| Project/Area Number |
21791835
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pathobiological dentistry/Dental radiology
|
|---|
| Research Institution | Hyogo College of Medicine |
|---|
Principal Investigator |
YAMANEGI Koji Hyogo College of Medicine, 医学部, 講師 (00434944)
|
|---|
| Project Period (FY) |
2009 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 骨肉腫 / histone deacetylase inhibitor / NKG2D / NKG2D ligand / Valproic acid / NKG2D ligand (MICs) / soluble MICs |
|---|
| Research Abstract |
We investigated the effects of valproic acid (VPA) (a histone deacetylase inhibitor) in combination with hydralazine (Hy) (a DNA methylation inhibitor) on expression of cell-surface Fas and MHC-class I-related chain molecules A and B (MICA and B), which are ligands of NKG2D, and on production of their soluble forms in HOS, U-2 OS and SaOS-2 human osteosarcoma cells. VPA showed no significant effect on expression of Fas on surface of osteosarcoma cells while Hy increased it and their combination showed the more increasing effect. VPA decreased the production of soluble Fas by osteosarcomas cells but Hy increased it and VPA reduced the increasing effect of Hy. VPA or hydralazine increased expression of cell-surface MICA and B, and their combination induced its further increase. VPA inhibited the production of soluble MICA and B in osteosarcoma cells and the inhibitory effect of VPA did not affected by Hy, which alone showed no significant effect. VPA and Hy enhanced Fas-mediated cell death and susceptibility to NK cells on osteosarcoma cells and their combination showed the more augmenting effect. These results suggest that combined administration of VPA and hydrazine may be useful for enhancing the therapeutic effect of immunotherapy for osteosarcomas.
|
