Development of targeted therapy to overcome drug resistance in malignant mesothelioma
Project/Area Number |
26461183
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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 |
Respiratory organ internal medicine
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Research Institution | University of Tsukuba (2015-2017) Chiba Cancer Center (Research Institute) (2014) |
Principal Investigator |
SEKINE Ikuo 筑波大学, 医学医療系, 教授 (10508310)
|
Co-Investigator(Kenkyū-buntansha) |
田川 雅敏 千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)
岩澤 俊一郎 千葉大学, 医学(系)研究科(研究院), その他 (00527913)
瀧口 裕一 千葉大学, 医学部附属病院, 教授 (30272321)
|
Project Period (FY) |
2014-04-01 – 2018-03-31
|
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 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ペメトレキセド / 薬物耐性 / CARP / AMPK / ANKRD1 / 悪性中皮腫 / 耐性 / 薬剤耐性 / 増殖因子 / インシュリン様増殖因子 / 化学療法 / 遺伝子発現 |
Outline of Final Research Achievements |
We established pemetrexed (PEM)-resistant mesothelioma cells which did not show any increase of the relevant enzyme activities. We found that expression of CARP was elevated in the PEM-resistant cells with a microarray and Western blot analysis. However, down-regulation of CARP expression with si-RNA did not influence the PEM resistance.Next, we found increased phosphorylated AMPK and p70S6K levels in PEM-resistant cells, and PEM stimulation augmented these phosphorylation. An AMPK activator increased PEM resistance in the parent cells and an inhibitor decreased PEM resistance of the PEM-resistant cells. These data indicated that constitutive activation of AMPK was associated with PEM resistance.
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] Combination of a third generation bisphosphonate and replication-competent adenoviruses augments the cytotoxicity on mesothelioma2016
Author(s)
Jiang, Y., Zhong, B., Kawamura, K., Morinaga, T., Shingyoji, M., Sekine, I., Tada, Y., Tatsumi, K., Shimada, H., Hiroshima, K. and Tagawa, M.
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Journal Title
BMC Cancer
Volume: 16
Issue: 1
Pages: 455-455
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] An intrapleural administration of zoledronic acid for inoperable malignant mesothelioma patients: a phase I clinical study protocol.2016
Author(s)
Tada, Y., Hiroshima, K., Shimada, H., Shingyoji, M., Suzuki, T., Umezawa, H., Sekine, I., Takiguchi, Y., Tatsumi, K. and Tagawa, M.: An intrapleural administration of zoledronic acid for inoperable malignant mesothelioma patients: a phase I clinical study protocol
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Journal Title
SpringerPlus
Volume: 5
Issue: 1
Pages: 195-202
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene.2015
Author(s)
Tada, Y., Hiroshima, K., Shimada, H., Morishita, N., Shirakawa, T., Matsumoto, K., Shingyoji, M., Sekine, I., Tatsumi, K. and Tagawa, M.
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Journal Title
SpringerPlus
Volume: 4
Issue: 1
Pages: 358-368
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Molecular-targeted therapy for malignant mesothelioma2015
Author(s)
Tada, Y., Suzuki, T., Shimada, H., Hiroshima, K., Tatsumi, K. and Tagawa, M
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Journal Title
Pleura
Volume: 1
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] MDM2 and MDM4 inhibitors in combination with adenoviruses up-regulating p53 produce synergistic anti-tumor effects on mesothelioma through augmenting apoptotic processes2016
Author(s)
Masatoshi Tagawa, Taka-aki Kozono, Yiyang Qin, Xue Rao Ning, Takao Morinaga, Shuji Kubo, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima
Organizer
22th annual meeting of Japan Society of Gene Therapy
Place of Presentation
Tokyo, Japan
Year and Date
2016-07-28
Related Report
Int'l Joint Research
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[Presentation] Combination of Forced Transduction of P53 and an Agent That Blocks MDM2-p53 Interactions Produces Synergistic Cytotoxicity on Mesothelioma Defective of the INK4A/ARF Region2016
Author(s)
Masatoshi Tagawa, Takao Morinaga, Zhihan Li, Thao Thi Thanh Nguyen, Boya Zhong, Shuji Kubo, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima
Organizer
19th annual meeting of American Society of Gene and Cell Therapy
Place of Presentation
Washington DC, USA
Year and Date
2016-05-04
Related Report
Int'l Joint Research
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[Presentation] Combination of nutlin-3a and HSP90 inhibitors produces synergistic cytotoxicity on mesothelioma with the wild-type p53.2016
Author(s)
Masatoshi Tagawa, Shinya Okamoto, Takao Morinaga, Masato Shingyoji, Ikuo Sekine, Toshio Suzuki, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima
Organizer
The 13th international conference of the international mesothelioma interested group
Place of Presentation
Birmingham, UK
Year and Date
2016-05-01
Related Report
Int'l Joint Research
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