Role of glucose metabolism in hematological malignancy

• Project/Area Number: 19591103
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Yamanashi
• Principal Investigator: KEITA Kirito University of Yamanashi, 医学部・附属病院, 准教授 (90306150)
• Co-Investigator(Kenkyū-buntansha): NORIO Komatsu 山梨大学, 大学院・医学工学統合研究部, 教授 (50186798)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 白血病 / HIF-1 / 糖代謝 / Warbrug効果 / ミトコンドリア / 活性酸素 / PDK-1 / グルコース / PDK1 / 解糖 / GLUT1

Research Abstract

細胞のエネルギーは、主に糖を基にして産生される。一般に、糖の代謝には酸素が利用されるが、がん細胞では酸素を用いない特殊な形式をとる。この研究では、血液腫瘍を対象として、これらの細胞における糖利用の特徴を明らかにし、新しい治療方法へ結びつけることを目標とした。その結果、悪性リンパ腫細胞では、糖代謝酵素であるヘキソキナーゼの機能を抑制することによって、放射線治療への反応性を増加させうることが分かった。

Research Products

• [Journal Article] Thrombopoietin (TPO) regulates HIF-1alpha levels through generation of mitochondrial reactive oxygen species (2008)
  • Author(s): Yoshida K, Kirito K, Yongzhen H, Ozawa K, Kaushansky K, Komatsu N
  • Journal Title: International journal of hematology 88 Pages: 43-51
  • Peer Reviewed
• [Journal Article] A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies (2008)
  • Author(s): Kirito K, Sakoe K, Shinoda D, Takiyama Y, Kaushansky K, Komatsu N
  • Journal Title: Haematologica 93 Pages: 155-6
  • Peer Reviewed
• [Journal Article] Long-term results of dose-intensive chemotherapy with G-CSF support (TCC-NHL-91) for advanced intermediate-grade non-Hodgkin's lymphoma : a review of 59 consecutive cases treated at a single institute (2008)
  • Author(s): Akutsu M, Tsunoda S, Izumi T, Kirito, K(18人)
  • Journal Title: Oncology research 17 Pages: 137-49
  • Peer Reviewed
• [Journal Article] Throrabopoietin (TPO) regulates HIF-lalpha levels through generation of mitochondrial reactive oxvgen species (2008)
  • Author(s): Yoshida, K., Kirito, K., Yongzhen, H., Ozawa, K., Kaushansky, K., Komatsu, N.
  • Journal Title: Int J Hematol 88 Pages: 43-51
  • Peer Reviewed
• [Journal Article] Long-term results of dose-intensive chemotherapy with G-CSF support (TCC-NHL-91) for advanced intermediate-grade non-Hodgkin's lymphoma : a review of 59 consecutive cases treated at a single institute (2008)
  • Author(s): Akulsu, M., Tsiinoda, S., lzumi, T., Tanaka, M., Kalaiio, S., Inoue, K., Igarashi, S., Hirabayashi, K., Furukawa, Y., Ohmine, K., Saio, K., Kobayashi, H., Ozawa, K., Kirito, K., Nagashima, T., Teramukai, S., Fukushima, M., Kano, Y.
  • Journal Title: Oncol Res 17 Pages: 137-149
  • Peer Reviewed
• [Journal Article] .A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies (2008)
  • Author(s): K. Kirito, K. Sakoe, D. Shinoda, Y. Takiyama, K. Kaushansky and N. Komatsu
  • Journal Title: Haematologica 93 Pages: 155-156
  • Peer Reviewed
• [Journal Article] Activation of FKHRL1 plays an important role in protecting erythroid cells from erythropoietin deprivation-induced apoptosis in a human erythropoietin-dependent leukemia cell line, UT-7/EPO (2007)
  • Author(s): Uchida M, Kirito K, Endo H, Ozawa K, Komatsu N
  • Journal Title: International journal of hematology 86 Pages: 315-24
  • NAID: 10019990096
  • Peer Reviewed
• [Journal Article] Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand (2007)
  • Author(s): Kikuchi S, Nagai T, Kunitama M, Kirito K, Ozawa K, Komatsu N.
  • Journal Title: Cancer science 98 Pages: 1949-58
  • NAID: 10019996600
  • Peer Reviewed
• [Journal Article] Divergent cytotoxic effects of PKC412 in combination with conventional antileukemic agents in FLT3 mutation-positive versus-negative leukemia cell lines (2007)
  • Author(s): Furukawa Y, Vu HA, Akutsu M, Kirito, K(11人)
  • Journal Title: Leukemia 21 Pages: 1005-14
  • Peer Reviewed
• [Journal Article] Divergent cytotoxic effects of PKC412 in combination with conventional antileukemic agents in FLT3 mutation-positive versus-negative leukemia cell lines (2007)
  • Author(s): Y. Furukawa, H. A. Vu, M. Akutsu, T. Odgerel, T. Izumi, S. Tsunoda, Y. Matsuo, K. Kirito, Y. Sato, H. Mano and Y. Kano
  • Journal Title: Leukemia 21 Pages: 1005-1014
  • Peer Reviewed
• [Journal Article] .Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand (2007)
  • Author(s): S. Kikuchi, T. Nagai, M. Kunitama, K. Kirito, K. Ozawa and N. Komatsu
  • Journal Title: Cancer Science 98 Pages: 1949-1958
  • NAID: 10019996600
  • Peer Reviewed
• [Journal Article] Activation of FKHRL1 plays an important role in protecting erythroid cells from erythropoietin deprivation-induced apoptosis in a human erythropoietin-dependent leukemia cell line, UT-7/EPO (2007)
  • Author(s): M. Uchida, K. Kirito, H. Endo, K. Ozawa and N. Koroatsu
  • Journal Title: Int J Hematol 86 Pages: 315-324
  • NAID: 10019990096
  • Peer Reviewed
• [Presentation] HIF-1 Prevents Hematopoietic Cells from Cell Damage by Overproduction of Mitochondrial ROS after Cytokine Stimulation through Induction of PDK-1 (2008)
  • Author(s): 1.Kirito K, Yoshida K, Hu Y, Qiao Q, Sakoe K, Komatsu N.
  • Organizer: 第50回米国血液学会
  • Place of Presentation: San Fransico
  • Year and Date: 2008-12-07
• [Presentation] HIF-1 Prevents Hematopoietic Cells from Cell Damage by Overproduction of Mitochondrial ROS after Cytokine Stimulation through Induction of PDK-1 (2008)
  • Author(s): Kirito, K., Yoshida, K., Yongzhen H., Qiao Q., Sakoe, K., Komatsu, N.
  • Organizer: 50 th Annual Meeting of American Society of Hematology
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2008-12-07
• [Presentation] HIF-1 Supports the Survival of Multiple Myeloma Cells through the Induction of Survivin Gene (2007)
  • Author(s): Kirito K, Yongzhen H, Yoshida K, et.al.
  • Organizer: 第49回米国血液学会
  • Place of Presentation: Atlanta
  • Year and Date: 2007-12-09
• [Presentation] HIF-1 Supports the Survival of Multiple Myeloma Cells through the Induction of Survivin Gene (2007)
  • Author(s): Kirito, K. Yongzhen, Hu., Yoshida, K., Mitsumori, T., Nakajima, K., Nozaki, Y., Nagashima, T., Kunitamae, M., Sakoe, K., Komatsu, N.
  • Organizer: 49th Annual Meeting of American Society of Hematology
  • Place of Presentation: Atlanta, GA, USA
  • Year and Date: 2007-12-09