Molecular basis for resistance to erlotinib and development of agents that reverse the resistance
Project/Area Number |
23790189
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Medical pharmacy
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Research Institution | Kagoshima University |
Principal Investigator |
IKEDA Ryuji 鹿児島大学, 医学部・歯学部附属病院, 准教授 (50398278)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | がん分子標的薬 / erlotinib / major vault protein / vault / PAK-104P / エルロチニブ / 抗がん剤耐性 / MVP / MRP3 / がん分子標的治療薬 |
Research Abstract |
Erlotinib, EGFR tyrosine kinase inhibitor, is an effective therapeutic agent for non-small cell lung cancer. However, inherent or acquired chemoresistance is known to be a major obstacle for anti-cancer therapies. I have isolated erlotinib resistant human non-small cell lung cancer A549 cells. PAK-104P inhibits the functions of p-gp, MRP1, MRP2 and Major vault protein (MVP). PAK-104P partially reversed the erlotinib resistance. It has been reported that the MVP mediates resistance to epidermal growth factor receptor-targeting agent such as erlotinib. I identified the crucial MVP promoter elements that regulate MVP expression. By deletion analysis, a conserved proximal E-box binding site was demonstrated to be important for human MVP promoter transactivation. Introduction of siRNA against USF 1 , which is known to bind the E-box binding site, decreased the expression of MVP. These findings suggest that USF1 binding to an E-box element may be critical for basal MVP promoter activation.
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Factors involved in the cisplatin resistance of KCP-4 human epidermoid carcinoma cells2014
Author(s)
Oiso, S., Takayama, Y., Nakazaki, R., Matsunaga, N., Motooka, C., Yamamura, A., Ikeda, R., Nakamura, K., Takeda, Y., Kariyazono, H
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Journal Title
Oncol. Rep
Volume: 31
Pages: 719-726
Related Report
Peer Reviewed
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[Journal Article] Regulation of Major Vault Protein Expression by Upstream Stimulating Factor 1 in SW620 Human Colon Cancer Cells, Oncol2014
Author(s)
Ikeda, R., Nishizawa, Y., Tajitsu, Y., Minami, K., Mataki, H., Masuda, S., Furukawa, T., Akiyama, S., Yamada, K., Takeda, Y
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Journal Title
Rep.
Volume: 31
Pages: 197-201
Related Report
Peer Reviewed
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[Journal Article] Antimicrobial effect of an ultrasonic levitation washer disinfector with silver electrolysis and ozone oxidation on methicillin-resistant Staphylococcus aureus2013
Author(s)
Tamai, M., Matsushita, S., Miyanohara, H., Imuta, N., Ikeda, R., Kawai, K., Nishi, J., Sakamoto, A., Shigihara, T., Kanekura, T
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Journal Title
J. Dermatol
Volume: 40
Pages: 1020-1026
Related Report
Peer Reviewed
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[Journal Article] Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma2013
Author(s)
Shinsato, Y., Furukawa, T., Yunoue, S., Yonezawa, H., Minami, K., Nishizawa, Y., Ikeda, R., Kawahara, K., Yamamoto, M., Hirano, H., Tokimura, H., Arita, K
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Journal Title
Oncotarget
Volume: 4
Pages: 2261-2270
Related Report
Peer Reviewed
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[Journal Article] Molecular basis for the expression of major vault protein induced by hyperosmotic stress in SW620 human colon cancer cells2013
Author(s)
Tajitsu, Y., Ikeda, R., Nishizawa, Y., Mataki, H., Che, X.F., Sumizawa, T., Nitta, M., Yamaguchi, T., Yamamoto, M., Tabata, S., Akiyama, SI., Yamada, K., Furukawa, T., Takeda, Y
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Journal Title
Int. J. Mol. Med
Volume: 32
Pages: 703-708
Related Report
Peer Reviewed
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[Journal Article] Molecular basis for the regulation of hypoxia-inducible factor-1αlevels by 2-deoxy-D-ribose2013
Author(s)
Ikeda, R., Tabata, S., Tajitsu, Y., Nishizawa, Y., Minami, K., Furukawa, T., Yamamoto, M., Shinsato, Y., Akiyama, SI., Yamada, K, Takeda Y
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Journal Title
Oncol. Rep
Volume: 30
Pages: 1444-1448
Related Report
Peer Reviewed
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[Journal Article] VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts2013
Author(s)
Wang, J., Ikeda, R., Che, X.F., Ooyama, A., Yamamoto, M., Furukawa, T., Hasui, K., Zheng, C.L., Tajitsu, Y., Oka, T., Tabata, S., Nishizawa, Y., Eizuru, Y., Akiyama, SI
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Journal Title
J. Oncol
Volume: 43
Pages: 746-754
Related Report
Peer Reviewed
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[Journal Article] Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts2013
Author(s)
Saito, H., Nakamachi, T., Inoue, K., Ikeda, R., Kitamura, K., Minamino, N., Shioda, S., Miyata, A
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Journal Title
J. Endocrinol
Volume: 217
Pages: 141-150
Related Report
Peer Reviewed
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[Journal Article] Molecular basis for the expression of major vault protein induced by hyperosmotic stress in SW620 human colon cancer cells2013
Author(s)
Yusuke Tajitsu, Ryuji Ikeda, Yukihiko Nishizawa, Hirofumi Mataki, Xiao-Fang Che, Tomoyuki Sumizawa, Mina Nitta, Tatsuya Yamaguchi, Masatatsu Yamamot, Sho Tabata, Shin-ichi Akiyama, Katsushi Yamada, Tatsuhiko Furukawa, Yasuo Takeda
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Journal Title
International Journal of Molecular Medicine
Volume: 32
Pages: 703-708
Related Report
Peer Reviewed
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[Journal Article] Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose2013
Author(s)
Ryuji Ikeda, Sho Tabata, Yusuke Tajitsu, Yukihiko Nishizawa, Kentaro Minami, Tatsuhiko Furukawa, Masatatsu Yamamoto, Yoshinari Shinsato, Shin-Ichi Akiyama, Katsushi Yamada, Yasuo Takeda
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Journal Title
Oncology Reports
Volume: 30
Pages: 1444-1448
Related Report
Peer Reviewed
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[Journal Article] VEGF expression is augmented by hypoxia-induced PGIS in human fibroblasts2013
Author(s)
Jia Wang, Ryuji Ikeda, Xiao-Fang Che, Akio Ooyama, Masatatsu Yamamoto, Tatsuhiko Furukawa, Kazuhisa Hasui, Chun-Lei Zheng, Yusuke Tajitsu, Toshinori Oka, Sho Tabata, Yukihiko Nishizawa, Yoshito Eizuru, Shin-Ichi Akiyama
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Journal Title
International Journal of Oncology
Volume: 43
Pages: 746-754
Related Report
Peer Reviewed
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[Journal Article] Reichelderfer, M., Kolesar, J.M., Stability of infliximab in polyvinyl chloride bags2012
Author(s)
Ikeda, R., Vermeulen, L.C., Lau, E., Jiang, Z., Saha, S
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Journal Title
Am. J. Health Syst. Pharm
Volume: 69
Pages: 1509-1512
Related Report
Peer Reviewed
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[Journal Article] p53R2 is a prognostic factor of melanoma and regulates proliferation and chemosensitivity of melanoma cells2012
Author(s)
Matsushita, S., Ikeda, R., Fukushige, T., Tajitsu, Y., Gunshin, K., Okumura, H., Ushiyama, M., Akiyama, S., Kawai, K., Takeda, Y., Yamada, K., Kanekura T
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Journal Title
J. Dermatol. Sci
Volume: 68
Pages: 19-24
Related Report
Peer Reviewed
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[Journal Article] Analysis of the outcome of concurrent neoadjuvant chemoradiotherapy with S-1 compared to super-selective intra-arterial infusion for oral squamous cell carcinoma2012
Author(s)
Miyawaki, A., Hijioka, H., Ikeda, R., Ishida, T., Nozoe, E., Nakamura, N
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Journal Title
Oncol. Lett
Volume: 3
Pages: 995-1001
Related Report
Peer Reviewed
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[Journal Article] Neuromedin B stimulates proliferation of mouse chondrogenic cell line ATDC52012
Author(s)
Saito, H., Ikeda, R., Inoue, K., Nagata, S., Kitamura, K., Minamino, N., Kangawa, K., Miyata, A
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Journal Title
Peptides
Volume: 36
Pages: 299-302
Related Report
Peer Reviewed
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[Journal Article] Involvement of NF-κB activation in the cisplatin resistance of human epidermoid carcinoma KCP-4 cells, Oncol2012
Author(s)
Oiso, S., Ikeda, R., Nakamura, K., Takeda, Y., Akiyama, S., Kariyazono, H
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Journal Title
Rep
Volume: 28
Pages: 27-32
Related Report
Peer Reviewed
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[Journal Article] Thymidine phosphorylase activity is involved in augmented reactive oxygen species and interleukin-8 production in human cancer cells2012
Author(s)
Tabata, S., Ikeda, R., Yamamoto, M., Furukawa, T., Kuramoto, T., Takeda, Y., Yamada, K., Haraguchi, M., Nishioka, Y., Sone, S., Akiyama, S
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Journal Title
Oncol. Rep
Volume: 28
Pages: 895-902
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Peer Reviewed
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[Journal Article] Thymidine phosphorylase activity is involved in augmented reactive oxygen species and interleukin-8 production in human cancer cells2012
Author(s)
Tabata, S., Ikeda, R., Yamamoto, M., Furukawa, T., Kuramoto, T., Takeda, Y., Yamada, K., Haraguchi, M., Nishioka, Y., Sone, S., Akiyama, S.
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Journal Title
Oncol. Rep.
Volume: In press
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Peer Reviewed
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[Journal Article] Effect of 5-fluorouracil treatment on SN-38 absorption from intestine in rats2011
Author(s)
Shibayama, Y., Iwashita, Y., Yoshikawa, Y., Kondo, T., Ikeda, R., Takeda, Y., Osada, T., Sugawara, M., Yamada, K., Iseki, K
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Journal Title
Biol. Pharm. Bull
Volume: 34
Pages: 1418-1425
NAID
Related Report
Peer Reviewed
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[Journal Article] Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib2011
Author(s)
S hibayama, Y., Nakano, K., Maeda, H., Taguchi, M., Ikeda, R., Sugawara, M., Iseki, K., Takeda, Y., Yamada, K
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Journal Title
Biol. Pharm. Bull
Volume: 34
Pages: 433-435
NAID
Related Report
Peer Reviewed
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[Journal Article] Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib2011
Author(s)
Shibayama, Y., Nakano, K., Maeda, H., Taguchi, M., Ikeda, R., Sugawara, M., Iseki, K., Takeda, Y., Yamada, K.
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Journal Title
Biol. Pharm. Bull.
Volume: 34
Pages: 433-435
NAID
Related Report
Peer Reviewed
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[Journal Article] Effect of 5-fluorouracil treatment on SN-38 absorption from intestine in rats2011
Author(s)
Shibayama, Y., Iwashita, Y., Yoshikawa, Y., Kondo, T., Ikeda, R., Takeda, Y., Osada, T., Sugawara, M., Yamada, K., Iseki, K.
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Journal Title
Biol. Pharm. Bull.
Volume: 34
Pages: 1418-1425
NAID
Related Report
Peer Reviewed
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[Presentation] Molecular basis for the induction of vaults by anti-cancer agent and the role of vaults in resistance to anti-cancer agents2012
Author(s)
Ikeda, R., Tajitsu, Y., Nishizawa, Y., Tominaga, N., Mataki, H., Yamada, K., Takeda, Y
Organizer
第6回次世代を担う若手医療薬科学シンポジウム
Place of Presentation
京都市
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[Presentation] Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells2011
Author(s)
Ikeda, R., Tajitsu, Y., Nishizawa, Y., Tabata, S., Ushiyama, M., Furukawa, T., Akiyama, S., Yamada, K., Takeda, Y
Organizer
第5回次世代を担う若手医療薬科学シンポジウム
Place of Presentation
名古屋市
Related Report
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[Presentation] Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells2011
Author(s)
Ikeda, R., Tajitsu, Y., Nishizawa, Y., Tabata, S., Ushiyama, M., Furukawa, T., Akiyama, S., Yamada, K., Takeda., Y.
Organizer
5th Young Investigators Symposium on Clinical Pharmacetical Sciences
Place of Presentation
名古屋大学医学部付属病院(名古屋市)
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