Molecular basis for the induction of vaults by anti-cancer agents, and the role of vaults in resistance to anti-cancer agents.
Project/Area Number |
21590168
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | Kagoshima University |
Principal Investigator |
YAMADA Katsushi 鹿児島大学, 医歯学総合研究科, 客員研究員 (00037491)
|
Co-Investigator(Kenkyū-buntansha) |
TAKEDA Yasuo 鹿児島大学, 医学部・歯学部附属病院, 教授 (60245462)
IKEDA Ryuji 鹿児島大学, 医学部・歯学部附属病院, 副薬剤部長 (50398278)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | Vaults / 抗がん剤耐性 / apoptosis / caspase / adriamycin / major vault protein / Sp-1 / vault / caspase 3 / E-box / upstream stimulatory factor 1 |
Research Abstract |
The major vault protein(MVP) is the main constituent of the vault ribonucleoprotein particle. Although the role in multidrug resistance has been suggested, the physiological function of vaults remains unclear. It has been reported that MVP levels were elevated after treatment with the DNA-damaging agents such as adriamycin(ADR). The aim of this study was to investigate molecular basis for the induction of MVP by ADM, and to investigate the potential role of MVP in drug resistance. Expression levels of both MVP protein and MVP mRNA were increased by ADM. ADM could also enhance MVP promoter activity. Introduction of siRNA against Sp-1 in SW620cells attenuated the expression of MVP induced by ADM. Down-regulation of MVP expression by MVP RNAi in SW620cells increased the sensitivity of the cells to ADM. Furthermore, ADM enhanced the activation of caspase 3 and caspase 8 in the MVP knock-down cells, but not in control cells. Our data demonstrate that exposure of cancer cells to DNA-damaging agents induces MVP that might have an important role in the resistance to chemotherapeutic agents.
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Report
(4 results)
Research Products
(60 results)
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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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Oncology Reports
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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
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Miyawaki, A., Hijioka, H., Ikeda, R., Ishida, T., Nozoe, E., Nakamura, N.
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Journal Title
Oncology letters
Volume: (in press)
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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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Oncol.Rep.
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[Journal Article] Safety analysis of liposomal amphotericin B in adult patients : anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia2011
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Shigemi, A., Matsumoto, K., Ikawa, K., Yaji, K., Shimodozono, Y., Morikawa, N., Takeda, Y., Yamada, K.
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International Journal of Antimicrobial Agents
Volume: 38
Pages: 417-420
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[Journal Article] Effect of 5-fluorouracil treatment on SN-38absorption from intestine in rats2011
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Shibayama, Y., Iwashita, Y., Yoshikawa, Y., Kondo, T., Ikeda, R., Takeda, Y., Osada, T., Sugawara, M., Yamada, K., Iseki, K.
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Biological and Pharmaceutical Bulletin
Volume: 34
Pages: 1418-1425
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[Journal Article] Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib2011
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Shibayama, Y., Nakano, K., Maeda, H., Taguchi, M., Ikeda, R., Sugawara, M., Iseki, K., Takeda, Y., Yamada, K.
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Biological and Pharmaceutical Bulletin
Volume: 34
Pages: 433-435
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[Journal Article] Isolation and Characterization of Gemcitabine-resistant in Human Non-small Cell Lung Cancer A549cells2011
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Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., Kolesar, J. M.
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International Journal of Oncology
Volume: 38
Pages: 513-519
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[Journal Article] Isolation and Characterization of Erlotinib-resistant in Human Non-small Cell Lung Cancer A549cells2011
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Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Kavanaugh, S. M., Yamada, K., Kolesar, J. M.
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Journal Title
Oncology Letters
Volume: 2
Pages: 91-94
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[Journal Article] Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib2011
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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
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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
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[Journal Article] Safety analysis of liposomal amphotericin B in adult patients : anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia2011
Author(s)
Shigemi, A., Matsumoto, K., Ikawa, K., Yaji, K., Shimodozono, Y., Morikawa, N., Takeda, Y., Yamada, K.
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Journal Title
Int.J.Antimicrob.Agents
Volume: 38
Pages: 417-420
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[Journal Article] Isolation and Characterization of Erlotinib-resistant in Human Non-small Cell Lung Cancer A549 cells2011
Author(s)
Ikeda, R., Vermeulen, L.C., Lau, E., Jiang, Z., Kavanaugh, S. M. Yamada, K., Kolesar, J.M.
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Journal Title
Oncology Letters
Volume: 2
Pages: 91-94
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[Journal Article] Isolation and Characterization of Gemcitabine-resistant in Human Non-small Cell Lung Cancer A549 cells2011
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Ikeda, R., Vermeulen, L.C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., Kolesar, J.M.
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Journal Title
Int.J.Oncol.
Volume: 38
Pages: 513-519
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[Journal Article] p53 Plays an Important Role in Cell Fate Determination after Exposure to Microcystin-LR2010
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Takumi, S., Komatsu, M., Furukawa, T., Ikeda, R., Sumizawa, T., Akenaga, H., Maeda, Y., Aoyama, K., Arizono, K., Ando, S., Takeuchi T.
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Environmental Health Perspectives
Volume: 118
Pages: 1292-1298
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[Journal Article] SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma2010
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Miyawaki, A., Ikeda, R., Hijioka, H., Ishida, T., Ushiyama, M., Nozoe, E., Nakamura, N.
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Journal Title
Oncology Reports
Volume: 23
Pages: 1205-1212
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[Journal Article] Alternative Splicing of the Pituitary Adenylate Cyclase-activating Polypetide(PACAP) Receptor Contributes to Function of PACAP-272010
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Ushiyama, M., Ikeda, R., Yoshida, M., Mori, K., Kangawa, K., Sugawara, H., Inoue, K., Yamada, K., and Miyata, A.
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Journal of Molecular Neuroscience
Volume: 42
Pages: 341-348
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[Journal Article] Establishment and Characterization of Irinotecan-resistant Human Non-small Cell Lung Cancer A549cells2010
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Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Pomplun, M. and Kolesar, J. M.
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Journal Title
Molecular Medicine Reports
Volume: 6
Pages: 1031-1034
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[Journal Article] The role of thymidine phosphorylase in the induction of early growth response protein-1and thrombospondin-1by5-fluorouracil in human cancer carcinoma cells2010
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Matsushita, S., Ikeda, R., Nishizawa, Y., Che, X. F., Furukawa, T., Miyadera, K., Tabata, S., Ushiyama, M., Tajitsu, Y., Yamamoto, M., Takeda, Y., Minami, K., Mataki, H., Kanzaki, T., Yamada, K., Kanekura, T., Akiyama, S.
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Journal Title
International Journal of Oncology
Volume: 36
Pages: 1193-1200
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[Journal Article] Major vault protein forms complexes with hypoxia-inducible factor(HIF)-1α and reduces HIF-1α level in ACHN human renal adenocarcinoma cells2010
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Iwashita, K., Ikeda, R., Takeda, Y., Sumizawa, T., Furukawa, T., Yamaguchi, T., Akiyama, S., Yamada K.
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Journal Title
Cancer Science
Volume: 101
Pages: 920-926
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[Journal Article] Establishment and Characterization of Irinotecan-resistant Human Non-small Cell Lung Cancer A549 cells2010
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Ikeda, R., Vermeulen, L.C., Lau, E., Jiang, Z., Pomplun, M., Kolesar, J.M.
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Journal Title
Molecular Medicine Reports
Volume: 6
Pages: 1031-1034
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[Journal Article] Alternative Splicing of the Pituitary Adenylate Cyclase-activating Polypetide (PACAP) Receptor Contributes to Function of PACAP-272010
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Ushiyama, M., Ikeda, R., Yoshida, M., Mori, K., Kangawa, K., Sugawara, H., Inoue, K., Yamada, K., Miyata, A.
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J.Mol.Neurosci.
Volume: 42
Pages: 341-348
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[Journal Article] SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma2010
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Miyawaki, A., Ikeda, R., Hijioka, H., Ishida, T., Ushiyama, M., Nozoe, E., Nakamura, N.
-
Journal Title
Oncol.Rep.
Volume: 23
Pages: 1205-1212
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[Journal Article] p53 Plays an Important Role in Cell Fate Determination after Exposure to Microcystin-LR2010
Author(s)
Takumi, S., Komatsu, M., Furukawa, T., Ikeda, R., Sumizawa, T., Akenaga, H., Maeda, Y., Aoyama, K., Arizono, K., Ando, S., Takeuchi T.
-
Journal Title
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[Journal Article] The role of thymidine phosphorylase in the induction of early growth response protein-1 and thrombospondin-1 by 5-fluorouracil in human cancer carcinoma cells2010
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Matsushita, S., Ikeda, R., Nishizawa Y., Che X.F., Furukawa T., Miyadera K., Tabata S., Ushiyama M., Tajitsu Y., Yamamoto M., Takeda Y., Minami K., Mataki H., Kanzaki, T., Yamada K., Kanekura T., Akiyama S.
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[Journal Article] Correlation between meropenem and doripenem use density and the incidence of carbapenem-resistant Pseudomonas aeruginosa2009
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[Journal Article] Adverse effects of superselective intra-arterial infusion chemotherapy in patients with oral cancer2009
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Volume: 7
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[Journal Article] Stability of hospital preparations of Azunol Water Gargles for pain relief in oral cancer patients with oral mucositis2009
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[Journal Article] Enhanced platelet responsiveness due to chilling and its relation to CD40ligand level and platelet-leukocyte aggregate formation2009
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[Journal Article] Enhanced platelet responsiveness due to chilling and its relation to CD40 ligand level and platelet-leukocyte aggregate formation2009
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Blood Coagulation and Fibrinolysis 20
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[Journal Article] Stability of hospital preparations of Azunol Water Gargles for pain relief in oral cancer patients with oral mucositis2009
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Ushiyama, M., Ikeda, R., Nitta, T., Tazitsu, Y., Miyawaki, A., Nishizawa, Y., Yamaguchi, T., Yamaguchi, H., Akatsuka, C., Shimodouzono, Y., Ushinohama, K., Sugawere, H., Sugihara, K., Nakamura N., Takeda, Y., Yamada, K.
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Journal Title
Cancer Therapy 7
Pages: 277-281
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[Journal Article] Adverse effects of superselective intra-arterial infusion chemotherapy in patients with oral cancer2009
Author(s)
Ushiyama, M., Ikeda, R., Yamaguchi, H., Miyawaki, A., Nitta, T., Yamaguchi, T., Matsumoto, K., Shimodouzono, Y., Furukawa, T., Akiyama, S., Nakamura N., Yamada, K.
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Journal Title
Journal of Applied Therapeutic Research 7
Pages: 58-64
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[Journal Article] Correlation between meropenem and doripenem use density and the incidence of carbapenem-resistant Pseudomonas aeruginosa2009
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Shigemi A, Matsumoto K, Yaji K, Shimodozono Y, Takeda Y, Miyanohare H, Kawamura H, Orita M, Tokuda K, Nishi J, Yamada K
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Journal Title
International Journal of Antimicrobial Agents 34
Pages: 589-591
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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
5^<th> 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)
Year and Date
2011-11-27
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[Presentation] 高浸透圧によるmajor vault protein (MVP)発現制御におけるSp1の役割2011
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田實裕介, 池田龍二, 田畑祥, 西澤由紀彦, 山口辰哉, 牛山美奈, 山本雅達, 古川龍彦, 秋山伸一, 山田勝士, 武田泰生
Organizer
第64回日本薬理学会西南部会
Place of Presentation
KKRホテル博多(福岡市)
Year and Date
2011-11-20
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[Presentation] チミジンホスホリラーゼ発現腫瘍での5-fluorouracil (5-FU)によるthrombospondin-1 (TSP-1)発現誘導2011
Author(s)
西澤由紀彦, 池田龍二, 田畑祥, 田實裕介, 俣木博徳, 古川龍彦, 牛山美奈, 山口辰哉, 山本雅達, 松下茂人, 秋山伸一, 山田勝士, 武田泰生
Organizer
第64回日本薬理学会西南部会
Place of Presentation
KKRホテル博多(福岡市)
Year and Date
2011-11-20
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[Presentation] 5-fluorouracilの血中濃度および遺伝子診断に基づいた投与量に関する検討2010
Author(s)
新塘麻奈, 松元一明, 池田龍二, 牛山美奈, 横山雄太, 武田泰生, 石神純也, 前村公成, 有上貴明, 夏越祥次, 山田勝士
Organizer
第27回日本薬学会九州支部大会
Place of Presentation
長崎大学大学院医歯薬学総合研究科(長崎市)
Year and Date
2010-12-11
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[Presentation] 抗癌剤によって誘導されるmajor vault protein (MVP)の発現亢進機序の解明2010
Author(s)
俣木博徳, 池田龍二, 田畑祥, 田實裕介, 西澤由紀彦, 南謙太朗, 山口辰哉, 牛山美奈, 山本雅達, 武田泰生, 秋山伸一, 山田勝士
Organizer
第63回日本薬理学会西南部会
Place of Presentation
鹿児島県民交流センター(鹿児島市)
Year and Date
2010-11-26
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[Presentation] チミジンホスホリラーゼ発現腫瘍での5-fluorouracil(5-FU)による early growth response factor-1(EGR-1)発現誘導2009
Author(s)
西澤由紀彦, 池田龍二, 田實裕介, 俣木博徳, 武田泰生, 古川龍彦, 牛山美奈, 山口辰哉, 車暁芳, 山本雅達, 松下茂人, 秋山伸一, 山田勝士
Organizer
第26回日本薬学会九州支部大会
Place of Presentation
九州大学大学院薬学研究院(福岡市)
Year and Date
2009-12-12
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[Presentation] 高浸透圧によって誘導される major vault protein(MVP)の発現亢進機構の解明2009
Author(s)
田實裕介, 池田龍二, 岩下健一, 田畑祥, 西澤由紀彦, 山口辰哉, 牛山美奈, 山本雅達, 車暁芳, 古川龍彦, 武田泰生, 秋山伸一, 山田勝士
Organizer
第62回日本薬理学会西南部会
Place of Presentation
リジェール松山(松山市)
Year and Date
2009-11-27
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[Presentation] チミジンホスホリラーゼによるNF-KBの活性化機構2009
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田畑祥, 山本雅達, 池田龍二, 古川龍彦, 車暁芳, 新里能成, 南謙太朗, 向田直史, 武田泰生, 山田勝士, 秋山伸一
Organizer
第68回日本癌学会学術総会
Place of Presentation
パシフィコ横浜(横浜市)
Year and Date
2009-10-03
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