DIVERSITY OF METABOLIC PATTERNS IN HUMAN BRAIN TUMORS—I. HIGH ENERGY PHOSPHATE COMPOUNDS AND BASIC COMPOSITION<sup>1</sup>

Lowry, Oliver H.; Berger, Sosamma J.; M.-Y., M.; Carter, J. G.; Blackshaw, A. W.; Outlaw, William H.

doi:10.1111/j.1471-4159.1977.tb06500.x

Cited by 86 publications

(41 citation statements)

References 18 publications

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“…This ratio was not different in various grades of gliomas similar to Arnold et al findings [19]. Significant increased ratio of PDE / βATP in metastases may be attributed to increase in PDE from degraded cell membranes from accelerated catabolism [1,25,26].…”

supporting

confidence: 66%

“…Tuberculoma and high grade glioma show higher levels of β ATP when compared to other pathologies in our study but was not statistically significant. This could be due to presence of more inflammatory cells in tuberculoma and high levels of lipid and glycogen in grade 4 glioma [25].…”

mentioning

confidence: 99%

“…Thus a hypoxic internal milieu could contribute to Pi in inflammatory and neoplastic lesions and a significant overlap in energy ratios between these lesions [25].…”

mentioning

confidence: 99%

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Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

Kamble¹

2014

JCDR

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Aim: Intracranial space occupying lesions can be infective or tumour. There are various advanced Magnetic resonance imaging techniques like perfusion, diffusion and proton spectroscopy which can differentiate between them. However, 31 Phosphorus spectroscopy studies the energy status and the metabolism pattern of various tissues and can be used potentially to differentiate between them depending on their Metabolism pattern. Thus, we aimed to study energy status of various intracranial lesions and try to differentiate between them including grades of gliomas. Materials and Methods:31 PMRS was done in 1.5T MRI in 43 patients prior to surgery or through/via stereo-tactic biopsy, of which 25 were men and 18 women with mean age 41.34 y ranging from 7-71 y. Single voxel phosphorus spectroscopy was done from the solid portion of the lesions and data was analysed and post processed.Results: Study includes Lymphoma (n=6), Grade 1 and 2 glioma (n=5), grade 3 glioma (n=9), grade 4 glioma(n=6), metastases (n=5), tuberculoma (n=7) and pyogenic abscesses (n=5). The integral values of PME, Pi, PDE, γ-ATP, α-ATP, β-ATP with reference to the position of PCr were calculated along with various ratios. Integral values of Pi and PDE were significantly increased in metastases but decreased in gliomas grade 1-2 compared to other pathologic conditions. Mean integral values of LEP (low energy phosphates) and total phosphates were significantly decreased in gliomas grades 1 and 2 and increased in metastases when compared with other pathologic conditions. PCr /Pi was increased in glioma grades 1, 2 and 3 but decreased in metastases; the significance was observed only in gliomas grade 3 and metastases. Metabolic ratios of PDE/βATP and Pi/ βATP were decreased in glioma grades 1 and 2 and increased in metastases with statistical significance. Conclusion:31 PMRS may help in differentiating primary from secondary lesions and assess grades of gliomas. P MR spectroscopy (TR = 400ms, TE=1ms, 512 acquisitions) using intravoxel in-vivo spectroscopy localization method with head quadrature dual-tuned coil. Care was taken to include mainly the solid portion of the lesion in the MRS voxel which ranged from 2 cm 3 -4 cm 3 . The duration of spectroscopy examination was about 5 min. Spectroscopy data were transferred to an installed software programme (Numaris spectroscopy analysis package VB33A). All post-processing techniques like apodization, zero and first order phase corrections were performed and spectra were plotted, analyzed and fitted to Lorentzian lines shapes.The following well resolved phosphorus metabolite peaks were observed in all patients-Phosphomonoesters (PME), Inorganic phosphate (Pi), Phosphodiesters (PDE), Phosphocreatine (PCr), γ, β, and α resonances of adenosine triphosphate (ATP). The chemical

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confidence: 66%

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confidence: 99%

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Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

Kamble¹

2014

JCDR

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“…Brain tumours have much lower metabolic rates than brain and each particular tumour appears to have a unique metabolic pattern" (Lowry et al, 1977). In the past, determining the uniqueness of a brain tumour's metabolic pattern was difficult and time consuming.…”

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confidence: 99%

In vivo nuclear magnetic resonance spectroscopy of a transplanted brain tumour

Koeze¹,

Iles²,

Gordon³

1984

Br J Cancer

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Summary In vivo nuclear magnetic resonance 31P spectroscopy was used to demonstrate different patterns of high energy phosphate metabolism in a group of malignant tumours of glial origin. In some of the more malignant tumours a decrease in adenylate energy charge was found. This was associated with a decline in phosphocreatine and an increase in sugar phosphate and inorganic phosphorus."Human brain tumours have two metabolic features which sharply distinguish them from brain. Brain tumours have much lower metabolic rates than brain and each particular tumour appears to have a unique metabolic pattern" (Lowry et al., 1977). In the past, determining the uniqueness of a brain tumour's metabolic pattern was difficult and time consuming. Recent developments in nuclear magnetic resonance (NMR) spectroscopy (Gadian, 1977;Griffiths & Iles, 1980;Koeze, 1982) have made it possible to assess rapidly several aspects of high energy phosphate metabolism and pH of tumours in vivo. This study was undertaken to examine tumours for differences in high energy phosphate metabolism using NMR spectroscopy and to determine if these differences could be related to such factors as tumour size, degree of malignancy and histological features. Materials and methodsTen BD IX rats were injected with a suspension of cells, designated A15A5, which originated from a clone of neoplastic astrocytes derived from a mixed glioma induced transplacentally by N-ethyl-Nnitrosourea (Lantos et al., 1976). The cell lines were maintained and all injections were performed in the Department of Neuropathology of the Institute of Psychiatry.Four animals were injected intracerebrally with a cell suspension which had undergone 23 passages. The injections were performed 27 days before the in vivo NMR studies. The remaining 6 rats were injected extracranially beneath the scalp with cells at passage 34. The in vivo NMR spectroscopy was performed 37 days after the injection. attempt was made to demonstrate glial fibrillary acidic protein using the PAP method. Of the remaining 6 animals with extracerebral tumours two were killed after the spectroscopy and the tumour tissue was processed for histological sections. Another two animals were allowed to recover from the anaesthesia after the in vivo NMR spectroscopy. One of these animals was killed 4 days after the spectroscopy and the tumour extracted for in vitro spectroscopy as described below. The other animal of this pair was killed 39 days after the in vivo NMR spectroscopy. The final two animals had tumours too small to scan properly. One of these was killed, the other was allowed to survive for a further 66 days. It was then killed and the tumour extracted for in vitro spectroscopy as described below.The in vivo 31P NMR spectroscopy was performed at 32.5MHz with an Oxford Research Systems TMR 32/200 (Gordon et al., 1982) spectrometer. After the animal was anaesthetized, a single turn surface coil (Ackerman et al., 1980) -10mm in diameter was placed directly over the tumour. In some animals records were obtained w...

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“…The metabolism of human gliomas remain largely unknown except for energy metabolism. The activities of many enzymes involved in glycolysis (Lowry et al, 1983;Marzatico et al, 1986) and the quantification of high-energy phosphate compounds (Lowry et al, 1977) suggest that gliomas have lower metabolic rates than normal brain tissue. Despite contradictory previous results (Lowry et al, 1983;Mangiardi & Yodice, 1990, Pillwein et al, 1990, the low levels of guanylate and adenylate pools in human gliomas were recently confirmed by Pillwein et al (1990).…”

Section: Disc-ssiommentioning

confidence: 99%

Purine and pyrimidine metabolism in human gliomas: relation to chromosomal aberrations

Bardot

Dutrillaux²,

Delattre³

et al. 1994

Br J Cancer

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3Clinique Neurologique, H6pital de la Salptriere, 47 boulevard de l'Hopital, 75 651 Paris cedex 13, France. SmaryChromosomal aberrations in human gliomas are principally numerical. In tumours of low malignancy, karyotypes are frequently normal, but occasionally an excess of chromosome 7 and a loss of sex chromosome are observed. In highly malignant tumours, the most frequent aberrations are gain of chromosome 7, loss of chromosome 10 and less frequently losses or deletions of chromosomes 9, 22, 6, 13 and 14 or gains of chromosomes 19 and 20. To understand the meaning of these chromosome imblances, the relationships between chromosome abnormalities and metabolic disturbances were studied. The losses or deletions observed affected principally chromosomes carrying genes encoding enzymes involved in punne metabolism. The activities of ten enzymes were measured: adenosine kinase, adenine phosphoribosyltransferase, adenylate kinase, methylthioadenosine phosphorylase, hypoxanthine phosphoribosyltransferase, adenylosuccinate lyase, inosine monophosphate dehydrogenase, adenosine deaminase, nuckoside phosphorylase and adenosine monophosphate deaminase. In paralkle, two enzymes involved in pyrimidine metabolism, thymidine kinase and thymidylate synthase (TS), were studied. The activities of all these enzymes were measured on samples from 30 human primary glial tumours with low or high malignancy, six xenografted tumours at different passages, four portions of normal brain tissue and four non-gal brain neoplasms. As suggested by cytogenetic data, the enzymatic results showed a relatively low activity of puine metabolism in ghal tumours when compared with normal brain and non-glial brain neoplasms. Considering the two enzymes involved in pyrimidine metabolism, only T'S had higher activity in glial tumours of high malignancy than in normal brain. In comparison with normal brain, the balanc between salvage and de novo pathways changes in gliomas, and even more in grafted tumours, in favour of de novo synthesis. The relation between chromosomes and metabolic imbalancs does not correspond to a simple gene dosage effect in these tumours.These data suggest that the dcrease of adenosine metabolism ocus before chromosomal aberrations appear, since it is observed in tumours of low malignancy when most karyotypes are still normal, and that the de novo pathway increases with tumour progression.

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DIVERSITY OF METABOLIC PATTERNS IN HUMAN BRAIN TUMORS—I. HIGH ENERGY PHOSPHATE COMPOUNDS AND BASIC COMPOSITION¹

Cited by 86 publications

References 18 publications

Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

In vivo nuclear magnetic resonance spectroscopy of a transplanted brain tumour

Purine and pyrimidine metabolism in human gliomas: relation to chromosomal aberrations

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DIVERSITY OF METABOLIC PATTERNS IN HUMAN BRAIN TUMORS—I. HIGH ENERGY PHOSPHATE COMPOUNDS AND BASIC COMPOSITION1

Cited by 86 publications

References 18 publications

Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

Energy Status And Metabolism in Intracranial Space Occupying Lesions: A Prospective 31p Spectroscopic Study

In vivo nuclear magnetic resonance spectroscopy of a transplanted brain tumour

Purine and pyrimidine metabolism in human gliomas: relation to chromosomal aberrations

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DIVERSITY OF METABOLIC PATTERNS IN HUMAN BRAIN TUMORS—I. HIGH ENERGY PHOSPHATE COMPOUNDS AND BASIC COMPOSITION¹