Enhancement of hypoxic cell killing and gene therapy applications to cancer treatment

• Project/Area Number: 21591618
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kitasato University
• Principal Investigator: KAGIYA Go 北里大学, 医療衛生学部, 講師 (30524243)
• Co-Investigator(Kenkyū-buntansha): OGAWA Ryohei 富山大学, 大学院・医学薬学研究部, 講師 (60334736)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Hideki 福井大学, 高エネルギー医学研究センター, 准教授 (40142377)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 低酸素細胞領域 / ニトロキシド化合物 / 殺細胞効果 / HIF-1α / テンポール / 遺伝子発現 / 5-FU / ニトロオキシド化合物 / 遺伝子治療 / 低酸素細胞

Research Abstract

We have found that tempol, one of nitoxides, strongly induced the expression of hypoxia inducible-factor(HIF) 1alpha with a combination of hypoxic conditions. The aim of this study is to construct the plasmids that regulate the expression of suicide gene with tempol and to evaluate the enhancement of the cell killing effect by tempol. The transfected cells with the plasmid encoding suicide gene indicated the highest cell killing effect after treatment of 5-FC, tempol and hypoxic mimic CoCl_2.

Research Products

• [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, T. Kondo, N. Doi, L. B. Feril
  • Journal Title: Ultrason Sonochem Volume: 20 Issue: 1 Pages: 460-467
  • DOI: 10.1016/j.ultsonch.2012.05.007
  • Peer Reviewed
• [Journal Article] Regulation of gene expression in retrovirus vectors by X-ray and proton beam radiation with artificially constructed promoters (2012)
  • Author(s): Ogawa, R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, S. Fukuda, K. Kume, T. Hasegawa, M. Hatashita, H. Izumi and T. Ishimoto
  • Journal Title: J Gene Med Volume: 14 Issue: 5 Pages: 316-327
  • DOI: 10.1002/jgm.2625
  • Peer Reviewed
• [Journal Article] An artificially constructed radiation responsive promoter is activated with doxorubicin treatment (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, N. Doi, Q. L. Zhao, L. B. Feril, Jr
  • Journal Title: Cancer Gene Ther Volume: 19 Issue: 5 Pages: 345-351
  • DOI: 10.1038/cgt.2012.7
  • Peer Reviewed
• [Journal Article] Stimulatory effect ofα-Synuclein on the tau-phosphorylation by GSK-3ss (2011)
  • Author(s): Kawakami F., M. Suzuki, N. Shimada, G. Kagiya, E. Ohta, K. Tamura, H. Maruyama and T. Ichikawa
  • Journal Title: FEBS J Volume: 278 Issue: 24 Pages: 4895-4904
  • DOI: 10.1111/j.1742-4658.2011.08389.x
  • Peer Reviewed
• [Journal Article] Stimulatory effect of α-Synuclein on the tau-phosphorylation by GSK-3ss (2011)
  • Author(s): Kawakami F., Suzuki M., Shimada N., Kagiya G., Ohta E., Tamura K., Maruyama H., Ichikawa T.
  • Journal Title: FEBS Journal Volume: 278 Pages: 4895-4904
  • Peer Reviewed
• [Journal Article] Improvement and induction property of radiation-responsive promoter through DNA shuffling of 5'-flanking regions of the human p21 gene (2010)
  • Author(s): Kagiya, G., R. Ogawa, J. A. Cook, R. Choudhuri, M. Hatashita, Y. Tanaka, B. G. DeGraff, and J. B. Mitchell
  • Journal Title: J. Biosci. Bioeng Volume: 110 Issue: 1 Pages: 118-123
  • DOI: 10.1016/j.jbiosc.2009.12.013
  • NAID: 110007681457
  • Peer Reviewed
• [Journal Article] Improvement and induction property of radiation-responsive promoter through DNA shuffling of 5'-flanking regions of the human p21 gene (2010)
  • Author(s): Kagiya, G., R.Ogawa, J.A.Cook, R.Choudhuri, M.Hatashita, Y.Tanaka, B.G.DeGraff, J.B.Mitchell.
  • Journal Title: J.Biosci.Bioeng. Volume: 110 Pages: 118-123
  • NAID: 110007681457
  • Peer Reviewed
• [Journal Article] Improvement and induction property of radiation-responsive promoter through DNA shuffling of 5'-flanking regions of the human p21 gene (2010)
  • Author(s): Kagiya, G., R.Ogawa, J.A.Cook, R.Choudhuri, M.Hatashita, Y.Tanaka, B.G.DeGraff, J.B.Mitchell.
  • Journal Title: J.Biosci. Bioeng. (In press)
  • NAID: 110007681457
  • Peer Reviewed
• [Journal Article] Identification of a cis-acting element responds to ultrasound in 5'-flanking region of human heme oxygenase-1 gene. (2009)
  • Author(s): Kagiya, G., R.Ogawa, S.Ito, S.Fukuda, M.Hatashita, T.Yoshikazu, K.Yamamoto, T.Kondo.
  • Journal Title: Ultrasound in Med. 35 Pages: 155-164
  • Peer Reviewed
• [Journal Article] Enhancement of artificial promoter activity by ultrasound-induced oxidative stress. (2009)
  • Author(s): Ogawa, R., S.Lee, H.Izumi, G.Kagiya, T.Yohsida, A.Watanabe, A.Morii, S.Kakutani, T.Kondo, L.B.Feril, Jr., T.Ishimoto.
  • Journal Title: Ultrasonics Sonochemistry 16 Pages: 379-386
  • Peer Reviewed
• [Journal Article] Construction of artificial promoters sensitively responsive to sonication (2009)
  • Author(s): Watanabe, A., S.Kakutani, R.Ogawa, Sung-il Lee, T.Yoshida, A.Morii, G.Kagiya, LB.Feril, Jr., H.Fuse, T.Kondo
  • Journal Title: J.Med.Ultrasonics. 36 Pages: 9-17
  • Peer Reviewed
• [Journal Article] An artificially constructed radiation responsive promoter is activated by doxorubicin
  • Author(s): Ogawa R., A.Morii, A.Watanabe, Z.G.Cui, G.Kagiya, N.Doi, A.L.Zhao, L.B.Feril
  • Journal Title: Cancer Gene Therapy Volume: (In press)
  • Peer Reviewed
• [Presentation] Enhancement of hypoxic cell killing by the nitroxide Tempol (2012)
  • Author(s): Go Kagiya, R. Ogawa, M. Hatashita, Y. Tanaka, K. Kouda, S. Fukuda, and J. B. Mitchell
  • Organizer: 10th International Congress on Targeted Anticancer Therapies
  • Place of Presentation: Amsterdam
  • Year and Date: 2012-03-08
• [Presentation] Enhancement of hypoxic cell killing by the nitroxide Tempol (2012)
  • Author(s): Go Kagiya, R.Ogawa, M.Hatashita, Y.Tanaka, K.Kouda, S.Fukuda, J.B.Mitchell
  • Organizer: 10^<th> International Congress on Targeted Anticancer Therapies
  • Place of Presentation: RAI Elicium(アムステルダム、オランダ)
• [Presentation] ニトロオキシド化合物テンポールを用いた低酸素細胞に対する殺細胞効果の増強 (2011)
  • Author(s): 鍵谷豪, 小川良平, 畑下昌範, 田中良和, 幸田華奈, 福田茂一
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-11-17
• [Presentation] ニトロキシド化合物テンポールを用いた低酸素細胞に対する殺細胞効果の増強 (2011)
  • Author(s): 鍵谷豪、小川良平、畑下昌範、田中良和、幸田華奈、福田茂一
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸商工会議所会館(神戸市)
  • Year and Date: 2011-11-17
• [Presentation] ニトロオキシド化合物によるHIF-1αの発現増強 (2010)
  • Author(s): 鍵谷豪, 小川良平, 畑下昌範, 田中良和, 松本英樹
  • Organizer: 第49回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-07-09
• [Presentation] ニトロオキシド化合物によるHIF-1αの発現増強 (2010)
  • Author(s): 鍵谷豪、小川良平、畑下昌範、田中良和、松本英樹
  • Organizer: 第49回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 札幌市ホテルさっぽろ芸文館
• [Presentation] 超音波応答性遺伝子発現誘導メカニズムの解析 (2009)
  • Author(s): 小川良平, 鍵谷豪, 近藤隆
  • Organizer: 第8回日本超音波治療研究会・基礎シンポジウム
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2009-11-28
• [Presentation] 超音波応答性遺伝子発現誘導メカニズムの解析 (2009)
  • Author(s): 小川良平、鍵谷豪、近藤隆
  • Organizer: 第8回日本超音波治療研究会・基礎シンポジウム
  • Place of Presentation: 日本学士会館
  • Year and Date: 2009-11-28
• [Presentation] 診療放射線技師教育における学術国際交流 (2009)
  • Author(s): 佐藤英介, 鍵谷豪, 稲田龍司, 梅田徳男, 小川幸次, 五味勉, 斉藤京子, 長谷川智之, 原秀剛, 村石浩, 尾崎正則, 武田徹, 丸山浩一
  • Organizer: 第3回日本診療放射線学教育学会大会
  • Place of Presentation: 相模原市
  • Year and Date: 2009-08-01
• [Presentation] プロモーターシャッフリングを用いた放射線応答プロモーターの構築 (2009)
  • Author(s): 鍵谷豪, 小川良平, 畑下昌範, 田中良和
  • Organizer: 第48回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 富山市
  • Year and Date: 2009-07-10
• [Presentation] プロモーターシヤッフリングを用いた放射線応答プロモーターの構築 (2009)
  • Author(s): 鍵谷豪, 小川良平, 畑下昌範, 田中良和
  • Organizer: 第48回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 富山国際会議場