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)

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma fluid and proteins through the interendothelial spaces. Tumor-associated cysts (TACs) are observed more commonly with benign gliomas that are not associated with PVBE. This study investigates the hypothesis that these morphologically distinct epiphenomena of microvascular extravasation are linked by a common pathophysiological mechanism involving vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignant effusions, and brain edema. Furthermore, VEG/PF has been isolated from cultured glioma cells, and both VEG/PF protein and messenger RNA transcripts are expressed in brain tumor tissue. To further elucidate the relationship of VEG/PF to PVBE and TACs, the authors examined 34 pathological specimens for VEG/PF expression. Nineteen primary low-grade tumors, 11 primary high-grade tumors, and four gliosis controls were immunostained with a polyclonal anti-VEG/PF immunoglobulin G antibody. Magnetic resonance imaging was used to quantitate PVBE and to determine the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, whereas 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs. Notably, eight of nine benign TACs that were not associated with PVBE immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrence of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF's pivotal role as the common pathophysiological link between these processes.
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PMID:Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts. 767 19

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-gamma. Central nervous system toxicity induced blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-gamma gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.
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PMID:RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. 772 57

Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.
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PMID:[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas]. 775 90

Chemotherapy results in glioma are poor. In addition to chemotherapy most patients are treated with dexamethasone (Dex) to reduce brain edema. Therefore we examined the influence of Dex on the sensitivity of C6 glioma cells to methotrexate (MTX) using MTT-tests. The LD50 of MTX was 3*10(-8)M, 10(-7)M, 4*10(-6)M and 4*10(-4)M after 72, 24, 6 and 1 hour treatment, respectively. After incubations with combinations of Dex and MTX, twice as many cells survived high MTX concentrations. This protection could be overcome by addition of 10 to 100 fold more MTX. It was not species-specific since the effect was also found in human TE671 cells.
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PMID:Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. 797 89

CT scans of 12 cases of intracranial trigeminal neuroma were presented. Three of the neuromas were located in petrous apex-middle cranial fossa, two in posterior cranial fossa, and 7 in both the middle and posterior cranial fossae. The tumors appeared hypo- and isodense on the plain CT scan. After contrast infusion, all tumors were well circumscribed with marked enhancement, which was homogeneous, inhomogeneous or circular. None of the trigeminal neuroma had surrounding brain edema. Of 12 cases, 10 showed change of cranial bones, which included dilatation of Meckle's cave and destructions of petrous apex, clivus and the bottom of middle cranial fossa. The tumor in one case extended to paranasopharyngeal space from the bottom of middle cranial fossa, Various features of trigeminal neuroma on CT were reviewed. Also presented were the author's experiences in differentiating intracranial trigeminal neuroma from meningiom, from pituitary adenoma spreading to parasella and glioma adjacent to cranial bottom in middle cranial fossa, and from acoustic neuroma, meningioma, cholesteatoma in cerebellopontine angle.
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PMID:[Computed tomography in the diagnosis of intracranial trigeminal neuroma]. 815 Apr 46

Lactacidosis occurring in cerebral ischemia or trauma is a major mechanism of cytotoxic brain edema and brain damage. Respective effects of lactacidosis were currently analyzed in vitro by employment of the murine neuronal cell line, Neuro-2A, in order to obtain a better understanding of specific mechanisms underlying cell swelling and cell death in comparison with glial cells. The cells were suspended in a physiological medium in the presence of lactic acid at increasing concentrations. Levels of acidosis reaching from pH 6.8-5.6 were obtained while other parameters, such as osmolarity and electrolyte concentrations, were maintained in the physiological range. Assessment of cell swelling and cell viability using exclusion of propidium iodide was made by flow cytometry with employment of an advanced Coulter system. Swelling of Neuro-2A cells commenced once the pH in the medium was lowered to 6.8 or below. From this level downward, cell swelling was a function of the severity of acidosis and duration of exposure. For example, lactacidosis of pH 6.8 or 5.6 lasting 90 min led to an increase in cell volume to 109.5% or 159.6% of normal, respectively. Viability of the neuronal cells was 85% under control conditions. It remained in this range down to pH 6.2. At pH 5.6, however, cell viability decreased in a time-dependent fashion. At 90 min, only 48.9% of the neuronal cells were viable at pH 5.6. The swelling response and impairment of viability of the neuronal cells was compared with that of C6 glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Swelling and death of neuronal cells by lactic acid. 824 14

Anti-normal brain antibodies were studied in glioma cyst fluids. Cyst fluids were obtained by stereotaxic puncture from 34 patients with cystic gliomas. Immunoglobulins were analyzed by immunohistochemistry, immuno-Western blotting, concentration measures, and isoelectrofocalization. 80% of cyst fluids stained astrocytes and/or microvessels in non-tumoral white matter. In white matter extracts, cyst fluids recognized five immunoreactive bands having apparent molecular masses of 50-75 kDa. Although cyst proteins could be of systemic origin, isoelectrofocalization analysis suggests an additional local immune response. These antibody activities could be involved in certain peritumoral events such as brain edema.
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PMID:Characterization of normal brain-reactive antibodies in glioma cyst fluids. 837 49

The feline infusion model of brain edema was used to evaluate the pathophysiological effects of 0.6 ml infusions of autologous serum protein (66%), human serum protein (66%), human glioma cyst fluid and a tissue culture medium (TCM) on the structure and function of the forebrain white matter. These infusions increased local white matter water content by between 10.8 and 12.5 ml/100 g brain and were associated with moderate increases in ICP and CSF outflow resistance and a significant decrease in lumped craniospinal compliance. Cortical somatosensory potentials, motor evoked potentials, EEG and local cerebral blood flow (rCBF) at normocapnia were generally unchanged by the various infusions. All infusates except the 66% autologous serum protein infusion impaired rCBF CO2 reactivity. Histologically all infusates caused marked extracellular edema. The autologous serum protein infusion caused no additional histological changes whereas the glioma cyst infusates caused profound endothelial and astrocytic swelling, focal endothelial necrosis, basement membrane disruption, perivascular microglial reaction and pavementation and perivascular migration of polymorphonuclear leukocytes. Similar but less marked changes were seen after infusion of human serum protein whilst the TCM produced only minimal changes. The intensity and extent of Evans Blue extravasation into the forebrain white matter was greatest with glioma cyst infusates and with all infusions reflected the extent to microvascular changes. These studies show that products derived from gliomas cause additional damage to the blood-brain-barrier than that caused by non-autologous serum proteins. These results add further support for the existence of glioma derived permeability factors (GDPF), but suggest neither serum proteins nor glioma derived compounds in the white matter interstitium significantly influence local electrophysiological function. Some limitations of the infusion edema model when using non-autologous infusions and difficulties quantitating brain dysfunction are emphasised.
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PMID:Neuropathological and neurophysiological effects of interstitial white matter autologous and non-autologous protein containing solutions: further evidence for a glioma derived permeability factor. 846 May 70

In response to hyponatremia, brain cells extrude electrolytes and organic osmolytes, thereby minimizing brain edema. We demonstrate that rat brain is depleted of the antioxidant glutathione in response to hyponatremia and that osmotically-induced loss of glutathione makes neuronal cells more susceptible to oxidative injury. Total glutathione content of brain tissue decreased from 6.80 +/- 0.14 mumol/g dry wt in normonatremic controls to 5.00 +/- 0.31 mumol/g dry wt after 72 hours of hyponatremia. Following slow correction of hyponatremia, brain glutathione content returned to control values (6.77 +/- 0.34 mumol/g dry wt). Brain content of taurine, a beta-amino acid with antioxidant properties, similarly decreased in hyponatremia (29.6 +/- 0.9 to 17.1 +/- 1.2 mumol/g dry wt), then increased with slow correction (24.8 +/- 1.3 mumol/g dry wt). Although taurine served as an osmolyte in rat heart, liver and brain, osmotically-induced changes in glutathione content were found only in brain. We also studied osmotically-induced changes in glutathione and taurine content in C6 glioma and SK-N-SH neuroblastoma cells. In both cell lines, adaptive decreases in glutathione and taurine content were found in response to lowering medium sodium concentration from 140 mM to 100 mM. The cell content of these solutes increased after returning to media containing 140 mM sodium. Following exposure of both cell lines to hypoosmolar media, there was no increase in media content of glutathione. This suggest that osmotic depletion of glutathione is not due to cellular efflux of intact glutathione. We questioned if osmotic depletion of glutathione and taurine renders brain cells more susceptible to oxidative stress. Incubation of SK-N-SH cells with 1.0 mM H2O2 for four hours induced greater cytolytic injury in cells adapted to hypoosmolar media than in isoosmolar controls. Hypoosmolar C6 glioma cells were not significantly more sensitive to cytolytic injury from H2O2 than were cells grown in isosmolar media. We conclude that hypoosmolality induces glutathione depletion in rat brain in vivo and in cultured brain cells in vitro. Osmotic depletion of this antioxidant renders SK-N-SH neuronal cells more susceptible to oxidative injury.
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PMID:Depletion of glutathione from brain cells in hyponatremia. 882 31

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.
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PMID:Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. 901 Apr 29


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