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

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.
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PMID:A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. 156 40

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

'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.
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PMID:Spindle-cell glioblastoma or gliosarcoma? 162 Feb 80

Recently the authors have identified a major component of Rosenthal fibers as alpha B-crystallin, a major lens protein. In the current study the authors investigated the expression of alpha B-crystallin in four cultured glioma cell lines and in 115 human neuroectodermal tumors. alpha B-crystallin was expressed differentially by those glioma cell lines, but not by neuroblastoma cell lines. Northern blot analysis revealed two distinct messages for alpha B-crystallin in C-6, whereas only a single message in U-373MG and G26-24. In human surgical specimens positive immunostaining was frequently observed in the following brain tumors: pilocytic astrocytoma of the juvenile type, anaplastic astrocytoma, glioblastoma multiforme, and subependymal giant cell astrocytoma. The astrocytic elements of mixed oligoastrocytomas, glioblastomas with sarcomatous components, and gangliogliomas were likewise strongly stained. In contrast, little immunoreactivity was observed in ependymal and choroid plexus tumors. Thus, alpha B-crystallin is mainly expressed by astrocytic tumors among neuroectodermal neoplasms, without regard to the presence of Rosenthal fibers.
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PMID:Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors. 165 7

Two human cell lines (GL15 and GL22) derived from glioblastoma multiforme were established and characterized by immunohistochemical and cytogenetic techniques. The expression of glial fibrillary acidic proteins and the karyotype were analyzed at different passages for both cell lines. The course of marker-pattern differed in the two cell lines. The main findings were a cell-density-dependent expression of glial fibrillary acidic protein in the cell line GL15 at all passages and a decreased expression of this protein over time in the cell line GL22. Both cell lines had hyperdiploid karyotypes and exhibited glioma-specific chromosomal abnormalities (gain of chromosome 7 and loss of chromosome 10). In the GL15 cell line no relevant chromosomal changes were produced during culturing, whereas in the GL22 cell line a hypodiploid clone appeared at the 42nd passage. The immunohistochemical and cytogenetic data resulting from this study confirm that the two cell lines established in our laboratory originated from astrocytic tumor cells.
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PMID:Changes in glial fibrillary acidic protein and karyotype during culturing of two cell lines established from human glioblastoma multiforme. 165 72

For 100 operated patients with malignant gliomas of the brain (63 malignant gliomas WHO grade IV--including 50 glioblastoma multiforme- and 37 astrocytomas WHO grade III-IV) the average survival time is 332 days. The survival rates show 6, 12 and 24 months after operation 55%, 32% and 12% of the patients alive. In addition to therapy there are some favourable prognostic factors: Young patients age at the onset of illness, localization in the non-dominant hemisphere, minor preoperative neurological deficit. On the other side unfavourable prognostic factors are: parietal localization (average survival time = 120 days), tumorous infiltration of the brain stem (average survival time = 143 days), preoperative clouding of consciousness (average survival time = 185 days). These factors influence survival time. The most important prognostic factor of therapy is the extent of operation: In case of macroscopical total resection of the tumor the mean survival time amounts to 554 days as compared to 202 days in subtotal tumor resection. The well known positive influence of postoperative radiation therapy is demonstrated by the high mean survival time of 456 days. In case of recurrent operation of the tumor (28 patients), the average survival time amounts to 443 days. In contrast to the literature our own analysis shows no prognostic value of histological variants in case of malignant glioma WHO grade IV. Two patients, whose histological slide preparations were neuropathologically graded a second time independent from the first view (1 anaplastic ependymoma WHO grade III and 1 glioblastoma multiforme WHO grade IV), are still alive more than 8 years after operation without any neurological deficit.
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PMID:[Malignant brain glioma--a catamnestic study of 100 operated patients]. 165 65

Postmortem histopathology of eight gliomas was studied in correlation with magnetic resonance imaging (MRI) and computed tomography (CT) findings. MRI demonstrated the lesions more clearly and widely than CT. Also, T2-weighted images (T2WI) had a greater ability to depict the lesion than T1-weighted images (T1WI). The areas in which neoplastic cells had invaded corresponded to the high intensity areas on T2WI in four cases of glioblastoma multiforme. In the case of a grade II astrocytoma, neoplastic cells were scattered beyond the region corresponding to the high intensity area on T2WI. In the case of a grade III astrocytoma, neoplastic cells did not come up to the line corresponding to the margin of the high intensity area on T2WI. In the remaining two cases, although the high intensity areas on T2WI were depicted as being larger than the areas in which neoplastic cells were seen histopathologically, the high intensity regions corresponding to the outside zones of the tumour-infiltrated area were thought to be a radiation necrosis in one case and a 'periventricular high intensity' in the other. The high cellularity of the glioma was seen mainly as a low intensity area on T1WI and as an isointensity or a slightly high intensity area on T2WI. However, the signal intensities of glioma on MRI, reflecting T1 or T2 values of the tumour tissues, did not correlate with the malignancy of the tumour.
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PMID:Correlation between magnetic resonance imaging and histopathology of intracranial glioma. 167 47

Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high concentrations in the central nervous system, and bleomycin has been reported to have antitumoral activity as well, we studied this combination in a Phase II clinical trial. In addition, we purified calmodulin from normal brain and malignant gliomas to determine its biochemical and pharmacological characteristics. Seventeen patients were entered onto this study and all were evaluable. There were no partial or complete responses. There was one case of fatal pulmonary toxicity in a patient showing an objective tumor response. Otherwise, the treatment was well tolerated. Calmodulin purified from the normal brain and gliomas of patients undergoing resection was identical to each other and to calmodulin prepared from rat cerebrum and glioma. These characteristics included elution from a TSK phenyl high pressure liquid chromatography column, migration on 16% sodium dodecyl sulfate gels, amino acid composition, and inhibition by drugs. Therefore, the failure of this combination therapy was not due to a difference in human glioma calmodulin as compared to previously reported studies with calmodulin from murine sources.
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PMID:The effect of calmodulin inhibitors with bleomycin on the treatment of patients with high grade gliomas. 169 40

A novel tool in diagnostic and experimental pathology, the AgNOR-technique, which consists of visualization of ribosomal gene activity by selective silver staining, was applied to 144 cytological specimens of human tumours of the nervous system. The number of silver-stained nucleolar organizer regions (AgNORs) was correlated with the biological behaviour of the tumours investigated; low AgNOR number were observed in benign neoplasms such as meningiomas and schwannomas and higher AgNOR numbers in glioblastomas and metastases. The mean AgNOR number per cell was 3.15 in astrocytomas, 4.5 in anaplastic astrocytomas and 5.86 in glioblastoma multiforme. Benign and malignant lesions showed different distribution patterns of AgNORs, with few but centrally located AgNORs in benign, and multiple but scattered AgNORs in malignant tumours. AgNOR number per cell and AgNOR area revealed an inverse relationship (correlation coefficient -0.15, linear regression). In addition to the human tumours, two N-nitroso-N-ethyl-urea (NEU) induced tumors in BD-IX rats a mixed glioma (G-XIII) and a malignant schwannoma (N-XII), were investigated. Twelve G-XIII gliomas revealed homogenous AgNOR-counts (standard error of the mean less than 10%), with absolute values between the values obtained for human glioblastomas and metastases. Seven N-XIII subcutaneously transplanted schwannomas revealed higher AgNOR values than human schwannomas, but lower than experimental gliomas. It is concluded that the AgNOR method, as a technique for visualization of ribosomal gene activity, is valuable for assessing proliferative activity and malignancy in both diagnostic and experimental neuropathology.
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PMID:Cell proliferation in intracranial tumours: selective silver staining of nucleolar organizer regions (AgNORs). Application to surgical and experimental neuro-oncology. 171 8

The authors report malignant glioma occurring in two sibling cases. The elder brother presented with right hemiparesis and hemihypesthesia at 14-year-old. Computed tomographic (CT) scanning demonstrated a low-density area in the left frontoparietal lobe. The tumor was partially removed. Histologic diagnosis was glioblastoma multiforme. Radiation therapy was given postoperatively, but he died due to tumor recurrence 15 months after onset. The younger sister was admitted comatose due to intratumoral bleeding at 19-year-old. CT scans showed a high-density area in the right temporal lobe. The tumor was excised subtotally. Histological diagnosis was malignant astrocytoma (grade III). Radiation therapy, chemotherapy (ACNU), and immunotherapy (interferon) were given postoperatively, but she died due to recurrence 34 months after onset.
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PMID:Siblings with malignant glioma--report of two cases. 171 48


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