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)

The formation of ATP at the cell surface of intact glia and glioma cells in culture has been established. The ATP-forming capacity at the surface of the malignant cells was several times greater than that of the normal glia cells. The ATP-forming capacity was about the same on reincubation one hour after the first incubation. The cells were kept in Eagle's medium in the meantime. ADP, NAD+ and 3-phosphoglyceraldehyde could all be available from a postulated intramembranous metabolic pool and take part in biochemical reactions at the cell surface, provided that albumin was not present in the incubation medium. An incubation medium which was complete except for 3-phosphoglyceraldehyde was only slightly less effective as regards ATP formation at the surface of both glia and glioma cells, compared with the complete incubation medium. The presence of nucleoside diphosphate kinase at the glioma cell surface was confirmed. When intact cells were incubated with only the phosphoryl group donor (ATP) of the reaction but with the acceptor nucleoside diphosphates (CDP, GDP, UDP) ommitted, only CTP and GTP were formed. No UTP was found. Thes latter results indicate that both CDP and GDP are available from the postulated intramembranous metabolic pool, while UDP is not.
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PMID:On the availability of certain metabolites at the outer surface of normal and malignant cells for the membranous de novo synthesis of ATP and other nucleotides. 114 98

Exposure of C62B rat glioma cells to fresh medium containing fetal bovine serum induced a sensitization of the subsequent ability of isoproterenol and forskolin to stimulate cyclic AMP accumulation, compared to cells exposed to fresh medium without serum. Isoproterenol stimulation was typically increased by 2- to 4-fold and forskolin stimulation by 3- to 5-fold. Sensitization occurred rapidly, was rapidly reversible and appeared to result from an increase in maximal stimulation. A commercial preparation of albumin, purified chromatographically so as to retain bound lipids and other factors, was able to mimic the effect of serum. In contrast to the effects of serum, exposure of cells to phorbol 12-myristate, 13-acetate induced little or no change in forskolin stimulation but a marked desensitization of isoproterenol stimulation that was due primarily to a decrease in potency. Neither the protein kinase C inhibitor staurosporine or overnight exposure to phorbol 12-myristate, 13-acetate to down-regulate protein kinase C prevented serum-induced sensitization. Pertussis toxin almost completely blocked serum-induced sensitization, suggesting involvement of a pertussis toxin-sensitive guanine nucleotide-binding protein in mediating the effects of serum. Sensitization was poorly retained in membrane adenylate cyclase assays. Studies with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, direct assays of cyclic AMP degradation by intact cells and assays of phosphodiesterase activity in cell lysates all indicated that degradation of cyclic AMP was decreased in serum-pretreated cells. Thus, both increased cyclic AMP synthesis and decreased cyclic AMP degradation may contribute to sensitization in these cells.
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PMID:Serum-induced sensitization of cyclic AMP accumulation in C62B rat glioma cells. 138 77

Cat brain tumors were produced by stereotactical xenotransplantation of rat glioma clone F98 into the internal capsule of the left hemisphere. Two to four weeks after implantation, the tissue content of water, sodium, potassium, calcium, magnesium, serum albumin, serum immunoglobulin, and hemoglobin was measured in samples taken from the tumor, from peritumoral white and gray matter, and from homotopic regions of the opposite hemisphere. Extravasated serum protein content was determined by subtracting intravascular from total tissue protein, using the hemoglobin content as a marker of blood volume. The development of brain tumors was accompanied by severe vasogenic brain edema, which was clearly confined to the ipsilateral white matter. The increase of water was paralleled by an increase of sodium, calcium, and serum proteins. Potassium and magnesium content remained constant. The calculated sodium and calcium content of edema fluid approximated that of blood serum. The content of blood proteins was about 50% lower, but the ratio of albumin/immunoglobulin was the same as in blood. It is concluded that peritumoral edema is a combination of plasma ultrafiltrate and whole plasma extravasation with different modes of formation. Implications for the pathophysiology and therapy of peritumoral edema are discussed.
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PMID:Quantitative analysis of experimental peritumoral edema in cats. 239 38

The nitrosourea-induced rat glioma clone RG2 was tested for its capacity to form multicellular tumor spheroids (MTS's). Resulting spheroids were investigated by light and electron microscopy with regard to their proliferation patterns and morphological features. Using microsurgical techniques and avoiding mechanical injury of the brain tissue, the authors successfully transplanted avascular MTS's under the dura of the cerebellum, above the vermis, in 43 adult syngeneic Fischer CD rats. The rate of tumor establishment was 93%, and the tumors that were solid and spheroid in shape grew exponentially. Neovascularization could be observed at 3 days after implantation, and invasion of the cerebellum occurred by 3 to 5 days. Neurological deterioration, including ataxia, impairment of walking, and apathy, could be observed after 10 days. The mean survival time was approximately 16 days. The subdural cerebellar tumors were studied by histological techniques, and two morphometric methods were applied to check the growth of implanted spheroids. All tumors were deeply stained with the Evans blue dye-albumin complex, demonstrating disturbance of the blood-brain barrier. The easy accessibility of the cerebellar vermis in rats, the microsurgical implantation of glioma spheroids under the dura avoiding nerve tissue disruption, and the high percentage of reproducible establishment of tumors favor this experimental brain-tumor model. This should be an excellent model for study of experimental therapies.
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PMID:RG2 glioma growth in rat cerebellum after subdural implantation. 242 62

The leakage of different serum proteins, including immunoglobulins, into human cerebral gliomas was studied by use of the unlabeled peroxidase-antiperoxidase (PAP) method on cryostat and paraffin sections. Our series of 50 tumour biopsies included 21 isomorphic astrocytomas and oligodendrogliomas (grade II), 19 anaplastic astrocytomas and oligodendrogliomas (grade III), and 10 glioblastomas (grade IV). The immunohistochemical staining of the serum proteins was similar on paraffin and cryostat sections and graded with respect to occurrence, distribution, and intensity. Serum proteins of a small hydrodynamic radius with a low serum concentration (prealbumin) or with a high serum concentration (albumin) were diffusely present in the interstitial spaces of all glioma types. Serum proteins with a medium molecular size and variable serum concentrations, i.e. IgG, IgA, and ceruloplasmin, were detected preferentially in anaplastic gliomas and in glioblastomas (grade III and IV) displaying comparable distribution patterns but different intensities. Alpha-2-macroglobulin a serum protein with a large hydrodynamic radius was also demonstrated in grade III and IV gliomas, whereas IgM and beta-lipoprotein being the largest serum proteins tested were almost restricted to blood vessels and tumour necroses. In addition, most serum proteins occurred with high intensities in those areas of isomorphic grade II gliomas that showed a macro- or microcystic or mucinous tissue degeneration. The varying immunohistochemical staining results for the serum proteins studied indicate that the blood-brain barrier within isomorphic and anaplastic gliomas is not completely disturbed. It appears that the vascular permeability is preferentially increased for small-sized serum proteins, whereas the leakage of larger serum proteins into the glioma interstitium seems to depend on the tumour type and on increasing malignancy.
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PMID:Immunohistochemical demonstration of serum proteins in human cerebral gliomas. 244 Feb 23

Routinely processed biopsy material, including 56 gliomas of varying malignancy, 10 meningiomas, 10 brain metastases and 12 brain abscesses, was examined for the presence and distribution of IgG, IgA, IgM, IgD and albumin using the unlabeled antibody peroxidase-antiperoxidase technique. In all specimens the deposition of stained immunoglobulins (Ig) was strictly associated with that of albumin even on cell surfaces. Thus there was no evidence for specific membrane binding or cytotoxicity. The interstitial proteins demonstrated are most likely derived from the plasma by blood-brain barrier breakdown which occurs in nearly all tumors and abscesses. Obvious intracellular staining for Ig and albumin was seen in glioma cells and astrocytes only. This is suggested to be due to active protein uptake as a specific feature of astrocyte differentiation which decreases with malignancy and is lost in glioblastomas. Evidence for local Ig production was found in 8 out of 10 metastases with striking IgG- and IgA-positive plasma cells within lymphocytic infiltrations and in one meningioma showing conspicuous plasma cells components. No glioma contained Ig-bearing plasma cells, though round cell infiltrations were present in 64% of the unselected cases. The significance of these findings regarding the immunological situation in brain tumors is briefly discussed.
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PMID:Immunohistochemical demonstration of immunoglobulins and albumin in human brain tumors. 254 57

Tumours were produced in the adult cat brain by injection of the rapidly growing anaplastic rat glioma clone F98 in order to study their neuropathology, pathophysiology, regional biochemistry and magnetic reasonance imaging. We report here the neuropathological behaviour of cell suspensions in the basal ganglia and the left cerebral hemisphere one, two, three, four and six weeks after stereotactic implantation with respect to tumour growth, immunological tumour regression and alterations of the blood-brain barrier with associated vasogenic brain oedema. Injected cell suspensions produce consistently growing tumours during the first, second and third weeks. Tumour sizes varied according to the survival time and were only slightly dependent on the inoculated cell number, i.e., 3 and 6 x 10(6) tumour cells, respectively. Immunohistochemistry with respect to proteins of the cytoskeleton and other cell markers showed positive tumour cell immunoreactions for vimentin and S 100, but not for GFAP, Leu-7, Leu-M1 and MBP. While leucocyte infiltration is apparent after only one week, major tumour regression phenomena develop after three weeks in conjunction with severe lymphocytic reactions of the host, resulting in complete tumour rejection with scar gliosis after four and six weeks, respectively. This transplantation glioma model is accompanied by vasogenic brain oedema both within the tumour area and in the homolateral hemisphere. Immunohistochemistry of serum proteins, i.e. total serum protein, albumin and IgG reveals impairment of the blood-brain barrier after one week, reaching its maximum after two and three weeks. The oedematous changes decrease dramatically after four and six weeks, when most of the serum proteins are reabsorbed by cellular activities in the tumour scar. The vasogenic brain oedema in this xenogeneic glioma transplantation model may be enhanced by the immunological reactions in the brain.
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PMID:Experimental transplantation gliomas in the adult cat brain. 1. Experimental model and neuropathology. 274 39

In adult cats experimental brain tumours were produced by stereotactical xenotransplantation of the rat glioma clone F 98 into the internal capsule of the left hemisphere. Two to four weeks after transplantation tumours and peritumoural oedema were investigated by magnetic resonance imaging (MRI), electrophysiological recording and analysis of tissue content of water, electrolytes and extravasated serum proteins. Spherical tumours with a diameter of about 10 mm developed at the injection site and were surrounded by massive white matter oedema. Water content in peritumoural white matter increased from 2.63 +/- 0.17 to 3.65 +/- 0.19 ml/g d.w. (means +/- SD), sodium from 187 +/- 11 to 351 +/- 55 mueq/g d.w. and calcium from 7.4 +/- 1.1 to 13.3 +/- 1.3 +/- 1.3 mueq/g d.w. Potassium and magnesium did not change. Oedema development was associated with the extravasation of 18.0 +/- 16.8 mg/g d.w. albumin and 15.8 +/- 12.2 mg/g d.w. immunoglobulin. The calculated electrolyte content of oedema fluid approximated that of plasma but the serum protein content was about 40% lower. The ratio of low (albumin) to high (immunoglobulin) molecular weight proteins was the same in blood and oedema fluid. It is, therefore, concluded that peritumoural oedema consist of two components, a whole plasma extravasate and a protein-free ultrafiltrate. Peritumoural oedema could be clearly detected by MRI but differentiation between tumour and oedema was only possible after contrast enhancement with gadolinium-DTPA. The ratios of the intensities of the MR signal correlated linearly with the water content within white matter. MRI, in consequence, allows quantification of oedema provided a reference area with normal water content is present.
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PMID:Experimental transplantation gliomas in the adult cat brain. 2. Pathophysiology and magnetic resonance imaging. 274 48

In human and animal brain microvessels beta-adrenergic receptors have been identified which are suggested to subserve the regulation of capillary function in both physiological and pathological conditions. Brain tumors are supplied by vessels that differ from those supplying normal cerebral tissue in various structural and functional parameters. In order to study the characteristics of brain tumor microcirculation, we have investigated the presence of beta-adrenergic receptors in capillaries isolated from different types of neoplasms using the specific radioligand 125I-iodocyanopindolol (ICYP). The microvessels were isolated and prepared by albumin flotation and glass bead filtration from normal and pathological tissues. No ICYP-specific binding was detected in the microvessels of tumors of glial origin, while capillaries obtained from meningiomas and neurinomas showed, like the normal brain, a specific binding of the radioligand. The data indicate that the regulation of capillary function in glial tumors differs from that of normal cerebral tissue and extraparenchymal tumors, thus indicating an impaired control of the vascular permeability.
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PMID:Glial brain tumors lack microvascular adrenergic receptors. 283 43

To test the results of blood-brain barrier (BBB) disruption in the treatment of brain tumor, RG-C6 glioma was transplanted into the brains of rats. Intracarotid infusions of normal saline and hyperosmotic mannitol were then made, followed by intravenous injection of Evans blue dye plus albumin (EB, MW 68,000), horseradish peroxidase (HRP, MW 40,000), and 5-fluorouracil (5-FU, MW 130). Uptake of the drug and the consistency of drug levels in the normal brain and tumor varied widely among these three agents. Both EB and HRP penetrated the brain tumors but did not stain the normal brain tissues. After BBB opening, penetration of EB and HRP into the normal brain was drastically increased; however, the uptake of EB and HRP in the tumor was not increased. The concentration of 5-FU in the tumor was higher than that in the serum and, although it increased 1.5-fold after BBB opening, the increase was not statistically significant. Conversely, there was a progressive increase in concentrations of 5-FU in the tumor-free brain regions (p less than 0.05). These observations suggest that an intracarotid infusion of hyperosmotic mannitol may increase neurotoxicity because it allows greater delivery of anticancer drugs into the normal brain tissue than into the tumor tissues.
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PMID:Hyperosmotic blood-brain barrier disruption in brains of rats with an intracerebrally transplanted RG-C6 tumor. 310 Jul 31


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