Re-profiling of protein kinase inhibitors for next generation molecular target therapy
Project/Area Number |
24590469
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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 |
Experimental pathology
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Research Institution | Hokkaido University |
Principal Investigator |
TSUDA Masumi 北海道大学, 医学(系)研究科(研究院), 講師 (30431307)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 腫瘍 / 分子標的治療 / キナーゼ阻害剤 / 薬剤耐性 / シグナル伝達 / 分子標的治療薬 / キナーゼ阻害薬 |
Outline of Final Research Achievements |
Several molecular therapeutics targeting protein tyrosine kinases have recently been attempted; however, an emerging drug resistance is a crucial issue. Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor. Despite technological advances in surgery, combined with regimens of radiotherapy and new generation chemotherapy with temozolomide, the median survival is still 15 months. Here, we established cell lines acquired drug resistance to individual tyrosine kinase inhibitor (TKI) for EGFR, c-Met, and PDGFR that highly expressed in GBM, and characterized the underlying mechanisms. We found that c-Met inhibitor effectively abrogated TKIs-dependent enhancement of phosphorylation of EGFR, although it did not effect on the ATP-binding ability of EGFR. In addition, the combination therapy of c-Met and PI3K inhibitors might be a powerful approach to abolish the TKI resistance for molecular target therapy in GBM, by inhibiting phosphorylations of Akt, Src, and p38 MAPK.
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Report
(4 results)
Research Products
(70 results)
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[Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop.2015
Author(s)
Matsumoto R, Tsuda M, Wang L, Maishi N, Abe t, Kimura T, Tanino M, Nishihara H, Hida K, Ohba Y, Shinohara N, Nonomura K, Tanaka S.
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Journal Title
Cancer Sci
Volume: in press
Issue: 6
Pages: 709-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma.2014
Author(s)
Kohsaka, S., Hinohara, K., Wang, L., Nishimura, T., Urushido, M., Yachi, K., Tsuda, M., Tanino, M., Kimura, T., Nishihara, H., Gotoh, N., Tanaka, S.
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Journal Title
Neuro Oncol.
Volume: 16
Pages: 960-970
Related Report
Peer Reviewed
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[Journal Article] C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma2014
Author(s)
Kawamata F, Homma S, Kamachi H, Einama T, Kato Y, Tsuda M, Tanaka S, Maeda M, Kajino K, Hino O, Takahashi N, Kamiyama T, Nishihara H, Taketomi A, Todo S
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Journal Title
J Gastroenterology
Volume: 49
Issue: 1
Pages: 81-92
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1.2014
Author(s)
Minami, Y., Kohsaka, S., Tsuda, M., Yachi, K., Hatori, N., Tanino, M., Kimura, T., Nishihara, H., Minami, A., Iwasaki, N., Tanaka, S.
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Journal Title
Cancer Sci.
Volume: 105
Issue: 9
Pages: 1152-1159
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differential diagnosis of small cell glioblastoma and anaplastic oligodendroglioma: a case report of an elderly man.2014
Author(s)
Takahashi, K., Tsuda, M., Kanno, H., Murata, J., Mahabir, R., Ishida, Y., Kimura, T., Tanino, M., Nishihara, H., Nagashima, K., and Tanaka, S.
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Journal Title
Brain Tumor Pathol.
Volume: 31
Issue: 2
Pages: 118-23
DOI
Related Report
Peer Reviewed
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[Journal Article] Relationship between Methyl CpG Binding Protein 2 and JC Viral Proteins2013
Author(s)
Takahashi K, Orba Y, Kimura T, Wang L, Kohsaka S, Tsuda M, Tanino M, Nishihara H, Nagashima K, Sawa H, Tanaka S
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Journal Title
Japanese Journal of Infectious Diseases
Volume: 66
Issue: 2
Pages: 126-132
DOI
NAID
ISSN
1344-6304, 1884-2836
Related Report
Peer Reviewed
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[Journal Article] Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the SAPSCR1-TFE3 fusion oncoprotein.2013
Author(s)
Kobos, R., Nagai, M., Tsuda, M., Merl, MY., Saito, T., Laé, M., Mo, Q., Olshen, A., Lianoglou, S., Leslie, C., Ostrovnaya, I., Antczak, C., Djaballah, H., and Ladanyi, M.
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Journal Title
J Pathol.
Volume: 229
Issue: 5
Pages: 743-754
DOI
Related Report
Peer Reviewed
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[Journal Article] The relationship between methyl CpG binding protein 2 and JC viral proteins.2013
Author(s)
Takahashi K, Orba Y, Kimura T, Wang L, Kohsaka S, Tsuda M, Tanino M, Nishihara H, Nagashima K, Sawa H, Tanaka S.
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Journal Title
Jpn J Infect Dis.
Volume: 66
Pages: 126-132
NAID
Related Report
Peer Reviewed
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[Journal Article] C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.2013
Author(s)
Kawamata F, Homma S, Kamachi H, Einama T, Kato Y, Tsuda M, Tanaka S, Maeda M, Kajino K, Hino O, Takahashi N, Kamiyama T, Nishihara H, Taketomi A, Todo S.
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Journal Title
J Gastroenterol.
Volume: in press
NAID
Related Report
Peer Reviewed
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[Presentation] Preclinical evaluation of EZH2 inhibitors in models of human synovial sarcoma.2014
Author(s)
Heike Keilhack, Satoshi Kawano, Sarah K. Knutson, Natalie M. Warholic, Jamie Kubica, Galina Kuznetsov, Shanqin Xu, Yonghong Xiao, Roy M. Pollock, Jesse S. Smith, Kevin K. Kuntz, Yukinori Minoshima, Masumi Tsuda, Shinya Tanaka, Robert A. Copeland
Organizer
Connective Tissue Oncology Society, 2014 Annual Meeting
Place of Presentation
InterContinental Berlin Hotel, Berlin, Germany
Year and Date
2014-10-15 – 2014-10-18
Related Report
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[Presentation] EMT-stemnesss transition and functional properties of IGFBP2 in acquired drug resistance to TKIs targeting EGFR, c-Met, and PDGFR in glioblastoma.2014
Author(s)
Masumi Tsuda, Lei Wang, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Shinya Tanaka
Organizer
Cold Spring Harbor Laboratory Meeting, Mechanisms and Model of Cancer,
Place of Presentation
New York, USA
Year and Date
2014-08-12 – 2014-08-16
Related Report
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[Presentation] Crk adaptor protein induces EMT and metastasis via novel Rac1/Snail and RhoA/Slug signaling along with TGF-β1 positive feedback loop in lung cancer cell A549.2014
Author(s)
Aiman Elmansuri, Mishie Tanino, Roshan Mahabir, Lei Wang, Taichi Kimura, Hiroshi Nishihara, Yasuhiro Hida, Hirotoshi Akita, Masumi Tsuda, Shinya Tanaka
Organizer
Cold Spring Harbor Laboratory Meeting, Mechanisms and Model of Cancer
Place of Presentation
New York, USA
Year and Date
2014-08-12 – 2014-08-16
Related Report
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[Presentation] Mechanisms of drug resistance to molecular target therapeutics against tyrosine kinases as EGFR,c-Met,andPDGFR in GBM.2013
Author(s)
Masumi Tsuda, Lei wang, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Shinya Tanaka.
Organizer
AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics.
Place of Presentation
Hynes Convention Center, Boston, USA
Related Report
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[Presentation] The mesenchymal phenotype in recurrent glioblastoma is due to irradiation induced Snail expression and resultant EMT.2013
Author(s)
Roshan Mahabir, Mishie Tanino, Aiman Elmansuri, Masumi Tsuda, Taichi Kimura, Lei Wang, Hiroshi Nishihara, Shinya Tanaka
Organizer
AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics.
Place of Presentation
Hynes Convention Center, Boston, USA
Related Report
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[Presentation] CrkI and CrkII adaptor proteins promotes invasiveness and metastasis via epithelial-mesenchymal transition (EMT) in A549 lung adenocarcinoma cells.2013
Author(s)
Aiman Elmansuri, Mishie Tanino, Roshan Mahabir, Lei Wang, Masumi Tsuda, Taichi Kimura, Hiroshi Nishihara, Shinya Tanaka
Organizer
AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics.
Place of Presentation
Hynes Convention Center, Boston, USA
Related Report
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[Book] Biosensors and Cancer2012
Author(s)
Ohba Y, Darmanin S, Mizutani T, Tsuda M, Kondo T.
Publisher
Biosensors for BCR-ABL activity and their application to cancer.
Related Report
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