didimethylsulfoxide-dichloroplatinum(ii) and Glioma

Cis-diamminedichloroplatinum (CDDP) was administered by selective continuous internal carotid infusion to nine patients with malignant brain tumors, including five glioblastomas, one mixed glioma, and three metastatic tumors. CDDP was infused through a catheter in the internal carotid artery at 100 mg/hr in all cases, except one glioblastoma case in which the lower rate of 10 mg/hr was used. The results of CDDP concentration measurements were: 1) CDDP in the blood peaked at termination of CDDP infusion and then decreased slowly, 2) CDDP infiltrated intratumoral cysts and accumulated there, 3) CDDP in the cerebrospinal fluid peaked 6-18 hours after infusion, and 4) the tumor/plasma CDDP ratio varied from 2 to 8. The size of tumors decreased moderately in three of the nine cases, but no complete response was achieved. The histological changes due to CDDP were observed in the tumor tissue and were absent in the normal brain parenchyma.

Topics: Adult; Aged; Brain Neoplasms; Carotid Artery, Internal; Drug Evaluation; Female; Glioblastoma; Glioma; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Organoplatinum Compounds

The cytokinetic response of three murine (AC) and human (GB-1 and GB-2) glioma cell lines to cisdichlorodiammineplatinum (II) (CDDP) was investigated by flow cytometry. Using the 5-bromodeoxyuridine (BrdU)-Hoechst technique, percentages of cultured glioma cells in the various phases of the cell cycle, and relative phase duration were calculated. This technique proved to be a rapid and easily performed method to characterize phase length and transition rate for the complete cell cycle. In the presence of CDDP IC10 (a concentration in which 10% inhibition of cell growth be induced as compared to controls), perturbations of the cell cycle in AC and GB-1 cells included G2 delay or block, decreased transit velocity from G1 to S phase, and prolongation of G1 phase. The mean cell cycle time increased 1.4 times in AC and 1.6 times in GB-1 as compared to controls. In CDDP IC 50-treated GB-2 cells, the mean cell cycle time was prolonged three times longer than control: however, duration of each phase could not be calculated because of significant perturbation of cell cycle. These results suggest that CDDP influences glioma cells at the G1/S boundary and in the G2 phase, resulting in prolongation of the G1 phase and, to a minor degree, in block of the G2 phase.

Topics: Animals; Bromodeoxyuridine; Cell Cycle; Cell Line; Flow Cytometry; Glioma; Humans; Organoplatinum Compounds; Rats; Tumor Cells, Cultured