Targeting Hedgehog in a CML Stem Cell Pathway
Project/Area Number |
23501312
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Clinical oncology
|
Research Institution | Tokyo Medical University |
Principal Investigator |
OKABE Seiichi 東京医科大学, 医学部, 講師 (40366109)
|
Co-Investigator(Kenkyū-buntansha) |
木口 亨 東京医科大学, 医学部, 助教 (70453727)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 分子標的治療 |
Research Abstract |
Hedgehog (Hh)-glioma-associated oncogene homolog (Gli) signaling is implicated in a large number of human cancers. In this study, we investigated the effects of the potent Hh antagonist GDC-0449 on the BCR-ABL-positive cell line and primary samples when leukemia cells were protected by a feeder cell line. The numbers of OM9;22 cells significantly increased with S9 cells. Treatment of OM9;22 cells with GDC-0449 caused cell growth inhibition. Treatment of Ph-positive leukemia cells with GDC-0449 and dasatinib in the presence of S9 caused significantly more cytotoxicity than that caused by each drug alone. Inhibition of Gli1 or Gli2 by siRNA transfection reduced the growth of the Ph-positive cell line K562 and increased cytotoxicity of dasatinib. Data from this study suggest that administration of the Hh inhibitor GDC-0449 inhibits BCR-ABL-positive cell growth and enhances the cytotoxic effects of dasatinib in the presence of feeder cells.
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Report
(4 results)
Research Products
(16 results)
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[Presentation] Combined Effects of a Pan-ABL1 Kinase Inhibitor, Ponatinib and Dasatinib Against T315I Mutant Forms of BCR-ABL1: In Vitro and In Vivo Studies2011
Author(s)
Tetsuzo Tauchi, M.D.1*, Seiichiro Katagiri, M.D.1*, Seiichi Okabe, M.D.1*, Eishi Ashihara, MD, PhD2, Shinya Kimura, MD, PhD3*, Taira Maekawa, MD, DMSci2* and Kazuma Ohyashiki, MD, PhD1
Organizer
53rd ASH(American Society of Hematology) Annual Meeting
Place of Presentation
San Diego, California
Related Report
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[Presentation] Combining ABL1 Kinase Inhibitor, Ponatinib and the Histone Deacetylase (HDAC) Inhibitor Vorinostat: A Potential Treatment for BCR-ABL Positive Leukemia Cells2011
Author(s)
Seiichi Okabe, M.D.1*, Tetsuzo Tauchi, MD, PhD1*, Shinya Kimura, MD, PhD2*, Taira Maekawa, MD, PhD3* and Kazuma Ohyashiki, MD, PhD1
Organizer
53rd ASH(American Society of Hematology) Annual Meeting
Place of Presentation
San Diego, California
Related Report
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[Presentation] Targeting the Hedgehog Signaling Pathway in Therapy-Resistant BCR-ABL1 Positive Leukemia with Ponatinib2011
Author(s)
Seiichiro Katagiri, M.D.1*, Tetsuzo Tauchi, M.D.1*, Seiichi Okabe, M.D.1*, Eishi Ashihara, MD, PhD2, Shinya Kimura, MD, PhD3*, Taira Maekawa, MD, DMSci2* and Kazuma Ohyashiki, MD, PhD1
Organizer
53rd ASH(American Society of Hematology) Annual Meeting
Place of Presentation
San Diego, California
Related Report