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)

Two tumor cell lines were established from each of three human malignant glioma biopsy specimens (M059, M067, M071) and sensitivity to treatment with radiation or chemotherapeutic agents (BCNU, nitrogen mustard) was determined. The effects of recombinant human interferon-alpha (rIFN) on the radiation response and of buthionine sulfoximine (BSO) on the drug response were investigated as well. For tumor M059, two cell lines that differed significantly in radiosensitivity were isolated (surviving fractions at 2 Gy = 0.02 and 0.64). The chemosensitivity and response to chemical modification differed as well. Cell lines established from tumor M071 differed in their response to rIFN only and were not sensitized by BSO. M067 cell lines showed little difference and were not sensitized by either agent. These results suggest that differences may exist both within and among human malignant gliomas with regard to their sensitivity to drugs, radiation, and the ability of chemical agents to modify treatment responses.
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PMID:Heterogeneity in response to treatment with buthionine sulfoximine or interferon in human malignant glioma cells. 154 50

Melphalan, a nitrogen mustard derivative of the neutral amino acid L-phenylalanine, was transported across the rat blood-brain barrier by the large (L-system) neutral amino acid transporter in tumor-bearing brain, but no evidence for blood-brain barrier transport by the alanine-serine-cysteine system carrier was obtained in the present study. The ability of melphalan to inhibit phenylalanine uptake was compared in rats implanted with two experimental CNS tumors: the C-6 glioma (a model of primary brain tumors) and Walker carcinoma (a model of metastatic brain tumors). The melphalan concentration which caused 50% inhibition of blood-brain barrier (BBB) phenylalanine uptake (Ki) was 0.49 +/- 0.18 mM in the Walker tumor, compared with 0.46 +/- 0.19 mM in the contralateral control brain. In the ipsilateral hemisphere (Ki = 0.59 +/- 0.25 mM) and contralateral hemisphere (Ki = 0.45 +/- 0.19 mM), drug entry was also via the neutral amino acid transporter. In C-6 gliomas (Ki = 0.77 +/- 0.20 mM) and contralateral control brain (Ki = 0.84 +/- 0.29 mM), melphalan also inhibited BBB phenylalanine transport. A major finding was that, at melphalan concentrations greater than 1.0 mM, BBB permeability of radiolabeled indium (chelated to EDTA) increased in proportion to melphalan concentration. In the contralateral hemisphere of rats implanted with C-6 gliomas, brain extractions of indium-EDTA measured 3 to 4% in the absence of drug, 5 to 6% at 2.5 mM melphalan, and 9 to 10% at 5 mM melphalan. A similar phenomenon was observed in the nontumoral brain regions of rats implanted with Walker carcinoma cells. In normal (nonimplanted) rats, melphalan's inhibition (Ki = 0.29 mM) of phenylalanine and tryptophan (Ki = 0.20 mM) uptake was confirmed, and brain extraction of sucrose (a nonspecific marker which does not penetrate the intact BBB) was observed to increase in proportion to melphalan concentration. We conclude that melphalan not only enters the brain via the neutral amino acid transporter, but at higher concentrations (greater than 1 mM) may open the blood-brain barrier in a nonspecific manner.
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PMID:Melphalan penetration of the blood-brain barrier via the neutral amino acid transporter in tumor-bearing brain. 172 74

Biopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36 +/- 0.44 vs. 11.42 +/- 2.32 nmol/10(6) cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals.
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PMID:Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells. 174 83

The present study describes a new microscopic perifusion technique for detecting momentary alterations in cell volume and shape. The method has been applied for evaluating early signs of cytotoxicity following chemotherapeutic treatments. The effects of estramustine phosphate (EMP) have been evaluated. EMP is a complex between oestradiol-17 beta and the alkylating agent nor-nitrogen mustard and has recently demonstrated a marked cytotoxicity against malignant glioma cells. The results showed a concentration-dependent increase in cell size and a concomitant decrease in shape factor following EMP-treatment of glioma cells. These changes correlated with cytotoxicity evaluated as cell proliferation and cell membrane alterations shown by 86Rb fluxes and ultrastructural visible membrane damage. The colon cancer line HT-29 displayed no reactions at all following EMP treatment. It is suggested that acute alterations in cell morphology and shape display a strong correlation to the cytotoxicity of EMP encountered by traditional cell culture systems. The findings are discussed with respect to cell membrane disturbances caused by EMP and its potential role as an early test of cytotoxicity.
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PMID:Early morphological detection of estramustine cytotoxicity measured as alteration in cell size and shape by a new technique of microperifusion. 183 1

Estramustine phosphate (EMP), a complex between estradiol-17 beta and nor-nitrogen mustard, commonly used in treatment of prostatic cancer, also exerts marked antiproliferative effects on cultured human malignant glioma cells. The mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically via the mitotic spindle, and related to the intact estramustine complex. EMP cytotoxicity was studied on the malignant glioma cell line U-251 MG. A dose-dependent increase in DNA strand breaks was demonstrated at EMP-concentrations ranging 10-40 mg/l. The uptake of 86Rb, used as a tracer for potassium to study ion transport and membrane permeability, was reduced after incubation with EMP. The mean decline in 86Rb accumulation by U-251 MG cells was 12, 20 and 32% at EMP concentrations 10, 20 and 40 mg/l respectively. Scanning electron microscopy gave further evidence for cell membrane damage. In conclusion, EMP seems to affect malignant glioma cells on several vital functions and the results indicate the the cytotoxic potential may at least partially be related to effects on DNA and cell membrane.
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PMID:Effects of estramustine on DNA and cell membrane in malignant glioma cells. 195 92

We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.
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PMID:Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study. 223 Aug 93

Estramustine, a conjugate of estradiol-17 beta and nor-nitrogen mustard currently used in prostatic cancer, was found to exert a dose-dependent antiproliferative effect on the human malignant glioma cell lines U-251 MG and U-105 MG. At equimolar concentrations the inhibitory effects of the estramustine complex were clearly more pronounced than those of estradiol and nor-nitrogen mustard given alone or in combination. Flow cytometric analyses support the concept that estramustine cytotoxicity is mediated via separate mechanisms. The intact estramustine complex may be important for effects related to microtubule function which add to the cytotoxic potential of the alkylating component.
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PMID:Effects of estramustine and its constituents on human malignant glioma cells. 236 85

Membrane fluidity in membrane phospholipids of brain tumours was investigated and compared with those of white and grey matter. Fifteen brain tumours including 5 gliomas, 5 meningiomas and 5 metastatic cancers were examined. These samples were frozen immediately after extirpation in liquid nitrogen. After extraction of total lipids from the tumour tissues, membrane phospholipids were separated and analysed by thin-layer and gas-liquid chromatography. The fluidity of the phospholipid membrane was studied by electron spin resonance (ESR) spectroscopy, using a stearate spin probe. The fatty acid composition of total phospholipid of brain tumours was characterized by an increase in linoleic and arachidonic acids when compared to the control brain. The percentage of palmitoleic acid was higher in gliomas and metastatic tumours than in meningiomas. Furthermore, in the brain tumour tissues, the decreases of phosphatidylethanolamine and phosphatidylserine and the increase of phosphatidylcholine were observed when compared with grey or white matter with the exception of meningioma. There was some difference in phospholipid membrane fluidity between brain tumour and control brain tissue. The order parameter calculated from ESR spectra became higher in the following order: metastatic brain tumour, less than meningioma, less than grey matter, less than glioma, less than white matter. These results suggest that the phospholipid metabolism in the brain tumour is different from that of the normal brain, and this difference may affect the alteration of membrane physical properties which exhibit in part the character of the transformation.
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PMID:Membrane phospholipid composition and membrane fluidity of human brain tumour: a spin label study. 288 5

The cytotoxic and cytogenetic effects 1-(4-amino-2-methyl 1-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) treatments on five cell lines derived from human malignant glioma were studied. Compared to sensitive cell line SF-126, SF-188 cells were 3- to 6.9 fold more resistant to the cytotoxic effect and 8 to 14 fold more resistant to the induction of sister chromatid exchanges (SCEs). Cytotoxic effects and induction of SCEs were intermediate for SF-268, SF-210 and SF-295 cell lines compared with SF-126 and SF-188. There was a good correlation between susceptibility to the cytotoxic effects and formation of DNA interstrand crosslinks for cells treated with ACNU and BCNU. The effects of cis-diamminedichloroplatinum (II) (cis-Pt) and nitrogen mustard (HN2) in these cells were also studied. Cis-Pt was equally cytotoxic and induced the same number of SCEs and DNA interstrand cross-links in all five cel lines. In contrast to the results obtained by treatment with chloroethylnitrosoureas (CENUs), SF-126 cells treated with HN2 were more resistant to the cytotoxic effects, the induction of SCEs, and the induction of DNA interstrand cross-links than were SF-188 cells. The repair of O6-methylguanine after treatment of these cell lines with (3H) methylnitrosourea were quantitated. SF-126 cells showed no detectable repair of O6-methylguanine, SF-268, SF-210 and SF-295 cells had intermediate levels of repair, and SF-188 had very high level of repair. These results suggest that cellular resistance to CENUs dose not result in cross-resistance to HN2 or cis-Pt, and that one of mechanisms of cellular resistance to CENUs is increased repair of O6-alkylguanine derivatives in DNA, which prevents DNA interstrand cross-links and then reduces both cytotoxic effects and the induction of SCEs in cell resistant to CENUs.
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PMID:[Mechanisms of cellular resistance to chloroethylnitrosourea in cell lines derived from human brain tumors]. 316 99

Sixty consecutive evaluable children with recurrent primary tumors of the central nervous system were treated with a regimen of vincristine, nitrogen mustard, procarbazine, and prednisone over a 12-year period. Tumor types included medulloblastoma (19), brain-stem glioma (16), astrocytoma (13), and a miscellaneous glioma (12). Responses and sustained survivals were achieved. Responses were highly dependent on tumor type. Disease progression was halted in 73% of the children with medulloblastoma, and three have survived in complete remission for more than 10 years from the start of therapy with vincristine, nitrogen mustard, procarbazine, and prednisone. Two of four patients with anaplastic glioma, are long-term survivors. In contrast, less than one third of children with brain-stem gliomas responded. Toxicity consisted mainly of neutropenia, thrombocytopenia, infections, and rarely a procarbazine rash.
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PMID:Salvage chemotherapy for recurrent primary brain tumors in children. 341 10


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