Roles of transcription factors for carcinogenesis and carcinogenesisdefense
Project/Area Number |
17013017
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Tohoku University (2007-2009) University of Tsukuba (2005-2006) |
Principal Investigator |
MASAYUKI Yamamoto Tohoku University, 大学院・医学系研究科, 教授 (50166823)
|
Co-Investigator(Kenkyū-buntansha) |
RITSUKO Shimizu 東北大学, 大学院・医学系研究科, 教授 (40226262)
KINUKO Ohneda 高崎健康福祉大学, 薬学部・薬学科, 教授 (50323291)
|
Project Period (FY) |
2005 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥124,000,000 (Direct Cost: ¥124,000,000)
Fiscal Year 2009: ¥24,800,000 (Direct Cost: ¥24,800,000)
Fiscal Year 2008: ¥24,800,000 (Direct Cost: ¥24,800,000)
Fiscal Year 2007: ¥24,800,000 (Direct Cost: ¥24,800,000)
Fiscal Year 2006: ¥24,800,000 (Direct Cost: ¥24,800,000)
Fiscal Year 2005: ¥24,800,000 (Direct Cost: ¥24,800,000)
|
Keywords | 転写因子 / 発癌 / 癌抑制 / 多段階発がん / GATA1 / 白血病幹細胞 / 幹細胞性 / 治療抵抗性 / 巨核芽球白血病 / ダウン症候群 / 一過性骨髄増殖症 / 前赤芽球性性白血病 / 質的異常 / 量的異常 / GATA-1 / GATA-2 / Nrf2 / Keap1造血 / 白血病 / 酸化ストレス / 遺伝子改変マウス |
Research Abstract |
In this study, we investigated roles transcription factors play on carcinogenesis and carcinogenesis defense in vivo, focusing on the Nrf2 and GATA transcription factors. We have found that co-operative function of Nrf2 and Keap1, which mediates cellular stress response, is important for the cancer carcinogenesis defense so that the failure in Nrf2-Keap1 system leads to the onset of cancer and poor prognosis. We have further found that deregulated function of GATA factors, which act as key molecules in hematopoietic homeostasis, causes leukemogenesis.
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Report
(5 results)
Research Products
(215 results)
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[Journal Article] Novel regulation of the Nrf2-Keap1 pathway by the selective autophagy substrate p622010
Author(s)
Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou Y-S, Ueno I, Sakamoto A, Tong KI, Kim M, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M
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Journal Title
Nature Cell Biol 12
Pages: 213-223
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[Journal Article] Novel regulation of the Nrf2-Keap1 pathway by the selective autophagy substrate p622010
Author(s)
Komatsu M, Kurokawa H, Waqun S, Iaguchi K, Kobayashi A, Ichimura Y, Sou Y-S, Ueno I, Sakamoto A, Tong KI, Kim M, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M
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Journal Title
Nature Cell Biol 12
Pages: 213-223
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[Journal Article] Genetic versus chemoprotective activation of Nrf2 signaling : overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid treated mice2009
Author(s)
Yates MS, Tran QT, Dolan PM, Osburn WO, Shin S, McCulloch CC, Silkworth JB, Taguchi K, Yamamoto M, Williams CR, Liby KT, Sporn MB, Sutter TR, Kensler TW
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Journal Title
Carcinogenesis 30
Pages: 1024-1031
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[Journal Article] Nrf2 enhances cell proliferation and resistance to anticancer drugs in hum an lung cancer2009
Author(s)
Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N, Kikuchi N, Satoh H, Sakamoto T, Hizawa N, Itoh K, Yamamoto M
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Journal Title
Clin Cancer Res 15
Pages: 3423-3432
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[Journal Article] Targeting Nrf2 with the Triterpenoid CDDO-Imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice2009
Author(s)
Sussan IE, Hangasamy T, Blake DJ, Mainotra U, El-Haddad H, Bedja D, Yates MS, Kombairaju P, Yamamoto M, Liby KT, Sporn MB, Gabrielson KL, Champion HC, Tuder RM, Kensler TW, Biswal S
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Journal Title
Proc Natl Acad Sci USA 106
Pages: 250-255
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[Journal Article] Nrf2 counteracts cholestatic liver injury via stimulation of hepatic defense systems2009
Author(s)
Okada K, Shoda J, Taguchi K, Maher JM, Ishizaki K, Inoue Y, Ohtsuki M, Goto N, Sugimoto H, Utsunomiya H, Oda K, Warabi E, Ishii T, Yamamoto M
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Journal Title
Biochem Biophys Res Commun 389
Pages: 431-436
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Peer Reviewed
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[Journal Article] Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs2009
Author(s)
Singh A, Ling G, Suhasini AN, Z hang P, Yamamoto M, Navas-Acien A, Cosgrove G, Tuder RM, Kensler TW, Watson WH, Biswal S
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Journal Title
Free Radic Biol Med 46
Pages: 376-386
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[Journal Article] Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice2008
Author(s)
Yoh K, Hirayama A, Ishizaki K, Yamada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, Yamamoto M
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Journal Title
Genes Cells 13
Pages: 1159-1170
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[Journal Article] Loss of Keap 1 function activates Nrf2 and provides advantages for lung cancer cells growth2008
Author(s)
Ohta T, Iijima K, Miyamoto M, Nakahara I, Odagawa R, Mimaki S, Sakiyama T, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Shibata T, Yamamoto M, and Hirohashi S
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Journal Title
Cancer Res 68
Pages: 1303-1309
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[Journal Article] Attenuation of UVB-induced sunburn reaction and oxidative DNA damage with no alterations in UVB-induced skin carcinogenesis in Nrf2 gene-deficient mice2008
Author(s)
Kawachi Y, Xu X, Taguchi S, Sakurai H, Nakamura Y, Ishii Y, Fujisawa Y, Furuta J, Takahashi T, Itoh K, Yamamoto M, Yamazaki F, and Otsuka F
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Journal Title
J Invest Dermatol 128
Pages: 1773-1779
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[Journal Article] Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction2008
Author(s)
Pearson KJ, Lewis KN, Price NL, Chang JW, Perez E, Cascajo M V, Tamashiro KL, Poosala S, Csiszar A, Ungvari Z, Kensler TW, Yamamoto M, Egan JM, Longo DL, Ingram DK, Navas P, de Cabo R
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Journal Title
Proc Nati Acad Sci USA 105
Pages: 2325-2330
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[Journal Article] Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells2008
Author(s)
Taguchi K, Shimada M, Fujii S, Sumi D, Pan X, Yamano S, Nishiy ama T, Hiratsuka A, Yamamoto M, Cho AK, Froines JR, and Kumagai Y
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Journal Title
Free Radic Biol Med 44
Pages: 1645-1655
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[Journal Article] Activation of nuclear factor E2-related factor 2 in hereditary tyrosinemia type 1 and its role in survival and tumor development2008
Author(s)
Marhenke S, Lamle J, Buitrago-Molina LE, Canon JM, Geffers R, Finegold M, Sporn M, Yamamoto M, Manns MP, Grompe M, and Vogel A
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Journal Title
Hepatology 48
Pages: 487-496
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[Journal Article] Activation of nuclear factor E2-related factor 2 in hereditary tyrosinemia type 1 and its role in survival and tumor development2008
Author(s)
Marhenke S, Lamle J, Buitrago-M olina LE, Cali& JM, Geffers R, Finegold M, Sporn M, Yamamoto M, Manns MP, Grompe M, and Vogel A
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Journal Title
Hepatology 48
Pages: 487-496
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[Journal Article] Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice2008
Author(s)
Yoh K, Hirayama A, Ishizaki K, Y amada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, and Yamamoto M
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Journal Title
Genes Cells 13
Pages: 1159-1170
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[Journal Article] Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes2007
Author(s)
Zhang J, Hosoya T, Maruyama A, Nishikawa K, Maher JM, Ohta T, Motohashi H, Fukamizu A, Shibahara S, Itoh K, Yamamoto M
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Journal Title
Biochem J 404
Pages: 459-466
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[Journal Article] Potential involvement of pathophysiologically formed 8-nitorguanosine 3', 5'-cyclic monophosphate in nitric oxide-induced signal transduction2007
Author(s)
Sawa T, Zaki MH, Okamoto T, Akuta T, Tokutomi Y, Kim-Mitsuyama S, Ihara H, Kobayashi A, Yamamoto M, Fujii S, Arimoto H, Akaike T
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Journal Title
Nature Chem Biol 3
Pages: 727-735
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[Journal Article] Loss of p62/SQSTM1 suppresses cytoplasmic inclusion body formation and liver injury in autophagy-deficient mouse2007
Author(s)
Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, Tanaka K
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Journal Title
Cell 131
Pages: 1149-1163
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[Journal Article] Molecular basis distinguishing the DNA binding profile of NRF2-MAF heterodimer from that of MAF homodimer2007
Author(s)
Kimura M, Yamamoto T, Zhang J, Itoh K, Kyo M, Kamiya T, Aburatani H, Katsuoka F, Kurokawa H, Tanaka T, Motohashi H, Yamamoto M
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Journal Title
J Biol Chem 282
Pages: 33681-33690
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[Journal Article] Characterization of GATA-1^+ hemangioblastic cells in the mouse embryo.2007
Author(s)
Yokomizo T, Takahashi S, Mochizuki N, Kuroha T, Ema M, Wakamatsu A, Shimizu R, Ohneda O, Osato M, Okada H, Komori T, Ogawa M, Nishikawa S, Ito Y, and Yamamoto M.
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Journal Title
EMBO J. 26
Pages: 184-196
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[Journal Article] Increased susceptibility to hepatocarcinogenicity of Nrf2-deficient mice exposed to 2-amino-3-methylimidazo [4, 5-f] quinoline.2007
Author(s)
Kitamura Y, Umemura T, kanki K, Kodama Y, Kitamoto S, Saito K, Itoh K, Yamamoto M, Masegi T, Nishikawa A, and Hirose M.
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Journal Title
Cancer Sci. 98
Pages: 19-24
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[Journal Article] Inchinkoto, an herbal medicine, and its ingredients dually exert Mrp2/MRP2-mediated choleresis and Nrf2-mediated antioxidative action in ratlivers.2007
Author(s)
Okada K, Shoda J, Kano M, Suzuki S, Ohtake N, Yamamoto M, Takahashi H, Utsunomiya H, Oda K, Sato K, Watanabe A, Ishii T, Itoh K, Yamamoto M, Yokoi T, Yoshizato K, Sugiyama Y and Suzuki H.
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Journal Title
Am J Physiol Gastrointestinal Liver Physiol. 295
Pages: 1450-1463
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[Journal Article] Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes.2007
Author(s)
Yates MS, Tauchi M, Katsuoka F, Flanders KC, Liby KT, Honda T, Gribble GW, Johnson DA, Johnson JA, Burton NC, Guilarte TR, Yamamoto M, Sporn MB, and Kensler TW.
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Journal Title
Mol Cancer Therapeutics. 6
Pages: 154-161
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[Journal Article] Functional polymorphisms in the transcription factor NRF2 increase the risk of acute lung injury.2007
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Marzec JM, Christie JD, Reddy SP, Jedlicka AE, Vuong H, Lanken PN, Aplenc R, Yamamoto T, Yamamoto M, Cho, H-Y, and Kleeberger SR.
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Journal Title
FASEB J. 21
Pages: 2237-2246
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[Journal Article] Nrf2 Neh5 domain is differentially utilized in the transactivation of cytop rotective genes.2007
Author(s)
Zhang J, Hosoya T, Maruyama A, Nishikawa K, Maher JM, Ohta T, Motohashi H, Fukamizu A, Shibahara S, Itoh K, and Yamamoto M.
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Journal Title
Biochem J. 404
Pages: 459-466
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[Journal Article] Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4.2007
Author(s)
Tanabe O, McPhee D, Kobayashi S, Shen Y, Brandt W, Jiang X, Campbell AD, . Chen YT, Chang C, Yamamoto M, Tanimoto K, Engel JD.
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EMBO J. 26
Pages: 2295-2306
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[Journal Article] Oxidative and electrophilic stress induces Mrp transporters via the Nrf2 transcriptional pathway.2007
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Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, and Klaassen CD.
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Journal Title
Hepatology. 46
Pages: 1597-1610
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[Journal Article] In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression.2007
Author(s)
Takeuchi Y, Yahagi N, Nakagawa Y, Matsuzaka T, Shimizu R, Sekiya M, Iizuka Y, Ohashi K, Gotoda T, Yamamoto M, Nagai R, Kadowaki T, Yamada N, Osuga JI, and Shimano H.
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Journal Title
Biochem Biophys Res Commun. 363
Pages: 329-335
NAID
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[Journal Article] Potential involvement of pathophysiologically formed 8-nitroguanosine 3', 5'-cyclic monophosphate in nitric oxide-induced signal transduction.2007
Author(s)
Sawa T, Zaki MH, Okamoto T, Akuta T, Tokutomi Y, Kim-Mitsuyama S, Ihara H, Kobayashi A, Yamamoto M, Fujii S, Arimoto H, and Akaike T.
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Journal Title
Nature Chem Biol. 3
Pages: 727-735
Related Report
Peer Reviewed
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[Journal Article] Loss of p62/SQSTM1 suppresses cytoplasmic inclusion body formation and liver injury in autophagy-deficient mouse.2007
Author(s)
Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E and Tanaka K
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Journal Title
Cell. 131
Pages: 1149-1163
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Peer Reviewed
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[Journal Article] Molecular basis distinguishing the DNA binding profile of NRF2-MAF heterodimer from that of MAF homodimer.2007
Author(s)
Kimura M, Yamamoto T, Zhang J, Itoh K, Kyo M, Kamiya T, Aburatani H, Katsuoka F, Kurokawa H, Tanaka T, Motohashi H, and Yamamoto M.
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Journal Title
JBiol Chem. 282
Pages: 33681-33690
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Peer Reviewed
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[Journal Article] Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions2005
Author(s)
Tauchi M, Hida A, Negishi T, Katsuoka F, Noda S, Mimura J, Hosoya H, Yanaka A, Aburatani H, Fujii-Kuriyama Y, Motohashi H, Yamamoto M
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Mol Cell Biol 25
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[Journal Article] Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema2005
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Iizuka T, Ishii Y, Itoh K, Kiwamoto T, Kimura T, Matsuno Y, Morishima Y, Hegab AE, Homma S, Nomura A, Sakamoto T, Shimura M, Yoshida A, Yamamoto M, Sekizawa K
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[Presentation] Regulation of erythropoietin gene expression in mouse2009
Author(s)
Masayuki Yamamoto, Xiaoqing Pan, Syun Yamazaki, Ikuo Hirano, Naoko Minegishi, Norio Suzuki
Organizer
8th International Luebeck Conference on the Pathophysiology and Pharmacology of Erythropoietin and other Hemopoietic Growth Factors
Place of Presentation
Luebeck, Germany
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[Presentation] 遺伝子組換え実験および遺伝子組み換え動物モデルと医学研究の発展2009
Author(s)
Masayuki Yamamoto, Tatsuhiro Shibata, Ohta Tsutomu, Kit Tong, Hirofumi Kurokawa, Takafumi Suzuki, Keiko Taguchi, Hozumi Motohashi
Organizer
第68回 日本癌学会学術総会シンポジウム
Place of Presentation
横浜
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[Presentation] GATA因子と白血病2007
Author(s)
山本雅之
Organizer
第2回つくば医科学研究交流会ランチョンセミナー
Place of Presentation
三菱化学つくばクリエーションセンター
Year and Date
2007-11-10
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