Development of anti-cancer agents targeting R-spondin-LGR4/5/6-ZNRF3/RNF43 axis
Project/Area Number |
15H04806
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | The University of Tokyo |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
池田 祐一 東京大学, 医学部附属病院, 特任准教授 (10744419)
熊谷 英敏 東京大学, 医学部附属病院, 特任助教 (20281008)
山下 裕玄 東京大学, 医学部附属病院, 講師 (50599397)
森田 啓行 東京大学, 医学部附属病院, 講師 (60323573)
浅岡 良成 東京大学, 医学部附属病院, 助教 (90431858)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | Wntシグナル / R-spondin / 抗癌剤 / 低分子化合物ライブラリー / 腸管幹細胞 / R-spondin代替え低分子化合物 / 内科 / 消化器内科 / 下部消化管 |
Outline of Final Research Achievements |
Utilizing a novel assay system targeting R-spondin-LGR4/5/6-ZNRF3/RNF43 axis, we first screened a small-molecule compound library to elucidate the R-spondin inhibitors as the anti-cancer agents and the R-spondin substitutes as the stimulating factors of intestinal stem cells. As the results, 60 compounds for inhibitor and one compound for stimulator became the candidates. As the succeeding analysis, the stimulator was confirmed to act through R-spondin-LGR4/5/6-ZNRF3/RNF43 axis, which indicated that the compound would be a promising seed of agents in the field of gastrointestinal regenerative medicine.
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Report
(4 results)
Research Products
(124 results)
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[Journal Article] A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial2018
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Niikura R, Nagata N, Yamada A, Doyama H, Shiratori Y, Nishida T, Kiyotoki S, Yada T, Fujita T, Sumiyoshi T, Hasatani K, Mikami T, Honda T, Mabe K, Hara K, Yamamoto K, Takeda M, Takata M, Tanaka M, Shinozaki T, Fujishiro M, Koike K
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Journal Title
Trials
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Pages: 214
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[Journal Article] Gastric Cancer With Primitive Enterocyte Phenotype: An Aggressive Subgroup of Intestinal-type Adenocarcinoma.2017
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Yamazawa S, Ushiku T, Shinozaki-Ushiku A, Hayashi A, Iwasaki A, Abe H, Tagashira A, Yamashita H, Seto Y, Aburatani H, Fukayama M.
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Am J Surg Pathol.
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[Journal Article] Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering2017
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Takanashi M, Taira Y, Okazaki S, Takase S, Kimura T, Li CC, Xu PF, Noda A, Sakata I, Kumagai H, Ikeda Y, Iizuka Y, Yahagi N, Shimano H, Osuga J, Ishibashi S, Kadowaki T, Okazaki H.
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J Atheroscler Thromb.
Volume: 24
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Int Heart J.
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[Journal Article] Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population2016
Author(s)
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Journal Title
J Gastroenterol.
Volume: 52
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Kimura K, Morita H, Daimon M, Horio M, Kawata T, Nakao T, Hirokawa M, Kitao R, Watanabe D, Komori T, Nagata T, Takeda S, Komaki H, Segawa K, Nakajima T, Takenaka K, Komuro I.
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Journal Title
International Heart Journal
Volume: 57
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[Journal Article] Comparative analysis of upper gastrointestinal endoscopy, double-contrast upper gastrointestinal barium X-ray radiography, and the titer of serum anti-Helicobacter pylori IgG focusing on the diagnosis of atrophic gastritis.2016
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Yamamichi N, Hirano C, Takahashi Y, Minatsuki C, Nakayama C, Matsuda R, Shimamoto T, Takeuchi C, Kodashima S, Ono S, Tsuji Y, Fujishiro M, Wada R, Mitsushima T, Koike K.
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Journal Title
Gastric Cancer.
Volume: 19
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[Journal Article] Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer.2016
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Dig Endosc.
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[Journal Article] Outcome of salvage surgery for colorectal cancer initially treated by upfront endoscopic therapy.2016
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Surgery.
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[Journal Article] Efficacy of lymph node dissection for each station based on esophageal tumor location.2016
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Tachimori Y, Ozawa S, Numasaki H, Fujishiro M, MatsubaraH, Oyama T, Shinoda M, Toh Y, Udagawa H, Uno T, The Registration Committee for Esophageal Cancer of the Japan Esophageal Society.
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Journal Title
Esophagus.
Volume: 13
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[Journal Article] Phosphatidylserine-specific phospholipase A1 (PS-PLA1) expression in colorectal cancer correlates with tumor invasion and hematogenous metastasis.2015
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Iida Y, Sunami E, Yamashita H, Hiyoshi M, Ishihara S, Yamaguchi H, Inoue A, Makide K, Tsuno NH, Aoki J, Kitayama J, Watanabe T.
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Journal Title
Anticancer Res.
Volume: 35
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[Journal Article] Evaluation of 18F-FDG uptake for detecting lymph node metastasis of gastric cancer: a prospective pilot study for one-to-one comparison of radiation dose and pathological findings.2015
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Okumura Y, Aikou S, Onoyama H, Jinbo K, Yamagata Y, Mori K, Yamashita H, Nomura S, Takahashi M, Koyama K, Momose T, Abe H, Matsusaka K, Ushiku T, Fukayama M, Seto Y
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World J Surg Oncol.
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[Journal Article] Serum Alpha-Fetoprotein Has High Specificity for the Early Detection of Hepatocellular Carcinoma After Hepatitis C Virus Eradication in Patients.2015
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Medicine (Baltimore).
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[Journal Article] Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma.2015
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Fujiwara N, Nakagawa H, Kudo Y, Tateishi R, Taguri M, Watadani T, Nakagomi R, Kondo M, Nakatsuka T, Minami T, Sato M, Uchino K, Enooku K, Kondo Y, Asaoka Y, Tanaka Y, Ohtomo K, Shiina S, Koike K.
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J Hepatol.
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[Journal Article] Comparison of improved prognosis between hepatitis B- and hepatitis C-related hepatocellular carcinoma.2015
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Minami T, Tateishi R, Shiina S, Nakagomi R, Kondo M, Fujiwara N, Mikami S, Sato M, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Yoshida H, Koike K.
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Hepatol Res.
Volume: 45
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[Journal Article] Neuromedin S-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms.2015
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Lee IT, Chang AS, Manandhar M, Shan Y, Fan J, Izumo M, Ikeda Y, Motoike T, Dixon S, Seinfeld JE, Takahashi JS, Yanagisawa M
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Journal Title
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[Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling.2015
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Kumagai H, Ikeda Y, Motozawa Y, Fujishiro M, Okamura T, Fujio K, Okazaki H, Nomura S, Takeda N, Harada M, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Yamamoto K, Komuro I, Yanagisawa M
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