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)

A total of 474 adult patients with malignant glioma (astrocytoma) grade 3 or 4 were randomised into an MRC study (BR2) comparing 45 Gy (in 20 fractions over 4 weeks) with 60 Gy (in 30 fractions over 6 weeks) of radiotherapy given post-operatively. Using 2:1 randomisation, 318 patients were allocated the 60 Gy course and 156 the 45 Gy course. Adjuvant chemotherapy was not given. The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival. They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group (hazard ratio = 0.75, chi 2 = 7.36, d.f. = 1, P = 0.007). Over 80% of patients reported no morbidity from the radiotherapy, and there was no evidence of increased short-term morbidity in the higher dose group. Late morbidity was not assessed. A prognostic index defined in a previous MRC study was validated in this new cohort. It identifies a group of patients (20% of the total) with a 2 year survival rate of 28% (95% confidence interval 19% to 38%). It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index.
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PMID:A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. 165 87

Although the prognosis of high grade malignant glioma patients is generally poor, it is possible to identify groups of patients with varying prognoses. Basing our results on the first MRC glioma study, multivariate methods were used to identify prognostic factors independently associated with the length of survival. Young age, the presence of fits, especially of long duration, extensive surgical removal of tumour and good clinical performance status were found to be the most important predictors of longer survival. The effect of tumour grade (3 or 4) was not significant, being considerably diluted by an association with extent of neurosurgery. A prognostic index was derived which split the patients into 6 groups of varying prognoses, with 2-year survival rates of between 1 and 32%. The results were verified in patients entered into a subsequent MRC trial. The successful identification of different prognostic groups suggests the use of this index as an aid in making treatment decisions for individual patients, and in interpreting the results of uncontrolled phase II studies.
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PMID:Prognostic factors for high-grade malignant glioma: development of a prognostic index. A Report of the Medical Research Council Brain Tumour Working Party. 221 15

We recently purified human monocyte chemoattractant protein-1 (MCP-1) from culture fluids of either human glioma cell lines or mitogen-stimulated human peripheral blood mononuclear leukocytes. It has now been shown that MCP-1 is the product of the gene JE, which was first recognized by its expression in fibroblasts stimulated with platelet-derived growth factor (PDGF). We therefore studied secretion of MCP-1 by three human fibroblast cell lines. Monocyte chemotactic activity was found in culture fluids of all three lines after growth to confluence in DMEM-10% FCS, and the amounts secreted per cell were comparable for the three lines. The MRC-5 line was chosen for further study. Monocyte chemotactic activity secretion by confluent MRC-5 cultures continued after a switch to serum-free medium and was not inhibited by anti-PDGF antibody, indicating that secretion may not have been caused by autocrine release of PDGF. When concentrated serum-free MRC-5 culture fluid was injected into an HPLC gel filtration column, only one chemotactic activity peak was observed, which was in the same location as glioma-derived MCP-1. The activity was completely absorbed out by an anti-MCP-1 affinity column, which indicates that all the chemotactic activity in MRC-5 culture fluid was accounted for by MCP-1. PDGF caused a marked increase in chemotactic activity over that found in serum-free culture fluid of MRC-5 or 501T cells. Immunoprecipitation by anti-human MCP-1 showed two bands, corresponding to the two forms of MCP-1 previously described (MCP-1 alpha and beta); and the amounts increased in response to PDGF stimulation. Thus, the reported increase in human fibroblast JE mRNA in response to PDGF-containing serum stimulation is reflected in increased secretion of the MCP-1 gene product.
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PMID:Secretion by human fibroblasts of monocyte chemoattractant protein-1, the product of gene JE. 231 97

During the late stages of cell spreading in vitro, the cells extrude a vesicular material into the medium. This phenomenon was observed in human glia and glioma cells as well as in human diploid fibroblasts MRC-5 and WI-38 cells. This extrusion of vesicular material is inhibited by cytochalasin-B and colcemid suggesting the involvement of microfilaments and microtubules and the active nature of this event. It appears that the cells may be excreting damaged surface components by a mechanism similar to patching, capping and endocytosis.
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PMID:Novel vesicular extrusions during cell spreading. 720 9

Radiotherapy, although clearly beneficial in patients with high-grade glioma, is largely palliative, and a protracted course of treatment may not be the most appropriate approach in the context of limited survival. We therefore assessed the feasibility, toxicity and survival results of a short accelerated radiotherapy regimen given twice daily over a period of 3 weeks. A total of 116 patients with high-grade glioma were treated with radiotherapy in a prospective study using an accelerated fractionation regimen. The total dose of 55 Gy was given in 32-36 fractions of 1.72-1.53 Gy, twice daily 5 days a week, with a minimum 6 h interval between fractions. Toxicity was assessed using Karnofsky performance status scale and in the later part of the study with the Barthel index. Survival data were compared with a control group treated with 60 Gy in 30 daily fractions in a previous MRC study, matched for known prognostic factors. The median survival of 116 patients treated with accelerated radiotherapy was 10 months. Survival comparison of accelerated patients with matched controls treated with conventional fractionation demonstrated a hazard ratio of 1.13 (95% confidence interval 0.85-1.51; P = 0.39). Early treatment toxicity was acceptable, with only seven patients developing transient decrease in performance status. The accelerated radiotherapy regimen was logistically feasible and acceptable to patients, carers and staff. Treatment time was reduced without apparent increase in early toxicity and there was no loss of survival benefit. The effectiveness and convenience of a short accelerated regimen makes this a suitable alternative to a 6 week course of radiotherapy in patients with high-grade glioma. However, a full randomised trial comparing conventional and accelerated radiotherapy may be required as proof of equivalence.
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PMID:Improving the acceptability of high-dose radiotherapy by reducing the duration of treatment: accelerated radiotherapy in high-grade glioma. 777 33

Thirty-two patients prospectively identified as having poor prognosis high grade glioma, with a MRC prognostic score >25, were treated with a short palliative course of radiotherapy. A total dose of 36 Gy in 12 fractions was given to the tumour, including oedema and a 2 cm margin, using parallel pair fields prescribed to the midplane with MV photons. Twenty-eight patients completed treatment as planned, while four failed to complete treatment because of clinical deterioration or death. The median survival for the whole group was 16 weeks, with seven patients surviving for more than 6 months. Approximately two-thirds of the surviving patients remained at home after the completion of treatment. A matched case-control comparison with data from patients in previous MRC studies who had received a 6-week course of treatment shows that, for this group of patients, survival is similar (hazard ratio 1.0; 95% confidence interval (CI) 0.57-1.74). The 95% CI for the difference in median survival time excludes a reduction of more than 7 weeks with the 36 Gy course. This shortened radiotherapy regimen may therefore be satisfactory for most poor prognosis patients. However, patients with performance status 3 gained little benefit from treatment, and it is suggested that this group should have a trial period of assessment at home prior to a decision on treatment.
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PMID:A short fractionation radiotherapy treatment for poor prognosis patients with high grade glioma. 903 9

To determine whether patients with malignant glioma (glioblastoma and anaplastic astrocytoma) had longer survival times, and lower morbidity and mortality if operated on by a surgical neuro-oncologist rather than a general neurosurgeon the outcomes of 236 patients managed within a university surgical neurology department were analysed. Although both surgical morbidity (8.9 versus 11.8%) and mortality (3.6 versus 8.8%) were lower following surgery by the specialist neuro-oncologist neither difference was statistically significant. Crude outcome data suggested patients operated upon by a specialist surgical neuro-oncologist survived longer (p = 0.067). However, after adjustment for case mix (type of tumour, year of treatment, MRC prognostic index) using multiple logistic regression and a hazards model, there was no difference in outcome (p = 0.46, HR 0.884, 95% CI 0.639-1.22). This retrospective study (i) suggests that other outcome measures are required to validate specialist surgical neuro-oncologist treatment of patients with malignant glioma; and (ii) confirms the importance of adjustment for case mix when comparing non-randomized treatment outcomes.
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PMID:Treatment by a specialist surgical neuro-oncologist does not provide any survival advantage for patients with a malignant glioma. 1101 44

Malignant glioma (glioblastoma and anaplastic astrocytoma) remain incurable despite extensive resection, radiotherapy, chemotherapy and experimental therapies. Few studies have addressed either the costs of various treatments for malignant glioma or their cost effectiveness. The aims of this study were to identify direct hospital costs of treating patients with biopsy proven malignant glioma. The study was carried out within the setting of a dedicated neuro-oncology clinic at a university teaching hospital and included 236 patients treated between 1989 and 1995. The study used the unit costing of each item of treatment according to NHS National Costing Project. The cost of treatment was broken down into its various components: bed days, investigations, surgery, radiotherapy, chemotherapy and neuro-oncology out-patient follow-ups. The mean costs for each of the items based on 1995 figures for the 157 patients having surgery followed by radiotherapy were neuroradiological investigations (442 Pounds), neurosurgical bed days (2407 Pounds), neurosurgery (2068 Pounds), neuropathology (434 Pounds), radiotherapy (8832 Pounds), out-patients (1078 Pounds) and chemotherapy (440 Pounds). Total treatment costs per patient ranged from 1978 Pounds to 26,980 Pounds. Median costs of care decreased sequentially with worsening MRC Brain Tumour prognostic group. Management of patients with the best prognosis (MRC index score of 1-10) cost a median of 16,550 Pounds (range 4572-26,090 Pounds) whilst the median management cost of those in the worst prognostic group (MRC score 34-38) was 6514 Pounds (range 1978-18,360 Pounds). The median cost of each week of survival in the patients with the best outcome (MRC score 1-10) was < 150 Pounds compared to 232 Pounds for each week of survival for patients in the worst prognostic group (MRC score 34-38). This study made no attempt to collect costs of supportive or community-based care. Prospective studies are required to collect such data, as well as assessing the costs effectiveness of alternative treatment strategies.
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PMID:The costs of managing patients with malignant glioma at a neuro-oncology clinic. 1101 62

An E1B-defective adenovirus, named r2/Ad carrying the neo expression cassette, was constructed by homologous recombination. The construction, selection (using neomycin as a selective marker), and propagation of the recombinant virus was performed in human embryonic kidney 293 cells (HEK 293). An in vitro study demonstrated that this recombinant virus has the ability to replicate in and lyse some p53-deficient human tumor cells such as human glioma tumor cells (U251) and human bladder cells (EJ), but not in some cells with functional p53, such as human adenocarcinoma cells (A549) and human fibroblast cells (MRC-5). Also, based on the cytopathic effect (CPE), it was demonstrated, under identical conditions, that the U251 cells were more sensitive to r2/Ad replication than the EJ cells. In this paper, we report that r2/Ad could be very useful in studying the in vitro selective replication of E1B-defective adenovirus and has great potential in cancer gene therapy.
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PMID:Conditional replication of a recombinant adenovirus studied using neomycin as a selective marker. 1278 82

The results of a recently concluded phase III study have shown that Gliadel therapy (biodegradable polymer impregnated with 3.85% BCNU placed into the surgical cavity) significantly prolongs survival and time to relapse in patients having initial resective surgery for malignant glioma followed by radiotherapy. The indications and exclusion criteria for patients in this study were well defined. To determine the relative frequencies of Gliadel 'eligible' and 'ineligible' patients, and differences in prognostic variables between these two cohorts, we conducted a review of all Edinburgh patients with an initial diagnosis of malignant glioma managed throughout the period of patient accrual into the phase III Gliadel study (Edinburgh was one of 38 contributing centres). Independent predictors of outcome were taken from the MRC prognostic index. Analysis was done on an intention to treat basis. Only 25% of patients (14/56) with malignant glioma managed over this period were eligible for the Gliadel study and all were recruited. The patients in the study group were younger (median 51 v. 59 years, p = 0.085); in better clinical grade (median Karnofsky score 85 v. 80, p = 0.038); more likely to have resective surgery (86% v. 38%, p = 0.0001); more likely to have postoperative radiotherapy (93% v. 55%, p = 0.0001) and more likely to survive longer, even though one half of the Gliadel cohort received placebo, (66 v. 19 weeks, p = 0.06) than those not eligible. If the future use of Gliadel is limited to the eligibility criteria used in the phase III trial about 20% (95% confidence intervals 13-34%) of patients with newly diagnosed malignant glioma will receive this therapy.
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PMID:Gliadel therapy given for first resection of malignant glioma: a single centre study of the potential use of Gliadel. 1457 2


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