| Project/Area Number |
15591596
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
HONOKI Kanya (2004) Nara Medical University, Dept.of Orthopedic Surgery, MD., PhD., Research Associate, 医学部, 助手 (40336863)
森下 亨 (2003) 奈良県立医科大学, 医学部, 講師 (80326321)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MII Yoshio Nara Medical University, Surgical Center, Professor, MD., 医学部, 名誉教授 (70145845)
朴木 寛弥 奈良県立医科大学, 医学部, 助手 (40336863)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Osteosarcoma / Malignant Fibrous Histiocytoma / Rat / Tyrosine kinase inhibitor / p16 / Methylation / CDK inhibitor / 2-methxyestradiol / histone deacethylase inhibitor / hypoxia inducible factor / 微小環境 |
|---|
| Research Abstract |
1)The effect of STI571 was investigated on rat osteosarcoma and MFH cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were greater for MFH cell lines, about 40%, while about 20% for osteosarcoma cell lines. The difference of effectiveness was depend on PDGFRα expression.
2)We investigated the expression and methylation status of p16^<INK4a> gene in rat osteosarcoma and malignant fibrous histiocytoma as well as rat lung adenocarcinoma cell lines. The PCR-SSCP analysis showed no expression of p16 gene in lung adenocarcinoma, while similar expression in ostesarcomas and MFHs as normal fibroblasts. The region close to coding region was hypermethylated in osteosarcoma, in contrast, the region nearby TATA box was consistently methylated in lung adenocarcinoma. MFHs and fibroblasts were hypomethylated in both regions.
3)The effect of HMR1275 (flavopiridol) was investigated on rat osteosarcoma, MFH cell lines and lung adenocarcinoma cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were the greatest for lung adenocarcinoma cell lines, about 80%, while about 60% for osteosarcoma and MFH cell lines. The induction of p16 gene by the treatment of 5-aza 2'-deoxycytidine enhances the effects of HMR1275.
4)The effects of 2-methoxyestradiol and histone deacethylase inhibitor were investigated on rat osteosarcoma and MFH cell lines. The cell growth of both cell lines was inhibited in a time- and dose-dependent manner by both 2-methoxyestradiol and histone deacethylase inhibitor. The investigation of the effect mechanisms for these drugs is now on-going including the gene expression such as hypoxia inducible factor, caspase etc.
|
