Investigation of intratumoral heterogeneity in intrahepatic cholangiocarcinoma using multiregional analysis and innovative drug target discovery
Project/Area Number |
15K10170
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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 |
Digestive surgery
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Research Institution | National Hospital Organization, Kyushu Cancer Center (2016-2017) Kyushu University (2015) |
Principal Investigator |
Iguchi Tomohiro 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 肝胆膵外科医師 (30598959)
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Co-Investigator(Kenkyū-buntansha) |
鈴木 穣 東京大学, 大学院新領域創成科学研究科, 教授 (40323646)
宮野 悟 東京大学, 医科学研究所, 教授 (50128104)
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Co-Investigator(Renkei-kenkyūsha) |
MIYANO Satoru 東京大学, 医科学研究所, 教授 (50128104)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
|
Keywords | 肝内胆管癌 / 腫瘍内不均一性 / 全エキソームシーケンス / RNAシーケンス / clonal evolution / clonal evolution / クローン進化 |
Outline of Final Research Achievements |
Cancer cells evolve by a reiterative process of clonal expansion through the accumulations of mutations and a single cancer harbors diverse genetically distinct subclones (intra-tumor heterogeneity). As a major cause of therapeutic failure, the understanding of intra-tumor heterogeneity is clinically necessary. Intrahepatic cholangiocarcinoma (ICC) is resistant to chemotherapy and radiation and is known as high-grade cancer. There have been many molecular researches associated with ICC, however, the accumulations of mutations through the process of clonal evolution is not fully understood. We performed genomic analysis for ICC considered in three dimensions (multiregional analysis). Intra-tumor heterogeneity is found to exist in ICC as well as others. However, the genetic drivers of ICC are not universal and when considered as the therapeutic target, a personalized and elaborate gene therapy strategy is necessary.
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Report
(4 results)
Research Products
(30 results)
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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
Pages: 2255-2263
DOI
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: 93
Pages: 67-74
DOI
Related Report
Peer Reviewed
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[Journal Article] Phosphoserine Phosphatase Is a Novel Prognostic Biomarker on Chromosome 7 in Colorectal Cancer.2017
Author(s)
Sato K, Masuda T, Hu Q, Tobo T, Kidogami S, Ogawa Y, Saito T, Nambara S, Komatsu H, Hirata H, Sakimura S, Uchi R, Hayashi N, Iguchi T, Eguchi H, Ito S, Nakagawa T, Mimori K.
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Journal Title
Anticancer Res.
Volume: 37
Pages: 2365-2371
DOI
Related Report
Peer Reviewed
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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: 64
Pages: 107666-107677
DOI
Related Report
Peer Reviewed
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[Journal Article] Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer.2017
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: 45
Pages: 78598-78613
DOI
Related Report
Peer Reviewed
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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: 1;76
Pages: 3265-7
DOI
Related Report
Peer Reviewed
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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
Pages: 2139-44
Related Report
Peer Reviewed
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[Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.2016
Author(s)
Uchi R, Takahashi Y, Niida A, Shimamura T, Hirata H, Sugimachi K, Sawada G, Iwaya T, Kurashige J, Shinden Y, Iguchi T, Eguchi H, Chiba K, Shiraishi Y, Nagae G, Yoshida K, Nagata Y, Haeno H, Yamamoto H, Ishii H, Doki Y, Iinuma H, Sasaki S, Nagayama S, Yamada K,
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Journal Title
PLoS Genet
Volume: 18;12
Pages: e1005778
DOI
Related Report
Peer Reviewed
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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 S, Takano Y, Uchi R, 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
Pages: 2073-80
DOI
Related Report
Peer Reviewed
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[Journal Article] HOXB7 Expression is a Novel Biomarker for Long-term Prognosis after Resection of Hepatocellular Carcinoma2016
Author(s)
Komatsu H, Iguchi T, Masuda T, Ueda M, Kidogami S, Ogawa Y, Nambara S, Sato K, Hu Q, Saito T, Hitarta H, Sakimura S, Uchi R, Hayashi N, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K
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Journal Title
Anticancer Res
Volume: accept
Pages: accept
Related Report
Peer Reviewed
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[Journal Article] Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular Carcinoma Patients.2015
Author(s)
Sugimachi K, Sakimura S, Tomokuni A, Uchi R, Hirata H, Komatsu H, Shinden Y, Iguchi T, Eguchi H, Masuda T, Morita K, Shirabe K, Eguchi H, Maehara Y, Mori M, Mimori K.
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Journal Title
J Clin Med.
Volume: 4
Pages: 1600-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma.2015
Author(s)
Hirata H, Sugimachi K, Takahashi Y, Ueda M, Sakimura S, Uchi R, Kurashige J, Takano Y, Nanbara S, Komatsu H, Saito T, Shinden Y, Iguchi T, Eguchi H, Atsumi K, Sakamoto K, Doi T, Hirakawa M, Honda H, Mimori K.
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Journal Title
Ann Surg Oncol.
Volume: 3
Pages: 1402-9
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] in silico解析による肝細胞癌の新規関連遺伝子SF3B4(Splicing factor B,subunit 4)の同定と臨床病理学的意義の検討2017
Author(s)
井口 友宏,辻田 英司, 信藤 由成, 吉田 大輔, 太田 光彦, 南 一仁, 池部 正彦, 森田 勝, 増田 隆明, 三森 功士, 藤 也寸志
Organizer
第117回日本外科学会定期学術集会
Related Report
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