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)

Dosage and schedules for the treatment of malignant glial tumors using IFN (interferon) are still uncertain and controversial. In this study we give the preliminary results of treatment in 28 patients with glioblastoma multiforme (GBM). 6 patients were treated with local injection of beta-IFN through an Ommaya reservoir; 4 patients with beta-IFN followed by systemic chemotherapy (Cisplatin + Etoposide), and 18 patients with chemotherapy only. Two end points were evaluated: 1) Whether or not the patients responded to treatment. 2) Length of Time to Tumor Progression (TTP) after surgery. We found that IFN alone was ineffective. Results were improved when local immunotherapy was associated with systemic chemotherapy. New drugs and investigation of possible pharmacological synergism are needed.
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PMID:Local immunotherapy (beta-IFN) and systemic chemotherapy in primary glial tumors. 164 48

Carboplatin has lower nephro- and neurotoxicities and better penetration into brain tissue than cisplatin. If carboplatin has comparable cytotoxicity against glioma cells, it might have a therapeutic advantage in the treatment of malignant gliomas. Using an assay of colony-forming efficiency, we compared the cytotoxicity of these two drugs in human glioma cell lines SF-126, SF-188, U87-MG, and U251-MG. The experiments were designed so that the product of in vitro drug concentration (C) and time (T) would encompass the same range of values as the C x T of the ultrafilterable platinum plasma fraction as determined by pharmacokinetic studies in man. The in vitro stability of the drugs was evaluated by measuring the cytotoxicity of aged drugs with a microculture tetrazolium assay. Cisplatin and carboplatin were both stable during the 2-h treatment. The cytotoxic activities of these drugs at clinically achievable levels of drug exposure were of the same order of magnitude. These results, in conjunction with the lower nephro- and neurotoxicities of carboplatin, the higher platinum levels in brain tissue after treatment with carboplatin, and the encouraging results of carboplatin in the clinical treatment of brain tumors that have been demonstrated in other studies, suggest that carboplatin might be preferable to cisplatin in the treatment of patients with malignant glioma.
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PMID:Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures. 191 43

Experimental evidence indicating potentiation of the cytotoxic effect of drugs at high temperatures suggests that the utilization of drug-heat combinations for gliomas of the brain might be therapeutically useful. Hyperthermia may increase the cytotoxicity of a particular drug in areas of low drug concentration/time and in cell populations resistant to the drug. We report in vitro experiments with a BCNU resistant, U-373MG, and a BCNU sensitive, U-87MG, human derived glioma cell lines under hyperthermic conditions. Temperatures equal or above 42 degrees C potentiate BCNU cell kill in both lines. The thermo-sensitizer lidocaine increases thermal cell kill but only minimally with concentrations corresponding to therapeutic plasma lidocaine levels. Within our experimental conditions, the best strategy to overcome BCNU resistance involved a combination of heat, BCNU and cis-DDP. BCNU resistant cells have no cross resistance to cis-DDP and the combination of BCNU and cis-DDP is synergistic. At modest hyperthermic conditions (42 degrees C) 99.4% BCNU resistant cells are killed by a combination of BCNU and cis-DDP at drug concentrations identical to plasma concentrations after standard IV doses. Clinical protocols using heat and drug may need to incorporate two or more drugs for optimal effects.
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PMID:Hyperthermic potentiation of BCNU toxicity in BCNU-resistant human glioma cells. 191 44

Intratumoral heterogeneity was observed in two tumor lines (SbC11 and SbC12) derived from a single biopsy of a melanoma patient. Differences in drug sensitivity were observed in three cell lines of small cell lung carcinoma derived from the same patient, before (AE1), and after (AE2 and AE3) therapy with Adriamycin (ADM) and Cisplatinum (DDP). Moreover, heterogeneity in biological features and in drug sensitivity was observed in three continuous human glioma derived cell lines (LI, DF, and DP). The results show the importance of continuous cell lines for studying tumor heterogeneity and evaluating the effectiveness of antineoplastic agents.
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PMID:[The use of continuous cell cultures for the study of tumor heterogeneity and drug sensitivity]. 196 94

Twenty-eight patients with high-grade cerebral gliomas (16 biopsy-proven and 12 diagnosed clinically and by computed tomography scan) were treated with altered fraction radiation and concomitant cisplatin (C-DDP). Twenty cases (Groups IA and IB) whose Karnofsky performance status (KPS) was 60% or less received hypofractionation and C-DDP. All these patients had received high-dose Decadron (Merck Sharp & Dohme, West Point, PA), and their conditions were not improving or progressively deteriorating. The first 11 patients (Group IA) received from 600 cGy twice weekly to 3600 cGy over 3 weeks combined with C-DDP IV at 40 mg/M2 every 2 weeks for two courses. The nine subsequent patients (Group IB) received from 600 cGy weekly to 3600 cGy over 5 to 6 weeks with C-DDP IV at 40 mg/M2 every 1 to 2 weeks for four courses. The target volume in all cases was confined to the tumor as defined on computed tomography (CT) scan with a 2 cm to 3 cm margin. The C-DDP at 40 mg/M2 was administered immediately (within 5 minutes after radiation). Eight cases (Group II) with a KPS of more than 60% were treated with hyperfractionation, i.e., from 200 cGy twice daily to 4800 cGy in just under 3 weeks. The C-DDP was administered every 2 weeks for a total of two courses, as for Group IA. In Group I, 15 of 20 (75%) patients experienced rapid improvement in their performance status, which usually becoming evident within 1 to 2 weeks from the initiation of treatment, and progressed over time. Four patients with a KPS of 10% improved their KPS to over 60%. This regimen was both well tolerated and logistically very convenient both for the patients and attending staff. Follow-up CT scans in three of 16 evaluable patients in the hypofractionated group showed complete tumor resolution. Median survival for Group IA was 7 months, for Group IB was 12 months, and overall was eight months. The Group II median survival was 9 months. This experience suggests that hypofractionated radiation in combination with C-DDP may offer rapid palliation with improvement in functional status in severely compromised patients with malignant glioma.
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PMID:Hypofractionated radiation therapy and concurrent cisplatin in malignant cerebral gliomas. Rapid palliation in low performance status patients. 247 66

Cisplatin (DDP) is a chemotherapeutic agent that has shown efficacy against primary CNS malignancies. Intra-arterial (IA) administration of DDP to patients with brain tumors should produce higher peak levels of drug than intravenous (IV) administration of an identical dose and reduce systemic toxicity. Twelve patients with malignant glioma were entered into the study. All had failed irradiation, 11 had failed IA BCNU. Each patient received IA DDP, 58-100 mg/m2, into the internal carotid artery at four to six week intervals. One of 12 patients had a partial response of 6 months. The remaining 11 patients had progressive disease or severe complications. Toxicity included seizures in four patients, weakness and/or aphasia in four patients, coma in two patients, and visual deterioration in two patients. IA DDP has very limited efficacy in patients with malignant gliomas after failure of nitrosoureas and is associated with an unacceptable level of toxicity. IA DDP may be more effective when used as initial chemotherapy of malignant gliomas.
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PMID:Intra-arterial cisplatin for the treatment of malignant gliomas. 254 32

DNA damaging agents such as nitrosoureas are widely used for the treatment of malignant gliomas. Therefore, quantitative measurement of DNA damages induced by antineoplastic drugs is useful to judge the efficacy of the drug and understand the pharmacological action of the drug. We have utilized in situ nick translation method to demonstrate "nicks" in DNA of glioma cells treated by various antineoplastic agents. Exponentially growing rat 9 L glioma cells (4 x 10(4] were seeded in the chamber slide. After fourty eight hours, the medium was changed to that containing various concentration of the drug (ACNU, cis-DDP, BLM, ADM and VP-16) and the cell was treated for 1 hour. Then, the cell was fixed for 10 minutes in methanol-acetic acid (v/v 3:1). Following fixation, the cell was incubated in the nick translation mixture containing E. coli DNA polymerase I, 3H-TTP, and 4 dNTP's (ATP, GTP, CTP, CTP and TTP) for 10 minutes at room temperature. The slide was dipped in the autoradiographic emulsion, exposed for 4 days at 4 degrees C, and then developed, the number of the silver grains over nuclei was counted under the microscope. For comparison of the effect of the drug to glioma cells, IC50 (inhibitory concentration of the drug for 50% cell kill) of each drug was determined by treating the cell for 48 hours at the various concentration of the drug. Small number of the silver grains was noted in cells with no treatment. Over IC50 as the concentration of the drug increased, the number of the nick increased in cells treated with bleomycin or adriamycin which are known to produce single strand breaks in DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[In situ nick translation for detection of DNA damages in glioma cells]. 262 7

The rationale for, methodology of, and experience with intra-arterial BCNU infusion therapy of malignant glioma are described. This approach achieves tumor levels of drug four times greater than equal doses infused intravenously, and has been used to treat 79 patients over the course of 4 years. The drug was given in 192 infraophthalmic and 66 supraophthalmic carotid artery infusions. Patients who were treated via infraophthalmic carotid artery infusion following tumor recurrence (after both operation and irradiation) survived 54 additional weeks (92 weeks after initial diagnosis). Patients who were treated with BCNU immediately after initial irradiation therapy survived 64 weeks (infraophthalmic carotid artery infusion) and 49.5 weeks (supraophthalmic carotid artery infusion). The major ocular complications (pain and diminished visual acuity) associated with infraophthalmic carotid artery infusion are avoided by selective balloon-guided supraophthalmic carotid artery administration. However, both approaches were associated with white-matter changes, seen as diminished absorption on computerized tomography scans, in 20% of patients treated following irradiation therapy. This toxicity appears to preclude intra-arterial BCNU treatment in the immediate postirradiation period. Better results are being achieved with our current therapy, which involves four infusions of BCNU (400 mg every 4 weeks) into the infraophthalmic or supraophthalmic carotid artery in advance of irradiation. Cisplatin infusions (60 to 90 mg/sq m every 5 weeks) are offered for recurrent glioblastoma.
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PMID:The rationale and methodology for intra-arterial chemotherapy with BCNU as treatment for glioblastoma. 299 15

Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.
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PMID:Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP). 303 19

The malignant glioma cell line U-87MG was used for 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), aziridinylbenzoquinone (AZQ), cis-diaminodichloroplatinum (II) (cis-DDP), and spirohydantoin mustard (SHM) treatments at 37 degrees and 42 degrees C. With the exception of SHM, all drugs killed a greater proportion of cells at the higher temperature, as assessed by the colony-formation assay. Drug-dose enhancement ratios were 1.6, 2.8, 2, and 1:1 for BCNU, AZQ, cis-DDP, and SHM, respectively. Because methods to heat discrete volumes of brain are now available, we conclude that hyperthermic increase of BCNU, AZQ, and cis-DDP cytotoxicity might have therapeutic application for malignant gliomas.
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PMID:Drug cytotoxicity at elevated temperature. In vitro study on the U-87MG glioma cell line. 368 26


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