Identification of novel therapeutic targets on alternative pre-mRNA splicing in digestive malignancy
Project/Area Number |
26461967
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General surgery
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Research Institution | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
Principal Investigator |
MIURA Koh 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (40282074)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 消化器癌 / 選択的pre-mRNAスプライシング / 治療標的 / 新規治療法 / 浸潤転移 / 発がん / 大腸癌 |
Outline of Final Research Achievements |
Pyruvate kinase gene, which codes an enzyme essential for glycolytic pathway, has four isoforms of transcripts: L, R, M1 and M2. We especially focused on the M2 isoform and analyzed its expression levels in cancerous and corresponding normal tissues from gastric cancer patients and normal tissues from healthy individuals. The analysis revealed that the M2 isoform is highly expressed in cancer and normal tissues from gastric cancer patients. Along with in vivo experiments, the M2 isoform was shown to be important in development of gastric cancer (Shiroki T, et al. Cancer Sci. 2017; 108:931-940). We are also analyzing alternative pre-mRNA splicing of dihydropyrimidine dehydrogenase gene, which codes a catabolizing enzyme of 5-FU, under collaboration with Department of Surgery, Tohoku University. We found serpini1 gene has an important role in epithelial-to-mesenchymal transition in colorectal cancer, and we are exploring functions of the splice variants located in the 5'-UTR region.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Drug delivery of oral anti-cancer fluoropyrimidine agents.2017
Author(s)
Miura K, Shima H, Takebe N, Julie R, Satoh K, Kakugawa Y, Satoh M, Kinouchi M, Yamamoto K, Hasegawa Y, Kawai M, Kanazawa K, Fujiya T, Unno M and Katakura R.
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Journal Title
Expert Opin.Drug Deliv
Volume: 印刷中
Issue: 12
Pages: 1-12
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced expression of PKM2 is involved in the gastric cancer development via regulating cancer specific metabolism.2017
Author(s)
Shiroki T, Yokoyama M, Tanuma N, Maejima R, Tamai K, Yamaguchi K, Oikawa T, Noguchi T, Miura K, Fujiya T, Shima H, Sato I, Kamiya N, Hatakeyama M, Iijima K, Shimosegawa T and Satoh K.
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Journal Title
Cancer Science
Volume: 印刷中
Issue: 5
Pages: 931-940
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] NDRG2, suppressed expression associates with poor prognosis in pancreatic cancer, is hypermethylated in the second promoter in human gastrointestinal cancers.2017
Author(s)
Yamamura A, Miura K, Karasawa H, Motoi F, Mizuguchi Y, Saiki Y, Fukushige S, Sunamura M, Shibata C, Unno M, Horii A.
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Journal Title
Biochem Biophys Res Commun
Volume: 484
Issue: 1
Pages: 138-143
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] SERPINI1 regulates epithelial– mesenchymal transition in an orthotopic implantation model of colorectal cancer.2016
Author(s)
Yasufumi Matsuda, Koh Miura, Junko Yamane, Hiroshi Shima, Wataru Fujibuchi, Kazuyuki Ishida, Fumiyoshi Fujishima, Shinobu Ohnuma, Hiroyuki Sasaki, Munenori Nagao, Naoki Tanaka, Kennichi Satoh, Takeshi Naitoh, Michiaki Unno
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Journal Title
Cancer Science
Volume: -
Issue: 5
Pages: 619-628
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced expression of semaphorin 3E is involved in the gastric cancer development.2016
Author(s)
Maejima R, Tamai K, Shiroki T, Yokoyama M, Shibuya R, Nakamura M, Yamaguchi K, Abue M, Oikawa T, Noguchi T, Miura K, Fujiya T, Sato I, Iijima K, Shimosegawa T, Tanaka N, Satoh K.
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Journal Title
Int J Oncol.
Volume: 49(5)
Issue: 3
Pages: 619-28
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis.2015
Author(s)
Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
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Journal Title
Cancer Lett.
Volume: 365
Issue: 2
Pages: 223-228
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The use of natural products in colorectal cancer drug discovery.2015
Author(s)
Koh Miura, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Yoichiro Kakugawa, Masaaki Kawai, Kiyoshi Uchimi, Hiroki Aizawa, Shinobu Ohnuma, Taiki Kajiwara, Hiroto Sakurai , Tsuneaki Fujiya
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Journal Title
Expert opinion on drug discovery
Volume: 10(4)
Issue: 4
Pages: 411-426
DOI
Related Report
Peer Reviewed
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[Journal Article] Gastrointestinal toxicities of 5-fluorouracil increase the proportion of regulatory T cells in intestinal tract: advantages of alternate-day S-1 administration.2015
Author(s)
Kajiwara T, Miura K, Ohnuma S, Shimada M, Komura T, Toshima M, Kohyama A, Kudoh K, Haneda S, Musha H, Naitoh T, Shirasaka T, Unno M.
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Journal Title
Int J Clin Oncol.
Volume: Not assigned yet
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects.2015
Author(s)
Komura T, Miura K, Shirasaka T, Ohnuma S, Shimada M, Kajiwara T, Fujishima F, Philchenkov A, Nakagawa K, Kudoh K, Haneda S, Toshima M, Kohyama A, Musha H, Naitoh T, Shibata C, Unno M.
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Journal Title
Int J Clin Oncol.
Volume: 20 (1)
Issue: 1
Pages: 117-125
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Natural products as possible anti-cancer agents for digestive malignancies.2015
Author(s)
Koh Miura, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Yoichiro Kakugawa, Masaaki Kawai, Kiyoshi Uchimi, Hiroki Aizawa, Hiroto Sakurai, Tsuneaki Fujiya.
Organizer
AACR Annual Meeting 2015
Place of Presentation
Philadelphia, PA, USA
Year and Date
2015-04-22
Related Report
Int'l Joint Research
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[Presentation] Natural products as possible anti-cancer agents for digestive malignancies2015
Author(s)
Koh Miura, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Yoichiro Kakugawa, Masaaki Kawai, Kiyoshi Uchimi, Hiroki Aizawa, Hiroto Sakurai, Tsuneaki Fujiya.
Organizer
AACR Annual Meeting 2015
Place of Presentation
Philadelphia
Year and Date
2015-04-22
Related Report
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