Targeting the ERK-MAP kinase pathway in cancer therapy
| Project/Area Number |
22300340
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Kyoto University (2011-2012)
Nagasaki University (2010) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Kei-ichi 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (50252466)
TANIMURA Susumu 長崎大学, 大学院・医歯薬学総合研究科, 助教 (90343342)
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| Co-Investigator(Renkei-kenkyūsha) |
UESATO Shin-ichi 関西大学, 工学部, 教授 (50111969)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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| Keywords | 細胞がん化 / がん化学療法 / ERK-MAP キナーゼ経路 / MEK 阻害剤 / 微小管重合阻害剤 / HDAC 阻害剤 / 併用療法 / Bcl-2 ファミリー蛋白質 / ERK-MAPキナーゼ経路 / MEK阻害剤 / 微小管阻害剤 / HDAC阻害剤 / 動物個体系 |
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| Research Abstract |
Specific blockade of the ERK pathway by MEK inhibitors alone induces mostly cytostatic rather than pro-apoptotic effects, resulting in a limited therapeutic efficacy of MEK inhibitors. However, MEK inhibitors specifically and markedly sensitize various humor tumor xenografts to microtubule-destabilizing agent-/HDAC inhibitor-induced cytotoxicity. Our results clearly indicate that administration of both a MEK inhibitor and a microtubule-destabilizing agent/HDAC inhibitor represents a promising chemotherapeutic strategy with improved safety for cancer patients.
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models2013
Author(s)
Sakamoto, T., Ozaki, K., Fujio, K., Kajikawa, S., Uesato, S., Watanabe, K., Tanimura, S., Koji, T. & Kohno, M
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 433
Pages: 456-462
Related Report
Peer Reviewed
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[Journal Article] Central role of the exchange factor GEF-H1 in TNF-α-induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells.2013
Author(s)
Waheed, F., Dan, Q., Amoozadeh, Y., Zhang, Y., Tanimura, S., Speight, P., Kapus, A. &Szaszi, K.
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Journal Title
Mol. Biol. Cell
Volume: 24
Pages: 1068-1082
NAID
Related Report
Peer Reviewed
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[Journal Article] Functional characterization of the novel BRAF complex mutation, BRAF(V600delinsYM), identified in papillary thyroid carcinoma2013
Author(s)
Matsuse, M., Mitsutake, N., Tanimura, S., Ogi, T., Nishihara, E., Hirokawa, M., Fuziwara, C. S., Saenko, V. A., Suzuki, K., Miyauchi, A. & Yamashita, S.
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Journal Title
Int. J. Cancer
Volume: 132
Pages: 738-743
Related Report
Peer Reviewed
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[Journal Article] SH3P2 is a negative regulator of cell motility whose function is inhibited by RSK-mediated phosphorylation.2011
Author(s)
Tanimura, S., Hashizume, J., Kurosaki, Y., Sei,K., Gotoh, A., Ohtake, R., Kawano, M., Watanabe, K. & Kohno. M.
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Journal Title
Genes Cells
Volume: 16
Pages: 514-526
Related Report
Peer Reviewed
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[Journal Article] Peumusolide A, unprecedented NES non- antagonistic inhibitor for nuclear export of MEK.2010
Author(s)
Tamura, S., Hattori, Y., Kaneko, M., Shimizu, N., Tanimura, S., Kohno, M. & Murakami, N.
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Journal Title
Tetrahedron Lett.
Volume: 51
Pages: 1678-1681
Related Report
Peer Reviewed
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[Journal Article] Blockade of the extracellularsignal-regulated kinase pathway enhances the therapeutic efficacy of microtubule destabilizing agents in human tumor xenograft models.2010
Author(s)
Watanabe, K., Tanimura, S., Uchiyama, A., Sakamoto, T., Kawabata, T., Ozaki, K. & Kohno, M.
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Journal Title
Clin. Cancer Res
Volume: 16
Pages: 1170-1178
Related Report
Peer Reviewed
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