| Project/Area Number |
11671241
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
TANGOKU Akira Yamaguchi University School of Medicine, Associate Professor, 医学部, 助教授 (10197593)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHINO Shigefumi Yamaguchi University School of Medicine, Research Associate, 医学部, 助手 (60294633)
HAZAMA Shoichi Yamaguchi University School of Medicine, Research Associate, 医学部, 助手 (50253159)
OKA Masaaki Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70144946)
IIZUKA Norio Yamaguchi University School of Medicine, Research Associate, 医学部, 寄附講座教員 (80332807)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | Esophageal cancer / chemotherapy / nm23-H1 / chemosensitivity / cisplatin / prognosis / 制癌剤感受性 / nm23-H1 / CDDP |
|---|
| Research Abstract |
The expression of nm23-H1 protein was examined immunohistochemically in 50 eligible patients with esophageal squamous cell carcinoma (OSCC). Reduced expression of nm23-H1 was associated with shorter overall survival in patients with involved lymph nodes. These data support the conclusion that reduced expression of nm23-H1 may be associated with poor prognosis of ESCC patients. Expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma. The nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and m
… More
itochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouablain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level inYES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to NA(+), K(+)-ATPase activity, which is responsible for intracellular cispla tin accumulation. Less
|
