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)

An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 x 10(6) or 5 x 10(5) 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7 +/- 1.9 days or 19.2 +/- 1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma. The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema. Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.
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PMID:A feline model for experimental studies of peritumor brain edema. 322 Dec 63

Photoradiation therapy is a form of local treatment that depends on the selective retention of a photosensitizer, such as hematoporphyrin derivative (HpD), by the tumor followed by treatment with light of an appropriate wavelength to activate the sensitizer in the tumor. The selective uptake of HpD by cerebral tumors has been demonstrated both in laboratory animal model studies and in clinical studies, and selective destruction of intracerebral tumors has been demonstrated in animal glioma models. The biological basis for photoradiation therapy and, in particular, the mechanisms for the selective uptake of the sensitizer into the tumor and the destruction of tumor with photoradiation therapy are discussed. Current evidence suggests that singlet oxygen is the major intermediary leading to cell damage, although other radicals such as hydrogen peroxide and hydroxyl radicals may be involved. Other studies suggest that the initial damage is to the blood vessels, and the tumor subsequently undergoes ischemic changes. Sixty-four patients treated with photoradiation therapy have been reported in the literature. The initial clinical studies were disappointing in their therapeutic effect but these studies often included treatment of recurrent gliomas and low doses of light were used. Technical advances, particularly in laser technology, have enabled more effective photoradiation therapy and the clinical trials are reviewed.
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PMID:Photoradiation therapy and its potential in the management of neurological tumors. 328 22

The in vivo high-energy phosphorus metabolic profile and pH of an experimental intracerebral C6 glioma in rats was examined using surface coil 31P NMR spectroscopy. Initially, phosphorus-containing metabolites of the glioma were characterized by in vivo 31P surface coil spectroscopy of subcutaneously implanted tumors and by high-resolution NMR studies of perchloric acid (PCA) extracts of both freeze-clamped subcutaneous tumor tissue and cultured cells. These studies demonstrated that the C6 glioma has reduced levels of phosphocreatine (PCr) compared to the levels found in normal rat brain. Thus, reduced spectral PCr levels were useful as a metabolic indicator for monitoring the spatial selectivity of tumor metabolism distinct from that of adjacent normal brain tissue. To maximize 31P NMR signals from intracerebral tumors, tumor cells were stereotaxically placed superficially in the brain. Proton magnetic resonance imaging (1H MRI) was used to determine the size and location of the resultant brain tumors in order to preselect rats with large superficial tumors for spectroscopic study. 31P NMR spectra of the glioma tumors revealed a consistent reduction in the PCr/ATP ratio, an increase in the Pi/ATP ratio, and a slightly increased tissue pH. No correlation was found between levels of Pi/ATP and tumor pH in subcutaneous or intracerebral gliomas and the amount of necrosis as determined histologically. This study demonstrates that phosphorus metabolites of an experimental brain tumor in the rat can be monitored in vivo with minimal contributions from adjacent normal brain tissue metabolites using surface coil 31P NMR spectroscopy.
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PMID:31P NMR spectroscopy of the in vivo metabolism of an intracerebral glioma in the rat. 338 2

Blood flow of transplanted intracerebral rat gliomas was measured before and after a constant I.V. infusion of angiotensin II-induced arterial hypertension using hydrogen clearance method. The brain tumor model was produced in syngeneic Wistar-King-Aptekman male rats by stereotaxic inoculation of ethylnitrosourea-induced glioma cells (KEG-1). Induced hypertension by angiotensin II infusion resulted in a significant increase in tumor blood flow compared with control levels (P less than 0.001). In addition, the therapeutic effect of administration of 3-[(4-amino-2-methyl-5-pyrimidinyl) ethyl] -1-(2-chloroethyl)-1-nitrosourea (ACNU) during angiotensin II-induced hypertension was evaluated. At 12 days after implantation, tumor-bearing rats were administrated angiotensin II as the mean blood pressure reached 150 mmHg, followed by ACNU injection, maintained the same blood pressure for 20 minutes. ACNU with induced hypertension group showed a median survival time of 27.0 days, which was significantly (P less than 0.02) longer than that of ACNU alone (22.0 days). It is therefore suggested that chemotherapy with angiotensin II-induced hypertension has a enhancing effect on chemotherapy for improving the drug delivery to tumor tissue by a increased tumor blood flow.
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PMID:[Experimental studies on induced hypertension chemotherapy of intracerebral inoculated gliomas in rats]. 346 30

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.
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PMID:Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements. 403 78

Proton NMR spectroscopy was used to study the effect of differentiation with prostaglandin E1 and theophylline on intact hybrid neuroblastoma X glioma cells. The standard proton NMR method showed more resolvable signals than the spin echo NMR spectra. The differentiated cells were found to contain significantly higher levels of glutamine than the undifferentiated precursors. Observations on cell extracts confirmed these results.
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PMID:Differences in metabolite levels upon differentiation of intact neuroblastoma X glioma cells observed by proton NMR spectroscopy. 631 24

Previous studies have shown that serum proteins are taken up from extracellular oedema fluid by reactive astrocytes and by tumour astrocytes. The present investigation was designed to define the mechanism of this protein uptake. Two or 3-week-old explant cultures from 26 astrocytic gliomas, one anaplastic ependymoma, and five non-glial intracranial tumours were treated with either human IgG (12 mg/ml), human serum albumin, (44 mg/ml) or horseradish peroxidase (0.1--4.0 mg/ml) for 4--24 h. Human IgG and albumin were subsequently detected in cultured cells by the indirect peroxidase-antiperoxidase (PAP) method for light microscopy or by direct peroxidase conjugate technique for electron microscopy. Horseradish peroxidase activity was localised by treatment with diaminobenzidine and hydrogen peroxide. Results of the study show that human serum proteins and horseradish peroxidase are taken up by tumour astrocytes and ependymal cells, and by macrophages, but not by non-glial tumour cells nor by mesenchymal elements in the glioma cultures. Electron immunocytochemistry suggests that the serum proteins are taken up by smooth walled micropinocytic vesicles (approximately 80 nm in diameter) which fuse to form larger endocytic vesicles (200--300 nm); these vacuoles in turn fuse with secondary lysosomes to form cytoplasmic bodies 1.2--3 mum in diameter.
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PMID:Mechanisms of uptake and the fate of serum proteins and horseradish peroxidase in cultured human glioma cells. A light- and electron-immunocytochemical study. 744 81

We studied the effect of intracarotid administration of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat C6 glioma by the hydrogen clearance method. Iloprost at doses of 0.1 and 0.5 micrograms/kg/min produced a selective increase of the regional cerebral blood flow in the tumour (17.8 +/- 5.6%, p < 0.05 and 27.3 +/- 10.3%, p < 0.05, respectively) without significant change of the regional cerebral blood flow in the ipsilateral hemisphere and the systemic arterial pressure. At a dose of 1 microgram/kg/min, iloprost produced a significant reduction of a systemic blood pressure, but did not change the regional cerebral blood flow significantly both in the tumour and the ipsilateral hemisphere. These results indicated that brain tumour vessels could respond to iloprost in a different fashion from the normal brain capillaries. The selective action of iloprost to the tumour vessels might contribute to the drug-delivery in malignant brain tumour.
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PMID:Effects of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat brain tumour. 751 Mar 71

We have cloned mouse and human cDNAs for a multifunctional DNA repair enzyme (APEX nuclease) having apurinic/apyrimidinic (AP) endonuclease, 3',5' exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities. To investigate the biological role of APEX nuclease, sense or antisense APEX RNA was stably expressed at a high level in cultured rat glioma cells by introducing plasmids (pABWN-HAPX1F for expression of sense RNA or pABWN-HAPX2R for expression of antisense RNA) constructed from the human APEX cDNA and an expression vector pABWN. Multiple copies of the construct were integrated into the glioma cells transfected with pABWN-HAPX1F or pABWN-HAPX2R. These transfectants showed markedly high expression of RNA hybridizable to human APEX cDNA, indicating the expression of the sense or antisense RNA. Activity blotting analyses of salt extracts of these transfectants showed that the sense RNA-expressed cells had higher AP endonuclease activity and that the antisense RNA-expressed cells had extremely lower AP endonuclease activity than the control cells. The APEX nuclease-depressed glioma cells became more sensitive to methyl methanesulfonate and hydrogen peroxide than the control cells or the APEX nuclease-overexpressed cells. The results indicate that APEX nuclease plays an important role in repair of DNA damage caused by these genotoxic agents. The present stable expression systems for the sense and antisense APEX RNAs should be useful for analyzing the biological functions such as an antimutagenic function of the enzyme.
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PMID:Stable expression in rat glioma cells of sense and antisense nucleic acids to a human multifunctional DNA repair enzyme, APEX nuclease. 751 11

Oxygen radicals induce cytotoxicity via a variety of mechanisms, including DNA damage, lipid peroxidation and protein oxidation. Here, we explore the use of a polyethylene glycol (PEG)-stabilised enzyme capable of producing reactive oxygen species (ROS), glucose oxidase (GO), for the purpose of harnessing the cytotoxic potential of ROS for treating solid tumours. PEG-GO (200 U), administered by two intratumoral injections 3 h apart, produced a significant growth delay in subcutaneous rat 9L gliomas as compared with control animals receiving heat-denatured PEG-GO. Rats were protected from systemic toxicity by subsequent i.v. administration of PEG-superoxide dismutase (PEG-SOD) and PEG-catalase. In vivo tumour metabolic changes, monitored using 31P magnetic resonance spectroscopy (31P-MRS) 6 h following initial administration of PEG-GO, revealed a 96 +/- 2% reduction in the ATP/Pi ratio and a 0.72 +/- 0.10 unit decline in intracellular pH. A 3-fold sensitisation of 9L glioma cells in vitro to hydrogen peroxide could be achieved by a 24 h preincubation with buthionine sulphoximine (BSO). This study suggests that oxidation therapy, the use of an intratumoral ROS-generating enzyme system for the treatment of solid tumours, is a promising area which warrants further exploration.
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PMID:Oxidation therapy: the use of a reactive oxygen species-generating enzyme system for tumour treatment. 798 Oct 65


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