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Molecular dissection of Cancer microenvironment-related genes

Research Project

Project/Area Number 15K08973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

YAMAMOTO Eiichiro  札幌医科大学, 医学部, 講師 (60567915)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords微小環境 / 大腸がん / 遺伝子発現 / 腫瘍血管新生 / がん間質 / 大腸癌 / 腫瘍血管
Outline of Final Research Achievements

We identified genes and splicing variant which were altered in the tumor endothelial cells. We then validated the results by RT-qPCR, and identified gene A as a novel candidate of the tumor endothelium-related gene. The Cancer Genome Atlas (TCGA) datasets revealed that higher expression of gene A is associated with worse overall survival of CRC patients. Knockdown of gene A in human umbilical vein endothelial cell (HUVEC) suppressed cell proliferation and in vitro tube formation. Injection of siRNA against gene A in mice transplanted with human CRC cells suppressed formation of microvessels in the xenografted tumors. Microarray analysis revealed that knockdown of gene A in HUVEC significantly affected gene expression signatures, including cell cycle regulation and interferon signaling. Our results suggest that gene A may play an important role in the angiogenesis in CRC, and that it could be a potential therapeutic target.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (28 results)

All 2018 2017 2016 2015

All Journal Article (21 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 21 results,  Open Access: 17 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Molecular profiling and genome-wide analysis based on somatic copy number alterations in advanced colorectal cancers2018

    • Author(s)
      Sugai T, Takahashi Y, Eizuka M, Sugimoto R, Fujita Y, Habano W, Otsuka K, Sasaki A, Yamamoto E, Matsumoto T, Suzuki H.
    • Journal Title

      Molecular Carcinogenesis

      Volume: 57 Issue: 3 Pages: 451-461

    • DOI

      10.1002/mc.22769

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic portal venous gas due to polystyrene sulfonate-induced enteritis.2018

    • Author(s)
      Kubo T, Yamashita K, Yokoyama Y, Hirayama D, Shirata T, Mitsuhashi K, Onodera K, Yamamoto E, Nosho K, Yamano H, Kubo T, Sugita S, Hasegawa T, Nakase H.
    • Journal Title

      Clin J Gastroenterol.

      Volume: 22 Issue: 3 Pages: 22-22

    • DOI

      10.1007/s12328-018-0818-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of a rectal stricture related to ischemic proctitis following rupture of an aortic aneurysm.2018

    • Author(s)
      Iida T, Ohkubo Y, Kubo T, Yamashita K, Onodera K, Yamamoto E, Nosho K, Ito T, Yamano H, Nakase H.
    • Journal Title

      Endosc Int Open.

      Volume: 6 Issue: 02 Pages: E186-E189

    • DOI

      10.1055/s-0043-117946

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status.2018

    • Author(s)
      Sugai T, Eizuka M, Arakawa N, Osakabe M, Habano W, Fujita Y, Yamamoto E, Yamano H, Endoh M, Matsumoto T, Suzuki H.
    • Journal Title

      Gastric Cancer.

      Volume: 21 Issue: 5 Pages: 765-775

    • DOI

      10.1007/s10120-018-0810-5

    • NAID

      40021642313

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.2018

    • Author(s)
      Aoki H, Yamamoto E, Yamano HO, Sugai T, Kimura T, Tanaka Y, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Harada T, Sudo G, Eizuka M, Yorozu A, Kitajima H, Niinuma T, Kai M, Nojima M, Suzuki H, Nakase H.
    • Journal Title

      Dig Dis Sci.

      Volume: 15 Issue: 7 Pages: 1920-1928

    • DOI

      10.1007/s10620-018-5016-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular subtypes of colorectal cancers determined by PCR-based analysis.2017

    • Author(s)
      Sugai T, Eizuka M, Takahashi Y, Fukagawa T, Habano W, Yamamoto E, Akasaka R, Otuska K, Matsumoto T, Suzuki H.
    • Journal Title

      Cancer Sci

      Volume: 108(3) Issue: 3 Pages: 427-434

    • DOI

      10.1111/cas.13164

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays.2017

    • Author(s)
      Eizuka M, Sugai T, Habano W, Uesugi N, Takahashi Y, Kawasaki K, Yamamoto E, Suzuki H, Matsumoto T.
    • Journal Title

      J Gastroenterol

      Volume: - Issue: 11 Pages: 1158-1168

    • DOI

      10.1007/s00535-017-1317-2

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer.2017

    • Author(s)
      Kai M, Yamamoto E, Sato A, Yamano HO, Niinuma T, Kitajima H, Harada T, Aoki H, Maruyama R, Toyota M, Hatahira T, Nakase H, Sugai T, Yamashita T, Toyota M, Suzuki H.
    • Journal Title

      Mol Carcinog

      Volume: - Issue: 7 Pages: 1743-1752

    • DOI

      10.1002/mc.22631

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoscopic and Molecular Characterization of Colorectal Sessile Serrated Adenoma/polyps with Cytological Dysplasia.2017

    • Author(s)
      Tanaka Y, Yamano HO, Yamamoto E, Matushita HO, Aoki H, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Eizuka M, Sugai T, Suzuki H, Nakase H.
    • Journal Title

      Gastrointest Endosc.

      Volume: 86 Issue: 6 Pages: 1131-1138

    • DOI

      10.1016/j.gie.2017.05.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the DNA methylation level of cancer-related genes in colorectal cancer and the surrounding normal mucosa.2017

    • Author(s)
      Sugai T, Yoshida M, Eizuka M, Uesugii N, Habano W, Otsuka K, Sasaki A, Yamamoto E, Matsumoto T, Suzuki H.
    • Journal Title

      Clin Epigenetics.

      Volume: 55 Issue: 1 Pages: 55-55

    • DOI

      10.1186/s13148-017-0352-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.2017

    • Author(s)
      Niinuma T, Kai M, Kitajima H, Yamamoto E, Harada T, Maruyama R, Nobuoka T, Kanda T, Hasegawa T, Tokino T, Sugai T, Shimomura Y, Nakase H, Suzuki H
    • Journal Title

      Oncology Letters

      Volume: 14 Pages: 5703-5710

    • DOI

      10.3892/ol.2017.6911

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.2017

    • Author(s)
      Aoki H, Yamamoto E, Takasawa A, Niinuma T, Yamano HO, Harada T, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Tanaka Y, Yoshida Y, Aoyama T, Eizuka M, Yorozu A, Kitajima H, Kai M, Sawada N, Sugai T, Nakase H, Suzuki H.
    • Journal Title

      Oncotarget.

      Volume: 9 Issue: 4 Pages: 4707-4721

    • DOI

      10.18632/oncotarget.23523

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship Between Noncoding RNA Dysregulation and Epigenetic Mechanisms in Cancer.2016

    • Author(s)
      Suzuki H, Maruyama R, Yamamoto E, Niinuma T, Kai M.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 927 Pages: 109-135

    • DOI

      10.1007/978-981-10-1498-7_4

    • ISBN
      9789811014963, 9789811014987
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer.2016

    • Author(s)
      Kumegawa K, Maruyama R, Yamamoto E, Ashida M, Kitajima H, Tsuyada A, Niinuma T, Kai M, Yamano HO, Sugai T, Tokino T, Shinomura Y, Imai K, Suzuki H.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 26699-26699

    • DOI

      10.1038/srep26699

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations.2016

    • Author(s)
      Sawada T, Yamamoto E, Yamano HO, Nojima M, Harada T, Maruyama R, Ashida M, Aoki H, Matsushita HO, Yoshikawa K, Harada E, Tanaka Y, Wakita S, Niinuma T, Kai M, Eizuka M, Sugai T, Suzuki H.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 23 Pages: 35106-35118

    • DOI

      10.18632/oncotarget.9044

    • NAID

      120006534714

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability-high phenotype2016

    • Author(s)
      Sugimoto R, Sugai T, Habano W, Endoh M, Eizuka M, Yamamoto E, Uesugi N, Ishida K, Kawasaki T, Matsumoto T, Suzuki H.
    • Journal Title

      Int J Cancer

      Volume: 1 Issue: 7 Pages: 1689-97

    • DOI

      10.1002/ijc.29916

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors2015

    • Author(s)
      Kamimae S, Yamamoto E, Kai M, Niinuma T, Yamano HO, Nojima M, Yoshikawa K, Kimura T, Takagi R, Harada E, Harada T, Maruyama R, Sasaki Y, Tokino T, Shinomura Y, Sugai T, Imai K, Suzuki H
    • Journal Title

      Oncotarget

      Volume: 6 Issue: 30 Pages: 29975-90

    • DOI

      10.18632/oncotarget.5034

    • NAID

      130005161526

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Low-frequency IL23R coding variant associated with Crohn's disease susceptibility in Japanese subjects identified by personal genomics analysis2015

    • Author(s)
      Onodera K, Arimura Y, Isshiki H, Kawakami K, Nagaishi K, Yamashita K, Yamamoto E, Niinuma T, Naishiro Y, Suzuki H, Imai K, Shinomura Y
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 9 Pages: e0137801-e0137801

    • DOI

      10.1371/journal.pone.0137801

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors.2015

    • Author(s)
      Isosaka M, Niinuma T, Nojima M, Kai M, Yamamoto E, Maruyama R, Nobuoka T, Nishida T, Kanda T, Taguchi T, Hasegawa T, Tokino T, Hirata K, Suzuki H, Shinomura Y
    • Journal Title

      PLoS One

      Volume: 10 Issue: 7 Pages: e0133754-e0133754

    • DOI

      10.1371/journal.pone.0133754

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer.2015

    • Author(s)
      5.Ichimura N, Shinjo K, An B, Shimizu Y, Yamao K, Ohka F, Katsushima K, Hatanaka A, Tojo M, Yamamoto E, Suzuki H, Ueda M, Kondo Y
    • Journal Title

      Cancer Prev Res (Phila)

      Volume: 10 Issue: 8 Pages: 702-11

    • DOI

      10.1158/1940-6207.capr-14-0306

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparative analysis of methods to determine DNA methylation levels of a tumor-related microRNA gene.2015

    • Author(s)
      Konishi Y, Hayashi H, Suzuki H, Yamamoto E, Sugisaki H, Higashimoto H.
    • Journal Title

      Anal Biochem

      Volume: 484 Pages: 66-71

    • DOI

      10.1016/j.ab.2015.05.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Molecular dissection of tumor angiogenesis in colorectal cancer2016

    • Author(s)
      Yamamoto E
    • Organizer
      UEG Week Vienna 2016
    • Place of Presentation
      オーストリア ウィーン
    • Year and Date
      2016-10-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大腸がんの腫瘍血管新生に関わる遺伝子異常の探索2016

    • Author(s)
      山本英一郎、萬顕、青木敬則、菅井有、仲瀬裕志、鈴木拓
    • Organizer
      日本消化器癌発生学会
    • Place of Presentation
      城山観光ホテル(鹿児島県 鹿児島市)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of tumor endothelium-related genes in colorectal cancer2016

    • Author(s)
      Akira Yorozu, Yamamoto Eiichiro , Reo Maruyama, Masahiro Kai, Takeshi Niinuma, Tomohisa Furuhata, Tomohiko Nishidate, Tamotsu Sugai, Hiromu Suzuki.
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      Maui, Hawaii, USA
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of aberrant DNA methylation associated with the development of traditional serrated adenoma.2016

    • Author(s)
      Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Takeshi Niinuma, Masahiro Kai, Reo Maruyama, Yasushi Adachi, Takao Endo, Tamotsu Sugai, Hiromu Suzuki.
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      Maui, Hawaii, USA
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Possible role of TET1 dysregulation in inducing aberrant DNA methylation in colorectal cancer.2016

    • Author(s)
      Hiromu Suzuki, Masahiro Kai, Takeshi Niinuma, Eiichiro Yamamoto, Reo Maruyama, Akira Yorozu, Kohei Kumegawa, Hironori Aoki, Tetsuya Shindo, Takashi Tokino, Kohzoh Imai.
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      Maui, Hawaii, USA
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Histone H3K27 trimethylation in normal colon is associated with development of colorectal tumor with CpG island methylator phenotype2015

    • Author(s)
      Eiichiro Yamamoto, Hiroo Yamano, Tamotsu Sugai, Hiromu Suzuki
    • Organizer
      United European Gastroenterology Week 2015
    • Place of Presentation
      Barcelona
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ENDOSCOPIC AND MOLECULAR FEATURES REVEAL PROGRESSION OF SERRATED LESIONS2015

    • Author(s)
      Hironori Aoki, Eiichiro Yamamoto, Hiroo Yamano, Takao Endo, Tamotsu Sugai, Hiromu Suzuki
    • Organizer
      United European Gastroenterology Week 2015
    • Place of Presentation
      Barcelona
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-12-27  

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