Showing papers by "Ulrich Bogdahn published in 1987"
TL;DR: ARA-A5'P is an effective drug in treatment of brain tumour cells in vitro and high gradegliomas were less sensitive to all three agents than low grade and infratentorial gliomas.
Abstract: BCNU (carmustine), VM26 (teniposide) and ARA-A5'P (vidarabin-monophosphate) were compared in their activity against 30 cell lines of primary (N = 21) and metastatic (N = 9) human brain tumours, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products c X t were correlated with in vitro pharmacokinetic data in order to evaluate in vitro drug sensitivity at relevant exposure doses. A microcytotoxicity assay was employed to screen for drug toxicity in individual tumour cell lines. Following drug exposure and 5 to 8 population doubling times of untreated controls, RNA-synthesis - as a parameter of cell metabolism and proliferation - was determined by incorporation of [5,6-3H]-uridine into cellular RNA (liquid scintillation counting protocol). The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index (SI); by these means effects of different drugs on individual tumour cell lines could be compared. Mean sensitivity indices of ARA-A5'P, BCNU and VM26 for primary brain tumour cell lines were 0.59, 0.82 and 0.54. ARA-A5'P and VM26 had almost similar activities against brain tumour cell lines, whereas BCNU was significantly (P less than 0.001) less active. High grade gliomas were less sensitive to all three agents than low grade and infratentorial gliomas. ARA-A5'P was also able to effectively reduce colony formation in brain tumour cell lines. A cross-resistance of ARA-A5'P to either BCNU or VM26 could not be observed. Clearly, ARA-A5'P is an effective drug in treatment of brain tumour cells in vitro.
39 citations
TL;DR: It is concluded that ARA‐A5'P and 5‐FU are potent agents in experimental therapy of human brain tumors, compared with BCNU.
Abstract: BCNU (carmustine), 5-Fluorouracil (5-FU) and Vidarabin-monophosphate (ARA-A5'P) were compared in their activities against 30 cell lines of primary (n = 21) and metastatic (n = 9) brain tumors, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products were correlated with in vitro pharmacokinetic data. A micro assay was employed to screen for drug toxicity in individual tumor cell lines; cells were exposed to the drugs at exposure doses relevant to in vivo pharmacokinetics. After 5-8 population doubling times of untreated controls, RNA-synthesis, as a parameter of cell metabolism and proliferation, was determined by incorporation of (5, 6-3H)-uridine into cellular RNA (liquid scintillation counting protocol). A tumor stem cell assay was performed under similar conditions. The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index SI (SI = 1 indicating complete resistance) to compare effects of different drugs on the individual tumor cell lines. Mean sensitivity indices for ARA-A5'P, BCNU and 5-FU in brain tumor cell lines (in brackets: primary CNS-tumors) were 0.64 (0.59), 0.89 (0.82) and 0.35 (0.33) respectively. 5-FU was significantly more active than BCNU and ARA-A5'P (P less than 0.001), whereas BCNU was significantly less active than ARA-A5'P (P less than 0.001). ARA-A5'P had a suppressive effect on formation of brain tumor stem cell colonies. There was no cross-resistance of ARA-A5'P to either BCNU or 5-FU. We conclude that ARA-A5'P and 5-FU are potent agents in experimental therapy of human brain tumors, compared with BCNU.
9 citations
01 Jan 1987
TL;DR: In correlating sensitivity indices for individual drugs/ tumours with recurrence free intervals of patients, it is thought there might be another step forward to better in vitro drug sensitivity prediction for individual tumour patients.
Abstract: Patients with malignant glial tumours (glioblastoma multiforme, anaplastic astrocytoma) have a Poor prognosis with median survival times approaching 50 to 60 months (25, 26); patients with metastatic brain tumours will have even shorter median survival times of approximately 4 months. In vitro assay systems have been one type of approach to improve therapeutic results in these patients, and in Some systems good correlations have been demonstrated between predictive test results and clinical Courses of brain tumour patients (6,19,24). However, discordant predictions (in vitro sensitive/in vivo resistent; in vitro resistent/in vivo. sensitive) and insufficient pharmacokinetic data limited the clinical impact of these assays so far. Consequently we have correlated in vitro and in vivo pharmacokinetic data and tried to employ CNS-pharmacokinetic values as far as available in order to improve the predictive capacity of in vitro assays. In correlating sensitivity indices for individual drugs/ tumours with recurrence free intervals of patients, we think there might be another step forward to better in vitro drug sensitivity prediction for individual tumour patients (2).
2 citations