Identification and control of factors which regulate CML stem cells

• Project/Area Number: 25461425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Saga University
• Principal Investigator: Kimura Shinya 佐賀大学, 医学部, 教授 (80359794)
• Co-Investigator(Kenkyū-buntansha): Kubota Yasuhi 佐賀大学, 医学部, 講師 (60570413)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 白血病 / 幹細胞 / 低酸素 / シクロデキストリン / BMI-1 / HIF-1α / 慢性骨髄性白血病

Outline of Final Research Achievements

We reported that higher expression of HIF-1alpha became a trigger of lymphoma. In addition, we reported that cyclodextrin and BIM-1 inhibitor showed higher efficacy against leukemic stem cells than normal hematopoietic stem cells and these compounds were promising candidates for novel agents for hematological malignancies. We made it clear that hypoxemia was closely related to hematological malignancies and novel agents which targeted for hypoxemia were very important.

Research Products

• [Journal Article] 2-Hydroxypropyl-β-cyclodextrin Acts as a Novel Anticancer Agent. (2015)
  • Author(s): Yokoo M, Kubota Y, Motoyama K, Higashi T, Taniyoshi M, Tokumaru H, Nishiyama R, Tabe Y, Mochinaga S, Sato A, Sueoka-Aragane N, Sueoka E, Arima H, Irie T, Kimura S.
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: 1705-1713
  • DOI: 10.1371/journal.pone.0141946
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the modification of membrane fluidity. (2015)
  • Author(s): Matsuda K, Hattori S, Kariya R, Komizu Y, Kudo E, Goto H, Taura M, Ueoka R, Kimura S, Okada S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 457(3) Issue: 3 Pages: 288-94
  • DOI: 10.1016/j.bbrc.2014.12.102
  • Peer Reviewed / Open Access
• [Journal Article] Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511 (2015)
  • Author(s): Yokoo M, Kubota Y, Tabe Y, Kimura S
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 3 Pages: 411-416
  • DOI: 10.1248/bpb.b14-00652
  • NAID: 130004872269
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Correlation between plasma DNA and tumor status in an animal model (2014)
  • Author(s): 12.Sueoka-Aragane N, Sato A, Kobayashi N, Ide M, Yokoo M, Nagano Y, Sueoka E, Okada S, Kimura S
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e111881-e111881
  • DOI: 10.1371/journal.pone.0111881
  • Peer Reviewed / Open Access
• [Journal Article] Combining the ABL1 kinase inhibitor ponatinib and the histone deacetylase inhibitor vorinostat: a potential treatment for BCR-ABL-positive leukemia. (2014)
  • Author(s): Okabe S, Tauchi T, Kimura S, Maekawa T, Kitahara T, Tanaka Y, Ohyashiki K
  • Journal Title: Plos One Volume: 9(2) Issue: 2 Pages: e89080-e89080
  • DOI: 10.1371/journal.pone.0089080
  • Peer Reviewed
• [Journal Article] Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ in combination with nilotinib against BCR-ABL-positive leukemia cells involves the ABL kinase domain mutation. (2014)
  • Author(s): Okabe S, Tauchi T, Tanaka Y, Kitahara T, Kimura S, Maekawa T, Ohyashiki K
  • Journal Title: Cancer Biol Ther Volume: 15 Issue: 2 Pages: 207-215
  • DOI: 10.4161/cbt.26725
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of lymphoproliferative diseases by hypoxia inducible factor-1alpha is associated with prolonged lymphocyte survival. (2013)
  • Author(s): Sueoka E, Sueoka-Aragane N, Sato A, Ide M, Nakamura H, Sotomaru Y, Taya C, Yonekawa H, Kitagawa T, Kubota Y, Kimura S, Nakachi K, Tanimoto K
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e57833-e57833
  • DOI: 10.1371/journal.pone.0057833
  • Peer Reviewed
• [Journal Article] Activity of histone deacetylase inhibitors and an Aurora kinase inhibitor in BCR-ABL expressing leukemic cells. (2013)
  • Author(s): Okabe S
  • Journal Title: Cancer Cell International Volume: 13(1) Issue: 1 Pages: 32-40
  • DOI: 10.1186/1475-2867-13-32
  • Peer Reviewed
• [Journal Article] Neuroprotective efficacy of a new brain-penetrating C-Abl inhibitor in a murine Parkinson's disease model. (2013)
  • Author(s): Imam SZ, Trickler W, Kimura S, Binienda ZK, Paule MG, Slikker W Jr, Li S, Clark RA, Ali SF.
  • Journal Title: PLoS One Volume: 8 Issue: 5 Pages: e65129-e65129
  • DOI: 10.1371/journal.pone.0065129
  • Peer Reviewed
• [Presentation] 2-Hydroxypropyl-b-cyclodextrin の抗白血病効果 (2013)
  • Author(s): 木村晋也、横尾眞子、久保田 寧、持永早希子、藤戸 博、東 大志、本山敬一、有馬英俊、入江徹美
  • Organizer: シクロデキストリン学会
  • Place of Presentation: 熊本
  • Invited
• [Remarks] 佐賀大学医学部 血液・呼吸器・腫瘍内科
  • URL: http://www.saga-hor.jp/main/
• [Remarks] 佐賀大学医学部 血液・呼吸器・腫瘍内科 HP
  • URL: http://www.saga-hor.jp/main/15.html
• [Remarks] 佐賀大学医学部 血液・呼吸器・腫瘍内科 HP
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/