ABSTRACT
PURPOSE: We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro. MATERIALS AND METHODS: The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity. RESULTS: Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells. CONCLUSION: Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect.
Subject(s)
Cell Line , Cisplatin , DNA , DNA Adducts , Stomach NeoplasmsABSTRACT
BACKGROUND: Because of the relative paucity of data regarding the clinical outcome in adult patients with acute lymphocytic leukemia (ALL) in Korea, we analyzed clinical courses in adult ALL patients treated with VPD (L) regimen (vincristine, prednisolone, daunorubicin, L-asparaginase) at the Seoul National University Hospital, and evaluated prognostic factors influencing the outcome. METHODS: Patients with ALL newly diagnosed between October 1994 and June 2000 at our hospital were analyzed retrospectively. Fifty-three patients were evaluable. Induction chemotherapy consisted of VPD with (46 cases) or without L-asparaginase (7 cases). After complete remission (CR), consolidation therapy, CNS prophylaxis and maintenance chemotherapy were administered. RESULTS: Ages ranged from 16 to 67 (median 30). CR rate was 86.8% (46/53) and no significant prognostic factor was found for the CR rate. With a median follow-up time of 27.2 months (range 12.9~83.0 months) in living patients, the median overall survival (OS) for all cases was 16.7 months (13.4~20.1 months, 95% C.I.) and the estimated 4-year OS rate was 25.4%+/-8.9%. The median relapse-free survival (RFS) was 12.2 months (8.4~16.0 months, 95% C.I.), and 3-year RFS rate was 29.9%+/-10.2%. Poor prognostic factors for OS were Ph chromosome (p=0.005) and T-cell immunophenotype (p=0.03). For RFS they were Ph chromosome (p=0.01) and the presence of a mediastinal mass (p=0.03). CONCLUSION: Despite an initial excellent response to the VPD (L) regimen, newer therapeutic strategies, including more intensive postremission therapies, are urgently needed because of the high relapse rate. Future therapeutic approaches need to be stratified according to several prognostic factors.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Administration, Oral , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Asparaginase/administration & dosage , Disease-Free Survival , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Drug Administration Schedule , Follow-Up Studies , Infusions, Intravenous , Maximum Tolerated Dose , Multivariate Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Prednisone/administration & dosage , Probability , Remission Induction , Retrospective Studies , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageABSTRACT
No abstract available.