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

High-resolution one-dimensional proton and phosphorus and two dimensional COSY proton Magnetic Resonance Spectroscopy were used to investigate the lipid and carbohydrate metabolism of human brain tumors. Sixteen meningioma (MG) (benign tumors) and ten glioblastoma (GB) (malignant tumors) samples from brain surgery were treated for dual extraction of lipidic and aqueous phases before NMR processing. A highly significant variation of the 1H metabolite spectral pattern was observed between benign and malignant tumors. Double extraction method combined with both 1H and 31P NMR in vitro analyses provided a large set of biochemical information which may be statistically analyzed to elucidate tumor-specific biochemical pathways and to improve interpretation of in vivo spectra.
 ...
PMID:Proton and phosphorus nuclear magnetic resonance spectroscopy of human brain tumor extracts with automatic data classification: a preliminary study. 929 89

The abilities of growth factors to cause normal cells to express the properties associated with transformed cells is discussed in specific reference to the oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. In the O-2A lineage, it has been possible to use growth factors and other defined molecules to induce or promote in normal cells all of the main properties of tumor cells, these being continued cell division in the absence of differentiation, more subtle modulations of self-renewal probabilities, promotion of cell migration and inhibition of programmed cell death. In addition to our studies on primary cells, our application to the growth of human tumor specimens of techniques utilized to study primary glial progenitor cells has allowed us to isolate 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 conservation 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. Our results thus demonstrate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. Our analyses further indicate that at least two distinct glial lineages can generate glioblastomas. 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.
 ...
PMID:Growth factors, glia and gliomas. 944 20

Recent studies have shown that MRS can substantially improve the non-invasive categorization of human brain tumours. However, in order for MRS to be used routinely by clinicians, it will be necessary to develop reliable automated classification methods that can be fully validated. This paper is in two parts: the first part reviews the progress that has been made towards this goal, together with the problems that are involved in the design of automated methods to process and classify the spectra. The second part describes the development of a simple prototype system for classifying 1H single voxel spectra, obtained at an echo time (TE) of 135 ms, of the four most common types of brain tumour (meningioma (MM), astrocytic (AST), oligodendroglioma (OD) and metastasis (ME)) and cysts. This system was developed in two stages: firstly, an initial database of spectra was used to develop a prototype classifier, based on a linear discriminant analysis (LDA) of selected data points. Secondly, this classifier was tested on an independent test set of 15 newly acquired spectra, and the system was refined on the basis of these results. The system correctly classified all the non-astrocytic tumours. However, the results for the the astrocytic group were poorer (between 55 and 100%, depending on the binary comparison). Approximately 50% of high grade astrocytoma (glioblastoma) spectra in our data base showed very little lipid signal, which may account for the poorer results for this class. Consequently, for the refined system, the astrocytomas were subdivided into two subgroups for comparison against other tumour classes: those with high lipid content and those without.
NMR Biomed
PMID:Towards a method for automated classification of 1H MRS spectra from brain tumours. 971 72

In vitro NMR spectroscopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. (31)P- and (1)H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. (31)P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the (1)H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the (31)P- and the (1)H-spectra. Based on the total detectable (31)P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary glioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and -23% (p = 0.0314) change, respectively]. (1)H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the (31)P-spectra, the (1)H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. (1)H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution (1)H- and (31)P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism.
NMR Biomed 2001 Aug
PMID:1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components. 1147 51

It is often difficult to make a correct diagnosis of ring-like enhanced lesions on Gd-enhanced MR brain images. To differentiate these lesions using proton MR spectroscopy (1H-MRS), we retrospectively evaluated the correlation between the 1H-MR spectra and histopathological findings. We evaluated proton MR spectra obtained from the lesions in 45 patients, including metastasis (n = 19), glioblastoma (n = 10), radiation necrosis (n = 7), brain abscess (n = 5), and cerebral infarction (n = 4). The rate of misdiagnosis was found to be lowest at the threshold level of 2.48 for the (choline containing compounds)/(creatine and phosphocreatine) ratio (Cho/Cr) obtained from the whole lesions, which include the enhanced rim and the non-enhanced inner region. That is, the positively predictive values of a Cho/Cr greater than 2.48 for diagnosing metastasis or glioblastoma was 88.9 and 60.0%, respectively, and the positively predictive value of a Cho/Cr less than 2.48 for diagnosing radiation necrosis or cerebral infarction was 71.4 and 100%, respectively. For further differentiating between metastasis and glioblastoma, information about the presence and absence of an N-acetyl-aspartate (NAA) peak and lipid- or lactate-dominant peak was found to be useful. In 73.7% of metastasis cases a lipid-dominant peak was observed in the whole lesion without an NAA peak in the inner region, whereas the same pattern was observed in only 10% of the glioblastoma cases. Correlation with the histopathological findings showed that a high Cho signal is suggestive of neoplasm. Lipid signal in the non-enhanced central region was correlated to necrosis. Lactate signals were often observed in glioblastoma, abscess and sometimes metastasis, presumably reflecting the anaerobic glycolysis by the living cells in the ring-like enhanced rim. Single-voxel proton MR spectroscopy may serve as a potential tool to provide useful information of differentiation of ring-like enhanced lesions that cannot be diagnosed correctly using enhanced MR images alone.
NMR Biomed 2001 Oct
PMID:In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement. 1159 32

Localized phosphorus-31 MR spectra were obtained in vivo in a large series of normal human brain tissue specimens of healthy volunteers (n=36) and various brain tumours (n=52). Tumour types examined included grade II and grade III gliomas (n=15 and n=1, respectively), glioblastomas (n=16) and meningeomas (n=12). An additional eight tumours were analysed during chemo- or radiotherapy. Spectra were acquired using a modified ISIS pulse sequence with a repetition time of 3 s. Voxel sizes ranged from 56 to 129 ml. The spectra were evaluated using a least-square variable projection (VARPRO) fitting procedure in the time domain, which allows semi-quantitative determination of relative metabolite concentrations. The measurements in normal cerebrum of healthy volunteers revealed the following results of metabolite signal intensity ratios: pH 7.04 (+/- 0.01), PCr/alpha-ATP 0.51 (+/- 0.03), P(i)/alpha-ATP 0.17 (+/-0.02), PCr/P(i) 2.09 (+/-0.12), PDE/alpha-ATP 3.65 (+/-0.13) and PME/alpha-ATP 0.41 (+/-0.04). Meningiomas showed the most obvious changes when compared with normal brain tissue. They are characterized by an alkaline environment (pH 7.16 +/- 0.03; p<0.005), a decrease in the phosphocreatine peak (p<0.0001) and significantly decreased phosphodiesters (p<0.0001). Glioblastomas also showed alkalization (pH 7.12 +/- 0.02; p<0.001) and a decrease in PDE/alpha-NTP (p<0.05), but no significant changes in PCr/alpha-NTP or PCr/Pi. In gliomas with low malignancy, less distinct changes could be detected with slight alkalization (pH 7.09 +/- 0.02; p<0.05) and more than a two-fold reduction in the PDE/alpha-NTP ratio (p<0.05). The spectra of brain tumours during chemo- and radiotherapy indicated clear but inconsistent influence of the therapy.
NMR Biomed 2002 Feb
PMID:Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours. 1184 May 49

Multinuclear ((1)H, (13)C, and (31)P) magnetic resonance spectroscopy are applied to the biochemical characterization of the total lipid fraction of healthy and neoplastic human brain tissues. Lipid extracts from normal brains, glioblastomas, anaplastic oligodendrogliomas, oligodendrogliomas, and meningiomas are examined. Moreover, the unknown liquid content of a cyst adjacent to a meningioma is analyzed. Two biopsies from glioblastomas are directly studied by (1)H-NMR without any treatment (ex vivo NMR). The (1)H- and (13)C-NMR analysis allows full characterization of the lipid component of the cerebral tissues. In particular, the presence of cholesteryl esters and triglycerides in the extracts of high grade tumors is correlated to the vascular proliferation degree, which is different from normal brain tissue and low grade neoplasms. The (31)P spectra show that phosphatidylcholine is the prominent phospholipid and its relative amount, which is higher in gliomas, is correlated to the low grade of differentiation of tumor cells and an altered membrane turnover. The ex vivo (1)H-NMR data on the glioblastoma samples show the presence of mobile lipids that are correlated to cell necrotic phenomena. Our data allow a direct correlation between biochemical results obtained by NMR and the histopathological factors (vascular and cell proliferations, differentiation, and necrosis) that are prominent in determining brain tumor grading.
 ...
PMID:Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy. 1185 68

Three natural flavonols compounds have been isolated from the ethyl acetate fraction of Scurrula ferruginea Danser (Loranthaceae). Besides quercetin and quercitrin, an unusual flavonol glycoside 4"-O-acetylquercitrin was isolated. Structures were determined using spectroscopic methods including UV, NMR and HRMS-EI. The incidence of 4"-O-acetylquercitrin, not previously reported in the Loranthaceae, is discussed. Cytotoxic evaluation on four human cancer cell lines showed quercetin to be the most active with IC50 of 35 microM on U251 (human glioblastoma cells).
 ...
PMID:Flavonols from Scurrula ferruginea Danser (Loranthaceae). 1256

Glutathione (GSH) is a ubiquitous non-protein thiol essential for cellular homeostasis and protection. Diazenecarboxamides (diazenes) are new compounds that could, according to their biochemical properties, lower the intracellular GSH content, thus inhibiting the growth of tumour cells. In the present study we examined four such compounds: JK-914, JK-918, JK-1013 and UP-91. Their cytotoxic effect on the growth of eight human tumour cell lines (glioblastoma, cervical and laryngeal carcinoma cells, mammary carcinoma cells and four drug-resistant sublines) was determined using a modified colorimetric MTT assay. The rate of reaction of thiophenol (as a model thiol) with diazenes leading to diphenyl disulfide was established by chromatography (TLC). Reactivity of diazenes with GSH under quasi-physiological conditions was determined by NMR spectroscopy. Intracellular GSH content was examined spectrophotometrically by the procedure developed by Tietze (1969). Diazene UP-91 reduced significantly the cell survival of all eight examined cell lines, including four drug-resistant cell lines. Other diazenes did not influence the survival of tumour cells. Reaction time for quantitative conversion of thiophenol to diphenyl disulfide was shortest for diazene UP-91, which is highly consistent with high reactivity of the same diazene with GSH, observed under quasi-physiological conditions. UP-91 reduced intracellular GSH level, while other diazenes had no effect on it. Thus, diazenecarboxamides UP-91 is a potential anticancer agent that may inhibit the growth of tumour cells due to reduction in glutathione level.
 ...
PMID:Diazenecarboxamide UP-91, a potential anticancer agent, acts by reducing cellular glutathione content. 1257 33

The synthesis of pentacoordinated Tin(IV) compounds derived from aminoalcohols is described. The compounds were characterized by IR, 1H-, 13C-, and 119Sn-NMR, the mass spectrometry exhibits molecular ions corresponding to monomeric species. All compounds were evaluated for in vitro cytotoxic activities against five human tumor cell lines, U251 (human glioblastoma), PC-3 (human prostatic adenocarcinoma), K-562 (human chronic myelogenous leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma). The cytotoxic evaluation revealed that all compounds possess higher cytotoxic potency than that of the cisplatin, which was used as reference. Additionally, MT2 cells (human T-lymphocytes) were also evaluated.
 ...
PMID:Synthesis, characterization and in vitro cytotoxicity of pentacoordinated Tin(IV) complexes derived from aminoalcohols. 1639 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>