| Project/Area Number |
15591005
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
KIMURA Shinya Kyoto University, Dep.of Transfusion Medicine and Cell Therapy, Assistant Professor, 医学研究科, 助手 (80359794)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Taira Kyoto University, Dep.of Transfusion Medicine and Cell Therapy, Professor, 医学研究科, 教授 (80229286)
YUASA Takeshi Kyoto University, Dep.of Transfusion Medicine and Cell Therapy, Assistant Professor, 医学研究科, 助手 (00314162)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | RAS related proteins / bisphosphonates / zoledronate / imatinib mesykate / p53 / p-glycoprotein / YM529 / γδ T cell / 白血病 / 分子標的 / RAS / BCR-ABL / Zoledronate / imatinib mesylate / zoledronate / imatinib mysylate |
|---|
| Research Abstract |
We have studied about targeting RAS related proteins for leukemia therapy with grant-in-aid for scientific research (C)(2) and have reported as follows :
1)The third generation bisphosphonate(BP) zoledronate(ZOL) is a potent anti-leukemic agent that augments synergistically the anti-Ph^+ leukemia activity of imatinib.
2)ZOL is effective on the cell lines which p53 function are reduced, suggesting the p53-independent anti-tumor activities of ZOL. ZOL is also effective on p-glycoprotein over expressing leukemic cell line. These findings suggest that ZOL may be an attractive agent for treating cancers, including chemoresistant cases.
3)ZOL acts synergistically when administered concurrently with cytarabine (Ara-C) in some leukemic cell lines. Furthermore, one day of ZOL pre-treatment augmented the sensitivity of imatinib and Ara-C.
4)Another third generation BP, YM529 has also anti-leukemic effects both in vitro and in vivo.
5)ZOL and YM529 shows anti-tumor effects not only against leukemia but also lung cancer, renal cell cancer, prostate cancer cell lines. ZOL augments synergistically the anti-lung cancer activity of paclitaxel and YM529 augments synergistically the anti-renal cell cancer activity of interferon-α.
6)ZOL stimulates the proliferation of γδ. T cells and that pre-treatment with ZOL greatly enhances the cytotoxic activity of γδ T cells against target cells.
Based on our these studies, clinical trials for imatinib plus ZOL against chronic myeloid leukemia and Ph^+ acute lymphoblastic leukemia have started in United Kingdom and Germany, suggesting that these studies contribute translational research. We are currently preparing for a clinical trial on imatinib plus ZOL in Japan
|
