Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with 131I. Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (greater than 50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after II months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.
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PMID:Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I-labelled anti-tenascin monoclonal antibody BC-2. 137 10

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary's criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month follow-up examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disabled. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.
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PMID:Direct surgery for brainstem tumours. 180 73

Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720-3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour-surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated.
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PMID:Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN). 210 74

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.
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PMID:Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR. 403 75

Phospholipid extracts from 48 intracranial tumors were analyzed using 31P NMR. Phospholipids commonly identified in the tumor spectra included phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG), uncharacterized phospholipid (U), ethanolamine plasmalogen (EPLAS), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), lysophosphatidylcholine (LPC), phosphatidylinositol (PI), a choline phospholipid (CPLIP), and phosphatidylcholine (PC). Differences in the mean relative mole-percentage of phosphorus concentrations of individual phospholipids were used to differentiate among tumors. Neural sheath tumors (neurilemmoma, neurofibroma and fibrosarcoma) were noted to contain significantly elevated levels of SM relative to tumors of neural glial origin and individually, glioblastoma multiforme was noted to contain depressed levels of SM relative to neurilemmoma, neurofibroma and meningioma. Significantly decreased levels of PA were noted for glioblastoma relative to neurilemmoma along with significantly decreased levels of PE relative to meningioma. Elevated levels of LPC and CPLIP were seen in glioblastoma multiforme relative to meningioma. Additional findings included elevated levels of PC for glioblastoma multiforme relative to neurofibroma, and neurilemmoma was differentiated from neurofibroma with elevated levels of PA and depressed levels of PI. 31P NMR phospholipid analysis provides supplemental biochemical information which may be used to improve the interpretation of spectra acquired in vivo, and reveals important tumor-specific biochemical information which may further improve the understanding of the biological behavior of intracranial tumors.
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PMID:31P NMR phospholipid characterization of intracranial tumors. 795 20

NMR spectroscopy was used to analyse perchloric acid extracts of normal human brain, murine brain cell cultures, glioblastoma tissue and the glioblastoma cell line U-87. 1H NMR spectra revealed the presence of elevated levels of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine in glioblastoma extracts and the glioblastoma cell line U-87, in comparison with normal brain tissue and primary cell cultures of neurons and astrocytes. UDP-N-acetylhexosamines appear to accumulate in cells that are unable to differentiate. Furthermore, it was found that the culture medium had an effect on the concentration of UDP-N-acetygalactosamine in the glioblastoma cell line. Hypotaurine, previously only associated with oligodendrocytes, has been identified in astrocyte cultures and in cerebellar granule cells. In normal brain it was not observed by NMR spectroscopy, but was easily detectable in glioblastoma tissue extracts. UDP-N-acetylhexoseamines and hypotaurine might be useful markers for brain pathology and play a role in cell differentiation and cell division.
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PMID:UDP-N-acetylhexosamines and hypotaurine in human glioblastoma, normal brain tissue and cell cultures: 1H/NMR spectroscopy study. 807 80

Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified. T1 relaxation times for the most prominent compounds are presented. T1 values of lactate ranged between 450 ms and 850 ms. The intensity of the lactate signal revealed differences between individual spectra, but exhibited no correlation between different tumor specimens or degree of malignancy. It was shown that the lactate signal at 1.3 ppm is covered by peaks arising from threonine and fatty acids. The choline signal level varied among spectra of different tumors, among tumors with similar degree of malignancy, and within the same tumor. Further preliminary differences due to aspartate, inositol and glutamine/glutamate were found in 1D and 2D COSY spectra between normal glial cells as well as different tumors. These results indicate that some differences observed in in vivo spectra may be attributable to secondary macroscopic structural changes (hypoxia, necrosis) and not to tumor inherent characteristics. Further correlation between in vivo and in vitro spectroscopy is therefore required.
NMR Biomed 1994 May
PMID:High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells. 808 Jul 12

With only a few exceptions, the precursor cells representing the normal counterparts of human tumours are unknown. The comparative lack of information about the lineages involved in tissue development, and difficulties in growing many human tumors in a manner suitable for cellular biological analysis, together often make it difficult to study the differences between normal and tumor cells and to develop many of the model systems that would be useful in the study of human cancer. By applying techniques previously utilized to study glial progenitor cells, we have isolated a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conversation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible, and our results indicate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.
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PMID:From rodent glial precursor cell to human glial neoplasia in the oligodendrocyte-type-2 astrocyte lineage. 858 59

Cell culture techniques, high-resolution in vitro 1H NMR spectroscopy, and chromatographic analyses were used to compare the properties of three types of human brain and nervous system tumours. Cell lines were immunocytochemically characterized at all stages in culture with specific antibodies. Intracellular metabolites present in cell extracts were analysed by 1H NMR spectroscopy and by high performance liquid chromatography (HPLC). The spectra from meningiomas, neuroblastomas, and glioblastomas displayed, in addition to similarities-including the presence of signals from leucine, isoleucine, valine, threonine, lactate, acetate, glutamate, choline-containing compounds and glycine-certain distinguishing metabolic features. Spectra from meningiomas featured relatively high signals from alanine. Intense signals from creatine were present in neuroblastoma spectra, while in spectra from glioblastoma they were not detectable. We found statistically significant differences by 1H NMR spectroscopy in the amounts of alanine, glutamate, creatine, phosphorylcholine and threonine among the types of tumours examined. HPLC determinations confirmed that there were also other metabolites specific to a type of tumour, such as taurine, gamma-aminobutyric acid, and serine. We suggest that these findings have potential relevance for the development of non-invasive diagnosis of tumour lineage by 1H NMR spectroscopy in vivo.
NMR Biomed 1995 Sep
PMID:Characteristic metabolic profiles revealed by 1H NMR spectroscopy for three types of human brain and nervous system tumours. 873 81

Water-soluble metabolites extracted from 60 surgically excised samples of various brain tumors and four nontumorous lobectomized brains were measured quantitatively using in vitro high-resolution magnetic resonance spectroscopy. A detailed MR spectrum-histology correlation study in a glioblastoma was made, to reveal MR spectral changes in accordance with the density of glioma cells. Furthermore, three cases that had difficult preoperative diagnoses are discussed. MR spectra from gliomas exhibited characteristic patterns according to malignancy, presumably reflecting its metabolic effects. Concentrations of choline-containing compounds, inositol, alanine, glycine and phosphorylethanolamine (PEA) increased according to the degree of malignancy, but it was noteworthy that in glioblastoma the choline-containing compounds, inositol, alanine, glycine and phosphorylethanolamine increased according to the degree of malignancy. In particular, the glycine concentration was very high in glioblastoma. We also detected a large amount of taurine in medulloblastoma. Although the total creatine concentrations decreased according to the malignancy, the concentration of total creatine was relatively preserved in neuroectodermal tumors but was low in nonneuroectodermal tumors. N-acetyl-aspartate was unequivocally demonstrated in normal tissues, but could not be detected in nonneuroectodermal brain tumors such as metastatic brain tumor, meningioma, neurinoma and chordoma. In meningioma, although a high peak of choline-containing compounds has been reported uniquely by in vitro and in vivo 1H-MRS, we demonstrated that its concentration was not increased in meningioma; instead, there was an increased alanine content. 1H-MRS of neurinoma demonstrated high inositol peaks, and a large amount of inositol. The reason for the high inositol content in neurinoma is unknown, but the prominent peak of inositol on MR spectra should be useful for the differential diagnosis of neurinoma from meningioma. PEA concentration was increased four to five times in pituitary adenoma, malignant lymphoma, and medulloblastoma as compared with normal brain. Thus 1H-MRS might provide clinically useful information on tumor malignancy and characteristic tumor metabolism. Although excellent anatomical information of tumors can be readily obtained by magnetic resonance imaging. MRS provides metabolic information. MRS may provide additional information in cases in which the differential diagnosis of tumors by neuroimaging is difficult.
NMR Biomed 1997 Jan
PMID:Absolute concentrations of metabolites in human brain tumors using in vitro proton magnetic resonance spectroscopy. 925 Nov 9


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