Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.
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PMID:Combined intraarterial and systemic chemotherapy for intracerebral tumors. 244 73

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.
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PMID:Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. 266 38

Glioma 26 (G26) is a chemically induced ependymoblastoma of mouse. It was used through sub-cutaneous and/or intracranial injection in 7 experiences which showed that this experimental model was able to select drugs acting on intracranial tumors : nitrosourea (CCNU), VM 26, procarbazine (PCB). Combination chemotherapy (VM 26-CCNU ; VM 26 CCNU-PCB) was more active than monochemotherapy in 2 out of 3 experiences. It seems that the variability of the results is at least partly due to the important tumoral necrosis in tumors treated by combination chemotherapy and to technical problems. The latters can be avoided by the mechanical dispersion of tumor cells and by their injection through a stereotaxic frame. Selection of drugs is easier and cheaper to perform with G 26 than with other in vivo and in vitro experimental models. The main problem for all models remains their lack of specificity.
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PMID:[Interest of glioma 26 in the selected chemotherapy of intracranial tumors (author's transl)]. 625 44

Therapeutic goals cannot be the same for every patient with malignant glioma, as suggested by the study of 106 cases seen from 1975 to 1982. Seventy patients were uniformly treated by surgery, chemotherapy and radiotherapy. Two clinical parameters, i.e. age and postoperative neurological status (NS), were used to divide patients into three groups with a significantly different prognosis. Median survival was 59.5 months for group 1 (age 50 or less, good NS) and 11.5 months for group 2 (age 51 to 65 and good NS, or younger than 51 but poor NS). For group 3 (age 51 to 65 and poor NS, or older than 65), survival was six months. From 1978, two trials were carried out, with therapy being adjusted to each group. Whatever the group, surgical excision was done whenever it was consistent with preservation of the neurological status and followed by combination chemotherapy (Vincristine-VM 26-CCNU). For group 1, radiotherapy was not modified: 60 grays were delivered to the tumor and surrounding safety margin in 30 fractions over 6 weeks. Patients in group 2 received 69 grays in two daily fractions over 6 weeks (1.15 Gy each morning and evening five days a week). With this modified treatment, median survival was brought up to 20.5 months. Patients in group 3 were treated initially by surgery and chemotherapy; radiotherapy was restricted to recurrences. This policy significantly improved patients' comfort by enabling their prompt return to home. The median survival for 14 patients was 10.5 months. Our experience suggests that different therapeutic goals should be set for each group. In group 1, therapy should be aimed at obtaining prolonged survival. In group 3, survival remains short and the main concern is to improve patients' comfort. As patients in group 2 have an intermediate prognosis, they are the best candidates for therapeutic trials designed to improve the response to radiotherapy and chemotherapy.
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PMID:[Supratentorial malignant glioma in adults. Adjustment of the treatment of 3 groups according to a clinical classification]. 630 84

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of C6 and 9L glioma cells into Wistar and Fisher 344 rats, respectively. Chemotherapy of these models and in vitro chemosensitivity assay for these cell lines were studied with ACNU, BCNU and VM-26. In vitro chemosensitivity assay revealed that 9L cells were sensitive to all of the anticancer drugs above, and that C6 cells were resistant to ACNU and BCNU, but not to VM-26. In vivo experiment, the survival time of the rats inoculated with 9L glioma cells (9LMG) was prolonged by both ACNU and BCNU but not by VM-26. None of these drugs were effective against the rats inoculated with C6 glioma cells (C6MG). It is concluded that the result of in vitro chemosensitivity assay is not always correlative with that of in vivo. This implies that an in vivo chemosensitivity assay system including MG models is indispensable in researching into chemotherapy of brain tumor.
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PMID:[Meningeal gliomatosis models as a chemosensitivity assay system]. 658 85

Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Synchronization chemoradiotherapy for malignant gliomas]. 659 71

Steroids are commonly administered for the control of edema, mass effect, and side effects from therapy to patients with malignant glioma who are receiving radiotherapy and chemotherapy. Here, we report that therapeutic concentrations of dexamethasone (DEX) attenuate cytotoxicity and growth inhibition of human malignant glioma cells induced by exposure to several chemotherapeutics, including ACNU, VM-26, vincristine, cytarabine, methotrexate, and adriamycin. DEX-mediated cytoprotection is not linked to DEX effects on glioma cell proliferation. However, the cytoprotective effects of DEX appeared to be more prominent in cell lines with wild-type p53 status (n = 2) than in p53 mutant cell lines (n = 3). Further, DEX-mediated rescue from chemotherapy does not directly involve Bcl-2 family proteins since DEX failed to change the expression of Bcl-2 or Bax proteins and since bcl-2 gene transfer-mediated cytoprotection was not redundant with the effects of DEX. DEX thus appears to control a common, bcl-2-independent death pathway in glioma cells that is not limited to specific drug actions. Chemotherapy is usually given as an elective, adjuvant treatment to glioma patients in stable condition who can tolerate steroid withdrawal. To maximize therapeutic efficacy, steroids should be withdrawn from glioma patients prior to chemotherapy.
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PMID:Chemotherapy of human malignant glioma: prevention of efficacy by dexamethasone? 919 91

After a pre-operative 1-h i.v. infusion of 150 mg/m2 of teniposide (Vumon; VM26), the drug levels were determined in resected brain tumor specimens from three patients with malignant glioma and from three patients with brain metastases. Tissue dissections were performed within 0-2.5 h after drug administration in three patients and after 24 h in the other three patients. Teniposide was quantified by high-performance liquid chromatography and the levels of albumin in the resected tissue samples were quantified by radial immunodiffusion. In addition, albumin levels were quantified in normal brain tissue, in malignant glioma and in metastatic brain tumor tissue obtained post mortem from deceased patients. The albumin levels indicated that a substantial fraction (range: 0.16-0.50) of the resected brain tumor specimens consisted of blood. As the plasma concentration of teniposide during the first hours after infusion is high, the major part of the drug measured in the tumor specimens collected within 2.5 h after drug administration originated from the blood compartment. At 24 h after drug administration, when the plasma level of teniposide had declined to approximately 0.20 microgram/ml, we could discern a real tissue uptake of teniposide ranging from 0.15-0.27 microgram/g wet tissue weight in the resected tumor. Although the number of patients in this study is small, this work clearly illustrates that an accurate determination of the tissue concentration of teniposide is hindered by the high concurrent plasma levels. It is therefore essential that future tissue distribution studies also include a suitable procedure that establishes the contribution of drug originating from the blood compartment.
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PMID:The vascular compartment hampers accurate determination of teniposide penetration into brain tumor tissue. 922 51

Teniposide (VM26) enhanced the anti-glioma activity of the cytotoxic cytokine, CD95 ligand. Synergy was observed at concentrations of teniposide that were insufficient for cleavable DNA topoisomerase II complex formation. CD95 ligand did not modulate the formation or removal of such complexes after teniposide treatment. These processes were also unaffected by ectopic expression of bcl-2. Teniposide enhanced CD95 expression in a glioma cell line with wild-type p53 (LN-229) but not in two p53 mutant cell lines (T98G, LN-308). Forced expression of a transdominant negative p53 mutant prevented the teniposide induced augmentation of CD95 expression in LN-229 cells but did not prevent the synergy of CD95 ligand and teniposide. Teniposide did not alter CD95 ligand expression, and forced expression of CD95 did not modulate sensitivity to VM26. Thus, teniposide-induced DNA lesions and alterations in CD95 or CD95 ligand are not necessary for teniposide-induced sensitization of human malignant glioma cells to CD95-mediated apoptosis.
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PMID:Synergy of CD95 ligand and teniposide: no role of cleavable complex formation and enhanced CD95 expression. 954 55

Using the monolay tumor cell culture system and the method or MTT colorimetric analysis, the cytotoxicity of the anticancer drug VM-26 and Nicardipine(NCDP) in human malignant glioma cell line U251 was studied. The results showed that the cytotoxicity of VM-26 in U251 was enhanced by NCDP at a low dose which did not show direct cytotoxicity. The authors considered that VM-26 combined with NCDP can heighten the intracellular anticancer drug concentration, reverse the drug resistance and heterogeneity in human malignant glioma cells. The mechanism of the enhanced effect was also discussed. These findings will provide an alternative chemotherapeutic clue to treat the postoperative malignant gliomas.
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PMID:[Enhanced cytotoxicity of VM-26 in human malignant glioma cells by calcium channel blocker nicardipine in vitro]. 1193 73


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