Cell targeting therapy for acute myeloid leukemia

• Project/Area Number: 24591403
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: TAKIMOTO Rishu 札幌医科大学, 医学部, 准教授 (10336399)
• Co-Investigator(Kenkyū-buntansha): KATO Junji 札幌医科大学, 医学部, 教授 (20244345) ; KOBUNE Masayoshi 札幌医科大学, 医学部, 准教授 (90336389)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: AML / fucose / DDS / 白血病 / 細胞標的療法 / 急性骨髄性白血病 / ナノキャリア / フコース

Outline of Final Research Achievements

Acute myelogenous leukemia (AML) will achieve complete remission by induction therapy due to improvements in supportive and optimization therapy. In order to improve treatment efficacy by anti cancer drugs, specificity of drugs to leukemic cells should be important to ameliorate prognosis, since maximum dose of chemotherapeutic agents might be administered to AML patients, expecting less toxicity and more efficacy. We targeted AML cells utilizing fucose-bound liposome, since we found AML cells actively uptake L-fucose. Herein we report that intravenously injected L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells. This resulted in efficient tumor growth inhibition as well as prolonged survival in tumor-bearing mice. Thus, biological targeting utilizing characteristics of AML cells by fucose-bound liposome could be a promising new strategy for AML treatment.

Research Products

• [Journal Article] RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells. (2016)
  • Author(s): Tamura F, Sato Y, Hirakawa M, Yoshida M, Ono M, Osuga T, Okagawa Y, Uemura N, Arihara Y, Murase K, Kawano Y, Iyama S, Takada K, Hayashi T, Sato T, Miyanishi K, Kobune M, Takimoto R, Kato J.
  • Journal Title: Gastric Cancer. Volume: 23 Pages: 85-97
  • DOI: 10.1007/s10120-014-0454-z
  • NAID: 40020700032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis. (2015)
  • Author(s): Hoki T, Miyanishi K, Kato J, et al.
  • Journal Title: Hematology Volume: 印刷中 Pages: 751-61
  • DOI: 10.1002/hep.27774
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin (2014)
  • Author(s): Ono K, Sato T, Iyama S, Tatekoshi A, Hashimoto A, Kamihara Y, Horiguchi H, Kikuchi S, Kawano Y, Takada K, Hayashi T, Miyanishi K, Sato Y, Takimoto R, Kobune M,Kato J.
  • Journal Title: Blood Cancer J Volume: 4
  • DOI: 10.1038/bcj.2014.2
  • Peer Reviewed / Open Access
• [Journal Article] Fucosylated TGF-beta receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells. (2014)
  • Author(s): Hirakawa M, Takimoto R, Tamura F, Yoshida M, Ono M, Murase K, Sato Y, Osuga T, Sato T, Iyama S, Miyanishi K, Takada K, Hayashi T, Kobune M, Kato J.
  • Journal Title: Br J Cancer Volume: 7 Pages: 156-163
  • DOI: 10.1038/bjc.2013.699
  • Peer Reviewed / Open Access
• [Journal Article] Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes. (2013)
  • Author(s): Ishiwatari H, Sato Y, Murase K, Yoneda A, Fujita R, Nishita H, Birukawa NK, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kobune M, Ota S, Kimura Y, Hirata K, Kato J, Niitsu Y.
  • Journal Title: Gut Volume: 62(9) Pages: 1328-1339
  • DOI: 10.1136/gutjnl-2011-301746
  • Peer Reviewed
• [Journal Article] A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. (2013)
  • Author(s): Hirakawa M, Sato Y, Takimoto R, Kobune M, Hirata K, Kato J, et al.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 71 Pages: 789-797
  • Peer Reviewed
• [Journal Article] Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. (2013)
  • Author(s): Tanaka S, Miyanishi K, Kobune M, Takimoto R, Kato J, et al.
  • Journal Title: J Gastroenterol. Volume: -
  • Peer Reviewed
• [Journal Article] Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes. (2012)
  • Author(s): Ishiwatari H, Sato Y, Murase K, Yoneda A, Fujita R, Nishita H, Birukawa NK, Hayashi T, Sato T, Miyanishi K, Takimoto R, Kato J, Niitsu Y.
  • Journal Title: Gut. Volume: -
  • Peer Reviewed
• [Journal Article] 10. Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach. (2012)
  • Author(s): Yoshida M, Takimoto R, Murase K, Sato Y, Hirakawa M, Tamura F, Sato T, Iyama S, Osuga T, Miyanishi K, Takada K, Hayashi T, Kobune M, Kato J.
  • Journal Title: PLoS One. Volume: 7(7)
  • DOI: 10.1371/journal.pone.0039545
  • Peer Reviewed
• [Presentation] Targeting Pancreatic Cancer Stem Like Cells Using a Nanoparticle Modified by L-Fucose． (2013)
  • Author(s): Takimoto R，Yoshida M，Murase K，Sato Y，Hirakawa M，Tamura F，Sato T，Osuga T，Miyanishi K，Takada K，Hayash T，Kobune M，Kato J
  • Organizer: The American Association for the Study of Liver Diseases－Digestive Disease Week
  • Place of Presentation: Orlando, U.S.A.
  • Invited