Establishment of a novel treatment with ivermectin targeting the Hippo pathway to gastric cancer.
Project/Area Number |
16K07177
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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 |
Tumor therapeutics
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Research Institution | Kyushu University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
MIMORI KOSHI
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 胃癌 / Hippo経路 / YAP1 / イベルメクチン / リポジショニングドラッグ / 数理統計解析 / 膵癌 / 胃癌腹膜播種 |
Outline of Final Research Achievements |
We aimed to clarify whether ivermectin, an antiparasitic drug, had antitumor effects on gastric cancer (GC) through inhibition of YAP1. In GC cell xenografts, ivermectin suppressed tumor growth.we explored the mechanism through which ivermectin regulated YAP1 expression. Ivermectin inhibited YAP1 nuclear expression and the downstream gene CTGF expression in GC cells. Ivermectin decreased YAP1 mRNA expression, thereby inhibiting nuclear accumulation of YAP1 in MKN1 cells. In survival analysis, low YAP1 mRNA expression was associated with a better prognosis in three independent GC datasets.
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Academic Significance and Societal Importance of the Research Achievements |
スキルス胃癌は比極めて予後の悪い腫瘍であり、腹膜播種の機序については未知な部分が多く、有効な治療法の確立が待たれる。我々はイベルメクチンがHippo経路の転写因子であるYAP1の 阻害効果を有することを見出し、 同薬剤投与により腹膜播種の抑制効果が期待される。またイベルメクチンはリポジショニングドラッグとしても有用性が期待される。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] A clinical trial of somatic and germline analyses for healthy longevity in a postoperative cancer patient.2019
Author(s)
Hayashi N, Kuroda Y, Saito T, Tsuruda Y, Niida A, Otsu H, Eguchi H, Masuda T, Suzuki Y, Natsugoe S, Mimori K.
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Journal Title
Surg Today.
Volume: Epub
Issue: 9
Pages: 738-747
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Plastin3 is associated with epithelial-mesenchymal transition and poor prognosis in gastric cancer.2019
Author(s)
Kurashige J, Yokobori T, Mima K, Sawada G, Takahashi Y, Ueo H, Takano Y, Matsumura T, Uchi R, Eguchi H, Sudo T, Sugimachi K, Mori M, Baba H, Mimori K.
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Journal Title
Oncol Lett
Volume: 17(2)
Pages: 2393-2399
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.2018
Author(s)
Sugimachi K, Sakimura S, Kuramitsu S, Hirata H, Niida A, Iguchi T, Eguchi H, Masuda T, Morita M, Toh Y, Maehara Y, Suzuki Y, Mimori K.
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Journal Title
Br J Cancer.
Volume: 4
Issue: 4
Pages: 419-423
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Circulating Pre-microRNA-488 in Peripheral Blood Is a Potential Biomarker for Predicting Recurrence in Breast Cancer.2018
Author(s)
Masuda T, Shinden Y, Noda M, Ueo H, Hu Q, Yoshikawa Y, Tsuruda Y, Kuroda Y, Ito S, Eguchi H, Ohno S, Mimori K.
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Journal Title
Anticancer Res.
Volume: 38(8)
Issue: 8
Pages: 4515-4523
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer2018
Author(s)
Saito T, Niida A, Uchi R, Hirata H, Kodama M, Okimoto T, Murakami K, Suzuki Y, Ogawa S, Miyano S, Mimori K, et al.
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 2884-2884
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma.2018
Author(s)
Iguchi T, Ueda M, Masuda T, Nambara S, Kidogami S, Komatsu H, Sato K, Tobo T, Ogawa Y, Hu Q, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Maehara Y, Mimori K
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Journal Title
Oncology
Volume: 3
Issue: 3
Pages: 179-187
DOI
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Peer Reviewed / Open Access
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[Journal Article] Identification of ARL4C as a Peritoneal Dissemination-Associated Gene and Its Clinical Significance in Gastric Cancer.2018
Author(s)
Hu Q, Masuda T, Sato K, Tobo T, Nambara S, Kidogami S, Hayashi N, Kuroda Y, Ito S, Eguchi H, Saeki H, Oki E, Maehara Y, Mimori K
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Journal Title
Ann Surg Oncol
Volume: 25(3)
Issue: 3
Pages: 745-753
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer.2017
Author(s)
Nambara S, Masuda T, Nishio M, Kuramitsu S, Tobo T, Ogawa Y, Hu Q, Iguchi T, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Saeki H, Oki E, Maehara Y, Suzuki A, Mimori K
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Journal Title
Oncotarget.
Volume: 8(64)
Issue: 64
Pages: 107666-107677
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer2017
Author(s)
Takano Y, Masuda T, Iinuma H, Yamaguchi R, Sato K, Tobo T, Hirata H, Kuroda Y, Nambara S, Hayashi N, Iguchi T, Ito S, Eguchi H, Ochiya T, Yanaga K, Miyano S, Mimori K
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Journal Title
Oncotarget
Volume: 8(45)
Issue: 45
Pages: 78598-78613
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Up-regulation of SLC9A9 Promotes Cancer Progression and Is Involved in Poor Prognosis in Colorectal Cancer.2017
Author(s)
Ueda M, Iguchi T, Masuda T, Komatsu H, Nambara S, Sakimura S, Hirata H, Uchi R, Eguchi H, Ito S, Sugimachi K, Mizushima T, Doki Y, Mori M, Mimori K
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Journal Title
Anticancer Res.
Volume: 37(5)
Pages: 2255-2263
Related Report
Peer Reviewed
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[Journal Article] Altered expression of Hippo signaling pathway molecules in intrahepatic cholangiocarcinoma.2017
Author(s)
Sugimachi K, Nishio M, Aishima S, Kuroda Y, Iguchi T, Komatsu H, Hirata H, Sakimura S, Eguchi H, Bekki Y, Takenaka K, Maehara Y, Suzuki A, Mimori K.
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Journal Title
ONCOLOGY
Volume: -
Issue: 1
Pages: 67-74
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Peer Reviewed / Open Access
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[Journal Article] Clinical Significance of FANCD2 Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma.2017
Author(s)
Komatsu H, Masuda T, Iguchi T, Nambara S, Sato K, Hu Q, Hirata H, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K
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Journal Title
Anticancer Res.
Volume: 37(3)
Pages: 1083-1090
Related Report
Peer Reviewed
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[Journal Article] Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma2016
Author(s)
Komatsu H, Iguchi T, Masuda T, Hirata H, Ueda M, Kidogami S, Ogawa Y, Sato K, Hu Q, Nambara S, Saito T, Sakimura S, Uchi R, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
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Journal Title
Ann Surg Oncol.
Volume: 24(3)
Issue: 3
Pages: 850-859
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis.2016
Author(s)
Iguchi T, Nambara S, Masuda T, Komatsu H, Ueda M, Kidogami S, Ogawa Y, Hu Q, Sato K, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Maehara Y, Mimori K.
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Journal Title
PLoS One.
Volume: 11(11)
Issue: 11
Pages: e0165912-e0165912
DOI
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Peer Reviewed / Open Access
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[Journal Article] Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence2016
Author(s)
Ueda M, Iguchi T, Masuda T, Nakahara Y, Hirata H, Uchi R, Niida A, Momose K, Sakimura S, Chiba K, Eguchi H, Ito S, Sugimachi K, Yamasaki M, Suzuki Y, Miyano S, Doki Y, Mori M, Mimori K
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Journal Title
Oncotarget
Volume: 7(38)
Issue: 38
Pages: 62280-62291
DOI
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Peer Reviewed / Open Access
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[Journal Article] 8q24 Polymorphisms and Diabetes Mellitus Regulate Apolipoprotein A-IV in Colorectal Carcinogenesis2016
Author(s)
Sugimachi K, Yamaguchi R, Eguchi H, Ueda M, Niida A, Sakimura S, Hirata H, Uchi R, Shinden Y, Iguchi T, Morita K, Yamamoto K, Miyano S, Mori M, Maehara Y, Mimori K
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Journal Title
Ann Surg Oncol
Volume: 23(Suppl 4)
Issue: S4
Pages: 546-551
DOI
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Peer Reviewed / Open Access
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[Journal Article] HOXB7 Expression is a Novel Biomarker for Long-term Prognosis After Resection of Hepatocellular Carcinoma.2016
Author(s)
Komatsu H, Iguchi T, Masuda T, Ueda M, Kidogami S, Ogawa Y, Nambara S, Sato K, Hu Q, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
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Journal Title
Anticancer Res.
Volume: 36(6)
Pages: 2767-73
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer.2016
Author(s)
Sugimachi K, Matsumura T, Shimamura T, Hirata H, Uchi R, Ueda M, Sakimura S, Iguchi T, Eguchi H, Masuda T, Morita K, Takenaka K, Maehara Y, Mori M, Mimori K.
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Journal Title
Ann Surg Oncol.
Volume: 23(12)
Issue: 12
Pages: 3948-3955
DOI
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Peer Reviewed / Open Access
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[Journal Article] Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma.2016
Author(s)
Hirata H, Sugimachi K, Komatsu H, Ueda M, Masuda T, Uchi R, Sakimura S, Nambara S, Saito T, Shinden Y, Iguchi T, Eguchi H, Ito S, Terashima K, Sakamoto K, Hirakawa M, Honda H, Mimori K.
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Journal Title
Cancer Res.
Volume: 76(11)
Issue: 11
Pages: 3265-76
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Increased Copy Number of the Gene Encoding SF3B4 Indicates Poor Prognosis in Hepatocellular Carcinoma.2016
Author(s)
Iguchi T, Komatsu H, Masuda T, Nambara S, Kidogami S, Ogawa Y, Hu Q, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Maehara Y, Mimori K.
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Journal Title
Anticancer Res.
Volume: 36(5)
Pages: 2139-44
Related Report
Peer Reviewed / Open Access
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[Journal Article] Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.2016
Author(s)
Kurashige J, Hasegawa T, Niida A, Sugimachi K, Deng N, Mima K, Uchi R, Sawada G, Takahashi Y, Eguchi H, Inomata M, Kitano S, Fukagawa T, Sasako M, Sasaki H, Sasaki S, Mori M, Yanagihara K, Baba H, Miyano S, Tan P, Mimori K.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 22371-22371
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma.2016
Author(s)
Komatsu H, Iguchi T, Ueda M, Nambara S, Saito T, Hirata H, Sakimura S1, Takano Y1, Uchi R1, Shinden Y, Eguchi H, Masuda T, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
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Journal Title
Oncol Rep
Volume: 35
Issue: 4
Pages: 2073-80
DOI
Related Report
Peer Reviewed / Open Access
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