| Project/Area Number |
14571242
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Fujita Health University |
|---|
Principal Investigator |
NAKAMURA Yasuko Fujita Health Univ., Dept. of Surgery School of Medicine, Assistant Professor, 医学部, 講師 (50308871)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Yoichi Fujita Health Univ., School of Medicine, Associate Professor, 医学部, 助教授 (60170651)
OCHIAI Masahiro Fujita Health Univ., 医学部, 教授 (00051772)
今津 浩喜 藤田保健衛生大学, 医学部, 講師 (50298519)
野副 泰智 藤田保健衛生大学, 医学部, 助手
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Gastric cancer / Anticancer chemotherapy / Taxanes / Apoptosis / Nude mice / タキサン系薬 / thymidine phosphorylase / パクリタキセル / 5'DFUR / ヌードマウス可移植性ヒト胃癌株 / タキソール |
|---|
| Research Abstract |
Experimental anticancer chemotherapy was performed on human gastric cancer xenografts, MKN-45 and TMK-1, serially transplanted in nude mice. Anticancer effects and toxic efcts were examined after the oral administration of 5'fluorodeoxyuridine (5'dFUrd) and intravenous administration of weekly paclitaxel and their combination. The tumor growth curve and tumor five body weight were evaluated.. Gene expressions of thymidine phosphorylase (TP), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphribisyltransferase (OPRT), and uridine phosphorylase (UP) were examined after the administrations of 5'dFUrd, paclitaxel and their combination. Apoptosis occurred after these chemnotherapeutic regimens were also examined using TUNEL method and irmmnunohistochemical reactivity of cleaved cytokeratin 18. Combined chemotherapy of dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, and paclitaxel was likewise per-fonned..
The combined administration of 5'dFUrd and paclitaxel elicited the most effective anticancer effects, compared with 5'dFUrd alone and/or paclitaxel alone in both gastric cancer xenografts. There was no difference of the tumor free body weight, used as a reflection of toxic effects, between each getup. The administration of paclitaxel upregulated the gene expression of TP The expression of TP mRNA peaked 2 clays after the administration of paclitaxel. The administration of S-1 upregulated the gene expressions of TP, DPD. The gene expressions of TS, OPRT, UP did not changed after the administrations of these agents. Apoptosis index was significantly increased after the administration of paclitaxel.
|
