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)

Malignant gliomas are associated with a dysfunctional blood-tumor barrier (BTB) that causes substantial morbidity. Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth factor that correlates with glioma malignancy and has several biological properties that suggest a role in enhancing blood-glioma barrier permeability. In this study, we examined the effects of glioma cell SF/HGF expression on BTB permeability to horseradish peroxidase (HRP). Fischer 344 rats bearing intrastriatal 9L tumors engineered to secrete SF/HGF (9L-SF) and SF/HGF-negative control tumors (9L-neo) received intracardiac injections of HRP and were rapidly decapitated. Densitometric analysis of brain sections reacted with diaminobenzidine showed significantly greater extravascular HRP surrounding SF/HGF-secreting tumors than 9L-neo tumors of comparable size (p<0.05). HRP enzymatic activity associated with striata containing SF/HGF-expressing tumors was 1. 6-fold greater than that of striata containing control tumors (p<0. 05). Northern analysis showed that expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) did not differ between 9L-neo and 9L-SF tumors. These data demonstrate that SF/HGF expression by intracerebral glial tumors can enhance BTB permeability independent of changes in VEGF/VPF expression.
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PMID:Scatter factor/hepatocyte growth factor gene transfer increases rat blood-glioma barrier permeability. 1037 92

Human gliomas were analysed for the infiltration of neutrophils using immunohistochemistry by staining sections for CD15-positive and myeloperoxidase-positive cells. Over 70% of all glioma samples analysed (n = 105) had significant neutrophil infiltration, but there was a marked and significant correlation between tumour grade and the extent of the neutrophil infiltration. In the low grade tumours only 40-50% had significant infiltration, while in glioblastoma multiforme over 85% of the samples analysed had significant infiltration. Numbers of neutrophils infiltrating glioblastoma multiforme tumours were also greater than in the other tumour groups. Circulating white blood cell counts were elevated above the normal range in all glioma patients, but this elevation was entirely due to increased numbers of circulating neutrophils. Again, the highest numbers of circulating neutrophils were seen in the glioblastoma multiforme patients. These experiments indicate that glioma-derived factors may directly or indirectly affect the number of circulating neutrophils and influence their infiltration into the tumours.
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PMID:Neutrophil infiltration into human gliomas. 1050 39

Taurine monochloramine (Tau-Cl) is formed through the actions of a halide-dependent myeloperoxidase system associated with polymorphonuclear leukocytes (PMN). Tau-Cl inhibits production of inflammatory mediators by activated macrophages, and PMN. Recently, Tau-Cl was shown to inhibit production of nitric oxide and prostaglandin E2 by activated C6 glioma cells. Since chemokines, secreted by activated glial cells, play a prominent role in eliciting inflammatory responses in the central nervous system, the effects of Tau-Cl on production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were determined in activated C6 glioma cells. Tau-Cl inhibited production of MCP-1 and MIP-2 in a concentration-dependent manner, and was most potent against MCP-1. Tau-Cl exerted a transient inhibition of the temporal expression of MCP-1 and MIP-2 mRNAs during the first 4 h of activation. Although both chemokine mRNA levels were similar to those of control cells after 8-24 h of activation, production of the chemokine proteins, especially MCP-1, remained markedly low. These results suggest that Tau-Cl inhibits production of MCP-1 and MIP-2 in activated C6 cells primarily through post-transcriptional mechanisms.
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PMID:Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 production is inhibited by taurine chloramine in rat C6 glioma cells. 1054 Oct 46

The simultaneous detection of nitric oxide and glutamate using an array of individually addressable electrodes, in which the individual electrodes in the array were suitably modified with a highly sensitive nitric oxide sensing chemistry or a glutamate oxidase/redox hydrogel-based glutamate biosensor is presented. In a sequence of modification steps one of the electrodes was covered first with a positively charged Ni porphyrin entrapped into a negatively charged electrodeposition paint followed by the manual modification of the second working electrode by a bienzyme sensor architecture based on crosslinked redox hydrogels with entrapped peroxidase and glutamate oxidase. Adherently growing C6-glioma cells were grown on membrane inserts and placed in close distance to the modified sensor surfaces. The current responses recorded at each electrode after stimulation of glutamate and NO release by means of K+ and bradykinin clearly demonstrate the ability of the individual electrode in the array to detect the analyte towards which its sensitivity and selectivity was targeted without interference from the neighbouring electrode or other analytes present in the test mixture.
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PMID:Simultaneous detection of the release of glutamate and nitric oxide from adherently growing cells using an array of glutamate and nitric oxide selective electrodes. 1562 9

Aims-To compare immunostaining between the original Ki67 monoclonal antibody and a new polyclonal Ki67 antibody on frozen and paraffin wax sections of human glioblastomas.Methods-Frozen sections and formalin fixed, paraffin wax embedded sections of the same tumour specimens were included in the study (10 cases). Half of the paraffin wax sections were pretreated in a microwave oven. Standard immunohistochemical techniques were used (avidinbiotin peroxidase complex). Five high power fields were examined using an eye-piece graticule, and 500 to 2000 tumour cells were counted. The labelling index was defined as the percentage of positive tumour cells.Results-The Ki67 monoclonal antibody displayed positive immunostaining in all frozen sections (median labelling index 5.9, range 2.6-11.4) whereas only four paraffin wax sections stained positively and only after pretreatment in a microwave oven. The polyclonal Ki67 antibody elicited positive staining in both frozen sections (median labelling index 13.7, range 6.7-21.5) and in paraffin wax sections (median labelling index 12.0, range 2.2-22.7) but only after pretreatment in a microwave oven.Conclusion-The Ki67 monoclonal antibody is not recommended for use on paraffin wax sections of glioma tissues whereas the new polyclonal Ki67 antibody provides satisfactory immunostaining on both frozen and paraffin wax sections.
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PMID:Comparison of different Ki67 antibodies in human glioblastomas. 1669 4

An ex vivo system for simultaneous detection of nitric oxide (NO) and L-glutamate using integrated dual 250 microm platinum disk electrodes modified individually with suitable sensing chemistries has been developed. One of the sensors was coated with an electrocatalytic layer of Ni tetrasulfonate phthalocyanine tetrasodium salt (Ni-TSPc) covered by second layer of Nafion, which stabilises on the one hand the primary oxidation product NO(+) and prevents interferences from negatively charged compounds such as NO(2)(-). For glutamate determination, the second electrode was modified with a crosslinked redox hydrogel consisting of Os complex modified poly(vinylimidazol), glutamate oxidase and peroxidase. A manual x-y-z micromanipulator on top of an inverted optical microscope was used to position the dual electrode sensor at a defined distance of 5 microm from a cell population under visual control. C6 glioma cells were stimulated simultaneously with bradykinin or VEGF to release NO while KCl was used to invoke glutamate release. For evaluation of the glutamate sensors, in some experiments HN10 cells were used. To investigate the sensitivity and reliability of the system, several drugs were applied to the cells, e.g. Ca(2+)-channel inhibitors for testing Ca(2+)-dependence of the release of NO and glutamate, rotenone for inducing oxidative stress and glutamate antagonists for analysing glutamate release. With these drugs the NO and glutamate release was modulated in a similar way then expected from previously described systems or even in-vivo measurements. We therefore conclude that our system is suitable to analyse stress-induced mechanisms in cell lines.
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PMID:Simultaneous detection of L-glutamate and nitric oxide from adherently growing cells at known distance using disk shaped dual electrodes. 1673 97

There is an increasing interest in new strategies to detect neurotransmitters released from nerve cells in real time for brain science, drug assessment, and so on. Previously we reported real-time monitoring of dopamine release from nerve model cells by enzyme-catalyzed luminescence measurement with tyramine oxidase and peroxidase. In the present study, the system was modified with glutamate oxidase instead of tyramine oxidase to detect L-glutamate sensitively ( approximately 10 nM) and rapidly with high temporal resolution (<1 s). We applied this modified method successfully to perform real-time monitoring of L-glutamate release from brain model cell (C6 glioma cell) using a luminescence plate reader upon stimulation with high concentration of KCl (>10 mM) or 5-hydroxytryptamine (>1 microM). The measurement solution was not toxic and therefore the L-glutamate release from the cell was measured by the second stimulation after exchanging the measurement solution. We conclude that the developed monitoring system is suitable for real-time detection of dynamic L-glutamate release from nerve cells in vitro and will be suitable for application in assessment of drugs acting on the nervous system.
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PMID:Real-time detection of L-glutamate released from C6 glioma cells using a modified enzyme-luminescence method. 1784

Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and claudin-5 are attenuated by BK induction. Immunohistochemistry and immunofluorescence assays show that the attenuated expression of ZO-1, occludin, and claudin-5 and F-actin is most obvious in the smaller tumor capillaries (<20 microm) after BK infusion, and there is no change in the larger tumor capillaries (>20 microm). The redistribution of ZO-1, occludin, and claudin-5 and rearrangement of F-actin in brain microvascular endothelial cells are observed at the same time. Meanwhile, Evans blue assay shows that the permeability of BTB increases after BK infusion. Transmission electron microscopy indicates that TJ is opened and that pinocytotic vesicular density is increased. Transendothelial electrical resistance (TEER) and horseradish peroxidase flux assays also reveal that TJ is opened by BK induction. In addition, radioimmunity and Western blot assay reveal a significant decrease in expression levels of cAMP and catalytic subunit of protien kinase A (PKAcs) of tumor tissue. This study demonstrates that the increase of BK-mediated BTB permeability is associated with the down-regulation of ZO-1, occludin, and claudin-5 and the rearrangement of F-actin and that cAMP/PKA signal transduction system might be involved in the modulating process.
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PMID:Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton. 1818 15

Atypical adenomatous hyperplasia (AAH) is postulated to be the earliest morphologic precursor lesion in lung carcinogenesis. The epidermal growth factor receptor (EGFR), one of the members of the Erb-2 family of receptors, is commonly expressed in non-small cell lung carcinoma (NSCLC). A subset of the patients with NSCLC has molecular abnormalities in the EGFR gene, including missense mutations and deletions and/or abnormal gene copy numbers, and the relative importance of each of these for patient outcome is an area of great interest. Recent reports show that EGFR mutations are rare or absent in AAH and are rare in bronchioloalveolar carcinoma (BAC). However, the EGFR gene copy number status in AAH is unknown. In this study, we examined the EGFR gene copy number status in lung adenocarcinomas, synchronous AAH, and BAC in surgical pathology resection specimens. EGFR gene copy number was analyzed by chromogenic in situ hybridization (CISH) using formalin fixed paraffin embedded tissue sections and EGFR probes as recommended by the manufacturer. A known positive case of high-grade glioma was used as a positive control. The results indicate that four of eight adenocarcinomas (50%) had more than five EGFR signals per nucleus, suggesting a gain in copy number. Interestingly, in four of nine cases of AAH (44.4%) more than three EGFR signals per nucleus were noted, with scattered cells showing up to 6 signals per nucleus. In addition, in five of 12 cases of BAC (42%), more than three EGFR signals per nucleus were noted. In the remaining cases two to three intranuclear dot-like peroxidase positive signals were present consistent with non-amplification of the gene. Our study reveals an abnormal EGFR gene copy gain in several cases of AAH. In our cohort, the rate of EGFR gene copy abnormalities in AAH appears similar to BAC and lower than in lung adenocarcinomas. These findings suggest that although EGFR gene copy abnormalities may be an early event in lung carcinogenesis, they are associated with tumor progression to invasive cancer and highlight the complexity of tumor morphogenesis.
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PMID:Epidermal growth factor receptor gene amplification in atypical adenomatous hyperplasia of the lung. 2058 69

The research was conducted to study the increase of blood-tumor barrier (BTB) permeability through paracellular pathway by low-frequency ultrasound (LFU) irradiation in vitro. LFU (frequency=1.0 MHz) was performed to irradiate BTB model from the co-culture of rat C6 glioma cells and rat brain microvascular endothelial cells (RBMECs). The permeability of BTB was measured by transendothelial electrical resistance (TEER) and flux of horseradish peroxidase (HRP) assays after LFU irradiation. Western-blotting, immunohistochemistry, and immunofluorescence assays were used to investigate the changes of expressions and distributions of tight junction (TJ)-associated proteins ZO-1, occludin, and claudin-5. The TEER value began to decrease, and the minimum value appeared at 2 h, then gradually returned to the original level at 24 h after LFU irradiation. With time, flux of HRP gradually increased and reached the peak 2 h after LFU irradiation. The expressions of ZO-1, occludin, and claudin-5 in RBMECs decreased, and decreased most significantly at 2 h, then gradually restored to the original level at 24 h. Meanwhile, they were discontinuously distributed in the cellular boundaries after LFU irradiation. In summary, the expression of TJ-associated proteins was down-regulated, TJ was opened, and the permeability of BTB was increased through paracellular pathway by LFU irradiation.
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PMID:Increasing of blood-tumor barrier permeability through paracellular pathway by low-frequency ultrasound irradiation in vitro. 2110 56


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