2007 Fiscal Year Final Research Report Summary
Development ofa novel therapy for leukemia utilizing bisphcephonate triangle
| Project/Area Number |
18591056
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
KIMURA Shinya Kyoto University, Dep. of Transfusion Medicne and Cell Therapy, Assistant Professor (80359794)
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| Co-Investigator(Kenkyū-buntansha) |
ASHIHARA Eishi Kyoto University, Dep. of Transfusion Mediene and Cell Therapy, Assistant Professor (70275197)
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| Project Period (FY) |
2006 – 2007
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| Keywords | bisphosphonate / leukemia / Ras / ABL / osteoclast / γδTcell / Niche |
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| Research Abstract |
We have clarified the following issues about bisphosphonates triangle from 1st April 2006 to 31st March 2008.
1) BPs demonstrated the that in vitro antitumor effects against not only leukemia but also osteosarcoma(Brit J Cancer 2006, Cancer Left 2006) and bladder cancer (Bin Cancer 2006). Osteosarcoma cells showed higher sensitivity for BPs than other cancer cells Intravesical administration of BPs to bladder was extremely effective for orthotopic bladder cancer mice model. We also clarified that the concentration of BPs in bone marrow was enough to show the direct antitumor effects while that in peripheral blood was not enough. In addition, we reported that an ABL tyrosine kinase inhibitor, INNO-406 which was a good candidate for the combination therapy with BPs also augmented the effects of BCL-2 inhibitor (Cell Death Diff 2007), was effective against most mutated ABL (Leuk Res 2006) and central nervous leukemia (Blood 2007).
2) γδ T cells killed myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface (BBRC 2007).
3) Inoculated leukemic cells via tail vein were engrafted from the edge of bone where osteoclasts mainly existed. Reveromycin A which specifically inhibited the growth of osteoclasts reduced the engraftment of inoculated leukemic cells, suggesting BPs which also had anti-osteoclast activity also may had indirect antitumor effects via osteoclast destruction.
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Research Products
(166 results)
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[Journal Article] A third generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo2006
Author(s)
Sato, K., Yuasa, T., Nogawa, M., Kimura, S., et. al.
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Journal Title
Brit J Cancer 95
Pages: 1354-1361
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pro-apoptotic BH3-only proteins Bim and Bad mediate imatinib-induced killing of Bcr/Abl^+ leukemic cells and resistance due to their loss is overcome by a BH3 mimetic2006
Author(s)
Kuroda, J., Puthalakath, H., Cragg, MS., Kelly, PN., Bouillet, P., Huang, DCS., Kimura, S., et. al.
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Journal Title
Proc Natl Aced Sci USA 103
Pages: 14907-14912
Description
「研究成果報告書概要(欧文)」より
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[Presentation] INNO-406 Demonstrates Activity in Patients with Philadelphia Chromosome Positive Leukemias who are Intolerant or Resistant to Imatinib and Second Generation Tyrosine Kinase Inhibitors2007
Author(s)
Le, Coutre, P., Kantarjian, H., Cortes, J., Nagler, A., Pinilla, J., Hochhause, A., Jones, D., Kimura, S., Craig, A., Carroll, E., Giampalmi, J., Ottmann, O
Organizer
The American Society of Hematology 49th Annual Meeting and Exposition
Place of Presentation
Atlanta, USA
Year and Date
2007-12-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Comparison of Imatinib, Dasatinib, Nilotinib and INNO-406 in Imatinib-Resistant Cell Lines2007
Author(s)
Kimura, S., Deguchi, X. Ashihara, E., Niwa, T., Hodohara, K., Fujiyama, Y., Maekawa, T
Organizer
The American Society of Hematology 49th Annual Meeting and Exposition
Place of Presentation
Atlanta, USA
Year and Date
2007-12-10
Description
「研究成果報告書概要(欧文)」より
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