CAGE発現解析を用いた大腸がん肺転移予測マーカーの特定
Project/Area Number |
18K08798
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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 |
Review Section |
Basic Section 55040:Respiratory surgery-related
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Research Institution | Juntendo University |
Principal Investigator |
柳沼 行宏 順天堂大学, 医学部, 非常勤講師 (60338415)
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Co-Investigator(Kenkyū-buntansha) |
小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982)
茂櫛 薫 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (60569292)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Granted (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | 大腸癌 / 肺転移 / CAGE / 腫瘍マーカー / 大腸がん / CAGE法 / マーカー |
Outline of Annual Research Achievements |
我々はこれまで大腸癌をはじめとする癌の鋭敏な新規マーカー開発、分子標的治療の可能性を探り研究を進めてきた。とくに大腸癌では転移はリンパ節のほか、肝、肺に多く見られるが、現在は転移巣に対しても積極的治療が選択される。転移においても早期発見、早期治療は大腸癌患者の平均余命を向上させると考えら れている。しかし現状では転移を検出するための「転移マーカー」は存在しない。そのため一様に抗癌剤投与を施すのが現状である。このような事情から、転移を予測可能な、あるいは早期に発見するために有効な「転移マーカー」の開発が今後の大腸癌治療の進歩をもたらすものと考えられる。 我々はCAGE(Cap Analysis of Gene Expression)法を適用し大腸癌の転移有り・無しの症例サンプル間での比較解析を行い、転移特異的な遺伝子を特定することによる新たな診断マーカーの開発を着想した。 本研究はCAGE法によって抽出した候補遺伝子群から、大腸がんの肺転移マーカーを特定することを主目的とする。癌部組織および採血検体を用いその遺伝子発現を解析、肺転移症例に特異的な発現昂進または抑制を示す遺伝子のうち血中マーカー候補を選別する。また術後の患者の追跡により、採血検体で特定したマーカーのレベル変動による術後肺転移の予測も目指していく。以上、本研究では大腸癌の肺転移を予測できうるマーカーを取得を目指す。 現状では評価できない肺転移リスク、また初期の肺転移を、診断可能にすることまでを目的とする。
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
大腸がん肺転移を引き起こす原因遺伝子を突き止め、さらに大腸癌の肺転移マーカーを新たに開発することを目標とする。すでに患者から採取し保管してあるサンプルを用い、肺転移を起こした大腸がん原発巣の転移有り群と転移無し群の遺伝子の比較解析を行い、興味深い結果を得ている。
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Strategy for Future Research Activity |
複数のマーカー候補遺伝子群について、患者の臨床データを解析、さらに候補遺伝子の絞り込みを行う。腫瘍部よりRNAを抽出し転移巣の解析を行うことによって、肺転移マーカー候補を選別し肺転移マーカーを特定する計画である。
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Report
(2 results)
Research Products
(27 results)
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[Journal Article] Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state.2020
Author(s)
Mizukoshi K, Okazawa Y, Haeno H, Koyama Y, Sulidan K, Komiyama H, Saeki H, Ohtsuji N, Ito Y, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
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Journal Title
International Journal of Cancer,
Volume: 146
Pages: 2547-2562
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity.,2019
Author(s)
Matsumura Y, Ito Y, Mezawa Y, Sulidan K, Daigo Y, Hiraga T, Mogushi K, Wali N, Suzuki H, Itoh T, Miyagi Y, Yokose T, Shimizu S, Takano A, Terao Y, Saeki H, Ozawa M, Abe M, Takeda S, Okumura K, Habu S, Hino O, Takeda K, Hamada M, Orimo A.
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Journal Title
Life Sci. Alliance
Volume: 2(4):e201900425.
Pages: 1-24
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.2019
Author(s)
Horimoto Y, Terao T, Tsutsumi Y, Tanabe M, Mogushi K, Hlaing MT, Sasaki R, Saeki H, Okazaki M, Sonoue H, Arakawa A, Saito M.
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Journal Title
The American Journal of Surgical Pathology
Volume: 43(9)
Pages: 1221-1228
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-sensitivity detection of micrometastases in GFP-labelled colon tumor organoids extracted from patient-derived tumor xenografts.2019
Author(s)
OkazawaY, Mizukoshi K, KoyamaY, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
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Journal Title
J. Vis. Exp.
Volume: 136(e57374)
Pages: 136-136
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome2019
Author(s)
Borna NN, Kishita Y, Kohda M, Lim SC, Shimura M, Wu Y, Mogushi K, Yatsuka Y, Harashima H, Hisatomi Y, Fushimi T, Ichimoto K, Murayama K, Ohtake A, Okazaki Y.
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Journal Title
neurogenetics
Volume: 20(1)
Pages: 9-25
DOI
Related Report
Peer Reviewed
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[Journal Article] Comprehensive molecular and immunological characterization of hepatocellular carcinoma2019
Author(s)
Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Tanabe M, Wands JR, Tanaka S.
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Journal Title
EBioMedicine.
Volume: 40
Pages: 457-470
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy.2018
Author(s)
Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
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Journal Title
Journal of Neural Transmission
Volume: -
Pages: 937-944
DOI
Related Report
Peer Reviewed
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[Journal Article] Tumor sidedness and enriched gene groups for efficacy of first-line cetuximab treatment in metastatic colorectal cancer.2018
Author(s)
Sunakawa Y, Mogushi K, Lenz HJ, Zhang W, Tsuji A, Takahashi T, Denda T, Shimada K, Kochi M, Nakamura M, Kotaka M, Ichikawa W. et al
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Journal Title
Molecular Cancer Therapeutics
Volume: 17(12)
Pages: 2788-2795
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic neuroendocrine tumors.2018
Author(s)
Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
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Journal Title
Endocrine-Related Cancer
Volume: 25(6)
Pages: 619-631
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] <i>KCTD12</i> is negatively regulated by Kit in gastrointestinal stromal tumors2018
Author(s)
Suehara Y, Akaike K, Mukaihara K, Kurisaki-Arakawa A, Kubota D, Okubo T, Mitomi H, Mitani K, Takahashi M, Toda-Ishii M1, Kim Y, Tanabe Y, Takagi T, Hayashi T, Mogushi K, Kaneko K, Yao T, Saito T.
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Journal Title
Oncotarget
Volume: 9(43)
Pages: 27016-27026
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GCH1 mutations in dopa-responsive dystonia and Parkinson’s disease.2018
Author(s)
Yoshino H, Nishioka K, Li Y, Oji Y, Oyama G, Hatano T, Machida Y, Shimo Y, Hayashida A, Ikeda A, Mogushi K, Shibagaki Y, Hosaka A, Iwanaga H, Fujitake J, Ohi T, Miyazaki D, Sekijima Y, Oki M, Kusaka H, Fujimoto KI Ugawa Y, Funayama M, Hattori N.
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Journal Title
J Neurol.
Volume: 265(8)
Pages: 1860-1870
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review2018
Author(s)
Watanabe J, Togo S, Sumiyoshi I, Namba Y, Suina K, Mizuno T, Kadoya K, Motomura H, Iwai M, Nagaoka T, Sasaki S, Hayashi T, Uekusa T, Abe K, Urata Y, Sakurai F, Mizuguchi H, Kato S, Takahashi K.
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Journal Title
Oncotarget
Volume: 9(35)
Pages: 24000-24013
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Correction: Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients.2018
Author(s)
Kageyama SI, Nihei K, Karasawa K, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
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Journal Title
Oncotarget
Volume: 9(34)
Pages: 23844-23844
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study2018
Author(s)
Kato S, Imai H, Gamoh M, Takahata T, Ohori H, Yasuda K, Niitani T, Murakawa Y, Amagai K, Isobe H, Shindo Y, Kuroki M, Sakamoto Y, Shimodaira H, Yoshioka T, Ishioka C.
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 245(1)
Issue: 1
Pages: 21-28
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed / Open Access
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[Journal Article] Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients2018
Author(s)
Kageyama S, Nihei K, Karasawa K,, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
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Journal Title
Oncotarget.
Volume: 10;9(27)
Pages: 19368-19378
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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