1997 Fiscal Year Final Research Report Summary
Enhanced effect of combination chemotherapy based on induction of proliferative activity for advanceduro thelial cancers.
| Project/Area Number |
08671843
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
ASAKURA Hirotaka Keio Univ.school of Med.Instructor, 医学部, 助手 (50175840)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Kaoru Keio Univ.school of Med.Assistant Prof., 医学部, 講師 (10146673)
TACHIBANA Masaaki Keio Univ.school of Med.Assistant Prof., 医学部, 講師 (70129526)
BABA Shiro Keio Univ.school of Med.Associate Prof., 医学部, 助教授 (00051889)
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| Project Period (FY) |
1996 – 1997
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| Keywords | urothelial cancers / cell cycle / anti-cancer effects / proliferative activities |
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| Research Abstract |
Considerable attention has been given to combination chemotherapy for the treatment of advanced bladder ancer. However the effectiveness of the chemotherapy still remains unsatisfactory. The present study was undertaken to clarify the ideal chemotherapertic drug scheduling and the mechanism of action of methotrexate in combination chemotherapy against bladder cancer cells. KU-7 cells derived from bladder cancer were utilized as the target. The cells were exposed to various concentrations of methotrexate (MTX) and vinblastine (VBL) in different time schedules. Flow cytometric bromodeoxyuridine (BrdU) /deoxyribonucleic acid (DNA) bivariate analysis was performed to evaluate the proliferative activity of tumor cells. Furthermore, KU-7 cells were inoculated in nude mice, and anti-tumor effects following different schedules of the combination chemotherapy were assesed as an in vivo study. Twenty-four-hour preincubation with MTX in a concentration of 5 mcg/ml and subsequent exposure of VBL i
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n a concentration of 0.05 mcg/ml demonstrated 50% increased cytotoxicity when compared with simultaneous exposure of these agents. MTX preincubation at the concentration ranging from 0.5 to 5 mcg/ml resulted in significantly increased proliferative activity of cells estimated by BrdU-labeld cell ratio. In the in vivo study, a -20.5(]SY.+-。[)12.8% tumor volume reduction was obtained in MTX petreatment with subsequent administraion to the VBL group. On the other hand, a 28.8(]SY.+-。[)19.2% increased tumor volume was observed for the simultaneous administration group. The difference was statistically significant (p<0.01). These data indicate that MTX pretreatment can significantly enhance the antitumor effects when compared with simultaneous treatment and/or the reversed schedule in combined chemotherapy with MSX and VBL against bladder cancer cells.
Based on the fundamental experiments, multimodal treatment for locally invasive bladder cancer as a bladder reserving trials is being pursued in diverse protocols. Incorporating and combining with many potentially effective and complementary therapies demonstrate the possibility of improving the post-treatment quality of life and the curerate. We now planed the use of transurethral resection, systemic modified M-VAC chemotherapy and hyperfractionated pelvic irradiation as a bladder preserving treatment for locally advanced bladder cancer. A total of 27patients with histologically confirmed muscle-invasive bladder cancer (clinically stages T3/T4) were entered in this study. All patients underwent transurethral resection as a result of histological diagnosis along with mass reduction. Hyperfractionated radiotherapy in conjunction with systemic chemotherapy
may be an acceptable alternative to immediate cystectomy for the management of locally invasive bladder cancer. Less
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