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)

We used 31P-NMR spectroscopy to investigate the response of living C6 glioma cells to stimulation by a beta-adrenergic agonist, isoproterenol. In the presence of 3-isobutyl-1-methylxanthine, stimulation induced an accumulation of cAMP, making possible the NMR detection of the second messenger in living cells grown on microcarrier beads and perfused in the NMR tube. The cAMP signal rose to a maximum level within 20-25 min of stimulation; thereafter it decreased to the detection threshold within 60 min. At the same time, 40% increases of phosphomonoester and diphosphodiester signals were observed, whereas no significant change in phosphocreatine and nucleotide signals was detected. The kinetics of changes of the cellular content in phosphorylated metabolites were analyzed after recording 31P-NMR spectra of cell perchloric acid extracts as a function of time of stimulation. cAMP accumulation in stimulated cells was evidenced by a near linear increase of its NMR signal as a function of incubation time (from 0 to 60 min). Concomitantly with the production of cAMP, the data showed 30% decreases of phosphocreatine and ATP levels within 60 min of stimulation, and an unexpected redistribution of pyrimidine and purine nucleoside triphosphates. At the same time, levels of phosphomonoesters (phosphorylcholine and phosphorylethanolamine) and phosphodiesters (glycerophosphorylcholine and glycerophosphorylethanolamine) rose (50% increase). 13C-NMR spectra of cell perchloric acid extracts prepared after isoproterenol stimulation of cells incubated in the presence of [1-13C]glucose indicated a higher glucose content in stimulated cells, whereas the resonance of ribose C1 was diminished. Moreover, the resonances of C1 of ethanolamine and choline (and their derivatives) were increased in spectra of stimulated cells, whereas that of C3 of serine was decreased. In addition, the 13C-NMR data indicated that neither the pattern of glutamate carbon enrichment nor the glutamate/glutamine ratio was modified in stimulated cells. On the other hand, the heteronuclear coupling pattern of the lactate (methyl group) resonance in 1H-NMR spectra of cell incubation media indicated that no change occurred in the carbon flux through the pentose-phosphate shunt under stimulation. The results of this multinuclear NMR approach are discussed in terms of metabolic responses of C6 cells to beta-adrenergic stimulation and cAMP overproduction.
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PMID:Beta-adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites. A multinuclear NMR study. 133 May 56

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.
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PMID:Image-guided 1H NMR spectroscopical and histological characterization of a human brain tumor model in the nude rat; a new approach to monitor changes in tumor metabolism. 133 42

Cell volume regulation in the face of osmotic stress is a fundamental homeostatic activity, and is most critical in brain, which is spatially constrained. Despite the importance of this phenomenon, little is known about volume regulation in the brain, primarily because of the cellular heterogeneity in the tissue. We describe here simultaneous in vivo 31P nuclear magnetic resonance (NMR) measurements of cell volume, intracellular pH and phosphate metabolites during early responses to hyperosmotic stress in C6 glioma cells perfused in NMR-compatible bioreactors. Cell volume was measured using dimethyl methylphosphonate (DMMP) as a probe which has an intracellular NMR resonance shifted upfield from the extracellular resonance. The sensitivity of these measurements allowed 31P NMR spectra to be collected every 30 s. Following an increase in osmolarity from 320 to 480 mOsm by addition of NaCl to the perfusate, C6 glioma cells shrank to 67% of their original volume. We also observed a simultaneous increase of intracellular pH coincident with the decrease in cell volume. The signals from ATP decreased by 10%, but those from phosphocreatine (PCr) increased by 31% after hyperosmotic shock. However, correcting the ATP signals for the decrease in cell volume indicated that its intracellular concentrations increased after treatment. Signals from glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE) were not changed significantly. This is the first in vivo report of early cellular responses monitored by NMR spectroscopy following hyperosmotic shock in cultured cells.
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PMID:In vivo 31P NMR study of early cellular responses to hyperosmotic shock in cultured glioma cells. 146 47

Nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of cells from the central nervous system both in vitro on perchloric acid extracts obtained either from cultured tumoral cells (C6 rat glioma) or rat astrocytes in primary culture, and in vivo within the human brain. Analysis of carbon 13 NMR spectra of perchloric acid extracts prepared from cultured cells in the presence of NMR [1-13C] glucose as substrate allowed determination of the glutamate and glutamine enrichments in both normal and tumoral cells. Preliminary results indicated large changes in the metabolism of these amino acids (and also of aspartate and alanine) in the C6 cell as compared to its normal counterpart. Localized proton NMR spectra of the human brain in vivo were obtained at 1.5 T, in order to evaluate the content of various metabolites, including glutamate, in peritumoral edema from a selected volume of 2 x 2 x 2 cm3. N-acetyl aspartate, glutamate, phosphocreatine, creatine, choline and inositol derivative resonances were observed in 15 min spectra. N-acetyl-aspartate was found to be at a lower level in contrast to glutamate which was detected at a higher level in the injured area as compared to the contralateral unaffected side.
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PMID:Magnetic resonance spectroscopy and metabolism. Applications of proton and 13C NMR to the study of glutamate metabolism in cultured glial cells and human brain in vivo. 167 32

Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of phosphate-containing compounds and pH within brain cells. The authors obtained localized phosphorus MR spectra from 10 normal brains, four low-grade astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas and found differences in the spectra of each tumor type. Compared to normal brain, the spectra from low-grade astrocytomas showed a significant reduction of the phosphodiester (PDE) peak. Glioblastomas were characterized by a significant reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a relatively alkaline intracellular pH. The spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors. Meningiomas showed significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well as a relatively alkaline pH. Pituitary adenomas resembled meningiomas, but had a much higher PME peak. Although the number of tumors studied was small, there appears to be a characteristic spectrum associated with these different tumor types. The present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo.
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PMID:Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy. 199 10

Glioma are often histologically heterogenous. As many of these tumors are not removable in toto, due to their localisation, the most malignant part of the tumor may be missed and information for optimum therapeutic management is incomplete. Furthermore, low grade gliomas tend to become more malignant in their development; additional surgical intervention is often not possible. Non-invasive measurement of tumor glucose metabolism with (F-18)-2-fluoro-2-deoxyglucose (FDG) and positron-emission-tomography (PET) may be used to evaluate tumor malignancy. Malignant gliomas (astrocytoma III degree and glioblastoma) frequently showed increased peak metabolic rates (in comparison with normal white matter) and uncoupling of FDG transport and phosphorylation. Preliminary experiences with image-guided localized phosphorus-31 MR spectroscopy (P-31 MRS) demonstrated a decrease of phosphodiesters in malignant gliomas, whereas the phosphomonoesters showed an increase in several cases. The phosphocreatine peak was often reduced. A more active therapy of low grade gliomas might be indicated when signs of hypermetabolism in FDG-PET and alteration of energy-rich phosphates or membrane-phosphates in P-31 MRS are found.
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PMID:[Metabolic studies of gliomas with positron emission tomography and phosphorus 31 MR spectroscopy in diagnosis and treatment planning]. 268 95

High-resolution 1H surface coil NMR spectroscopy (MRS) was used to evaluate in vivo the cerebral metabolism changes in rat brain induced by a glial tumor growing in situ. Tumor cells (C6 glioma cells) were stereotaxically placed in the right hemisphere superficially. 1H MRS was performed using 5-mm surface coils implanted over the right hemisphere and the water was suppressed using a binomial sequence. As the intracerebral tumor size increased, there was a marked decrease in the N-acetyl aspartate level and an increase in the 1.3 ppm peak. Edition of this peak showed that lactate increased but lipids increased much more than lactate. Moreover the ratio between the choline-phosphocholine and creatine-phosphocreatine peaks changed. This study demonstrates that high-resolution surface coil 1H MRS can be used to monitor changes in metabolism associated with growth of an experimentally induced rat brain tumor in situ.
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PMID:In vivo 1H NMR spectroscopy of an intracerebral glioma in the rat. 271 5

The effect of chemotherapy against glioma in mouse was evaluated by 31P NMR spectroscopy and flow cytometry. We found that administration of ACNU or tegafur at a dose less than LD50 resulted in the partial suppression of the ratio of inorganic phosphate (Pi)/phosphocreatine (PCr) and phosphomonoester (PME)/creatine phosphate (PCr) after 24 or 48 hr, although these ratios are usually increased together with growth of tumors. Flow cytometric analysis of glioma in vivo showed an accumulation in cells containing tetraploid DNA by G2M block 24-48 hr after treatment. However, the change occurred at a period slightly later than that of the Pi/PCr ratio. In contrast, histological change was noted at eight days after administration. Hence, it is concluded that in vivo 31P NMR spectroscopy can detect a change in metabolic pathways in tumors as early as 24-48 hr after the administration of chemotherapeutic agents.
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PMID:Early stage detection of chemotherapeutic effect on 203 GL glioma in mice as studied by P-31 NMR and flow cytometry. 314 36

In vivo 31P-magnetic resonance spectra (MRS) were obtained by the surface coil method from rat glioma, human glioblastoma, and human neuroblastoma inoculated subcutaneously in CD Fisher rats and hamsters, and the effects of chemotherapy, photoradiation therapy, and radiofrequency hyperthermia as well as 60Co-irradiation were evaluated by sequentially observing spectral changes. In the 31P-spectra of tumour tissue, the nucleoside triphosphate (NTP), phosphomonoesters (PME) peaks were high and the phosphocreatine peak was low compared to those of normal brain. When the antitumour agents were given and were effective, NTP peaks decreased, and inorganic phosphate increased remarkably within several hours after the treatment. 1H-magnetic resonance imaging (MRI) were also obtained in some cases. Necrotic regions was detected by the 1H-MRI as image changes which appeared later than those detected by MRS. It proved practical to monitor the effect of therapy by employing either 31P-MRS or 1H-MRI. However, the image changes which demonstrated the effect of the therapy used closely resembled those changes which occurred with the onset of necrosis in tumour tissue during tumour growth. Several problems for future application of these techniques to human brain tumours are also mentioned.
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PMID:The investigation of experimental brain tumours using 31P-MRS and 1H-MRI. 321 41

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


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