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)

Three new esters of orsellinic acid, globosumones A-C (1-3), and three known compounds, orsellinic acid (4), orcinol, and trichodion (5), were isolated from Chaetomium globosum endophytic on Ephedrafasciculata (Mormon tea). The structures of the new compounds 1-3 were established spectroscopically, which included 2D NMR experiments and 1H NMR studies on Mosher's ester derivatives. All compounds were evaluated for inhibition of cell proliferation in a panel of four cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), SF-268 (CNS glioma), and MIA Pa Ca-2 (pancreatic carcinoma), and normal human fibroblast cells (WI-38). Only globosumones A (1) and B (2) were found to be moderately active.
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PMID:Globosumones A-C, cytotoxic orsellinic acid esters from the Sonoran desert endophytic fungus Chaetomium globosum. 1592 17

New complexes of rhenium(I) with some 5-nitrosopyrimidines with general formula [ReCl(CO)3L] have been prepared and characterized by elemental analysis, conductivity measurements, IR and 1H, 13C and 15N NMR spectroscopic methods. The complexes appear to be monomeric and the pyrimidine ligands act in a neutral form. The structure of [ReCl(CO)3(DANU)].CH3CN has been solved by X-ray diffraction. The coordination environment around the Re(I) may be described as a distorted octahedron in which the ligand behaves in a bidentate fashion through N5 and O4 atoms, making a five-membered chelate ring. The coordination sphere is completed with three carbonyl groups in fac-arrangement and one chlorine atom. The evaluation of the antiproliferative behavior against five human tumor cell lines (human breast cancer MCF-7 and EVSA-T, human neuroblastoma NB69, human glioma H4 and human bladder carcinoma cell line ECV) suggested a modulator behavior of cell growth at low concentrations due to their estrogenic-like characteristics.
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PMID:Synthesis, characterization and antiproliferative behavior of tricarbonyl complexes of rhenium(I) with some 6-amino-5-nitrosouracil derivatives: crystal structure of fac-[ReCl(CO)3(DANU-N5,O4)] (DANU=6-amino-1,3-dimethyl-5-nitrosouracil). 1596 33

An artificial tumor method was developed to study cells inside the sensitive volume of an NMR spectrometer during growth and apoptosis. The tumor was composed of a 50:50 mixture of tightly packed porous-collagen and nonporous-polystyrene microspheres. The porous collagen served as a growth surface for the tumor cells, and the nonporous polystyrene served as a structural support to limit compression of the packed bed during perfusion. The microspheres were held between two porous polyethylene discs that were tightly sealed inside the NMR perfusion chamber. The new method was evaluated with two cell types: a mouse mammary tumor line (EMT6/SF) and a human glioma line (SF188). The results indicate that for both lines, approximately 10(9) metabolically active cells could be sustained for at least 1 week in the 12-cm(3) artificial tumor. Further, cells undergoing chemotherapy-induced apoptosis (which is known to cause detachment of cells from their surroundings) were retained in the artificial tumor. In preliminary 31P NMR studies, glioma cells treated with temozolomide (TMZ) exhibited reduced phosphocholine (PCh) levels relative to glycerophosphocholine (GPC) and diphosphodiester (DPDE) levels. They also exhibited sharply reduced oxygen consumption and TCA cycle 13C labeling, while they retained glycolytic activity. These metabolic changes are consistent with those that would be expected during mitochondrially-mediated apoptosis.
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PMID:Artificial tumor model suitable for monitoring 31P and 13C NMR spectroscopic changes during chemotherapy-induced apoptosis in human glioma cells. 1596 47

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.
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PMID:Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy in rat glioma in vivo. 1611 4

1. Bisphosphonates are currently the most important class of antiresorptive drugs used for the treatment of diseases with excess bone resorption. On the basis of their molecular mechanism of action, bisphosphonates can be divided into two pharmacological classes; nitrogen-containing (N-BPs) and non-nitrogen-containing bisphosphonates (non-N-BP). Both classes induce apoptosis but they evoke it differently; N-BPs by inhibiting the intracellular mevalonate pathway and protein isoprenylation, and non-N-BPs via cytotoxic ATP analog-type metabolites. N-BPs are not metabolized to ATP analogs, but we report here that these bisphosphonates can induce formation of a novel ATP analog (ApppI) as a consequence of the inhibition of the mevalonate pathway in cells. We also investigated whether ApppI is involved in the apoptosis induced by N-BPs. 2. Mass spectrometry and NMR were used to identify ApppI in N-BP treated osteoclasts, macrophages and glioma cells. The potency of different bisphosphonates to promote ApppI production was tested in J774 macrophages. The effects of ApppI on ADP/ATP translocase in isolated mitochondria and its capability to induce apoptosis in osteoclasts were also studied. 3. ApppI production correlated well with the capacity of N-BPs to inhibit mevalonate pathway. ApppI inhibited the mitochondrial ADP/ATP translocase and caused apoptosis in osteoclasts. 4. In conclusion, these findings provide the basis for a new mechanism of action for N-BPs. Some of these very potent bisphosphonates, such as zoledronic acid, represent a third class of bisphosphonates that can act both via the inhibition of the mevalonate pathway and by the blockade of mitochondrial ADP/ATP translocase, which is known to be involved in the induction of apoptosis.
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PMID:A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. 1640 39

The aim of this work was to identify spectral markers of cell proliferation that could be of use in clinical MRS. Cultured C6 ATCC rat glioma cells were used as models for this purpose and metabolites were extracted with perchloric acid at three different growth curve stages: log, confluence and post-confluence. 1D and 2D in vitro(1)H NMR spectra were recorded at 9.4 T. Statistically significant changes in myo-inositol and glutamine concentrations between log phase and post-confluence were found when normalized to the creatine ratio. The myo-inositol/creatine ratio was 2.76 +/- 0.82 at log phase increasing to 7.43 +/- 1.34 at post-confluence, while the glutamine/creatine ratio decreased from 0.22 +/- 0.03 to 0.10 +/- 0.02. No significant differences were recorded for other metabolites investigated. The fact that both myo-inositol and glutamine are detectable by in vivo MRS at clinical fields makes their changes relevant as potential astrocytic tumour proliferation rate markers in clinical MRS.
NMR Biomed 2006 Apr
PMID:Analysis of the changes in the 1H NMR spectral pattern of perchloric acid extracts of C6 cells with growth. 1648 20

The functional genomic approaches of transcriptomics, proteomics and metabolomics aim to measure the mRNA, protein or metabolite complement of a cell, tissue or organism. In this study we have investigated the compatibility of transcriptional analysis, using Reverse Transcription (RT)-PCR, and metabolite analysis, by high-resolution magic angle spinning (HRMAS) 1H NMR spectroscopy, in BT4C rat glioma following the induction of programmed cell death. The metabolite and transcriptional changes that accompanied apoptosis were examined at 0, 4 and 8 days of ganciclovir/thymidine kinase gene therapy. Despite the high spinning speeds employed during HRMAS 1H NMR spectroscopy of one-half of the tumor samples, RT-PCR analysis of the pro-apoptotic transcripts Bcl-2, BAK-1, caspase-9 and FAS was possible, producing similar results to those detected in the unspun half of the tumors. Furthermore, the expression of FAS was inversely correlated with some of the key metabolic changes across the time period examined including the increases CH=CH and CH=CHCH2 lipid resonances which accompany apoptosis. This study demonstrates how combined transcriptomic and metabolomic studies of tumors can be used to understand the molecular events that accompany well documented metabolic perturbations during cell death processes.
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PMID:High-resolution magic angle spinning 1H NMR spectroscopy and reverse transcription-PCR analysis of apoptosis in a rat glioma. 1650 6

We demonstrate the feasibility of using ultra-short echo time (TE = 2 ms) magnetic resonance spectroscopic imaging (MRSI) to detect intracranial mobile lipids in the rat brain. High-performance outer volume suppression and pre-localization were demonstrated in phantoms and by the total absence of signals arising from extra-cranial lipids in MRSI spectra from control rats. The sequence performance was tested on glioma-bearing BDIX rats. Fast-relaxing lipid signals were spatially varied within a glioma during herpes simplex virus thymidine kinase-mediated gene therapy, demonstrating the potential application of this method.
NMR Biomed 2006 Aug
PMID:Ultra-short echo time spectroscopic imaging in rats: implications for monitoring lipids in glioma gene therapy. 1652 27

Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent effects in nanoparticles technology for biomedical applications. This work was thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various copolymer blend ratio, which were synthesized by ring-opening polymerization and characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80 copolymers were prepared by the dialysis method without surfactants/emulsifiers involved. Paclitaxel was chosen as a prototype anticancer drug due to its excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by various state-of-the-art techniques, including laser light scattering for particles size and size distribution, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler anemometry for zeta potential; differential scanning calorimetry (DSC) for the physical status of the drug encapsulated in the polymeric matrix; X-ray photoelectron spectrometer (XPS) for surface chemistry; high performance liquid chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6 cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid) (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol at the same 50 microg/mL drug concentration.
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PMID:In vitro investigation on poly(lactide)-Tween 80 copolymer nanoparticles fabricated by dialysis method for chemotherapy. 1660 31

2-Fluoro-4-nitrophenol-beta-D-galactopyranoside (OFPNPG) belongs to a novel class of NMR active molecules (fluoroaryl-beta-D-galactopyranosides), which are highly responsive to the action of beta-galactosidase (beta-gal). OFPNPG has a single 19F peak (-55 ppm relative to aqueous sodium trifluoroacetate). Upon cleavage by beta-gal, the pH sensitive aglycone 2-fluoro-4-nitrophenol (OFPNP) is observed at a chemical shift of -59 to -61 ppm. The chemical shift response is sufficient to observe beta-gal activity using chemical shift imaging (CSI). 19F CSI studies of enzyme activity and lacZ gene expression in 9L-glioma and MCF7 breast cancer cells are presented, providing further evidence for the utility of OFPNPG as a gene-reporter molecule for future in vivo studies.
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PMID:Imaging beta-galactosidase activity using 19F chemical shift imaging of LacZ gene-reporter molecule 2-fluoro-4-nitrophenol-beta-D-galactopyranoside. 1691 13


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