| Project/Area Number |
08457425
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
NAITO Seiji Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (40164107)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOTOH Shuji Kyushu University, Faculty of Medicine, Assistant, 医学部, 助手 (80294940)
KOGA Hirofumi Kyushu University, Faculty of Medicine, Assistant, 医学部, 助手 (20271108)
長谷川 周二 九州大学, 医学部, 医員
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥3,800,000 (Direct Cost: ¥3,800,000)
|
|---|
| Keywords | renal cell carcinoma / urogenital carcinoma / chemotherapy / multidrug resistance / P-glycoprotein / DNA topoisomerase II / glutathione / cisplatin / P-糖尿白 / DNAポイソメラーゼII / 抗癌剤耐性 / MDR1 / MRP / GST-π / 腎細胞癌 / 膀胱癌 |
|---|
| Research Abstract |
1. The mechanisms of cisplatin resistance was examined using newly established cisplatin resistant human baladder cancer and testicular cancer cell lines. Multiplemechansisms, including decreased drug accumulation, increased intracellular glutathione, overexpression of T-plastin, gamma-glutamylcysteinesynthetase, glutathione S-transferase pi and metallothionein genes were found to participate cooperatively in the acquisition of cisplatin resistance in human cancer.
2. It has been reported that the amount of DNA topoisomerase IIalpha (topo IIalpha) mRNA in cancer cells is increased by exposing them to heat shock stress at 430. We investigated the mechanisms of such phenomena using human bladder cancer cell line, and found that an inverted CCAAT element play an important role in transcriptional activation of the human topo IIalpha geneby heat shock.
3. We have screened newly synthesized dihydropyridine and imidazothiazole derivatives to determine whether they may be able to overcome multidrug resistance (MDR), and found several useful agents which reverse not only acquired MDR but also intrinsic MDR of kidney cancer without inducing significant toxicity.
4. Cisplatin resistant human testicular germ cell tumor cell line was established, and appropriate model of lymph node metastasis was established by injecting the cells into orthotopic site (testis) of the nude mice.
|
