| Project/Area Number |
10670158
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MATSUURA Nariaki Osaka University, School of Medicine, Professor, 医学部, 教授 (70190402)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Hideki Osaka University, School of Medicine, Professor, 医学系研究科, 教授 (60191558)
TAMAKI Yasuhiro Osaka University, School of Medicine, Associate Professor, 医学系研究科, 助教授 (10273690)
KAWAGUCHI Naoumasa Osaka University, School of Medicine, Assistant Professor, 医学部, 助手 (70224748)
HIGASHIYAMA Shigeki Osaka University, School of Medicine, Associate Professor, 医学部, 助教授 (60202272)
富田 尚裕 (冨田 尚裕) 大阪大学, 医学系研究科, 助手 (00252643)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Keywords | bone metastasis / chemotherapy / integrin α4β1 / transfection / インテグリン / 細胞運動 / VCAM-1 / 骨髄 / 破骨細胞 |
|---|
| Research Abstract |
In the previous study α4-CHO cell, transfectant of integrin α4β1 for Chinese hamster ovary cell, caused prominent bone metastasis in vivo and the interaction of α4β1 and *CAM-1 (vascular cell adhesion molecule-1) was important for the mechanism of bone metastasis in this model.
α4-CHO cell was used as a model of bone metastasis of hormone receptor negative breast cancer and the effect of UFT and medroxyprogesterone acetate (MPA) administration was examined. The degree of bone metastases was observed for the inhibitory effect of those drugs for bone metastasis. The adverse effect of drugs was evaluated for the diet volume and body weight changes. The drugs were administered orally every day and mice were sacrificed to examine metastasis. As a result, administration of middle dose of UFT (20mg/kg/day) or high dosage of UFT (30mg/kg/day) in combination with MPA suppressed bone metastasis. Administration of high dose of UFT in combination with MPA resulted in the suppression of adverse effects of UFT such as increased food intake, decreased body weight loss, and reduced necrotic change of liver. Therefore combination therapy of UFT and MPA would be useful for bone metastasis both in potentiation of effects and alleviation of *de effects.
Expression of mRNA (R-PCR) and protein (imuunohistochemistry) of integrin α4β1 was investigated in the primary and metastatic lesions of bone metastasis of breast cancer, prostate cancer and lung cancer. As a result, overexpression of α4β1 in the metastatic lesion was observed, while there was no difference of the α3β1 expression between primary and metastatic lesions. These data suggested α4β1 might play some roles in bone metastasis.
|
