Molecular dissection of Cancer microenvironment-related genes
Project/Area Number |
15K08973
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Sapporo Medical University |
Principal Investigator |
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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.
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Report
(4 results)
Research Products
(28 results)
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[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.
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Journal Title
Molecular Carcinogenesis
Volume: 57
Issue: 3
Pages: 451-461
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Clin J Gastroenterol.
Volume: 22
Issue: 3
Pages: 22-22
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Gastric Cancer.
Volume: 21
Issue: 5
Pages: 765-775
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Dig Dis Sci.
Volume: 15
Issue: 7
Pages: 1920-1928
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Mol Carcinog
Volume: -
Issue: 7
Pages: 1743-1752
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Gastrointest Endosc.
Volume: 86
Issue: 6
Pages: 1131-1138
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Oncology Letters
Volume: 14
Pages: 5703-5710
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Oncotarget.
Volume: 9
Issue: 4
Pages: 4707-4721
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 26699-26699
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Oncotarget
Volume: 7
Issue: 23
Pages: 35106-35118
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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.
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Journal Title
Int J Cancer
Volume: 1
Issue: 7
Pages: 1689-97
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Oncotarget
Volume: 6
Issue: 30
Pages: 29975-90
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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
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Journal Title
PLoS ONE
Volume: 10
Issue: 9
Pages: e0137801-e0137801
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
PLoS One
Volume: 10
Issue: 7
Pages: e0133754-e0133754
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cancer Prev Res (Phila)
Volume: 10
Issue: 8
Pages: 702-11
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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