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)

Bradykinin, infused in low doses (10 micrograms/kg/min) through the carotid artery ipsilateral to RG2 glioma in rats, significantly increased the permeability in tumor capillaries to six different tracers of varying molecular weights compared with intracarotid infusion of saline alone. Permeability in normal brain capillaries was not significantly increased by intracarotid bradykinin infusion. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horseradish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant K(i) (microliter/g/min). The permeabilities (K(i)) of tumors in the bradykinin group versus the control saline group for AIB, sucrose, inulin, and dextran were 25.91 +/- 6.78 vs. 13.95 +/- 4.29 (p < 0.01), 17.90 +/- 2.65 vs. 10.75 +/- 4.55 (p < 0.01), 23.92 +/- 6.99 vs. 6.20 +/- 4.37 (p < 0.01), and 17.84 +/- 1.00 vs. 1.47 +/- 1.24 (p < 0.001), respectively (mean +/- SD). Permeability of RG2 gliomas to high molecular weight dextran (70,000) was 12-fold higher in the bradykinin group than in the saline infusion group. Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. The permeability of normal brain capillaries was unaffected by intracarotid bradykinin infusion. The increased permeability was reversed 20 min after stopping the intracarotid infusion. Electron microscopic and gross qualitative analysis was performed using HRP and EB. Intracarotid bradykinin infusion increased HRP and EB within tumor tissue but not normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bradykinin selectively opens blood-tumor barrier in experimental brain tumors. 806 81

It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.
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PMID:Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen. 842 12

The cell surface sugar determinants (CSSD) were examined in C6 glioma cells in cultures at different conditions of growth by peroxidase conjugates of the lectins: peanut agglutinin (PNA), Ricinus communis agglutinin (RCA), Helix pomatia agglutinin (HPA), wheat germ agglutinin (WGA), lentil agglutinin (LCA), laburnum bork agglutinin (LABA), and lotus agglutinin (TPA). It was found that the cells bound more intensively WGA, LCA, and RCA compared to PNA, HPA; the weakest staining was provided by LABA and TPA. Binding intensity for PNA significantly increased after pretreatment of the cells with neuraminidase. This indicates that a part of the beta-D-galactose residues on the surface membrane of C6 glioma cells is covered by sialic acid. The process of sialization was increased during the culturing of C6 glioma cells. Addition of cis-DDP or dBcAMP to cultures growing in medium with 10% of CS increased the number of Gal residues which are not covered by sialic acid. The expression of beta-D-galactose (Gal), N-acetyl-D-galactosamine (NAcDGal), and fucose (Fuc) residues appeared to be most responsive to changes in growth conditions and degree of cell differentiation. The expressions of N-acetyl-D-glucosamine (NAcDGlc) and mannose (Man) residues were high and seems did not depend on changing of the conditions of culturing. In C6 glioma cells cultures in which the rate of cell division, formation of the cell processes, and adhesiveness of the cells to the substratum were reduced by growing cells in MEM+, expression of beta-Gal, NAcDGal, and Fuc was considerably reduced. The decrease of expression of beta-Gal, NAcDGal, and Fuc on the surface of cell membrane was more pronounced in MEM+ with 1% of CS than in MEM+ with 10% of CS. In DbcAMP and cis-DDP treated cultures, grown in medium with 1% serum, in which cell division was inhibited without obvious changes in cell adhesiveness to the substratum, binding of PNA and HPA was increased due to higher expression of beta-Gal and NAcDGal. From these observations it was concluded that the pattern of expression of sugar residues on the cell surface varies according to the biological state of the cells and are easily affected by tissue culture conditions.
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PMID:Growth related changes in sugar determinants on the surface of C6 glioma cells in culture: a cytochemical lectin-binding study. 856 19

There has been increasing interest in the possible use of boronophenylalanine as a capture agent for boron neutron capture therapy of brain tumors. The purpose of the present study was to determine whether the uptake of boronophenylalanine in F98 glioma-bearing rats could be enhanced by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D). Glioma cells (10(5)) were stereotactically implanted into the right cerebral hemisphere of Fischer rats, and 12 days later, BBB-D was performed by infusing 25% mannitol (1.373 mOsmol/ml) into the right carotid artery and then immediately injecting L-boronophenylalanine (300 mg/kg of body weight) intracarotidly. The animals were killed 0.5, 1, 2.5, and 4 hours later, and the brains were removed for boron determination by direct current plasma atomic emission spectroscopy. BBB-D was assessed by the intravenous injection of Evans blue or horseradish peroxidase, and the barrier-disrupted hemispheres and tumors showed intense staining with each. The mean tumor boron concentration after i.c. injection and BBB-D was 34.8 +/- 6.8 micrograms/g at 2.5 hours compared with 20.3 +/- 6.2 micrograms/g after i.c. injection without BBB-D and 10.7 +/- 0.7 micrograms/g after intravenous injection. No significant differences in boron concentration in muscle, skin, and eye were observed among the different groups. Boron concentrations in the ipsilateral, disrupted hemisphere increased transiently but rapidly returned to background levels by 2.5 hours after BBB-D. The tumor:brain and tumor:blood ratios were 5.2 and 5.6, respectively, compared to 3.2 and 2.1 for intravenous injection groups at 2.5 hours. The present study is the first to show that BBB-D combined with i.c. injection can enhance the tumor uptake of boron compounds for boron neutron capture therapy.
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PMID:Enhanced delivery of boronophenylalanine for neutron capture therapy by means of intracarotid injection and blood-brain barrier disruption. 872 25

Cell culture models have been widely used for screening of neurotoxicants and represent a viable alternative to direct in vivo experiments. We have developed a dynamic in vitro blood-brain barrier model designed to allow for extensive toxicological, pharmacological and physiological testing. Induction of blood-brain barrier properties in a tri-dimensional hollow fiber culturing apparatus was investigated by co-culturing a bovine aortic endothelial cell line (or rat brain endothelial cells) with rat brain astrocytes (or C6 rat glioma cells) under pulsatile flow conditions to mimic intraluminal blood flow. Cell growth was monitored over time by measuring glucose consumption and lactate production: these experiments confirmed that the hollow fiber cell culturing systems can maintain viable cells in culture for extended (> 1 month) periods of time. Cells were visually inspected after culturing and dissociation from the hollow fiber cartridge and identified as endothelial (by fluorescent Dil-Ac-LDL uptake) or glial (by GFAP immunoreactivity). Blood-brain barrier properties were tested by intraluminal injection of horse-radish peroxidase (HRP, mol. weight 44,000), glucose (m.w. 180) or potassium. Either procedure demonstrated that aortic cells co-cultured with astrocytes (or C6 cells) developed a selective barrier with an estimated electrical resistance of 2,900 omega/cm2. The electrophysiological and morphological properties of BAEC were also affected by the co-culturing process, suggesting that astrocytes induced CNS properties in these cells. These results demonstrate that the hollow fiber cell co-culturing system may be used as a dynamic model of the mammalian blood-brain barrier.
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PMID:A dynamic model of the blood-brain barrier "in vitro". 885 43

We have established an enzyme immunoassay for phosphoneuroprotein 14 (PNP 14) which is mainly localized in the cytoplasmic matrix in presynaptic axon terminals and which is phosphorylated in vivo, as well as in vitro. Fab' prepared from rabbit IgG antibodies against bovine PNP 14 was conjugated with maleimide-horseradish peroxidase. The enzyme-conjugated Fab' was used as a second antibody in a sandwich enzyme immunoassay. This assay was able accurately to quantify 0.5-100 ng of rat PNP 14, as well as bovine PNP 14, and it was used for the determination of concentrations of PNP 14 in various rat tissues, neuroblastoma cells, and brains of other vertebrates. The concentrations of PNP 14 in the rat cerebrum, cerebellum, and testis were 1.1, 1.0, and 0.28 micrograms/mg of protein, respectively, and those in other tissues examined were less than 0.1 microgram/mg of protein. PNP 14 was also found in cultured cells, such as rat pheochromocytoma PC12 cells, NG108-15 cells, which are a hybrid between a mouse neuroblastoma and a rat glioma, mouse neuroblastoma Neuro-2a cells, and human neuroblastoma IMR32 cells. Furthermore, PNP 14-specific immunoreactivity was evaluated in the brains of various vertebrates, such as fish, frog, snake and chicken by immunoblot and enzyme immunoassay. The results revealed the immunoreactivity in the brains of all vertebrates examined and the levels were determined to be 0.6-2.1 micrograms bovine PNP 14 equivalents per mg of protein, suggesting that PNP 14 might be an essential component of the central nervous systems of vertebrates.
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PMID:Distribution of phosphoneuroprotein 14 (PNP 14) in vertebrates: its levels as determined by enzyme immunoassay. 900 21

The pro-inflammatory and blood-brain barrier (BBB) effects of intratumoral (IT) injection of human recombinant tumor necrosis factor-alpha (rTNF-alpha) were studied in the Fischer rat RT-2 glioma model. Animals received a single stereotaxic injection of either 6 x 10(4) U rTNF-alpha or excipient (vehicle) into the center of an intracerebrally implanted glioma. In order to demonstrate any effects rTNF-alpha might have on the BBB, studies were conducted using endogenous IgG (150 kD) as a tracer. Forty-eight hours following injection of excipient, a margin of peritumoral IgG extravasation was observed while rats treated with 6 x 10(4) U rTNF-alpha showed a dense and extensive IgG extravasation involving both hemispheres. Histological examination revealed that an IT rTNF-alpha injection induced leukocytic adherence, neutrophilic cuffing and infiltration throughout the lesion from 12 to 72 h after injection. These histological observations were supported by quantification of cerebral myeloperoxidase (MPO) levels which indicated a significant increase in neutrophils over the excipient recipients at 4 and 12 h. These MPO levels contrasted with our earlier studies in normal rats which revealed no significant difference in tissue MPO levels following injection of excipient or rTNF-alpha. In addition, when MPO levels in tumor models and normal rats receiving TNF were compared, a significantly greater presence of neutrophils was seen in tumor models at 12 h post-TNF injection. We believe that the increased inflammatory response seen in a progressing glioma compared to normal brain may be the result of decreased resistance to leukocytic infiltration due to increased vascular surface area, the lack of infiltration-resistant perivascular basement membrane, and/or increased extracellular space.
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PMID:Effects of an intratumoral injection of human recombinant tumor necrosis factor-alpha on cerebrovascular permeability and leukocytic infiltration in a rat glioma model. 900 60

Hepatocyte growth factor/scatter factor (HGF/SF), which has various physiological functions, and its receptor c-Met, the human c-met proto-oncogene product, are thought to be determinant in the pathological processes of various malignancies. To investigate the possible role of HGF/SF in the progression of development of astrocytic tumors, we examined the expression of c-Met in these tumors. Immunohistochemistry using the streptavidin-biotin peroxidase complex method and immunofluorescence double staining with anti-c-Met polyclonal and anti-glial fibrillary acidic protein monoclonal antibodies were performed. Positive c-Met expression was detected in 31 of the 42 astrocytic tumors and some of the control cases analyzed. c-Met-positive cells showed morphological characteristics of astrocytes. Especially in the cases of high-grade tumors, c-Met positivity was abundant in cells in both vascular-rich and peripheral regions of the tumors but not in the cells with distinctly malignant features. Immunofluorescence double staining revealed that the c-Met-positive cells were in part of astrocytic origin. We suggest that c-Met-positive cells are affected by some factors in the lesions where the pathological processes are in a state of development. Our studies indicated that c-Met expression might take part in glioma invasion but not in the development of malignancy.
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PMID:Immunohistochemical examination of c-Met protein expression in astrocytic tumors. 956 11

Taurine prevents tissue damage in various models of inflammation through a mechanism postulated to involve taurine monochloramine (Tau-Cl). Tau-Cl is formed through the action of a halide-dependent myeloperoxidase system associated with polymorphonuclear leukocytes (PMN), eosinophils, and basophils. Production of nitric oxide (NO), PGE2, and other proinflammatory mediators by activated macrophages is inhibited by Tau-Cl. Since glial cells may be activated to produce NO, PGE2 and other proinflammatory mediators, similar to macrophages, we examined the effects of Tau-Cl on the production of NO and PGE2 by rat C6 glioma cells. C6 cells were seeded to grow over 2-3 days to approximately 90% confluency before exposure to various concentrations of Tau-Cl in HBSS for 2 h (37 degreesC, 5% CO2). The HBSS was replaced, after washing the cells, with DMEM containing 4% fetal calf serum and activators (LPS, 10 microgram/ml; rat rIFN-gamma, 50 U/ml; and human rTNF-alpha, 50 ng/ml). Media content of NO2- and PGE2 was measured 48 h after activation and cell lysates were subjected to SDS-PAGE followed by Western blot analyses to determine the relative expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Media accumulation of NO2- and PGE2 was inhibited by Tau-Cl in a concentration dependent manner and this was accompanied by decreased amounts of iNOS and COX-2 proteins in cell lysates. Additional experiments determined the effects of Tau-Cl on the kinetics of iNOS and COX-2 mRNA expression. Expression of iNOS mRNA was markedly inhibited in activated C6 cells that were previously exposed to Tau-Cl and this persisted for at least 24 h. In contrast, inhibition of COX-2 mRNA expression was only transiently reduced in Tau-Cl exposed cells during the first 4 h of activation and was relatively unimpaired thereafter (8-24 h). These results suggest that Tau-Cl inhibits the transcriptional expression of the iNOS gene but inhibits expression of COX-2 protein by post-transcriptional mechanisms.
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PMID:Taurine chloramine inhibits production of nitric oxide and prostaglandin E2 in activated C6 glioma cells by suppressing inducible nitric oxide synthase and cyclooxygenase-2 expression. 972 77

Many inherited neurological diseases and cancers could potentially benefit from efficient targeted gene delivery to neurons of the central nervous system. The nontoxic fragment C (HC) of tetanus toxin retains the specific nerve cell binding and transport properties of tetanus holotoxin. The HC fragment has previously been used to promote the uptake of attached proteins such as horseradish peroxidase, beta-galactosidase and superoxide dismutase into neuronal cells in vitro and in vivo. We report the use of purified recombinant HC fragment produced in yeast and covalently bound to polylysine [poly(K)] to enable binding of DNA. We demonstrate that when used to transfect cells, this construct results in nonviral gene delivery and marker gene expression in vitro in N18 RE 105 cells (a neuroblastoma x glioma mouse/rat hybrid cell line) and F98 (a glioma cell line). Transfection was dependent on HC and was neuronal cell type specific. HC may prove a useful targeting ligand for future neuronal gene therapy.
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PMID:Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin. 1009 62


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