Clarification of the bona-fide evolution from early to advanced CRC to establish the eradication methods.
Project/Area Number |
19H03715
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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 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Kyushu University |
Principal Investigator |
Mimori Koshi 九州大学, 大学病院, 教授 (50322748)
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Co-Investigator(Kenkyū-buntansha) |
新井田 厚司 東京大学, 医科学研究所, 講師 (00772493)
鈴木 穣 東京大学, 大学院新領域創成科学研究科, 教授 (40323646)
工藤 進英 昭和大学, 医学部, 特任教授 (70161643)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | 多領域シーケンス / がん微小環境 / spatial transcriptome / VISIUM / 共局在 / SPP1+マクロファージ / 大腸がん / シングルセル解析 / サイトカイン / 免疫応答 / ダーウイン進化 / 中立進化 / 腫瘍免疫応答 / VISIUM解析 / 大腸発がん / 選択圧 / 陥凹型大腸がん / CMS分類 / がん進化 / コピー数変異 |
Outline of Research at the Start |
大腸がんは高い致死率を示し続けており、従来とは異なる標的探索アプローチが求められている。大腸は初期病変(腫瘤型、平坦型、陥凹型)のいずれかより成育して、様々な進化様式(A直線的なダーウイン進化、B分岐型のダーウイン進化、C中立進化、D断続的進化)を経て、最終的には進行大腸がんに到りConsensus Molecular Subtype (CMS)の4群に分類されると考えられる。本研究では将来の進行がんの芽となる極めて初期の病変3群について、シングルセル全ゲノム解析(HM-SNS)および腫瘍免疫応答解析 (RNA Seq)を併施して発がんから進化への理解を深め分子治療の標的を求める。
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Outline of Final Research Achievements |
We have shown that founder mutations and block-specific progressor mutations form heterogeneity in colorectal cancer by multiregion analysis (MRA). We also showed that in precancerous lesions, subclones are eliminated at an early stage of cancer and that mutations in strong driver genes are selected as founder mutations, providing a model for cancer evolution. However, a perspective on the stromal response was lacking. This study performed spatially informative spatial transcriptome analysis of advanced colorectal cancer cases. The results revealed the presence of “specific cells” that cross-talk with colorectal cancer cells explicitly localized to the invasion front.
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Academic Significance and Societal Importance of the Research Achievements |
大腸癌は、日本において罹患率の高い癌であり、癌死患者総数も多く予後不良な疾患である。この為、大腸腫瘍の進化(特に発症のメカニズム)と免疫寛容獲得の機序を解明する事が求められている。これまでのゲノム解析では癌細胞にのみ特化しており間質における細胞とのクロストークが不明であった。腫瘍のゲノム多様性は治療標的の選定を困難にするが、間質における応答を治療標的とすることで将来的には最適な治療法を明らかにすることができる。
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Report
(4 results)
Research Products
(135 results)
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[Journal Article] Nano-scale physical properties characteristic to intestinal cancer cells identified by high speed-scanning ion conductance microscope2022
Author(s)
D. Wang, L. Sun, S. Okuda, D. Yamamoto, M. Nakayama, H. Oshima, H. Saito, Y. Kouyama, K. Mimori, T. Ando, S. Watanabe, M. Oshima
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Journal Title
Biomaterials
Volume: 280
Pages: 121256-121256
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma.2022
Author(s)
Takahashi J, Masuda T, Kitagawa A, Tobo T, Nakano Y, Abe T, Ando Y, Kosai K, Kobayashi Y, Matsumoto Y, Yoshizumi T, Mori M, Mimori K.
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Journal Title
Oncology.
Volume: 100(2)
Issue: 2
Pages: 101-113
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein.2022
Author(s)
Koike K, Masuda T, Sato K, Fujii A, Wakiyama H, Tobo T, Takahashi J, Motomura Y, Nakano T, Saito H, Matsumoto Y, Otsu H, Takeishi K, Yonemura Y, Mimori K, Nakagawa T.
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Journal Title
Cancer Sci.
Volume: 113(1)
Issue: 1
Pages: 156-169
DOI
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Peer Reviewed / Open Access
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[Journal Article] Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin.2021
Author(s)
Shimizu D, Taniue K, Matsui Y, Haeno H, Araki H, Miura F, Fukunaga M, Shiraishi K, Miyamoto Y, Tsukamoto S, Komine A, Kobayashi Y, Kitagawa A, Yoshikawa Y, Sato K, Saito T, Ito S, Masuda T, Niida A, Suzuki M, Baba H, Ito T, Akimitsu N, Kodera Y, Mimori K.
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Journal Title
Cancer Gene Ther.
Volume: Epub
Issue: 5
Pages: 1-1
DOI
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Peer Reviewed / Open Access
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[Journal Article] Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA.2021
Author(s)
Sakano Y, Noda T, Kobayashi S, Kitagawa A, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Gotoh K, Asaoka T, Tanemura M, Umeshita K, Mimori K, Doki Y, Eguchi H.
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Journal Title
Dig Dis Sci.
Volume: Epub
Issue: 8
Pages: 3817-3830
DOI
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Peer Reviewed / Open Access
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[Journal Article] The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.2021
Author(s)
Hirata H,...Masuda T, Saito T, Kageyama SI, Motomura Y, Ito S, Yoshitake T, Tsurumaru D, Nishimuta Y, Yokoyama A, Hasegawa T, Chiba K, Shiraishi Y, Du J, Miura F, Morita M, Toh Y, Hirakawa M, Shioyama Y, Ito T, Akimoto T, Miyano S, Shibata T, Mori M, Suzuki Y, Ogawa S, Ishigami K, Mimori K.
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Journal Title
Cancer Res.
Volume: 81(19)
Issue: 19
Pages: 4926-4938
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.2021
Author(s)
Hu Q, Masuda T, Koike K, Sato K, Tobo T, Kuramitsu S, Kitagawa A, Fujii A, Noda M, Tsuruda Y, Otsu H, Kuroda Y, Ito S, Oki E, Mimori K.
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Journal Title
Sci Rep.
Volume: 11(1)
Issue: 1
Pages: 19178-19178
DOI
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Peer Reviewed / Open Access
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[Journal Article] Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.2021
Author(s)
Ono H, Arai Y, Furukawa E, Narushima D, Matsuura T, Nakamura H, Shiokawa D, Nagai M, Imai T, Mimori K, Okamoto K, Hippo Y, Shibata T, Kato M.
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Journal Title
BMC Biol
Volume: 19(1)
Issue: 1
Pages: 207-207
DOI
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Peer Reviewed / Open Access
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[Journal Article] Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA.2021
Author(s)
Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N; Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic Medicine.
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Journal Title
Cancer Sci.
Volume: 112(9)
Issue: 9
Pages: 3911-3917
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer.2021
Author(s)
Kobayashi Y, Masuda T, Fujii A, Shimizu D, Sato K, Kitagawa A, Tobo T, Ozato Y, Saito H, Kuramitsu S, Noda M, Otsu H, Mizushima T, Doki Y, Eguchi H, Mori M, Mimori K.
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Journal Title
Cancer Sci.
Volume: 112(8)
Issue: 8
Pages: 3173-3189
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cancer-associated Fibroblast-derived Spondin-2 Promotes Motility of Gastric Cancer Cells. Cancer Genomics Proteomics.2021
Author(s)
Kuramitsu S, Masuda T, Hu Q, Tobo T, Yashiro M, Fujii A, Kitagawa A, Abe T, Otsu H, Ito S, Oki E, Mori M, Mimori K.
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Journal Title
Cancer Genomics Proteomics.
Volume: 18(4)
Issue: 4
Pages: 521-529
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer2021
Author(s)
Qingjiang Hu 1 , Kentaro Nonaka 1 , Hiroaki Wakiyama 2 , Yu Miyashita 1 , Yoshiaki Fujimoto 1 , Tomoko Jogo 1 , Kentaro Hokonohara 1 , Ryota Nakanishi 1 , Yuichi Hisamatsu 1 , Koji Ando 1 , Yasue Kimura 1 , Takaaki Masuda 2 , Eiji Oki 1 , Koshi Mimori 2 , Yoshinao Oda 3 , Masaki Mori 1
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Journal Title
Cancer Med.
Volume: -
Issue: 9
Pages: 3129-3138
DOI
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Peer Reviewed / Open Access
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[Journal Article] Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer.2020
Author(s)
Ito S, Masuda T, Noda M, Hu Q, Shimizu D, Kuroda Y, Eguchi H, Tobo T, Utsunomiya T, Mimori K.
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Journal Title
Oncology.
Volume: 98(7)
Issue: 7
Pages: 501-511
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] SF3B4 Plays an Oncogenic Role in Esophageal Squamous Cell Carcinoma.2020
Author(s)
Kidogami S, Iguchi T, Sato K, Yoshikawa Y, Hu Q, Nambara S, Komatsu H, Ueda M, Kuroda Y, Masuda T, Mori M, Doki Y, Mimori K.
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Journal Title
Anticancer Res.
Volume: 40(5)
Issue: 5
Pages: 2941-2946
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma.2020
Author(s)
Kitagawa A, Masuda T, Takahashi J, Tobo T, Noda M, Kuroda Y, Hu Q, Kouyama Y, Kobayashi Y, Kuramitsu S, Sato K, Fujii A, Yoshikawa Y, Wakiyama H, Shimizu D, Tsuruda Y, Eguchi H, Doki Y, Mori M, Mimori K.
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Journal Title
Cancer Genomics Proteomics.
Volume: 17(2)
Issue: 2
Pages: 141-149
DOI
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Peer Reviewed / Open Access
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[Journal Article] Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice.2020
Author(s)
Miki Nishio , Yoko To , Tomohiko Maehama , Yukari Aono , Junji Otani , Hiroki Hikasa , Akihiro Kitagawa , Koshi Mimori , Takehiko Sasaki , Hiroshi Nishina , Shinya Toyokuni , John P Lydon , Kazuwa Nakao , Tak Wah Mak , Tohru Kiyono , Hidetaka Katabuchi , Hironori Tashiro , Akira Suzuki
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Journal Title
Cancer science
Volume: 111
Issue: 10
Pages: 3576-3578
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor-suppressor gene TGFβR2 in colorectal cancer.2020
Author(s)
Nambara S, Masuda T, Kobayashi Y, Sato K, Tobo T, Koike K, Noda M, Ogawa Y, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Mimori K.
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Journal Title
Cancer Sci.
Volume: 111(2)
Issue: 2
Pages: 343-355
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma2020
Author(s)
Yuji Morine, Tohru Utsunomiya, Yu Saito, Shinichiro Yamada, Satoru Imura, Tetsuya Ikemoto, Akihiro Kitagawa, Yuta Kobayashi, Seiichiro Takao, Keisuke Kosai, Koshi Mimori, Yasuhito Tanaka, Mitsuo Shimada
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Journal Title
Oncotarget
Volume: 11
Issue: 52
Pages: 4803-4812
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel oncogene 5MP1 reprograms c-Myc translation initiation to drive malignant phenotypes in colorectal cancer.2019
Author(s)
Sato K, Masuda T, Hu Q, Tobo T, Gillaspie S, Niida A, Thornton M, Kuroda Y, Eguchi H, Nakagawa T, Asano K, Mimori K.
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Journal Title
EBioMedicine.
Volume: 44
Pages: 387-402
DOI
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Peer Reviewed / Open Access
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[Journal Article] Distinct methylation levels of mature microRNAs in gastrointestinal cancers2019
Author(s)
Konno Masamitsu、Koseki Jun、Asai Ayumu、Yamagata Akira、Shimamura Teppei、Motooka Daisuke、Okuzaki Daisuke、Kawamoto Koichi、Mizushima Tsunekazu、Eguchi Hidetoshi、Takiguchi Shuji、Satoh Taroh、Mimori Koshi、Ochiya Takahiro、Doki Yuichiro、Ofusa Ken、Mori Masaki、Ishii Hideshi
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 3888-3888
DOI
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Peer Reviewed / Open Access
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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
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Peer Reviewed / Open Access
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[Journal Article] miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells.2019
Author(s)
Mukohyama J, Isobe T, Hu Q, Hayashi T, Watanabe T, Maeda M, Yanagi H, Qian X, Yamashita K, Minami H, Mimori K, Sahoo D, Kakeji Y, Suzuki A, Dalerba P, Shimono Y.
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Journal Title
Cancer Res.
Volume: 79(20)
Pages: 5151-5158
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer.2019
Author(s)
Kouyama Y, Masuda T, Fujii A, Ogawa Y, Sato K, Tobo T, Wakiyama H, Yoshikawa Y, Noda M, Tsuruda Y, Kuroda Y, Eguchi H, Ishida F, Kudo SE, Mimori K.
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Journal Title
Cancer Sci.
Volume: 110(10)
Issue: 10
Pages: 3132-3144
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] CAFからのSpondin2は胃癌の運動性を促進する2020
Author(s)
斉藤秀幸,増田隆明,倉光正太郎,八代正和,高尾誠一朗,小齊啓祐,小林雄太,本村有史,小池健輔,高橋純一,大津甫,武石一樹,米村祐輔,佐伯浩司,三森功士
Organizer
第79回日本癌学会学術総会
Related Report
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[Presentation] Clinical significance of GET4 expression in colorectal cancer.2019
Author(s)
Kensuke Koike, Takaaki Masuda, Kuniaki Sato, Yushi Motomura, Junuchi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Atsushi Fujii, Akihiro Kitagawa, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yousuke Kuroda, Hidetoshi Eguchi, Takashi Nakagawa, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] Clinical significance of Fanconi anemia complementation group E (FANCE) DNA repair-related gene expression in hepatocellular carcinoma2019
Author(s)
Junichi Takahashi, Takaaki Masuda, Yosuke Kuroda, Akihiro Kitagawa, Yushi Motomura, Kensuke Koike, Dai Shimizu, Shotaro Kuramitsu,Atsushi Fujii, Miwa Noda, Kuniaki Sato, Yusuke Tsuruda, Hajime Otsu, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] Clinical significance of eif5 mimic protein 1 in pancreatic cancer.2019
Author(s)
Yushi Motomura, Takaaki Masuda, Kuniaki Sato, Atsushi Fujii, Akihiro Kitagawa, Hiroaki Wakiyama, Kensuke Koike, Junichi Takahashi, Dai Shimizu, Shitaro Kuramitsu, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Katsumi Sakamoto, Msakazu Hirakawa, Hiroshi Honda, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
Int'l Joint Research
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