoffman RM

    Anticancer research   36 ( 5 )   2125 - 30   2016.05( ISSN:0250-7005

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    PubMed

  • Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging Reviewed

    Takashi Murakami, Yong Zhang, Xiaoen Wang, Yukihiko Hiroshima, Hiroaki Kasashima, Masakazu Yashiro, Kosei Hirakawa, Atsushi Miwa, Tasuku Kiyuna, Ryusei Matsuyama, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman

    ANTICANCER RESEARCH   36 ( 5 )   2125 - 2130   2016.05( ISSN:0250-7005

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    Background/Aim: Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time. Materials and Methods: OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice. Results: Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI. Conclusion: These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential.

    PubMed

  • Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging. Reviewed

    Murakami T, Zhang Y, Wang X, Hiroshima Y, Kasashima H, Yashiro M, Hirakawa K, Miwa A, Kiyuna T, Matsuyama R, Tanaka K, Bouvet M, Endo I, Hoffman RM

    Anticancer research   36 ( 5 )   2125 - 30   2016.05( ISSN:0250-7005

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    PubMed

  • Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2 Reviewed

    Miura Kotaro, Kimura Kenjiro, Amano Ryosuke, Yamazoe Sadaaki, Ohira Go, Murata Akihiro, Nishio Kohei, Hasegawa Tsuyoshi, Yashiro Masakazu, Nakata Bunzo, Ohira Masaichi, Hirakawa Kosei

    BMC CANCER   16   268   2016.04( ISSN:1471-2407

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    DOI: 10.1186/s12885-016-2297-y

    PubMed

  • Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2 Reviewed

    Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Akihiro Murata, Kohei Nishio, Tsuyoshi Hasegawa, Masakazu Yashiro, Bunzo Nakata, Masaichi Ohira, Kosei Hirakawa

    BMC CANCER   16   268   2016.04( ISSN:1471-2407

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    Background: Anaplastic pancreatic cancer (APC) cell lines have been scarcely established.
    Methods: The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here.
    Results: OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines.
    Conclusions: The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer.

    DOI: 10.1186/s12885-016-2297-y

    PubMed

  • Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Ohira Masaichi, Hirakawa Kosei

    GASTRIC CANCER   19 ( 2 )   431 - 442   2016.04( ISSN:1436-3291

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    DOI: 10.1007/s10120-015-0510-3

    PubMed

  • Lysyl oxidaseは低酸素状態における胃癌細胞の上皮間葉移行に関連している(Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia) Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Ohira Masaichi, Hirakawa Kosei

    シュプリンガー・ジャパン(株) Gastric Cancer   19 ( 2 )   431 - 442   2016.04( ISSN:1436-3291

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    低酸素状態の胃癌細胞における上皮間葉移行(EMT)とlysyl oxidase(LOX)の関係を検討した。2種類の胃癌細胞株(OCUM-2MD3とOCUM-12)をin vitro試験に用いた。LOXの低分子干渉RNA(siRNA)がEMTに及ぼす影響、および低酸素状態での癌細胞の運動性を、逆転写PCR法、ウェスタンブロット法、創傷治癒アッセイ法および細胞浸潤アッセイ法により解析した。544例の胃癌患者におけるLOX発現と臨床病理学的特性との相関性を免疫組織化学法により検討した。低酸素状態によって、胃癌細胞のEMTに起因する多角細胞または紡錘状細胞が増加した。低酸素状態によって誘発された癌細胞のEMTは、LOXのsiRNA処理により抑制された。低酸素状態で遊走および浸潤する胃癌細胞数は、LOXノックダウンにより有意に減少した。LOXのsiRNAは、胃癌細胞のE-cadherin濃度を有意に増加させ、vimentin濃度を有意に低下させた。LOX発現は、深達度、腫瘍分化度、リンパ節転移、リンパ浸潤、血管浸潤および腹膜転移と有意に関係していた。多変量解析の結果、LOXは、全生存期間の独立したパラメータであった。

  • Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia Reviewed

    Hiroaki Kasashima, Masakazu Yashiro, Haruhito Kinoshita, Tatsunari Fukuoka, Tamami Morisaki, Go Masuda, Katsunobu Sakurai, Naoshi Kubo, Masaichi Ohira, Kosei Hirakawa

    GASTRIC CANCER   19 ( 2 )   431 - 442   2016.04( ISSN:1436-3291

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    It has been reported that lysyl oxidase (LOX) is a hypoxia-responsive factor and is associated with the malignant progression of carcinoma. The aim of this study was to clarify the relationship between the epithelial-mesenchymal transition (EMT) and LOX in gastric cancer cells under hypoxia.
    Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12, were used in an in vitro study. The effect of LOX small interfering RNA (siRNA) on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by reverse transcription PCR, Western blot, a wound-healing assay, and an invasion assay. Correlations between LOX expression and the clinicopathological features of 544 patients with gastric carcinoma were examined immunohistochemically.
    Hypoxic conditions increased the number of polygonal or spindle-shaped cells resulting from EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. The number of migrating and invading gastric cancer cells in hypoxia was significantly decreased by LOX knockdown. LOX siRNA significantly increased the E-cadherin level and decreased the vimentin level of gastric cancer cells. LOX expression was significantly associated with invasion depth, tumor differentiation, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal metastasis. Multivariable analysis revealed that LOX was an independent parameter for overall survival.
    LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.

    DOI: 10.1007/s10120-015-0510-3

    PubMed

  • Lysyl oxidaseは低酸素状態における胃癌細胞の上皮間葉移行に関連している(Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia) Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Ohira Masaichi, Hirakawa Kosei

    Gastric Cancer   19 ( 2 )   431 - 442   2016.04( ISSN:1436-3291

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    Publishing type:Research paper (scientific journal)  

    低酸素状態の胃癌細胞における上皮間葉移行(EMT)とlysyl oxidase(LOX)の関係を検討した。2種類の胃癌細胞株(OCUM-2MD3とOCUM-12)をin vitro試験に用いた。LOXの低分子干渉RNA(siRNA)がEMTに及ぼす影響、および低酸素状態での癌細胞の運動性を、逆転写PCR法、ウェスタンブロット法、創傷治癒アッセイ法および細胞浸潤アッセイ法により解析した。544例の胃癌患者におけるLOX発現と臨床病理学的特性との相関性を免疫組織化学法により検討した。低酸素状態によって、胃癌細胞のEMTに起因する多角細胞または紡錘状細胞が増加した。低酸素状態によって誘発された癌細胞のEMTは、LOXのsiRNA処理により抑制された。低酸素状態で遊走および浸潤する胃癌細胞数は、LOXノックダウンにより有意に減少した。LOXのsiRNAは、胃癌細胞のE-cadherin濃度を有意に増加させ、vimentin濃度を有意に低下させた。LOX発現は、深達度、腫瘍分化度、リンパ節転移、リンパ浸潤、血管浸潤および腹膜転移と有意に関係していた。多変量解析の結果、LOXは、全生存期間の独立したパラメータであった。

  • Current status in remnant gastric cancer after distal gastrectomy Reviewed

    Ohira Masaichi, Toyokawa Takahiro, Sakurai Katsunobu, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Onoda Naoyoshi, Hirakawa Kosei

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 8 )   2424 - 2433   2016.02( ISSN:1007-9327

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    DOI: 10.3748/wjg.v22.i8.2424

    PubMed

  • Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer Reviewed

    Yashiro Masakazu, Matsuoka Tasuku

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 8 )   2415 - 2423   2016.02( ISSN:1007-9327

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    DOI: 10.3748/wjg.v22.i8.2415

    PubMed

  • Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer Reviewed

    Masakazu Yashiro, Tasuku Matsuoka

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 8 )   2415 - 23   2016.02( ISSN:1007-9327

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    Fibroblast growth factor receptors (FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.

    DOI: 10.3748/wjg.v22.i8.2415

    PubMed

  • Current status in remnant gastric cancer after distal gastrectomy Reviewed

    Masaichi Ohira, Takahiro Toyokawa, Katsunobu Sakurai, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Naoyoshi Onoda, Kosei Hirakawa

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 8 )   2424 - 33   2016.02( ISSN:1007-9327

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    Remnant gastric cancer (RGC) and gastric stump cancer after distal gastrectomy (DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori (H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.

    DOI: 10.3748/wjg.v22.i8.2424

    PubMed

  • Predictive Potential of Preoperative Nutritional Status in Long-Term Outcome Projections for Patients with Gastric Cancer Reviewed

    Sakurai Katsunobu, Ohira Masaichi, Tamura Tatsuro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei

    ANNALS OF SURGICAL ONCOLOGY   23 ( 2 )   525 - 533   2016.02( ISSN:1068-9265

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    DOI: 10.1245/s10434-015-4814-7

    PubMed

  • Predictive Potential of Preoperative Nutritional Status in Long-Term Outcome Projections for Patients with Gastric Cancer Reviewed

    Katsunobu Sakurai, Masaichi Ohira, Tatsuro Tamura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa

    ANNALS OF SURGICAL ONCOLOGY   23 ( 2 )   525 - 33   2016.02( ISSN:1068-9265

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    Preoperative nutritional status not only correlates with the incidence of postoperative complications but also may be indicative of long-term outcomes for patients with cancer. The impact of preoperative nutritional status on outcomes for patients undergoing gastrectomy for gastric cancer (GC) was investigated.
    The study reviewed 594 patients treated for GC by gastrectomy at the authors' hospital between January, 2004 and December, 2010. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cut point to group patients as having high (PNI &gt; 45; n = 449) or low (PNI a parts per thousand currency sign 45; n = 145) nutritional status. Clinicopathologic features, perioperative results, and long-term outcomes, including cause of death, were compared.
    Multivariate analysis of 5-year overall survival (OS) and disease-specific survival (DSS) indicated that low PNI was independently associated with unfavorable outcomes for patients with GC. In subgroup analysis, the 5-year OS and DSS rates for patients with GC at stages 1 and 2 were significantly worse in the low PNI group than in the high PNI group. Although wound and extrasurgical field infections also tended to be more frequent in the low PNI group, postoperative intraabdominal infections did not differ significantly by group.
    Preoperative PNI may have merit as a gauge of prognosis for patients with GC at stages 1 and 2, but PNI and postoperative morbidity showed no correlation in this setting.

    DOI: 10.1245/s10434-015-4814-7

    PubMed

  • Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies Reviewed

    Matsuoka Tasuku, Yashiro Masakazu

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 2 )   776 - 789   2016.01( ISSN:1007-9327

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    DOI: 10.3748/wjg.v22.i2.776

    PubMed

  • Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 2 )   776 - 89   2016.01( ISSN:1007-9327

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    Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future.

    DOI: 10.3748/wjg.v22.i2.776

    PubMed

  • Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer Reviewed

    Masuda Go, Yashiro Masakazu, Kitayama Kishu, Miki Yuichiro, Kasashima Hiroaki, Kinoshita Haruhito, Morisaki Tamami, Fukuoka Tatshunari, Hasegawa Tsuyoshi, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Masaichi Ohira, Hirakawa Kosei

    ANTICANCER RESEARCH   36 ( 1 )   129 - 136   2016.01( ISSN:0250-7005

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  • Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer. Reviewed

    Masuda GO, Yashiro M, Kitayama K, Miki Y, Kasashima H, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Masaichi O, Hirakawa K

    Anticancer research   36 ( 1 )   129 - 36   2016.01( ISSN:0250-7005

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    PubMed

  • Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer Reviewed

    Go Masuda, Masakazu Yashiro, Kishu Kitayama, Yuichiro Miki, Hiroaki Kasashima, Haruhito Kinoshita, Tamami Morisaki, Tatshunari Fukuoka, Tsuyoshi Hasegawa, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Ohira Masaichi, Kosei Hirakawa

    ANTICANCER RESEARCH   36 ( 1 )   129 - 136   2016.01( ISSN:0250-7005

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    Aim: This study evaluated the clinicopathological significance of autophagy, an intracellular degradation system, in gastric cancer. Materials and Methods: The expression levels of three autophagy-related proteins, namely light chain 3 (LC3), Beclin 1 and p62, were analyzed by immunohistochemistry using samples from 510 patients with primary gastric cancer. Results: LC3, Beclin 1, and p62 expression was positive in 79 (15.5%), 126 (24.7%) and 251 (49.2%) out of 510 carcinomas, respectively. Autophagy was defined when samples were positive for at least two out of the three proteins. Autophagy-positive cases were 113 (22.1%) out of the 510. Autophagy determined by LC3, Beclin 1, and p62 significantly correlated with lymph node metastasis, vessel invasion, and hepatic metastasis. A Kaplan-Meier survival curve showed that autophagy was significantly associated with poor survival of patients with gastric cancer, especially for those with disease at stage I. Multivariate analysis indicated that autophagy was an independent prognostic factor. Conclusion: Autophagy promotes the progression of gastric cancer at an early clinical stage.

    PubMed

  • Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer. Reviewed

    Masuda GO, Yashiro M, Kitayama K, Miki Y, Kasashima H, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Masaichi O, Hirakawa K

    Anticancer research   36 ( 1 )   129 - 36   2016.01( ISSN:0250-7005

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    PubMed

  • Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia Reviewed

    Toshiki Hirakawa, Masakazu Yashiro, Yosuke Doi, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Kenjiro Kimura, Ryosuke Amano, Kosei Hirakawa

    PLOS ONE   11 ( 8 )   e0159912   2016( ISSN:1932-6203

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    Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O-2) and hypoxia (1% O-2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed alpha SMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

    DOI: 10.1371/journal.pone.0159912

    PubMed

  • 4ヵ月のプレドニゾロン療法とポリープ切除術により完全寛解したCronkhite-Canada症候群(Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy) Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    (一社)日本プライマリ・ケア連合学会 Journal of General and Family Medicine   16 ( 4 )   297 - 301   2015.12( ISSN:2189-6577

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    66歳男。脱毛症、味覚異常および下痢のため受診した。全身性脱毛、爪異栄養症、皮膚色素沈着および両下肢浮腫がみられ、リウマチ因子、メタロプロテアーゼ3および抗CCP抗体の上昇から自己免疫疾患が疑われた。上部消化管内視鏡および大腸鏡検査にて胃、十二指腸および結腸にポリープが観察された。以上の所見はCronkhite-Canada症候群(CCS)に一致した。生検にて胃ポリープに過形成、結腸ポリープに過形成および腺腫がみられた。CCSの診断後速やかに経口プレドニゾロン療法を開始し、症状の著明な改善を得た。4ヵ月間のプレドニゾロン漸減投与により上部消化管ポリープは消失し、残存していた4個の結腸ポリープは切除された。結腸ポリープの1つに粘膜内腺癌が発見されたが、断端に悪性所見はなく、CCSの完全寛解が確認された。プレドニゾロン療法中止から9ヵ月現在、再発はみられなかった。

  • Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    JOURNAL OF GENERAL AND FAMILY MEDICINE   16 ( 4 )   297 - 301   2015.12( ISSN:2189-7948

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  • Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer Reviewed

    Yamaguchi Hiroyuki, Kawazu Masahito, Yasuda Takahiko, Soda Manabu, Ueno Toshihide, Kojima Shinya, Yashiro Masakazu, Yoshino Ichiro, Ishikawa Yuichi, Sai Eirin, Mano Hiroyuki

    CANCER SCIENCE   106 ( 12 )   1687 - 1692   2015.12( ISSN:1347-9032

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    DOI: 10.1111/cas.12828

    PubMed

  • Diffuse-type gastric cancer cells switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis in hypoxic tumor microenvironments Reviewed

    Kinoshita Haruhito, Yashiro Masakazu, Fukuoka Tatsunari, Hasegawa Tsuyoshi, Morisaki Tamami, Kasashima Hiroaki, Masuda Go, Noda Satoru, Hirakawa Kosei

    CARCINOGENESIS   36 ( 12 )   1511 - 1520   2015.12( ISSN:0143-3334

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    DOI: 10.1093/carcin/bgv134

    PubMed

  • ヒト癌における哺乳類ラパマイシンキナーゼ標的蛋白質の形質転換体細胞変異(Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer) Reviewed

    Yamaguchi Hiroyuki, Kawazu Masahito, Yasuda Takahiko, Soda Manabu, Ueno Toshihide, Kojima Shinya, Yashiro Masakazu, Yoshino Ichiro, Ishikawa Yuichi, Sai Eirin, Mano Hiroyuki

    John Wiley & Sons Australia, Ltd Cancer Science   106 ( 12 )   1687 - 1692   2015.12( ISSN:1347-9032

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    ヒト癌における哺乳類ラパマイシン標的蛋白質(mTOR)遺伝子自体が体細胞変異を経て癌遺伝子となるか検討した。大細胞神経内分泌癌試料において、2209位のアミノ酸がロイシンからバリンに置換したmTORの体細胞非同義変異を同定した。mTOR(L2209V)変異はマウス3T3線維芽細胞を用いるフォーカス形成アッセイで顕著な形質転換能を示し、p70 S6キナーゼ、S6リボソーム蛋白質、真核生物翻訳開始因子4E結合蛋白質1のリン酸化を誘導した。追加の腫瘍標本や癌ゲノム変異データベースから種々の癌でmTORの別の独立した非同義変異が28同定され、そのうち12が形質転換能を示した。以上より、癌の変異によりmTORは形質転換能を獲得するため、このような腫瘍はmTOR阻害剤による分子標的治療の候補となり得ると考えられた。

  • 4ヵ月のプレドニゾロン療法とポリープ切除術により完全寛解したCronkhite-Canada症候群(Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy) Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    Journal of General and Family Medicine   16 ( 4 )   297 - 301   2015.12( ISSN:2189-6577

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    Publishing type:Research paper (scientific journal)  

    66歳男。脱毛症、味覚異常および下痢のため受診した。全身性脱毛、爪異栄養症、皮膚色素沈着および両下肢浮腫がみられ、リウマチ因子、メタロプロテアーゼ3および抗CCP抗体の上昇から自己免疫疾患が疑われた。上部消化管内視鏡および大腸鏡検査にて胃、十二指腸および結腸にポリープが観察された。以上の所見はCronkhite-Canada症候群(CCS)に一致した。生検にて胃ポリープに過形成、結腸ポリープに過形成および腺腫がみられた。CCSの診断後速やかに経口プレドニゾロン療法を開始し、症状の著明な改善を得た。4ヵ月間のプレドニゾロン漸減投与により上部消化管ポリープは消失し、残存していた4個の結腸ポリープは切除された。結腸ポリープの1つに粘膜内腺癌が発見されたが、断端に悪性所見はなく、CCSの完全寛解が確認された。プレドニゾロン療法中止から9ヵ月現在、再発はみられなかった。

  • Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer Reviewed

    Hiroyuki Yamaguchi, Masahito Kawazu, Takahiko Yasuda, Manabu Soda, Toshihide Ueno, Shinya Kojima, Masakazu Yashiro, Ichiro Yoshino, Yuichi Ishikawa, Eirin Sai, Hiroyuki Mano

    CANCER SCIENCE   106 ( 12 )   1687 - 92   2015.12( ISSN:1347-9032

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    Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that acts downstream of the phosphatidylinositol 3-kinase signaling pathway and regulates a wide range of cellular functions including transcription, translation, proliferation, apoptosis, and autophagy. Whereas genetic alterations that result in mTOR activation are frequently present in human cancers, whether the mTOR gene itself becomes an oncogene through somatic mutation has remained unclear. We have now identified a somatic non-synonymous mutation of mTOR that results in a leucine-to-valine substitution at amino acid position 2209 in a specimen of large cell neuroendocrine carcinoma. The mTOR(L2209V) mutant manifested marked transforming potential in a focus formation assay with mouse 3T3 fibroblasts, and it induced the phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eukaryotic translation initiation factor 4E-binding protein 1 in these cells. Examination of additional tumor specimens as well as public and in-house databases of cancer genome mutations identified another 28 independent non-synonymous mutations of mTOR in various cancer types, with 12 of these mutations also showing transforming ability. Most of these oncogenic mutations cluster at the interface between the kinase domain and the FAT (FRAP, ATM, TRRAP) domain in the 3-D structure of mTOR. Transforming mTOR mutants were also found to promote 3T3 cell survival, and their oncogenic activity was sensitive to rapamycin. Our data thus show that mTOR acquires transforming activity through genetic changes in cancer, and they suggest that such tumors may be candidates for molecularly targeted therapy with mTOR inhibitors.

    DOI: 10.1111/cas.12828

    PubMed

  • Diffuse-type gastric cancer cells switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis in hypoxic tumor microenvironments Reviewed

    Haruhito Kinoshita, Masakazu Yashiro, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Tamami Morisaki, Hiroaki Kasashima, Go Masuda, Satoru Noda, Kosei Hirakawa

    CARCINOGENESIS   36 ( 12 )   1511 - 20   2015.12( ISSN:0143-3334

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    Cancer-associated fibroblasts (CAFs) have been considered to play an important role for tumor progression of cancer. Solid tumors contain heterogeneous distribution of oxygen in their microenvironments. This study investigated the growth signaling of gastric cancer (GC) cells in focus on the interaction with CAFs and GC cells under normoxia and hypoxia. Four diffuse-type GC cell lines, two intestinal-type GC cell lines and three CAF cell lines were used. Cells were examined for expression of C-X-C chemokine receptor 4 (CXCR4), fibroblast growth factor receptor 2 (FGFR2) and stromal-derived factor 1 (SDF1) by RT-PCR, western blot, ELISA and immunohistochemical staining of xenografted tumors. GC cell proliferation was examined under hypoxia in the presence or absence of CAFs, a FGFR2 inhibitor, a CXCR4 inhibitor and HIF1a siRNA. Proliferation of diffuse-type GC cells, but not intestinal-type GC cells, was significantly increased by CAFs. CXCR4 expression by diffuse-type GC cells was significantly increased in hypoxia, while FGFR2 expression was decreased. CXCR4 expression was correlated with hypoxic microenvironment of xenografted tumor, but FGFR2 expression was not. FGFR2 inhibition significantly decreased the growth-stimulating activity of CAFs for diffuse-type GC cells in normoxia. In contrast, CXCR4 inhibition significantly decreased the growth-stimulating activity of CAFs in hypoxia. SDF1 production by CAFs was increased in hypoxia, while cancer cells did not produce SDF1. HIF1 siRNA significantly decreased both CXCR4 expression by diffuse-type GC cells and SDF1 production by CAFs. These findings suggest that diffuse-type GC cells might switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis through HIF1 in hypoxic tumor microenvironments.

    DOI: 10.1093/carcin/bgv134

    PubMed

  • ヒト癌における哺乳類ラパマイシンキナーゼ標的蛋白質の形質転換体細胞変異(Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer) Reviewed

    Yamaguchi Hiroyuki, Kawazu Masahito, Yasuda Takahiko, Soda Manabu, Ueno Toshihide, Kojima Shinya, Yashiro Masakazu, Yoshino Ichiro, Ishikawa Yuichi, Sai Eirin, Mano Hiroyuki

    Cancer Science   106 ( 12 )   1687 - 1692   2015.12( ISSN:1347-9032

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    Publishing type:Research paper (scientific journal)  

    ヒト癌における哺乳類ラパマイシン標的蛋白質(mTOR)遺伝子自体が体細胞変異を経て癌遺伝子となるか検討した。大細胞神経内分泌癌試料において、2209位のアミノ酸がロイシンからバリンに置換したmTORの体細胞非同義変異を同定した。mTOR(L2209V)変異はマウス3T3線維芽細胞を用いるフォーカス形成アッセイで顕著な形質転換能を示し、p70 S6キナーゼ、S6リボソーム蛋白質、真核生物翻訳開始因子4E結合蛋白質1のリン酸化を誘導した。追加の腫瘍標本や癌ゲノム変異データベースから種々の癌でmTORの別の独立した非同義変異が28同定され、そのうち12が形質転換能を示した。以上より、癌の変異によりmTORは形質転換能を獲得するため、このような腫瘍はmTOR阻害剤による分子標的治療の候補となり得ると考えられた。

  • Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    JOURNAL OF GENERAL AND FAMILY MEDICINE   16 ( 4 )   297 - 301   2015.12( ISSN:2189-7948

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    Publishing type:Research paper (scientific journal)  

  • 4ヵ月のプレドニゾロン療法とポリープ切除術により完全寛解したCronkhite-Canada症候群(Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy) Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    (一社)日本プライマリ・ケア連合学会 Journal of General and Family Medicine   16 ( 4 )   297 - 301   2015.12( ISSN:2189-6577

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    Publishing type:Research paper (scientific journal)  

    66歳男。脱毛症、味覚異常および下痢のため受診した。全身性脱毛、爪異栄養症、皮膚色素沈着および両下肢浮腫がみられ、リウマチ因子、メタロプロテアーゼ3および抗CCP抗体の上昇から自己免疫疾患が疑われた。上部消化管内視鏡および大腸鏡検査にて胃、十二指腸および結腸にポリープが観察された。以上の所見はCronkhite-Canada症候群(CCS)に一致した。生検にて胃ポリープに過形成、結腸ポリープに過形成および腺腫がみられた。CCSの診断後速やかに経口プレドニゾロン療法を開始し、症状の著明な改善を得た。4ヵ月間のプレドニゾロン漸減投与により上部消化管ポリープは消失し、残存していた4個の結腸ポリープは切除された。結腸ポリープの1つに粘膜内腺癌が発見されたが、断端に悪性所見はなく、CCSの完全寛解が確認された。プレドニゾロン療法中止から9ヵ月現在、再発はみられなかった。

  • Polymeric Micelle Platform for Multimodal Tomographic Imaging to Detect Scirrhous Gastric Cancer. Reviewed

    Miura Y, Tsuji AB, Sugyo A, Sudo H, Aoki I, Inubushi M, Yashiro M, Hirakawa K, Cabral H, Nishiyama N, Saga T, Kataoka K

    ACS biomaterials science & engineering   1 ( 11 )   1067 - 1076   2015.11

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    DOI: 10.1021/acsbiomaterials.5b00142

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  • Is Anaplastic Pancreatic Cancer Originated from Invasive Ductal Carcinoma of Pancreas? Reviewed

    Miura K., Kimura K., Amano R., Yamazoe S., Ohira G., Nishio K., Shibutani M., Sakurai K., Nagahara H., Toyokawa T., Kubo N., Tanaka H., Muguruma K., Otani H., Yashiro M., Maeda K., Ohira M., Hirakawa K.

    PANCREAS   44 ( 8 )   1398 - 1398   2015.11( ISSN:0885-3177

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  • Polymeric Micelle Platform for Multimodal Tomographic Imaging to Detect Scirrhous Gastric Cancer Reviewed

    Miura Yutaka, Tsuji Atsushi B., Sugyo Aya, Sudo Hitomi, Aok Ichio, Inubushi Masayuki, Yashiro Masakazu, Hirakawa Kosei, Cabral Horacio, Nishiyama Nobuhiro, Saga Tsuneo, Kataoka Kazunori

    ACS BIOMATERIALS SCIENCE & ENGINEERING   1 ( 11 )   1067 - 1076   2015.11( ISSN:2373-9878

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    DOI: 10.1021/acsbiomaterials.5b00142

  • Binding of Galectin-3, a beta-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy Reviewed

    Mori Yugo, Akita Kaoru, Yashiro Masakazu, Sawada Tetsuji, Hirakawa Kosei, Murata Takeomi, Nakada Hiroshi

    JOURNAL OF BIOLOGICAL CHEMISTRY   290 ( 43 )   26125 - 26140   2015.10( ISSN:0021-9258

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    DOI: 10.1074/jbc.M115.651489

    PubMed

  • Binding of Galectin-3, a beta-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy Reviewed

    Yugo Mori, Kaoru Akita, Masakazu Yashiro, Tetsuji Sawada, Kosei Hirakawa, Takeomi Murata, Hiroshi Nakada

    JOURNAL OF BIOLOGICAL CHEMISTRY   290 ( 43 )   26125 - 40   2015.10( ISSN:0021-9258

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    Both mucin 1 (MUC1) and galectin-3 are known to be over-expressed in various malignant tumors and associated with a poor prognosis. It has been extensively reported that MUC1 is involved in potentiation of growth factor-dependent signal transduction. Because some carbohydrate moieties carried on MUC1 change to preferable ones for binding of galectin-3 in cancer cells, we speculated that MUC1-mediated signaling may occur through direct binding of galectin-3. Immunochemical studies showed that the distribution of galectin-3 coincided with that of MUC1 in various human tumor tissues but not in human nonmalignant tissues, and the level of galectin-3 retained on the surface of various cancer cells paralleled that of MUC1. Treatment of MUC1-expressing cells with galectin-3 induced phosphorylation of ERK1/2 and Akt following enhanced phosphorylation of MUC1 C-terminal domain, consistently promoting tumor cell malignancy. It is also noted that this enhanced phosphorylation occurred independently of EGF receptor-mediated signaling in both EGF receptor-and MUC1-expressing cells, and multivalency of galectin-3 was important for initiation of MUC1-mediated signaling. Expectedly, both silencing of endogenous galectin-3 and treatment with galectin-3 antagonists down-regulated cell proliferation of MUC1-expressing cells. These results suggest that the binding of galectin-3 to MUC1 plays a key role in MUC1-mediated signaling. Thus, constitutive activation of MUC1-mediated signaling in an autocrine/paracrine manner caused by ligation of galectin-3 promotes uncontrolled tumor cell malignancy. This signaling may be another MUC1-mediated pathway and function in parallel with a growth factor-dependent MUC1-mediated signaling pathway.

    DOI: 10.1074/jbc.M115.651489

    PubMed

  • Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer Reviewed

    Tokumoto Mao Watanabe, Tanaka Hiroaki, Tauchi Yukie, Kasashima Hiroaki, Kurata Kento, Yashiro Masakazu, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Amano Ryosuke, Kimura Kenjiro, Muguruma Kazuya, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    BRITISH JOURNAL OF CANCER   113 ( 7 )   1046 - 1054   2015.09( ISSN:0007-0920

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    DOI: 10.1038/bjc.2015.282

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  • Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer Reviewed

    Mao Watanabe Tokumoto, Hiroaki Tanaka, Yukie Tauchi, Hiroaki Kasashima, Kento Kurata, Masakazu Yashiro, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Ryosuke Amano, Kenjiro Kimura, Kazuya Muguruma, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    BRITISH JOURNAL OF CANCER   113 ( 7 )   1046 - 54   2015.09( ISSN:0007-0920

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    Background: Tumour cells and stromal cells interact in the tumour microenvironment; moreover, stromal cells can acquire abnormalities that contribute to tumour progression. However, interactions between lymphatic endothelial cells (LECs) and tumour cells are largely unexamined. In this study, we aimed to determine whether tumour-specific LECs inhabit the tumour microenvironment and examine their influence on this microenvironment.
    Methods: We isolated normal LECs (NLECs) from a non-metastatic lymph node and tumour-associated LECs (TLECs) from cancerous lymph nodes. We examined proliferative and migratory potency, growth factor production, and gene expression of each type of LEC. Moreover, we developed a co-culture system to investigate the interactions between gastric cancer cells and LECs.
    Results: When compared with NLEC, TLECs had an abnormal shape, high proliferative and migratory abilities, and elevated expression of genes associated with inflammation, cell growth, and cell migration. NLECs co-cultured with gastric cancer cells from the OCUM12 cell line acquired TLEC-like phenotypes. Also, OCUM12 cells co-cultured with TLECs expressed high levels of genes responsible for metastasis.
    Conclusions: Our results demonstrated that LECs interacted with tumour cells and obtained abnormal phenotypes that could have important roles in tumour progression.

    DOI: 10.1038/bjc.2015.282

    PubMed

  • Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPAR gamma Reviewed

    Fukuoka Tatsunari, Yashiro Masakazu, Kinoshita Haruhito, Morisaki Tamami, Hasegawa Tsuyoshi, Hirakawa Toshiki, Aomatsu Naoki, Takeda Hiroshi, Maruyama Takayuki, Hirakawa Kosei

    INTERNATIONAL JOURNAL OF CANCER   137 ( 5 )   1235 - 1244   2015.09( ISSN:0020-7136

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    DOI: 10.1002/ijc.29392

    PubMed

  • Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPAR gamma Reviewed

    Tatsunari Fukuoka, Masakazu Yashiro, Haruhito Kinoshita, Tamami Morisaki, Tsuyoshi Hasegawa, Toshiki Hirakawa, Naoki Aomatsu, Hiroshi Takeda, Takayuki Maruyama, Kosei Hirakawa

    INTERNATIONAL JOURNAL OF CANCER   137 ( 5 )   1235 - 44   2015.09( ISSN:0020-7136

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    The antitumor activity of prostaglandin (PG) D-2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD(2) is not useful from a clinical point of view because it is rapidly metabolized in vivo. The aim of this study was to clarify the antitumor efficacy of an alternative, PGD synthase (PGDS), on gastric cancer cells. The effects of PGD(2) and PGDS on the proliferation of gastric cancer cells were examined in vivo and in vitro. The expression levels of PGD(2) receptors and peroxisome proliferator-activated receptor (PPAR) were evaluated by RT-PCR. The effects of a PPAR antagonist or siPPAR on the proliferation of cancer cells and the c-myc and cyclin D1 expression were examined in the presence or absence of PGD(2) or PGDS. PPAR was expressed in gastric cancer cell lines, but PGD(2) receptors were not. PGD(2) and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPAR. PGDS increased the PGD(2) production of gastric cancer cells. A PPAR antagonist and siPPAR transfection significantly suppressed the growth-inhibitory effects of PGD(2) and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD(2); this inhibitory effect was suppressed by PPAR antagonist. Both PGD(2) and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than PGD(2) treatment. These findings suggest that PGDS and PGD(2) decrease the proliferation of gastric cancer cells through PPAR signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPAR.
    What's new? Previous work suggests that prostaglandin D-2 (PGD(2)) exerts antiproliferative effects in certain types of cancer cells. But because PGD(2) is rapidly catalyzed to its inactive form, its clinical utility is limited. A possible alternative to PGD(2) is PGD synthase (PGDS), which synthesizes PGD2, but whether it also possesses antitumor activity is unknown. In this study, in PPAR-expressing gastric cancer cells, both PGD(2) and PGDS were found to significantly suppress cell proliferation. In vivo, they inhibited the growth of subcutaneous tumors. Tumor volume was markedly decreased with PGDS treatment, compared with PGD(2).

    DOI: 10.1002/ijc.29392

    PubMed

  • Epithelial mesenchymal transition may contribute to anaplastic change of pancreatic ductal adenocarcinoma Reviewed

    Miura Kotaro, Kimura Kenjiro, Amano Ryosuke, Yamazoe Sadaaki, Ohira Go, Nishio Kohei, Shibutani Masatsune, Sakurai Katsunobu, Nagahara Hisashi, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Otani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-5276

  • Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis Reviewed

    Yashiro Masakazu, Morisaki Tamami, Hasegawa Tsuyoshi, Kakehashi Anna, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Wanibuchi Hideki, Hirakawa Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-1405

  • Lysyl oxidase-like 2 (LOXL2) from cancer-associated fibroblasts stimulates the progression of gastric carcinoma Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Kitayama Kisyu, Masuda Go, Kinoshita Haruhito, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-5063

  • SDF1 alpha/CXCR4 axis might be associated with growth-interaction between cancer-associated fibroblasts and gastric cancer cells in hypoxic tumor microenvironment Reviewed

    Kinoshita Haruhito, Yashiro Masakazu, Kasashima Hiroaki, Masuda Go, Morisaki Tamami, Fukuoka Tatsunari, Sakurai Katsunobu, Toyokawa Takahiro, Kimura Kenjiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-436

  • Significance of an autophagy protein, microtubule-associated protein light chain 3 (LC3), in gastric cancer Reviewed

    Masuda Go, Yashiro Masakazu, Kasashima Hiroaki, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Hasegawa Tsuyoshi, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Chung Kosei

    CANCER RESEARCH   75   2015.08( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2015-992

  • Molecular Alterations of Colorectal Cancer with Inflammatory Bowel Disease Reviewed

    Yashiro Masakazu

    DIGESTIVE DISEASES AND SCIENCES   60 ( 8 )   2251 - 2263   2015.08( ISSN:0163-2116

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    Publishing type:Research paper (scientific journal)   Kind of work:Single Work  

    DOI: 10.1007/s10620-015-3646-4

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  • Molecular Alterations of Colorectal Cancer with Inflammatory Bowel Disease Reviewed

    Masakazu Yashiro

    DIGESTIVE DISEASES AND SCIENCES   60 ( 8 )   2251 - 63   2015.08( ISSN:0163-2116

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    Inflammatory bowel disease (IBD) is an important etiologic factor in the development of colorectal cancer (CRC). The risk of CRC begins to increase 8 or 10 years after the diagnosis of IBD. This type of cancer is called colitis-associated CRC (CA-CRC). The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CA-CRC. Genetic alterations detected in CA-CRC such as genetic mutations, microsatellite instability, and DNA hypermethylation are also recognized in sporadic CRC; however, there are differences in the timing and frequency of molecular events between CA-CRC and sporadic CRC. Interaction between gene-environmental factors, including inflammation, lifestyle, psychological stress, and prior appendectomy, might be associated with the etiopathology of IBD. The mucosal inflammatory mediators, such as oxidant stress, free radicals, and chemokines, may cause the genetic alterations. Understanding the molecular mechanisms of CA-CRC might be important to develop clinical efficacies for patients with IBD. This review discusses the molecular characteristics of CA-CRC, especially ulcerative colitis-associated CRC, including clinical features, signaling pathways, and interactions between genetic alterations and environment involved in inflammatory carcinogenesis.

    DOI: 10.1007/s10620-015-3646-4

    PubMed

  • Bone marrow-derived stromal cells are associated with gastric cancer progression Reviewed

    Kasashima H., Yashiro M., Nakamae H., Masuda G., Kinoshita H., Morisaki T., Fukuoka T., Hasegawa T., Sakurai K., Toyokawa T., Kubo N., Tanaka H., Muguruma K., Ohira M., Nakane T., Hino M., Hirakawa K.

    BRITISH JOURNAL OF CANCER   113 ( 3 )   443 - 452   2015.07( ISSN:0007-0920

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    DOI: 10.1038/bjc.2015.236

  • Bone marrow-derived stromal cells are associated with gastric cancer progression. Reviewed

    Kasashima H, Yashiro M, Nakamae H, Masuda G, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Ohira M, Nakane T, Hino M, Hirakawa K

    British journal of cancer   113 ( 3 )   443 - 52   2015.07( ISSN:0007-0920

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    DOI: 10.1038/bjc.2015.236

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  • Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer Reviewed

    Tokuhisa Motohiko, Ichikawa Yasushi, Kosaka Nobuyoshi, Ochiya Takahiro, Yashiro Masakazu, Hirakawa Kosei, Kosaka Takashi, Makino Hirochika, Akiyama Hirotoshi, Kunisaki Chikara, Endo Itaru

    PLOS ONE   10 ( 7 )   e0130472   2015.07( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0130472

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  • Tks5 activation in mesothelial cells creates invasion front of peritoneal carcinomatosis Reviewed

    Satoyoshi R., Aiba N., Yanagihara K., Yashiro M., Tanaka M.

    ONCOGENE   34 ( 24 )   3176 - 3187   2015.06( ISSN:0950-9232

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    DOI: 10.1038/onc.2014.246

  • Tks5 activation in mesothelial cells creates invasion front of peritoneal carcinomatosis. Reviewed

    Satoyoshi R, Aiba N, Yanagihara K, Yashiro M, Tanaka M

    Oncogene   34 ( 24 )   3176 - 87   2015.06( ISSN:0950-9232

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    DOI: 10.1038/onc.2014.246

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  • The Outcome of Surgical Treatment for Elderly Patients With Gastric Carcinoma Reviewed

    Sakurai Katsunobu, Muguruma Kazuya, Nagahara Hisashi, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Ohtani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    JOURNAL OF SURGICAL ONCOLOGY   111 ( 7 )   848 - 854   2015.06( ISSN:0022-4790

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    DOI: 10.1002/jso.23896

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  • The pretreatment Controlling Nutritional Status (CONUT) score as an independent prognostic factor in patients with clinical Stage I-III esophageal squamous cell carcinoma Reviewed

    Toyokawa T., Kubo N., Shibutani M., Sakurai K., Nagahara H., Tanaka H., Muguruma K., Ohtani H., Yashiro M., Maeda K., Ohira M., Hirakawa K.

    ANNALS OF ONCOLOGY   26   2015.06( ISSN:0923-7534

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    DOI: 10.1093/annonc/mdv233.45

  • The Outcome of Surgical Treatment for Elderly Patients With Gastric Carcinoma Reviewed

    Katsunobu Sakurai, Kazuya Muguruma, Hisashi Nagahara, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Hiroshi Ohtani, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    JOURNAL OF SURGICAL ONCOLOGY   111 ( 7 )   848 - 54   2015.06( ISSN:0022-4790

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    BackgroundThe aim of this study was to clarify the operative mortality and long-term survival of gastrectomy for elderly patients with gastric cancer.
    MethodsA total of 461 patients who underwent gastrectomy for gastric cancer in our hospital were classified as elderly group (80 years-old, 95 patients) and control group (60-69 years-old, 366 patients).
    ResultsThe frequency of comorbidities was significantly (P&lt;0.05) higher in elderly group (74.7%) than that in the control group (49.5%). No significant difference of the postoperative complication rate was found between the elderly group (23.2%) and the control group (23.2%). Adjuvant chemotherapy was 9.5% in the elderly group, which was significantly less than 29.0% of the control group (P&lt;0.05). Stage II and III elderly patients had worse disease specific survival (DSS) than controls did. In the elderly, overall survival (OS) was significantly worse than DSS in stage I patients (P&lt;0.05).
    ConclusionsThe operative complication rate of elderly patients was comparable to the control group. Comorbidity and occurrence of secondary malignant disease should be followed for elderly patients at stage I. For stage II and III disease patients, a novel drug which is acceptable for the elderly is needed as a postoperative therapy. J. Surg. Oncol. 2015 111:848-854. (c) 2014 Wiley Periodicals, Inc.

    DOI: 10.1002/jso.23896

    PubMed

  • Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection. Reviewed

    Yamada N, Amano R, Kimura K, Murata A, Yashiro M, Tanaka S, Wakasa K, Hirakawa K

    Hepato-gastroenterology   62 ( 138 )   389 - 92   2015.03( ISSN:0172-6390

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  • リンパ流に沿ったリンパ節内マクロファージ数と胃癌リンパ節転移との関係 Reviewed

    田内 幸枝, 田中 浩明, 崎村 千恵, 徳本 真央, 櫻井 克宣, 豊川 貴弘, 久保 尚士, 六車 一哉, 八代 正和, 澤田 鉄二, 大平 雅一, 平川 弘聖

    日本胃癌学会総会記事   87回   288 - 288   2015.03

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  • 胃癌におけるオートファジー関連蛋白p62の臨床病理学的意義 Reviewed

    増田 剛, 八代 正和, 笠島 裕明, 田内 幸枝, 徳本 真央, 木下 春人, 福岡 達成, 森崎 珠美, 櫻井 克宣, 豊川 貴弘, 久保 尚士, 田中 浩明, 六車 一哉, 大平 雅一, 平川 弘聖

    日本胃癌学会総会記事   87回   277 - 277   2015.03

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  • Impact of Body Mass Index on Surgical Outcomes after Esophagectomy for Patients with Esophageal Squamous Cell Carcinoma Reviewed

    Hasegawa Tsuyoshi, Kubo Naoshi, Ohira Masaichi, Sakurai Katsunobu, Toyokawa Takahiro, Yamashita Yoshito, Yamazoe Sadaaki, Kimura Kenjiro, Nagahara Hisashi, Amano Ryosuke, Shibutani Masatsune, Tanaka Hiroaki, Muguruma Kazuya, Ohtani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Hirakawa Kosei

    JOURNAL OF GASTROINTESTINAL SURGERY   19 ( 2 )   226 - 233   2015.02( ISSN:1091-255X

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    DOI: 10.1007/s11605-014-2686-y

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  • Protein-bound polysaccharide K suppresses tumor fibrosis in gastric cancer by inhibiting the TGF-beta signaling pathway Reviewed

    Shinbo Toshifumi, Fushida Sachio, Tsukada Tomoya, Harada Shinichi, Kinoshita Jun, Oyama Katsunobu, Okamoto Koichi, Ninomiya Itasu, Takamura Hiroyuki, Kitagawa Hirohisa, Fujimura Takeshi, Yashiro Masakazu, Hirakawa Kousei, Ohta Tetsuo

    ONCOLOGY REPORTS   33 ( 2 )   553 - 558   2015.02( ISSN:1021-335X

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    DOI: 10.3892/or.2014.3636

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  • Impact of Body Mass Index on Surgical Outcomes after Esophagectomy for Patients with Esophageal Squamous Cell Carcinoma Reviewed

    Tsuyoshi Hasegawa, Naoshi Kubo, Masaichi Ohira, Katsunobu Sakurai, Takahiro Toyokawa, Yoshito Yamashita, Sadaaki Yamazoe, Kenjiro Kimura, Hisashi Nagahara, Ryosuke Amano, Masatsune Shibutani, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Ohtani, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa

    JOURNAL OF GASTROINTESTINAL SURGERY   19 ( 2 )   226 - 33   2015.02( ISSN:1091-255X

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    Patients with overweight reportedly have more comorbidities, including diabetes mellitus and cardiovascular disease, and longer operating times as well as more blood loss during surgery compared with those with normal weight. However, the impact of overweight on the short-term outcome after transthoracic esophagectomy for patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We hypothesized that overweight has a negative impact on short-term surgical outcomes after esophagectomy for patients with ESCC.
    A total of 304 patients who underwent transthoracic esophagectomy for ESCC were included in this study. Body mass index (BMI) was classified into three categories, &lt; 18.49, 18.50-24.99, and &gt; 25.00 (kg/m(2)), defined as low, normal, and high BMI, respectively, according to the World Health Organization criteria. We investigated the association of BMI status with patient demographics and surgical outcomes after esophagectomy for patients with ESCC. In addition, overall survival and relapse-free survival stratified by BMI were compared.
    Fifty-nine (19.4 %) and 41 (13.4 %) patients were classified to low BMI and high BMI, respectively. The high-BMI group had significantly higher comorbidity rates of diabetes mellitus (p &lt; 0.01) and anastomotic leakage (p = 0.011) than the normal-BMI group. There were no significant association between high BMI and another various complications except for an anastomotic leakage, severe complications defined by Clavien-Dindo classification and in-hospital mortality. In multivariate analysis, high BMI was a significant risk factor for anastomotic leakage (p = 0.030, hazard ratio; 3.423, 95%CI; 1.128-10.38). On the other hand, no significant association was observed between low BMI and short surgical outcomes. There were no significant differences in overall and relapse-free survival among the three BMI groups in univariate and multivariate analysis (p = 0.128 and p = 0.584, respectively).
    The surgical treatment should not be denied for patients with ESCC due to overweight and underweight. However, intraoperative prevention and postoperative careful monitoring for anastomotic leakage might be required after esophagectomy for overweight patients with ESCC.

    DOI: 10.1007/s11605-014-2686-y

    PubMed

  • Protein-bound polysaccharide K suppresses tumor fibrosis in gastric cancer by inhibiting the TGF-beta signaling pathway Reviewed

    Toshifumi Shinbo, Sachio Fushida, Tomoya Tsukada, Shinichi Harada, Jun Kinoshita, Katsunobu Oyama, Koichi Okamoto, Itasu Ninomiya, Hiroyuki Takamura, Hirohisa Kitagawa, Takeshi Fujimura, Masakazu Yashiro, Kousei Hirakawa, Tetsuo Ohta

    ONCOLOGY REPORTS   33 ( 2 )   553 - 8   2015.02( ISSN:1021-335X

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    Peritoneal carcinomatosis (PC) is the most frequent metastatic pattern of gastric cancer and its prognosis is extremely poor. PC is characterized by rich fibrosis and the development of obstructive disorders such as ileus, jaundice and hydronephrosis. Epithelial-mesenchymal transition (EMT) is one of the major causes of tissue fibrosis and transforming growth factor beta (TGF-beta) has a pivotal function in the progression of EMT. Protein-bound polysaccharide K (PSK) is a biological response modifier that can modulate the TGF-beta/Smad signaling pathway in vitro. In the present study, we established a fibrotic tumor model using human peritoneal mesothelial cells (HPMCs) and a human gastric cancer cell line to evaluate whether PSK attenuates tumor fibrosis. HPMCs exposed to PSK did not undergo the morphological change from a cobblestone-like pattern to a spindle-shape pattern normally induced by treatment with TGF-beta. Immunofluorescence further demonstrated that PSK suppressed TGF-beta-induced overexpression of alpha-SMA in the HPMCs. We further showed that HPMCs contributed to the proliferation of tumor fibrosis by using a mouse xenograft model. Additionally, PSK treatment of these mice significantly reduced the area of observable tumor fibrosis. These results suggest that seeded cancer cells transformed HPMCs into myofibroblast-like cells through their release of TGF-beta in the microenvironment, facilitating the development of fibrous tumors in organs covered with HPMCs. Therefore, our study indicates that PSK has potential utility as an anti-fibrotic agent in the treatment of gastric cancer patients with PC.

    DOI: 10.3892/or.2014.3636

    PubMed

  • Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts Reviewed

    Satoyoshi R., Kuriyama S., Aiba N., Yashiro M., Tanaka M.

    ONCOGENE   34 ( 5 )   650 - 660   2015.01( ISSN:0950-9232

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    DOI: 10.1038/onc.2013.584

  • Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Reviewed

    Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M

    Oncogene   34 ( 5 )   650 - 60   2015.01( ISSN:0950-9232

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    DOI: 10.1038/onc.2013.584

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  • Sentinel node navigation surgery for gastric cancer: Overview and perspective Reviewed

    Yashiro Masakazu, Matsuoka Tasuku

    WORLD JOURNAL OF GASTROINTESTINAL SURGERY   7 ( 1 )   1 - 9   2015.01( ISSN:1948-9366

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    DOI: 10.4240/wjgs.v7.i1.1

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  • Sentinel node navigation surgery for gastric cancer: Overview and perspective. Reviewed

    Yashiro M, Matsuoka T

    World journal of gastrointestinal surgery   7 ( 1 )   1 - 9   2015.01( ISSN:1948-9366

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    DOI: 10.4240/wjgs.v7.i1.1

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  • Recent advances in the HER2 targeted therapy of gastric cancer Reviewed

    Matsuoka Tasuku, Yashiro Masakazu

    WORLD JOURNAL OF CLINICAL CASES   3 ( 1 )   42 - 51   2015.01( ISSN:2307-8960

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    DOI: 10.12998/wjcc.v3.i1.42

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  • Recent advances in the HER2 targeted therapy of gastric cancer Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    WORLD JOURNAL OF CLINICAL CASES   3 ( 1 )   42 - 51   2015.01( ISSN:2307-8960

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    Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2 (HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancer-resistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.

    DOI: 10.12998/wjcc.v3.i1.42

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  • Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells Reviewed

    Tsuji Tadahiro, Satoyoshi Rika, Aiba Namiko, Kubo Takanori, Yanagihara Kazuyoshi, Maeda Daichi, Goto Akiteru, Ishikawa Kazuo, Yashiro Masakazu, Tanaka Masamitsu

    CANCER RESEARCH   75 ( 2 )   356 - 366   2015.01( ISSN:0008-5472

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    DOI: 10.1158/0008-5472.CAN-14-1693

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  • Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells Reviewed

    Tadahiro Tsuji, Rika Satoyoshi, Namiko Aiba, Takanori Kubo, Kazuyoshi Yanagihara, Daichi Maeda, Akiteru Goto, Kazuo Ishikawa, Masakazu Yashiro, Masamitsu Tanaka

    CANCER RESEARCH   75 ( 2 )   356 - 66   2015.01( ISSN:0008-5472

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    Agr2 is a disulfide isomerase residing in the endoplasmic reticulum (ER), which physiologically regulates protein folding and mediates resistance to ER stress. Agr2 is overexpressed in adenocarcinomas of various organs, where it participates in neoplastic transformation and metastasis, therefore acts as a pro-oncogenic protein. Besides its normal localization in the ER, Agr2 is also found in the serum and urine of cancer patients, although the physiological significance of extracellular Agr2 is poorly understood. In this study, we demonstrated that extracellular Agr2 can activate stromal fibroblasts and promote fibroblast-associated cancer invasion in gastric signet-ring cell carcinoma (SRCC), where Agr2 is highly expressed. Agr2 secreted from SRCC cells was incorporated by the surrounding gastric fibroblasts and promoted invasion by these cells. In turn, activated fibroblasts coordinated the invasive behavior of fibroblasts and cancer cells. Our findings suggested that Agr2 drives progression of gastric SRCC by exerting paracrine effects on fibroblasts in the tumor microenvironment, acting also to increase the growth and resistance of SRCC cells to oxidative and hypoxic stress as cell autonomous effects. (C) 2014 AACR.

    DOI: 10.1158/0008-5472.CAN-14-1693

    PubMed

  • CD133 as biomarker in breast cancer Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    Biomarkers in Disease: Methods, Discoveries and Applications: Biomarkers in Cancer   429 - 445   2015.01

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    Breast cancer is one of the most common malignant diseases worldwide. Prognosis of breast cancer is still poor despite the diagnostic and therapeutic progress in recent years. In order to decrease breast cancer-related deaths, many studies are aimed at identifying novel screening- and prognosis-related biomarkers. Cancer stem cells (CSCs) are characterized by the capacity for self-renewal, tumorigenesis, and differentiation. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of CSC markers have been of great interest. CD133, five transmembrane single-chain glycoproteins, has been successfully used as a stem cell marker to identify and isolate CSCs in malignant tumors. CD133 can also be used to predict tumor metastasis, patient survival and resistance to therapy. This chapter provides an overview of the evidence regarding the existence and function of CD133 in breast cancers in the context of the experimental and clinical data. It also discusses CD133 as a possible target for breast cancer therapy.

    DOI: 10.1007/978-94-007-7681-4_24

  • Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer Reviewed

    Kurashige Junji, Mima Kosuke, Sawada Genta, Takahashi Yusuke, Eguchi Hidetoshi, Sugimachi Keishi, Mori Masaki, Yanagihara Kazuyoshi, Yashiro Masakazu, Hirakawa Kosei, Baba Hideo, Mimori Koshi

    CARCINOGENESIS   36 ( 1 )   133 - 141   2015.01( ISSN:0143-3334

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    DOI: 10.1093/carcin/bgu232

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  • G-factorを加えたTNM分類による胃癌の新規分子ステージング 日本消化器癌発生学会のGプロジェクト委員会による多施設共同研究(New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee) Reviewed

    Sawada Tetsuji, Yashiro Masakazu, Sentani Kazuhiro, Oue Naohide, Yasui Wataru, Miyazaki Kohji, Kai Keita, Fushida Sachio, Fujimura Takashi, Ohira Masaichi, Kakeji Yoshihiro, Natsugoe Shoji, Shirabe Ken, Nomura Sachiyo, Shimada Yutaka, Tomita Naohiro, Hirakawa Kosei, Maehara Yoshihiko

    シュプリンガー・ジャパン(株) Gastric Cancer   18 ( 1 )   119 - 128   2015.01( ISSN:1436-3291

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    Gプロジェクト委員会では、従来のTNM分類に分子生物学的特性に基づくG-factorを加えた新たな分類スキームを考案している。今回、胃癌に関する論文を検索し、G-factorの候補として8分子を選定した。根治的R0切除術を受けた胃癌患者210例から得られた切除標本を用いて、8分子に対する免疫染色を行い、臨床病理学的因子と各分子の発現との関連について検討した。8分子の免疫染色発現と術後再発の間に有意な相関は観察されなかった。しかし、p53およびマトリックスメタロプロテイナーゼ-7(MMP-7)の発現は全生存(OS)と有意に相関した。p53およびMMP-7の発現に基づいて210例を3群に分けた場合(G0群:両分子ともに陰性、G1群:どちらかが陽性、G2群:両分子ともに陽性)、G2群はG0群に比して有意に高い再発率を示した。多変量解析では、G2群が短い無病生存(DFS)と独立して関連することが示された。G2群のステージII患者はG0/G1群のステージII患者に比してOSとDFSに関して有意に予後が不良であり、生存曲線はステージIII患者と同様であった。p53およびMMP-7の発現に基づくG-factorは、ステージII/III胃癌の転帰を予測し、ステージII癌に対する治療選択において有用であると考えられた。

  • New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee Reviewed

    Sawada Tetsuji, Yashiro Masakazu, Sentani Kazuhiro, Oue Naohide, Yasui Wataru, Miyazaki Kohji, Kai Keita, Fushida Sachio, Fujimura Takashi, Ohira Masaichi, Kakeji Yoshihiro, Natsugoe Shoji, Shirabe Ken, Nomura Sachiyo, Shimada Yutaka, Tomita Naohiro, Hirakawa Kosei, Maehara Yoshihiko

    GASTRIC CANCER   18 ( 1 )   119 - 128   2015.01( ISSN:1436-3291

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    DOI: 10.1007/s10120-014-0338-2

    PubMed

  • Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer Reviewed

    Junji Kurashige, Kosuke Mima, Genta Sawada, Yusuke Takahashi, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Kazuyoshi Yanagihara, Masakazu Yashiro, Kosei Hirakawa, Hideo Baba, Koshi Mimori

    CARCINOGENESIS   36 ( 1 )   133 - 41   2015.01( ISSN:0143-3334

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    CAFs induced the hypermethylation of the miR-200b promoter regions and reduced miR-200b expression and there was a negative correlation between miR-200b expression in gastric cancer specimens and alpha-smooth muscle actin expression in the stroma of gastric cancer.Cancer-associated fibroblasts (CAFs) have recently been linked to the invasion and metastasis of gastric cancer. In addition, the microRNA (miR)-200 family plays a central role in the regulation of the epithelial-mesenchymal transition process during cancer metastasis, and aberrant DNA methylation is one of the key mechanisms underlying regulation of the miR-200 family. In this study, we clarified whether epigenetic changes of miR-200b by CAFs stimulate cancer invasion and peritoneal dissemination in gastric cancer. We evaluated the relationship between miR-200b and CAFs using a coculture model. In addition, we established a peritoneal metastasis mouse model and investigated the expression and methylation status of miR-200b. We also investigated the expression and methylation status of miR-200b and CAFs expression in primary gastric cancer samples. CAFs (CAF-37 and CAF-50) contributed to epigenetic changes of miR-200b, reduced miR-200b expression and promoted tumor invasion and migration in NUGC3 and OCUM-2M cells in coculture. In the model mice, epigenetic changes of miR-200b were observed in the inoculated high-frequency peritoneal dissemination cells. In the 173 gastric cancer samples, the low miR-200b expression group demonstrated a significantly poorer prognosis compared with the high miR-200b expression group and was associated with peritoneal metastasis. In addition, downregulation of miR-200b in cancer cells was significantly correlated with alpha-smooth muscle actin expression. Our data provide evidence that CAFs reduce miR-200b expression and promote tumor invasion through epigenetic changes of miR-200b in gastric cancer. Thus, CAFs might be a therapeutic target for inhibition of gastric cancer.

    DOI: 10.1093/carcin/bgu232

    PubMed

  • G-factorを加えたTNM分類による胃癌の新規分子ステージング 日本消化器癌発生学会のGプロジェクト委員会による多施設共同研究(New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee) Reviewed

    Sawada Tetsuji, Yashiro Masakazu, Sentani Kazuhiro, Oue Naohide, Yasui Wataru, Miyazaki Kohji, Kai Keita, Fushida Sachio, Fujimura Takashi, Ohira Masaichi, Kakeji Yoshihiro, Natsugoe Shoji, Shirabe Ken, Nomura Sachiyo, Shimada Yutaka, Tomita Naohiro, Hirakawa Kosei, Maehara Yoshihiko

    Gastric Cancer   18 ( 1 )   119 - 128   2015.01( ISSN:1436-3291

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    Gプロジェクト委員会では、従来のTNM分類に分子生物学的特性に基づくG-factorを加えた新たな分類スキームを考案している。今回、胃癌に関する論文を検索し、G-factorの候補として8分子を選定した。根治的R0切除術を受けた胃癌患者210例から得られた切除標本を用いて、8分子に対する免疫染色を行い、臨床病理学的因子と各分子の発現との関連について検討した。8分子の免疫染色発現と術後再発の間に有意な相関は観察されなかった。しかし、p53およびマトリックスメタロプロテイナーゼ-7(MMP-7)の発現は全生存(OS)と有意に相関した。p53およびMMP-7の発現に基づいて210例を3群に分けた場合(G0群:両分子ともに陰性、G1群:どちらかが陽性、G2群:両分子ともに陽性)、G2群はG0群に比して有意に高い再発率を示した。多変量解析では、G2群が短い無病生存(DFS)と独立して関連することが示された。G2群のステージII患者はG0/G1群のステージII患者に比してOSとDFSに関して有意に予後が不良であり、生存曲線はステージIII患者と同様であった。p53およびMMP-7の発現に基づくG-factorは、ステージII/III胃癌の転帰を予測し、ステージII癌に対する治療選択において有用であると考えられた。

  • New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee Reviewed

    Tetsuji Sawada, Masakazu Yashiro, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Kohji Miyazaki, Keita Kai, Sachio Fushida, Takashi Fujimura, Masaichi Ohira, Yoshihiro Kakeji, Shoji Natsugoe, Ken Shirabe, Sachiyo Nomura, Yutaka Shimada, Naohiro Tomita, Kosei Hirakawa, Yoshihiko Maehara

    GASTRIC CANCER   18 ( 1 )   119 - 28   2015.01( ISSN:1436-3291

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    The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.
    In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.
    No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 %) compared to 38 % in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 % CI 1.098-3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.
    G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.

    DOI: 10.1007/s10120-014-0338-2

    PubMed

  • Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy Reviewed

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    一般社団法人 日本プライマリ・ケア連合学会 Journal of General and Family Medicine   16 ( 4 )   297 - 301   2015( ISSN:2189-6577

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    The etiology of and optimal treatments for Cronkhite-Canada syndrome (CCS) are still undetermined. Fewer than 5% of CCS patients experience complete remission and 15% of CCS patients develop malignancies. Here, we present a case of CCS involving autoimmune disorders, in which rapid diagnosis, rapid commencement of therapy, and complete remission were achieved after 4 months of prednisolone therapy and polypectomy, although biopsy specimens from all residual colonic polyps revealed adenocarcinoma in one polyp 4 months after prednisolone therapy. It is important to identify gastrointestinal or colonic polyps harboring malignant changes and to examine the involvement of autoimmune mechanisms for better outcomes in CCS patients.

    DOI: 10.14442/jgfm.16.4_297

    CiNii Article

  • Two-Surgeon Technique For Liver Transection Using Precoagulation By A Soft-Coagulation System And Ultrasonic Dissection Reviewed

    Yamada Nobuya, Amano Ryosuke, Kimura Kenjiro, Murata Akihiro, Yashiro Masakazu, Tanaka Sayaka, Wakasa Kenichi, Hirakawa Kosei

    HEPATO-GASTROENTEROLOGY   62 ( 138 )   389 - 392   2015( ISSN:0172-6390

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    DOI: 10.5754/hge14950

  • Are gemcitabine sensitivity related molecules useful as predictor of prognosis for patients of unresectable or recurrent biliary tract cancer with gemcitabine treatment alone? Reviewed

    Miura Kotaro, Otani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei, Amano Ryosuke, Murata Akihiro, Nakata Bunzo, Kimura Kenjiro, Yamazoe Sadaaki, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   15 - 16   2015

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    DOI: 10.11241/jsmtmr.30.15

    CiNii Article

  • Clinicopathological Significance of Autophagy in Gastric Cancer Reviewed

    Masuda Go, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei, Yashiro Masakazu, Kitayama Kishu, Kasashima Hiroaki, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Kubo Naoshi, Tanaka Hiroaki

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   31 ( 0 )   70 - 70   2015

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    DOI: 10.11241/jsmtmr.31.70

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  • Clinicopathological meanings of Lysyl Oxidase family in Gastric Carcinoma Reviewed

    Kasashima Hiroaki, Ohira Masaichi, Hirakawa Kosei, Yashiro Masakazu, Masuda Go, Kinoshita Haruhito, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   43 - 44   2015

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    DOI: 10.11241/jsmtmr.30.43

    CiNii Article

  • Clinical significance of node infiltrating tumor–associated macrophage in gastric cancer Reviewed

    Tauchi Yukie, Toyokawa Takahiro, Amano Ryousuke, Kubo Naoshi, Muguruma Kazuya, Ohtani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei, Tanaka Hiroaki, Sakimura Chie, Tokumoto Mao, Shibutani Masatsune, Yamazoe Sadaaki, Sakurai Katsunobu, Nagahara Hisashi, Kimura Kenjiro

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   27 - 28   2015

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    DOI: 10.11241/jsmtmr.30.27

    CiNii Article

  • Bone marrow-derived stromal cells are associated with gastric cancer progression Reviewed

    Kasashima Hiroaki, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Nakane Takahiko, Hino Masayuki, Hirakawa Kosei, Yashiro Masakazu, Nakamae Hirohisa, Yuichiro Miki, Kitayama Kisyu, Masuda Go, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   31 ( 0 )   71 - 72   2015

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    DOI: 10.11241/jsmtmr.31.71

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  • RBBP6, a predictive prognosis marker in gastric cancer Reviewed

    Morisaki Tamami, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei, Yashiro Masakazu, Kasashima Hiroaki, Masuda Go, Kinoshita Haruhito, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki

    Japanese Society for Molecular Tumor Marker Research, Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   47 - 48   2015

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    DOI: 10.11241/jsmtmr.30.47

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  • Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer Reviewed

    Motohiko Tokuhisa, Yasushi Ichikawa, Nobuyoshi Kosaka, Takahiro Ochiya, Masakazu Yashiro, Kosei Hirakawa, Takashi Kosaka, Hirochika Makino, Hirotoshi Akiyama, Chikara Kunisaki, Itaru Endo

    PLOS ONE   10 ( 7 )   e0130472   2015( ISSN:1932-6203

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    Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC.

    DOI: 10.1371/journal.pone.0130472

    PubMed

  • Are gemcitabine sensitivity related molecules useful as predictor of prognosis for patients of unresectable or recurrent biliary tract cancer with gemcitabine treatment alone? Reviewed

    Miura Kotaro, Amano Ryosuke, Murata Akihiro, Nakata Bunzo, Kimura Kenjiro, Yamazoe Sadaaki, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Otani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   15 - 16   2015

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    DOI: 10.11241/jsmtmr.30.15

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  • Cronkhite-Canada Syndrome with Complete Remission after Four Months of Prednisolone Therapy and Polypectomy

    Namikawa Hiroki, Takemoto Yasuhiko, Kamata Noriko, Yashiro Masakazu, Hirohashi Kazuhiro, Shuto Taichi

    Journal of General and Family Medicine   16 ( 4 )   297 - 301   2015( ISSN:21896577

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    Publishing type:Research paper (scientific journal)  

    The etiology of and optimal treatments for Cronkhite-Canada syndrome (CCS) are still undetermined. Fewer than 5% of CCS patients experience complete remission and 15% of CCS patients develop malignancies. Here, we present a case of CCS involving autoimmune disorders, in which rapid diagnosis, rapid commencement of therapy, and complete remission were achieved after 4 months of prednisolone therapy and polypectomy, although biopsy specimens from all residual colonic polyps revealed adenocarcinoma in one polyp 4 months after prednisolone therapy. It is important to identify gastrointestinal or colonic polyps harboring malignant changes and to examine the involvement of autoimmune mechanisms for better outcomes in CCS patients.

    DOI: 10.14442/jgfm.16.4_297

    CiNii Article

  • Clinicopathological Significance of Autophagy in Gastric Cancer Reviewed

    Masuda Go, Yashiro Masakazu, Kitayama Kishu, Kasashima Hiroaki, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   31 ( 0 )   70 - 70   2015

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.11241/jsmtmr.31.70

    CiNii Article

  • Clinicopathological meanings of Lysyl Oxidase family in Gastric Carcinoma Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Masuda Go, Kinoshita Haruhito, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   43 - 44   2015

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.11241/jsmtmr.30.43

    CiNii Article

  • Clinical significance of node infiltrating tumor–associated macrophage in gastric cancer Reviewed

    Tauchi Yukie, Tanaka Hiroaki, Sakimura Chie, Tokumoto Mao, Shibutani Masatsune, Yamazoe Sadaaki, Sakurai Katsunobu, Nagahara Hisashi, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryousuke, Kubo Naoshi, Muguruma Kazuya, Ohtani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   27 - 28   2015

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.11241/jsmtmr.30.27

    CiNii Article

  • Bone marrow-derived stromal cells are associated with gastric cancer progression Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Nakamae Hirohisa, Yuichiro Miki, Kitayama Kisyu, Masuda Go, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Nakane Takahiko, Hino Masayuki, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   31 ( 0 )   71 - 72   2015

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    DOI: 10.11241/jsmtmr.31.71

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    Other URL: http://search.jamas.or.jp/link/ui/2016258151

  • RBBP6, a predictive prognosis marker in gastric cancer Reviewed

    Morisaki Tamami, Yashiro Masakazu, Kasashima Hiroaki, Masuda Go, Kinoshita Haruhito, Sakurai Katsunobu, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    Japan Journal of Molecular Tumor Marker Research   30 ( 0 )   47 - 48   2015

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    DOI: 10.11241/jsmtmr.30.47

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  • MUC1 Protein Induces Urokinase-type Plasminogen Activator (uPA) by Forming a Complex with NF-kappa B p65 Transcription Factor and Binding to the uPA Promoter, Leading to Enhanced Invasiveness of Cancer Cells Reviewed

    Mori Yugo, Akita Kaoru, Tanida Shuhei, Ishida Akiko, Toda Munetoyo, Inoue Mizue, Yashiro Masakazu, Sawada Tetsuji, Hirakawa Kosei, Nakada Hiroshi

    JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 51 )   35193 - 35204   2014.12( ISSN:0021-9258

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    DOI: 10.1074/jbc.M114.586461

    PubMed

  • MUC1 Protein Induces Urokinase-type Plasminogen Activator (uPA) by Forming a Complex with NF-kappa B p65 Transcription Factor and Binding to the uPA Promoter, Leading to Enhanced Invasiveness of Cancer Cells Reviewed

    Yugo Mori, Kaoru Akita, Shuhei Tanida, Akiko Ishida, Munetoyo Toda, Mizue Inoue, Masakazu Yashiro, Tetsuji Sawada, Kosei Hirakawa, Hiroshi Nakada

    JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 51 )   35193 - 204   2014.12( ISSN:0021-9258

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    Mucin 1 (MUC1) is overexpressed in various human malignant tumors and its expression is correlated with a poor prognosis. MUC1 engages in signal transduction by interacting with receptors for growth and differentiation factors, which contributes to the growth and survival of cancer cells. However, the mechanism by which MUC1 promotes cancer cell invasion remains unclear. Microarray analysis revealed that expression of urokinase-type plasminogen activator (uPA) was elevated in MUC1-overexpressing cells. Furthermore, up- and down-modulation of MUC1 expression was clearly correlated with the change of uPA expression. An immunochemical study showed that the distribution of uPA coincided with that of MUC1 in various human cancer tissues. The MUC1 C-terminal domain (MUC1-CD) was associated with nuclear factor-B (NF-B) p65 in MUC1-expressing cells. Chromatin immunoprecipitation (ChIP) assays demonstrated that MUC1-CD existed with NF-B p65 on the uPA promoter. Luciferase assays indicated that the uPA transcriptional activity was correlated with the level of MUC1 expression and that this MUC1-enhancing effect on the uPA transcription was abolished by introduction of mutations into the NF-B binding sites on the uPA promoter. These results indicate that formation of the MUC1-CD and NF-B p65 complex enhanced nuclear translocation of NF-B p65 and subsequent occupancy of NF-B binding region on the uPA promoter, leading to elevated transcription of uPA. We also demonstrated that uPA induced by MUC1 enhanced the matrix metalloproteinase (MMP)-2 and -9 activities, and consequently promoted cancer cell invasion. Thus, a MUC1 co-operating NF-B signaling pathway plays a critical role in cancer cell invasion in MUC1-expressing cells.

    DOI: 10.1074/jbc.M114.586461

    PubMed

  • Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Kinoshita Haruhito, Fukuoka Tatsunari, Morisaki Tamami, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER LETTERS   354 ( 2 )   438 - 446   2014.11( ISSN:0304-3835

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    DOI: 10.1016/j.canlet.2014.08.014

    PubMed

  • Ulcerative colitis-associated colorectal cancer Reviewed

    Yashiro Masakazu

    WORLD JOURNAL OF GASTROENTEROLOGY   20 ( 44 )   16389 - 16397   2014.11( ISSN:1007-9327

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    DOI: 10.3748/wjg.v20.i44.16389

    PubMed

  • Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer Reviewed

    Hiroaki Kasashima, Masakazu Yashiro, Haruhito Kinoshita, Tatsunari Fukuoka, Tamami Morisaki, Go Masuda, Katsunobu Sakurai, Naoshi Kubo, Masaichi Ohira, Kosei Hirakawa

    CANCER LETTERS   354 ( 2 )   438 - 46   2014.11( ISSN:0304-3835

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    The aim of this study was to clarify the role of fibroblast-derived Lysyl oxidase-like 2 (LOXL2) in the development of gastric cancer. The correlation between the clinicopathological features of 548 primary gastric carcinomas and LOXL2 expression in stromal cells was examined by immunohistochemistry. Two gastric cancer cell lines, OCUM-12 and NUGC-3, and cancer-associated fibroblasts (CAFs) were used in this in vitro study. The effect of fibroblast-derived LOXL2 on the motility of gastric cancer cells was analyzed by using a wound-healing assay, a double-chamber invasion assay, and western blot. LOXL2 expression in stromal cells was significantly associated with tumor invasion depth, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination. Multivariable logistic regression analysis revealed that LOXL2 expression in stromal cells could be an independent predictive parameter for the overall survival of patients. CAFs significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells. This motility-stimulating ability of CAFs was inhibited by LOXL2 siRNA. Western blot analysis indicated that phosphorylation of focal adhesion kinase (FAK) in cancer cells was increased by the conditioned medium from CAFs, and was decreased by the conditioned medium from LOXL2 siRNA-treated CAFs. LOXL2 expression in stromal cells may be a useful prognostic factor for patients with gastric cancer. Fibroblast-derived LOXL2 may stimulate the motility of gastric cancer cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.canlet.2014.08.014

    PubMed

  • Ulcerative colitis-associated colorectal cancer Reviewed

    Masakazu Yashiro

    WORLD JOURNAL OF GASTROENTEROLOGY   20 ( 44 )   16389 - 97   2014.11( ISSN:1007-9327

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    The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

    DOI: 10.3748/wjg.v20.i44.16389

    PubMed

  • Early gastric cancer with suspected brain metastasis arising eight years after curative resection: a case report. Reviewed

    Sakurai K, Muguruma K, Murata A, Toyokawa T, Amano R, Kubo N, Tanaka H, Yashiro M, Maeda K, Ohira M, Hirakawa K

    BMC research notes   7   818   2014.11

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    DOI: 10.1186/1756-0500-7-818

    PubMed

  • Early gastric cancer with suspected brain metastasis arising eight years after curative resection: A case report Reviewed

    Katsunobu Sakurai, Kazuya Muguruma, Akihiro Murata, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    BMC Research Notes   7 ( 1 )   818   2014.11( ISSN:1756-0500

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    Background: Brain metastasis from gastric cancer is fairly uncommon and prognosis is dismal. We report a case of early gastric cancer with brain metastasis arising 8 years after gastrectomy. Case presentation: A 78-year-old Japanese female presented to our hospital complaining of dizziness, 8 years after undergoing gastrectomy for gastric cancer. Histopathological type of the tumor was well-differentiated adenocarcinoma. Final TNM classification was T1b(sm1)N0M0, and pathological stage was IA. Further examination revealed a metastatic tumor in the cerebellum and multiple liver metastases. The brain metastasis was treated using radiotherapy and steroid. Systemic treatment for liver metastases was performed using the oral fluoropyrimidine drug S-1. Neurological symptoms decreased, enabling the patient to be discharged from hospital. However, chemotherapy was discontinued due to loss of appetite and general fatigue. She died 5 months after the diagnosis of brain metastasis due to progressive disease. Conclusions: Cases of brain metastasis arising 8 years after gastrectomy for early gastric cancer have rarely reported. Aggressive treatment for brain metastases may be effective for improvement of the damage to neurological function and quality of life.

    DOI: 10.1186/1756-0500-7-818

    PubMed

  • Comparative Proteomics Analysis of Gastric Cancer Stem Cells Reviewed

    Morisaki Tamami, Yashiro Masakazu, Kakehashi Anna, Inagaki Azusa, Kinoshita Haruhito, Fukuoka Tatsunari, Kasashima Hiroaki, Masuda Go, Sakurai Katsunobu, Kubo Naoshi, Muguruma Kazuya, Ohira Masaichi, Wanibuchi Hideki, Hirakawa Kosei

    PLOS ONE   9 ( 11 )   e110736   2014.11( ISSN:1932-6203

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    DOI: 10.1371/journal.pone.0110736

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  • Effect of recombinant human soluble thrombomodulin in patients with solid carcinoma with DIC Reviewed

    Yuka Asano, Shinichiro Kashiwagi, Masatsune Shibutani, Sadaaki Yamazoe, Satoru Noda, Katsunobu Sakurai, Hisashi Nagahara, Kenjiro Kimura, Hidemi Kawajiri, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Ohtani, Tsutomu Takashima, Masakazu Yashiro, Naoyoshi Onoda, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2503 - 2505   2014.11( ISSN:0385-0684

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    There are only a few reports in the literature about the effect of recombinant human soluble thrombomodulin (rTM) in Patients with solid carcinoma with disseminated intravascular coagulation (DIC). A retrospective study of 40 patients with solid carcinoma with DIC was performed between February 2009 and April 2013. The withdrawal rate was 32.5% (13/40 Patients) and the 28-day survival rate was 40.0% (16/40 patients). Patients with successful withdrawal of DIC had significantly better outcomes (p&lt
    0.001). Therapy with rTM is one of the treatment options for patients with solid carcinoma with DIC.

    PubMed

  • A case of lymph node recurrence occurring nine years after surgery for sigmoid colon cancer Reviewed

    Shingo Togano, Masatsune Shibutani, Kiyoshi Maeda, Masakazu Yashiro, Hisashi Nagahara, Hiroshi Ohtani, Katsunobu Sakurai, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1614 - 1616   2014.11( ISSN:0385-0684

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    A 64-year-old man underwent sigmoidectomy for sigmoid colon cancer 9 years ago. We attempted to discontinue surveillance, as the postoperative course was event free for 5 years
    however, we continued the follow-up on the patient's request. Nine years after the operation, elevation of the serum carcinoembryonic antigen (CEA) level was detected, and positron emission tomography-computed tomography (PET-CT) showed a 35-mm mass with an abnormal signal (SUVmax 18.6 Bq/mL). We performed an abdominal CT and magnetic resonance imaging and found the mass invading the sigmoid colon. We suspected lymph node recurrence of the sigmoid colon cancer and considered curative surgery to be appropriate as there were no other signs of recurrence. We therefore excised the tumor by sigmoidectomy. A histopathological examination revealed metastatic adenocarcinoma in the lymph node. One year after the second operation, there was no evidence of recurrence on imaging and the levels of tumor markers were within the normal limits. Few reports have documented recurrence over 5 years after surgery. We herein describe our case and report the characteristics of a recurrent lesion and also suggest a protocol for surveillance, taking into consideration the previous literature.

    PubMed

  • Stage IV small cell esophageal carcinoma that responded to various chemotherapeutic regimens with relative longevity - A case report Reviewed

    Yoshihito Yamakoshi, Naoshi Kubo, Masaichi Ohira, Katsunobu Sakurai, Takahiro Toyokawa, Masatsune Shibutani, Sadaaki Yamazoe, Hisashi Nagahara, Kenjiro Kimura, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Ohtani, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2021 - 2023   2014.11( ISSN:0385-0684

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    Small cell carcinoma of the esophagus is reported to be both rare and aggressive, and is commonly associated with a short Post-diagnosis survival period. We report a case of Stage IV small cell carcinoma of the esophagus involving a relatively long survival period of 2 years. The patient was a 70-year-old man with a chief complaint of epigastric discomfort. Upper gastrointestinal endoscopy by a local physician showed a protruding tumor at the mid-thoracic esophagus. Tumor biopsy revealed small cell carcinoma. Chest-abdominal computed tomography revealed multiple liver metastases, and swelling of a number of regional lymph nodes. The diagnosis was cT3N4M1, cStage IVb esophageal small cell carcinoma. According to the regimen used for lung small cell carcinoma, we administered CDDP/CPT-11. After administration of four courses, the primary lesion, liver metastases, and lymph node metastases significantly reduced, indicating a partial response. However, after completion of eight courses, liver metastasis and lymph node swelling recurred. The patient subsequently received other therapeutic regimens such as CBDCA/VP-16, AMR, NGT, and CDGP/5-FU. However, the tumor gradually progressed, and the patient died approximately 2 years after the first treatment.

    PubMed

  • [A case of lymph node recurrence occurring nine years after surgery for sigmoid colon cancer]. Reviewed

    Togano S, Shibutani M, Maeda K, Yashiro M, Nagahara H, Ohtani H, Sakurai K, Yamazoe S, Kimura K, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Ohira M, Hirakawa K

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 12 )   1614 - 6   2014.11( ISSN:0385-0684

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    PubMed

  • [Stage IV small cell esophageal carcinoma that responded to various chemotherapeutic regimens with relative longevity - a case report]. Reviewed

    Yamakoshi Y, Kubo N, Ohira M, Sakurai K, Toyokawa T, Shibutani M, Yamazoe S, Nagahara H, Kimura K, Amano R, Tanaka H, Muguruma K, Ohtani H, Yashiro M, Maeda K, Hirakawa K

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 12 )   2021 - 3   2014.11( ISSN:0385-0684

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    PubMed

  • [Effect of recombinant human soluble thrombomodulin in patients with solid carcinoma with DIC]. Reviewed

    Asano Y, Kashiwagi S, Shibutani M, Yamazoe S, Noda S, Sakurai K, Nagahara H, Kimura K, Kawajiri H, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Ohtani H, Takashima T, Yashiro M, Onoda N, Maeda K, Ohira M, Hirakawa K

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 12 )   2503 - 5   2014.11( ISSN:0385-0684

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    PubMed

  • Pazopanib, a Novel Multitargeted Kinase Inhibitor, Shows Potent In Vitro Antitumor Activity in Gastric Cancer Cell Lines with FGFR2 Amplification Reviewed

    Kim Seung Tae, Jang Hye-Lim, Lee Su Jin, Lee Jeeyun, Choi Yoon-La, Kim Kyoung-Mee, Cho Jeonghee, Park Se Hoon, Park Young Suk, Lim Ho Yeong, Yashiro Masakazu, Kang Won Ki, Park Joon Oh

    MOLECULAR CANCER THERAPEUTICS   13 ( 11 )   2527 - 2536   2014.11( ISSN:1535-7163

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    DOI: 10.1158/1535-7163.MCT-14-0255

    PubMed

  • 固形癌DICに対する遺伝子組換えヒトトロンボモジュリン製剤の臨床的検討 Reviewed

    浅野 有香, 柏木 伸一郎, 渋谷 雅常, 山添 定明, 野田 諭, 櫻井 克宣, 永原 央, 木村 健二郎, 川尻 成美, 豊川 貴弘, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 大谷 博, 高島 勉, 八代 正和, 小野田 尚佳, 前田 清, 大平 雅一, 平川 弘聖

    (株)癌と化学療法社 癌と化学療法   41 ( 12 )   2503 - 2505   2014.11( ISSN:0385-0684

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    背景:固形癌患者は凝固活性亢進状態にあり、播種性血管内凝固症候群(DIC)の基礎疾患として重要である。一方で、新たなDIC治療薬として注目されている遺伝子組換えヒトトロンボモジュリン製剤(rTM)は、感染に伴うDICでの有用性は散見されるが、担癌患者における有用性の証明は十分とはいえない。今回、固形癌担癌患者のDICを対象とし、rTMの有用性・安全性について検討を行った。対象と方法:固形癌担癌患者のDICに対してrTMを投与した40例を対象とし、rTM製剤の有用性・安全性を検討した。結果:固形癌担癌患者40例のうち、消化器系17例(42.5%)、泌尿器系が15例(37.5%)などであった。13例(32.5%)がDIC離脱に成功しており、離脱までに要した日数の中央値は3.0日であった。有害事象は4例(10.0%)に出血傾向などが認められた。臨床因子との検討では、出血症状を有する症例は有意に離脱困難であった(p=0.043)。また、DIC離脱に成功した症例は有意に良好な転帰であった(p<0.001)。結語:固形癌担癌患者のDICに対し、rTM療法は治療選択肢の一つになると考えられた。(著者抄録)

  • Significance of Ductal Region in Anaplastic Pancreatic Cancer Reviewed

    Miura K., Kimura K., Amano R., Yamazoe S., Ohira G., Nishio K., Shibutani M., Sakurai K., Nagahara H., Toyokawa T., Kubo N., Tanaka H., Muguruma K., Otani H., Yashiro M., Maeda K., Ohira M., Hirakawa K.

    PANCREAS   43 ( 8 )   1391 - 1391   2014.11( ISSN:0885-3177

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  • 術後9年目に局所リンパ節再発を来したS状結腸癌の1例 Reviewed

    栂野 真吾, 渋谷 雅常, 前田 清, 八代 正和, 永原 央, 大谷 博, 櫻井 克宣, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 大平 雅一, 平川 弘聖

    (株)癌と化学療法社 癌と化学療法   41 ( 12 )   1614 - 1616   2014.11( ISSN:0385-0684

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    症例は64歳、男性。55歳時にS状結腸癌に対してS状結腸切除術を施行した。術後5年間無再発で経過し、サーベイランス終了を予定していたが本人の希望で継続していた。術後9年目、CEA値の上昇を認めPET-CT検査を施行したところ、骨盤内に異常集積を伴う長径35mm大の腫瘍を認めた。腹骨盤CTおよびMRI検査の結果、S状結腸への浸潤を伴うリンパ節再発が疑われた。その他の部位に再発を示唆する病変を認めず、根治切除が可能と判断し、腫瘍摘出およびS状結腸切除を行った。病理検査の結果、リンパ節再発と診断された。現在、術後1年が経過するが無再発生存中である。術後5年以降の遠隔期再発についての報告は散見されるが、その特徴やサーベイランス法について文献的考察を加えて報告する。(著者抄録)

  • 様々な化学療法により長期生存したStage IVb食道小細胞癌の1例 Reviewed

    山越 義仁, 久保 尚士, 大平 雅一, 櫻井 克宣, 豊川 貴弘, 渋谷 雅常, 山添 定明, 永原 央, 木村 健二郎, 天野 良亮, 田中 浩明, 六車 一哉, 大谷 博, 八代 正和, 前田 清, 平川 弘聖

    (株)癌と化学療法社 癌と化学療法   41 ( 12 )   2021 - 2023   2014.11( ISSN:0385-0684

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    食道小細胞癌は、非常に予後が悪く、なかでもStage IVの長期生存例の報告は少ない。今回われわれは、種々の化学療法により約2年と比較的長期に生存したStage IVb食道小細胞癌の1例を経験したので報告する。症例は70歳、男性。主訴は心窩部不快感。上部消化管内視鏡検査で胸部中部食道に1型病変を認め、生検にて小細胞癌と診断された。胸腹部CT検査で多発肝転移、遠隔リンパ節転移を認め、食道小細胞癌cT3N4M1、cStage IVbと診断した。肺小細胞癌に準じてCDDP/CPT-11療法を開始。4コース施行後、腫瘍は著明に縮小し、PRと判定した。しかし、8コース施行後、腫瘍の再増大を認めたため、CBDCA/VP-16、AMR、NGT、CDGP/5-FUを順次投与したが腫瘍はしだいに増大し、治療開始から約2年後に永眠された。(著者抄録)

  • [A case of lymph node recurrence occurring nine years after surgery for sigmoid colon cancer]. Reviewed

    Togano S, Shibutani M, Maeda K, Yashiro M, Nagahara H, Ohtani H, Sakurai K, Yamazoe S, Kimura K, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Ohira M, Hirakawa K

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 12 )   1614 - 6   2014.11( ISSN:0385-0684

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    PubMed

  • Pazopanib, a Novel Multitargeted Kinase Inhibitor, Shows Potent In Vitro Antitumor Activity in Gastric Cancer Cell Lines with FGFR2 Amplification Reviewed

    Seung Tae Kim, Hye-Lim Jang, Su Jin Lee, Jeeyun Lee, Yoon-La Choi, Kyoung-Mee Kim, Jeonghee Cho, Se Hoon Park, Young Suk Park, Ho Yeong Lim, Masakazu Yashiro, Won Ki Kang, Joon Oh Park

    MOLECULAR CANCER THERAPEUTICS   13 ( 11 )   2527 - 36   2014.11( ISSN:1535-7163

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    Pazopanib is an orally bioavailable, ATP-competitive, multitargeted tyrosine kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biologic sequences of pazopanib activities beyond antiangiogenesis are poorly defined. We used a panel of 38 gastric cancer cell lines to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 mu mol/L, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with wild-type (WT) FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell-cycle analysis, FGFR2-amplified cells underwent cell-cycle arrest at the G(1)-S phase after pazopanib treatment, whereas there were no significant effects on cell-cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G(1) only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of gastric cancer patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors. (C) 2014 AACR.

    DOI: 10.1158/1535-7163.MCT-14-0255

    PubMed

  • [Stage IV small cell esophageal carcinoma that responded to various chemotherapeutic regimens with relative longevity - a case report]. Reviewed

    Yamakoshi Y, Kubo N, Ohira M, Sakurai K, Toyokawa T, Shibutani M, Yamazoe S, Nagahara H, Kimura K, Amano R, Tanaka H, Muguruma K, Ohtani H, Yashiro M, Maeda K, Hirakawa K

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 12 )   2021 - 3   2014.11( ISSN:0385-0684

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    PubMed

  • 固形癌DICに対する遺伝子組換えヒトトロンボモジュリン製剤の臨床的検討 Reviewed

    浅野 有香, 柏木 伸一郎, 渋谷 雅常, 山添 定明, 野田 諭, 櫻井 克宣, 永原 央, 木村 健二郎, 川尻 成美, 豊川 貴弘, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 大谷 博, 高島 勉, 八代 正和, 小野田 尚佳, 前田 清, 大平 雅一, 平川 弘聖

    癌と化学療法   41 ( 12 )   2503 - 2505   2014.11( ISSN:0385-0684

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    背景:固形癌患者は凝固活性亢進状態にあり、播種性血管内凝固症候群(DIC)の基礎疾患として重要である。一方で、新たなDIC治療薬として注目されている遺伝子組換えヒトトロンボモジュリン製剤(rTM)は、感染に伴うDICでの有用性は散見されるが、担癌患者における有用性の証明は十分とはいえない。今回、固形癌担癌患者のDICを対象とし、rTMの有用性・安全性について検討を行った。対象と方法:固形癌担癌患者のDICに対してrTMを投与した40例を対象とし、rTM製剤の有用性・安全性を検討した。結果:固形癌担癌患者40例のうち、消化器系17例(42.5%)、泌尿器系が15例(37.5%)などであった。13例(32.5%)がDIC離脱に成功しており、離脱までに要した日数の中央値は3.0日であった。有害事象は4例(10.0%)に出血傾向などが認められた。臨床因子との検討では、出血症状を有する症例は有意に離脱困難であった(p=0.043)。また、DIC離脱に成功した症例は有意に良好な転帰であった(p<0.001)。結語:固形癌担癌患者のDICに対し、rTM療法は治療選択肢の一つになると考えられた。(著者抄録)

  • 術後9年目に局所リンパ節再発を来したS状結腸癌の1例 Reviewed

    栂野 真吾, 渋谷 雅常, 前田 清, 八代 正和, 永原 央, 大谷 博, 櫻井 克宣, 山添 定明, 木村 健二郎, 豊川 貴弘, 天野 良亮, 久保 尚士, 田中 浩明, 六車 一哉, 大平 雅一, 平川 弘聖

    癌と化学療法   41 ( 12 )   1614 - 1616   2014.11( ISSN:0385-0684

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    症例は64歳、男性。55歳時にS状結腸癌に対してS状結腸切除術を施行した。術後5年間無再発で経過し、サーベイランス終了を予定していたが本人の希望で継続していた。術後9年目、CEA値の上昇を認めPET-CT検査を施行したところ、骨盤内に異常集積を伴う長径35mm大の腫瘍を認めた。腹骨盤CTおよびMRI検査の結果、S状結腸への浸潤を伴うリンパ節再発が疑われた。その他の部位に再発を示唆する病変を認めず、根治切除が可能と判断し、腫瘍摘出およびS状結腸切除を行った。病理検査の結果、リンパ節再発と診断された。現在、術後1年が経過するが無再発生存中である。術後5年以降の遠隔期再発についての報告は散見されるが、その特徴やサーベイランス法について文献的考察を加えて報告する。(著者抄録)

  • 様々な化学療法により長期生存したStage IVb食道小細胞癌の1例 Reviewed

    山越 義仁, 久保 尚士, 大平 雅一, 櫻井 克宣, 豊川 貴弘, 渋谷 雅常, 山添 定明, 永原 央, 木村 健二郎, 天野 良亮, 田中 浩明, 六車 一哉, 大谷 博, 八代 正和, 前田 清, 平川 弘聖

    癌と化学療法   41 ( 12 )   2021 - 2023   2014.11( ISSN:0385-0684

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    食道小細胞癌は、非常に予後が悪く、なかでもStage IVの長期生存例の報告は少ない。今回われわれは、種々の化学療法により約2年と比較的長期に生存したStage IVb食道小細胞癌の1例を経験したので報告する。症例は70歳、男性。主訴は心窩部不快感。上部消化管内視鏡検査で胸部中部食道に1型病変を認め、生検にて小細胞癌と診断された。胸腹部CT検査で多発肝転移、遠隔リンパ節転移を認め、食道小細胞癌cT3N4M1、cStage IVbと診断した。肺小細胞癌に準じてCDDP/CPT-11療法を開始。4コース施行後、腫瘍は著明に縮小し、PRと判定した。しかし、8コース施行後、腫瘍の再増大を認めたため、CBDCA/VP-16、AMR、NGT、CDGP/5-FUを順次投与したが腫瘍はしだいに増大し、治療開始から約2年後に永眠された。(著者抄録)

  • Rho/ROCK signaling in motility and metastasis of gastric cancer Reviewed

    Matsuoka Tasuku, Yashiro Masakazu

    WORLD JOURNAL OF GASTROENTEROLOGY   20 ( 38 )   13756 - 13766   2014.10( ISSN:1007-9327

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    DOI: 10.3748/wjg.v20.i38.13756

    PubMed

  • Rho/ROCK signaling in motility and metastasis of gastric cancer Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    WORLD JOURNAL OF GASTROENTEROLOGY   20 ( 38 )   13756 - 66   2014.10( ISSN:1007-9327

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    Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have revealed that the Rho/Rho-associated protein kinases (ROCK) pathway plays a critical role in the regulation of cancer cell motility and invasion. In addition, the Rho/ROCK pathway plays important roles in invasion and metastasis on the basis of its predominant function of cell cytoskeletal regulation in gastric cancer. According to the current understanding of tumor motility, there are two modes of tumor cell movement: mesenchymal and amoeboid. In addition, cancer cell movement can be interchangeable between the mesenchymal and amoeboid movements under certain conditions. Control of cell motility through the actin cytoskeleton creates the potential for regulating tumor cell metastasis. In this review we discuss Rho GTPases and ROCK signaling and describe the mechanisms of Rho/ROCK activity with regard to motility and metastasis in gastric cancer. In addition, we provide an insight of the therapeutic potential of targeting the Rho/ROCK pathway. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

    DOI: 10.3748/wjg.v20.i38.13756

    PubMed

  • Effect of cancer associated fibroblast on gastric cancer cells under hypoxia Reviewed

    Kinoshita Haruhito, Yashiro Masakazu, Masuda Go, Kasashima Hiroaki, Morisaki Tamami, Fukuoka Tatsunari, Shibutani Masatune, Yamazoe Sadaaki, Sakurai Katsunobu, Nagahara Hisashi, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Otani Hiroshi, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3612

  • Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma Reviewed

    Kubo Naoshi, Ohira Masaichi, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Onoda Naoyoshi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3818

  • The stemness of gastric cancer stem cells is sustained by TGF beta produced from cancer-associated fibroblasts Reviewed

    Yashiro Masakazu, Hasegawa Tsuyoshi, Fukuoka Tatsunari, Kinoshita Haruhito, Morisaki Tamami, Kasashima Hiroaki, Masuda Go, Kubo Naoshi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3863

  • The effect of PGE2 receptor inhibitor on the microenviroment of scirrhous gastric cancer Reviewed

    Fukuoka Tatsunari, Yashiro Masakazu, Takeda Hiroshi, Maruyama Takayuki, Kasashima Hiroaki, Masuda Go, Kinoshita Haruhito, Morisaki Tamami, Sakurai Katsunobu, Shibutani Masatsune, Yamazoe Sadaaki, Kimura Kenjiro, Nagahara Hisashi, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Otani Hiroshi, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3606

  • Extent of intranodal macrophage correlates with lymph node metastasis of gastric cancer Reviewed

    Go Yukie, Tanaka Hiroaki, Tokumoto Mao, Okita Yoshihiro, Shibutani Masatsune, Yamazoe Sadaaki, Sakurai Katsunobu, Nagahara Hisashi, Kimura Kenjiro, Toyokawa Takahiro, Amano Ryosuke, Kubo Naoshi, Muguruma Kazuya, Otani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-1081

  • Establishment and characterization of two cell lines of anaplastic pancreatic cancer Reviewed

    Miura Kotaro, Kimura Kenjiro, Amano Ryosuke, Yamazoe Sadaaki, Hirata Keiichiro, Shibutani Masatsune, Sakurai Katsunobu, Nagahara Hisashi, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Otani Hiroshi, Yashiro Masakazu, Maeda Kiyoshi, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3924

  • Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma Reviewed

    Kasashima Hiroaki, Yashiro Masakazu, Go Yukie, Masuda Go, Kinoshita Haruhito, Tokumoto Mao, Morisaki Tamami, Fukuoka Tatsunari, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Muguruma Kazuya, Ohira Masaichi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-1980

  • Stromal fibroblasts mediate extracellular matrix remodeling and invasion of scirrhous gastric carcinoma cells Reviewed

    Yamaguchi Hideki, Yanagihara Kazuyoshi, Yashiro Masakazu, Sakai Ryuichi

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3601

  • Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma Reviewed

    Kubo Naoshi, Ohira Masaichi, Sakurai Katsunobu, Toyokawa Takahiro, Tanaka Hiroaki, Muguruma Kazuya, Yashiro Masakazu, Maeda Kiyoshi, Onoda Naoyoshi, Hirakawa Kosei

    CANCER RESEARCH   74 ( 19 )   2014.10( ISSN:0008-5472

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    DOI: 10.1158/1538-7445.AM2014-3818

  • MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer Reviewed

    Naito Yutaka, Yasuno Kyohei, Tagawa Hiroko, Sakamoto Naoya, Oue Naohide, Yashiro Masakazu, Sentani Kazuhiro, Goto Keisuke, Shinmei Shunsuke, Oo Htoo Zarni, Yanagihara Kazuyoshi, Hirakawa Kosei, Yasui Wataru

    ONCOLOGY REPORTS   32 ( 4 )   1720 - 1726   2014.10( ISSN:1021-335X

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    DOI: 10.3892/or.2014.3333

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  • Significance of preoperative nutritional assessment for gastric cancer patients with gastrectomy Reviewed

    Sakurai Katsunobu, Muguruma Kazuya, Toyokawa Takahiro, Kubo Naoshi, Tanaka Hiroaki, Yashiro Masakazu, Ohira Masaichi, Hirakawa Kosei

    JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS   219 ( 4 )   E173 - E173   2014.10( ISSN:1072-7515

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  • MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer Reviewed

    Yutaka Naito, Kyohei Yasuno, Hiroko Tagawa, Naoya Sakamoto, Naohide Oue, Masakazu Yashiro, Kazuhiro Sentani, Keisuke Goto, Shunsuke Shinmei, Htoo Zarni Oo, Kazuyoshi Yanagihara, Kosei Hirakawa, Wataru Yasui

    ONCOLOGY REPORTS   32 ( 4 )   1720 - 6   2014.10( ISSN:1021-335X

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    Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. We previously demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC. In the present study, we investigated the role of miR-145 in scirrhous type GC. The expression levels of miR-145 assessed by quantitative RT-PCR were higher in scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding normal tissues. GC patients with high miR-145 expression were at a more advanced tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than those with low miR-145 expression. Furthermore, miR-145 expression was significantly associated with poor prognosis in GC patients (P=0.0438). miR-145 expression was localized in stromal fibroblasts of scirrhous type GC but not in cancer cells. miR-145 was induced by treatment by transforming growth factor-beta, and it enhanced the expression of a-smooth muscle actin, a marker of myofibroblasts, in both normal gastric fibroblasts and cancer-associated fibroblasts. These data suggest that miR-145 may contribute to the progression of scirrhous type GC by regulating activation of peri-tumoral fibroblasts.

    DOI: 10.3892/or.2014.3333

    PubMed

  • 胃癌所属リンパ節転移予測因子としてのマクロファージ関連リンパ管新生の検討 Reviewed

    呉 幸枝, 田中 浩明, 徳本 真央, 大北 仁裕, 櫻井 克宣, 豊川 貴弘, 久保 尚士, 六車 一哉, 八代 正和, 澤田 鉄二, 大平 雅一, 平川 弘聖

    日本消化器外科学会雑誌   47 ( Suppl.2 )   154 - 154   2014.10( ISSN:0386-9768

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  • Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection Reviewed

    Kotaro Kiga, Hitomi Mimuro, Masato Suzuki, Aya Shinozaki-Ushiku, Taira Kobayashi, Takahito Sanada, Minsoo Kim, Michinaga Ogawa, Yuka W. Iwasaki, Hiroyuki Kayo, Yoko Fukuda-Yuzawa, Masakazu Yashiro, Masashi Fukayama, Taro Fukao, Chihiro Sasakawa

    NATURE COMMUNICATIONS   5   4497   2014.09( ISSN:2041-1723

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    Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. Here we examine the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and find that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene is increased in Hp-positive human gastric biopsies as compared with Hp-negative controls. Moreover, silencing of miR-210 in gastric epithelial cells promotes proliferation. We identify STMN1 and DIMT1 as miR-210 target genes and demonstrate that inhibition of miR-210 expression augments cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.

    DOI: 10.1038/ncomms5497

    PubMed

  • Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection Reviewed

    Kiga Kotaro, Mimuro Hitomi, Suzuki Masato, Shinozaki-Ushiku Aya, Kobayashi Taira, Sanada Takahito, Kim Minsoo, Ogawa Michinaga, Iwasaki Yuka W., Kayo Hiroyuki, Fukuda-Yuzawa Yoko, Yashiro Masakazu, Fukayama Masashi, Fukao Taro, Sasakawa Chihiro

    NATURE COMMUNICATIONS   5   4497   2014.09( ISSN:2041-1723

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    DOI: 10.1038/ncomms5497

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  • The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma Reviewed

    Matsuoka Tasuku, Yashiro Masakazu

    CANCERS   6 ( 3 )   1441 - 1463   2014.09( ISSN:2072-6694

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    DOI: 10.3390/cancers6031441

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  • The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma Reviewed

    Tasuku Matsuoka, Masakazu Yashiro

    CANCERS   6 ( 3 )   1441 - 63   2014.07( ISSN:2072-6694

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    The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma.

    DOI: 10.3390/cancers6031441

    PubMed

  • A prognostic indicator for the resection of liver metastasis of colorectal cancer Reviewed

    Amano Ryosuke, Yamada Nobuya, Nakata Bunzo, Kimura Kenjiro, Yashiro Masakazu, Ohira Masaichi, Hirakawa Kosei

    SURGERY TODAY   44 ( 7 )   1287 - 1292   2014.07( ISSN:0941-1291

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    DOI: 10.1007/s00595-013-0699-x

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  • Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer. Reviewed

    Kinoshita J, Fushida S, Tsukada T, Oyama K, Watanabe T, Shoji M, Okamoto K, Nakanuma S, Sakai S, Makino I, Furukawa H, Hayashi H, Nakamura K, Inokuchi M, Nakagawara H, Miyashita T, Tajima H, Takamura H, Ninomiya I, Fujimura T, Masakazu Y, Hirakawa K, Ohta T

    Oncology reports   32 ( 1 )   89 - 96   2014.07( ISSN:1021-335X

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    DOI: 10.3892/or.2014.3210

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  • 大腸癌肝転移の切除の予後指標(A prognostic indicator for the resection of liver metastasis of colorectal cancer) Reviewed

    Amano Ryosuke, Yamada Nobuya, Nakata Bunzo, Kimura Kenjiro, Yashiro Masakazu, Ohira Masaichi, Hirakawa Kosei

    シュプリンガー・ジャパン(株) Surgery Today   44 ( 7 )   1287 - 1292   2014.07( ISSN:0941-1291

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    大腸癌肝転移の外科的切除の予後を予測する指標を検討とした。大腸癌肝転移患者117例に132ヶ所の肝切除を施行した。肝転移の範囲を大腸癌取扱い規約(JCCRC)に従って分類し、患者をJCCRC分類および原発腫瘍のリンパ節浸潤の状態に基づいて病期別に分類した。生存期間中央値は58ヵ月であり、生存率は1年目が92.3%、3年目が60.0%、および5年目が46.1%であった。多変量解析では、JCCRC病期分類が生存期間中央値および5年生存率の独立予後指標であった。JCCRC病期分類は大腸癌肝転移における有意な予後指標であり、肝転移の治療の選択に有用な可能性があることが示された。

  • Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer Reviewed

    Jun Kinoshita, Sachio Fushida, Tomoya Tsukada, Katsunobu Oyama, Toshihumi Watanabe, Masatoshi Shoji, Koichi Okamoto, Shinichi Nakanuma, Seisho Sakai, Isamu Makino, Hiroyuki Furukawa, Hironori Hayashi, Keishi Nakamura, Masahumi Inokuchi, Hisatoshi Nakagawara, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Takashi Fujimura, Yashiro Masakazu, Kosei Hirakawa, Tetsuo Ohta

    ONCOLOGY REPORTS   32 ( 1 )   89 - 96   2014.07( ISSN:1021-335X

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    Intraperitoneal (i.p) chemotherapy with paclitaxel (PTX) has been shown to be a promising treatment strategy for peritoneal metastasis. The present study focused on the comparative evaluation of the therapeutic efficacy of nanopartide albumin-bound PTX (Nab-PTX) and i.p. administration of the conventional solvent-based PTX (Sb-PTX). We also investigated the difference in antitumor activity depending on the route of administration in the Nab-PTX treatment. Nab-PTX was administered i.p. or intravenously (i.v) and Sb-PTX was administered i.p. at equitoxic and equal doses to nude mice bearing gastric cancer OCUM-2MD3 cell subcutaneous and peritoneal xenografts. Therapeutic efficacy of Sb-PTX and Nab-PTX was evaluated as inhibition of tumor growth using a peritoneal metastatic model with subcutaneous xenografts. The survival rate was also investigated using mouse peritoneal models. For assessment of subcutaneous tumors, the change in tumor volume was measured, and for assessment of peritoneal tumors, the weight of ascitic fluid and the total peritoneal tumor burden were measured for each individual mouse. At equitoxic doses, treatment with Nab-PTX resulted in a greater reduction in the size of subcutaneous tumors and the weight of ascites and peritoneal burden as compared with i.p. Sb-PTX (P&lt;0.05). Treatment with i.p. and i.v. Nab-PTX also achieved greater survival benefit than i.p. Sb-PTX (P&lt;0.05). In contrast, there was no significant difference in the degree of tumor reduction and the survival time between both drugs at equal doses. With regard to the route of administration, the antitumor efficacy of Nab-PTX after i.v. administration was equivalent to the efficacy after i.p. administration. These results suggest that i.v. Nab-PTX may be another encouraging treatment option that can target peritoneal dissemination in gastric cancer.

    DOI: 10.3892/or.2014.3210

    PubMed

  • A prognostic indicator for the resection of liver metastasis of colorectal cancer Reviewed

    Ryosuke Amano, Nobuya Yamada, Bunzo Nakata, Kenjiro Kimura, Masakazu Yashiro, Masaichi Ohira, Kosei Hirakawa

    SURGERY TODAY   44 ( 7 )   1287 - 92   2014.07( ISSN:0941-1291

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    We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer.
    Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer. The clinical, pathological, and outcome parameters affecting their prognoses were analyzed. The extent of the liver metastases was subdivided according to the Japanese Classification of Colorectal Carcinoma (JCCRC), and the patients were classified into different grades based on the JCCRC classification and the status of the nodal involvement of the primary tumor.
    The median survival time (MST) of the 117 patients was 58 months, and the actuarial survival rates at 1, 3, and 5 years were 92.3, 60.0, and 46.1 %, respectively. A multivariate analysis revealed that the JCCRC Grade classification was an independent prognostic indicator (Grade A vs. B vs. C: MST, 72 vs. 41 vs. 23 months; 5-year survival, 59.0 vs. 38.6 vs. 0 %: p &lt; 0.0001).
    Our findings indicate that the JCCRC Grade classification for liver metastasis of colorectal cancer is a significant prognostic indicator and may be useful for making decisions regarding the treatment of liver metastasis.

    DOI: 10.1007/s00595-013-0699-x

    PubMed

  • 大腸癌肝転移の切除の予後指標(A prognostic indicator for the resection of liver metastasis of colorectal cancer) Reviewed

    Amano Ryosuke, Yamada Nobuya, Nakata Bunzo, Kimura Kenjiro, Yashiro Masakazu, Ohira Masaichi, Hirakawa Kosei

    Surgery Today   44 ( 7 )   1287 - 1292   2014.07( ISSN:0941-1291

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    Publishing type:Research paper (scientific journal)  

    大腸癌肝転移の外科的切除の予後を予測する指標を検討とした。大腸癌肝転移患者117例に132ヶ所の肝切除を施行した。肝転移の範囲を大腸癌取扱い規約(JCCRC)に従って分類し、患者をJCCRC分類および原発腫瘍のリンパ節浸潤の状態に基づいて病期別に分類した。生存期間中央値は58ヵ月であり、生存率は1年目が92.3%、3年目が60.0%、および5年目が46.1%であった。多変量解析では、JCCRC病期分類が生存期間中央値および5年生存率の独立予後指標であった。JCCRC病期分類は大腸癌肝転移における有意な予後指標であり、肝転移の治療の選択に有用な可能性があることが示された。

  • Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast cancer patients treated with taxane and anthracycline Reviewed

    Aomatsu Naoki, Yashiro Masakazu, Kashiwagi Shinichiro, Kawajiri Hidemi, Takashima Tsutomu, Ohsawa Masahiko, Wakasa Kenichi, Hirakawa Kosei

    BMC CANCER   14   400   2014.06( ISSN:1471-2407

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    DOI: 10.1186/1471-2407-14-400

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  • Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast cancer patients treated with taxane and anthracycline Reviewed