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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IgG from immunized rabbits was labelled with Fluorescein Isothiocyanate, and conjugated in vitro with human and with rat glioblastoma. After absorption of the antisera with normal brain and liver, a heavy concentration of antibody was found in the rat tumour cells. A great amount of antibody was also found in the human neoplastic cells. The incorporation of this antibody in glioma cells of different rats developing new tumours indicates that transplantation antigens of the H-2 type are not the only ones capable of inducing specific antibody attachment.
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PMID:Heterologous antibodies in human and rat's glioblastoma. 96 4

Fluorescent dyes were used in conjunction with confocal microscopy to record the vitality status of cells in multicellular glioma spheroids. Multicellular spheroids are in vitro models for micrometastases or intravascular microregions of large tumors. With progressing growth three distinct concentric annular shells develop. A rim of proliferating cells in the periphery is followed towards the center by layers of quiescent cells and at a defined spheroid diameter cell death occurs in the central core. Fluorescein diacetate (FDA) and Calcein/AM were used as vital stains and Lucifer Yellow/VS (LYVS) was used as a marker for dead cells. For loading multicellular spheroids with the esterase substrate dyes we used a two step cold incubation technique to avoid dye accumulation in the most peripheral cell layers. Homogenously stained tissue allowed to describe the fluorescence attenuation in depth as a monoexponential decay. An attenuation coefficient C was calculated from calibration experiments to be 12.5 x 10(-3) in vital stained tissue and 17.9 x 10(-3) in lethal stained tissue. Using the respective attenuation coefficient the raw data were corrected for light absorption and scattering in depth. In radial recordings of the vitality status of multicellular glioma spheroids using CLSM-technique we showed that spheroids up to a diameter of 250 microns were homogenously stained with Calcein/AM and FDA. Spheroids larger than 250 microns consist of vital stained cells and unstained cells. They do not show dead cell staining until they reach a diameter of about 400 microns. The thickness of the rim of vital stained cells decreased with increasing diameter of the spheroids to 64 +/- 7 microns in spheroids of a diameter of 550 +/- 25 microns. Thereafter the thickness of the Calcein/AM or FDA stained rim augmented again, reaching 93 +/- 9 microns in spheroids of 700 microns in diameter. The first signs of dead cell staining in the central core occurred at a diameter of 400 +/- 25 microns. The radius of the core increased in an exponential way. The cell layer which was stained neither by vital nor by lethal dyes showed a thickness of 150 microns in spheroids of 550 +/- 25 microns in diameter. Our staining technique and the radial recording of mean field fluorescence signals in living multicellular spheroids will be a valuable tool for experimental cancer research providing a non invasive quantification of cell vitality in living multicellular spheroids.
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PMID:Quantitative recording of vitality patterns in living multicellular spheroids by confocal microscopy. 864 Mar 59

Using a fluorescein surgical microscope that we developed, we performed surgery on 30 cases of malignant glioma. Operative findings and histological findings were then compared in five of these cases. Fluorescein sodium was systemically administered intravenously as a fluorescent dye. About 20 min after intravenous administration, fluorescein activity in the blood decreased, and the fluorescence was observed only in the area lacking the blood-brain barrier function, such as tumors; then, resection of the tumor was started. The fluorescent regions coincided with the enhanced regions on CT and MRI. Fluorescein spread to the surrounding brain edematous region with time, but its intensity was very different from the tumor-associated one. In the histological examination of intensely fluorescent regions, abnormal tumor blood vessels with a thick wall and a small caliber, or with a thin wall and a large caliber, were observed. Dense tumor cells were found in these regions. On the other hand, in regions with weak or no fluorescence, infiltration of tumor cells was scant, and no abnormal blood vessels were found. Fluorescence was not observed in necrotic regions of the tumor center. These histological findings coincided with those obtained in large surgical specimen or autopsy, and tumor-cell rich regions seemed to be removed by resecting abnormal vascular regions (fluorescent regions). Enhanced regions on CT and MRI disappeared after operation by resecting intensely fluorescent regions. These results indicate that the fluorescein surgical microscope developed by us is a useful aid in operations on malignant glioma.
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PMID:Comparison between operative findings on malignant glioma by a fluorescein surgical microscopy and histological findings. 1004 72

Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cell death due to diffusion gradients in a three-dimensional system without confounding influences of immune response, pressure gradients, etc. Spheroid cultures were established from four malignant glioma cell lines: U87, U373, MOG-G-CCM and A172; harvested from culture at weekly intervals and stained with Haematoxylin and Eosin (H&E), TdT-mediated dUTP-X nick end labelling (TUNEL) and by immunohistochemistry for vimentin, Glial Fibrillary Acidic Protein (GFAP) and Ki67. Annexin V flow cytometry and counts of apoptotic cells on H & E stained sections were performed to assess levels of apoptosis. Modes of cell death were also characterized by electron microscopy. Spatially separate zones of proliferation, differentiation and central cell death developed with increasing spheroid diameter. Central cell death developed at a predictable radius (300-400 microm) for each cell line. Ultrastructural examination showed this to be necrotic in type. Apoptosis was most reliably assayed by morphological counts using H & E. Basal levels of apoptosis were low (< 0.5%), but increased with increasing spheroid diameter (> 2% in U87). In particular, levels of apoptosis rose following development of central necrosis and apoptoses were most abundant in the peri-necrotic zone. There were quantitative differences in the levels of apoptosis and necrosis between glioma cell lines. The predictable onset of necrosis in the spheroids will allow us to investigate the pathogenesis of necrosis and events in prenecrotic cells. There is a relationship between the development of necrosis and apoptosis in this model and these processes can be separately assayed. Further in vitro and genetic studies will enable us to study these events and interactions in greater detail than is possible using other cell culture and in vivo systems.
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PMID:The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems. 1153 60

The aim of this study was to examine the cytotoxicity and mechanism of apoptosis induction of verotoxin-1 (VT-1) in human glioma cell lines. VT-1 is a member of the shiga-toxin family expressed by some serotypes of Escherichia coli and Shigella dysenteriae. Shiga-toxins have been shown to induce apoptosis by binding to its membrane receptor Gb3. The human glioma cell lines SF-767, U-343 MG, and U-251 MG were studied together with BT4C, a rat glioma cell line. Cells were first screened for Gb3 expression by flow cytometry. Fluorescein diacetate was used to determine cell viability after VT-1 and irradiation exposure and apoptosis was studied by TUNEL staining, a mitochondrial membrane potential assay, and caspase activity assays. SF-767 and U-343 MG cells were found to express Gb3 and were also sensitive to VT-1-induced cytotoxicity, whereas nonGb3-expressing U-251 MG and BT4C glioma cells were not. VT-1 depolarized the mitochondrial membrane and activated caspase-9 and -3 of SF-767 and U-343 MG cells. VT-1 exposure for 72 h resulted in approx. 60 and 90% TUNEL-stained cells, respectively. D, L-Threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) an inhibitor of glucosylceramide synthesis was used to block Gb3 synthesis. Two mumol/L PPMP for 72 h abolished SF-767 and U-343 MG expression of Gb3 and made the cells completely resistant to VT-1 induced apoptosis. Key components of MAP kinase signalling pathways that control BAX and mitochondrial function were investigated. VT-1 induced JNK phosphorylation in both cell lines, suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. Immunohistochemistry of cryostat section from glioma biopsies demonstrated expression of Gb3 was in the vascular endothelial cells as well as tumor cells, but not in astrocytes. The high specificity and apoptosis inducing properties of verotoxin-1 indicates that the toxin may be a potential anti-neoplastic agent for Gb3-expressing gliomas.
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PMID:Verotoxin-1 induction of apoptosis in Gb3-expressing human glioma cell lines. 1720 57

The neurotoxin 1-methy-4-phenylpyridinium (MPP(+)) is used for its' capacity to induce Parkinsonism through its inhibitory effects on mitochondrial complex I. This inhibition disrupts cellular energy formation and aerobic glycolysis. The objective of this study was to demonstrate that the toxic effect of mitochondrial aerobic pathway inhibition with MPP(+ )can be reduced by stimulating anaerobic glycolysis using glucose supplementation. In this study, C6 Glioma cell viability was examined in the presence of different concentrations of MPP alone and with the addition of glucose. The results obtained indicate that there was a significant increase (P < 0.001) in cell viability in cells treated with glucose and MPP(+ )verses cells treated with MPP(+ )alone. Fluorometric analysis using 100 microM Rhodamine 123 indicated mitochondrial membrane potential was not restored in MPP(+ )treated cells with glucose; however, normal cell viability was confirmed using 2 microg/ml Fluorescein diacetate. This dual fluorescence indicated mitochondrial damage from MPP(+ )while glucose augmented cell survival. Further confirmation of cell survival upon damage to the mitochondria was evident in TUNEL staining. Positive staining was prominent only in MPP(+) treatment groups alone, while control and co-treated groups exhibited little to no TUNEL staining. ATP measurements of all MPP(+) treated groups exhibited a significant (P < 0.001) decrease verses control. Groups co-treated with MPP(+ )and glucose revealed a significant increase (250 microM group: P < 0.001) in ATP. It was concluded from this study that glucose supplementation was able to sustain cellular viability and ATP production through anaerobic glycolysis despite the inhibitory effect of MPP(+ )on aerobic glycolysis.
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PMID:Anaerobic glycolysis protection against 1-methy-4-phenylpyridinium (MPP+) toxicity in C6 glioma cells. 1740 69

NMR-visible lipid signals detected in vivo by 1H MRS are associated with tumour aggression and believed to arise from cytoplasmic lipid droplets. High-resolution magic angle spinning (HRMAS) 1H MRS and Nile Red staining were performed on human brain tumour biopsy specimens to investigate how NMR-visible lipid signals relate to viable cells and levels of necrosis across different grades of glioma. Presaturation spectra were acquired from 24 adult human astrocytoma biopsy samples of grades II (8), III (2) and IV (14) using HRMAS 1H MRS and quantified using LCModel to determine lipid concentrations. Each biopsy sample was then refrozen, cryostat sectioned, and stained with Nile Red, to determine the number of lipid droplets and droplet size distribution, and with Haematoxylin and Eosin, to determine cell density and percentage necrosis. A strong correlation (R=0.92, P<0.0001) was found between the number of Nile Red-stained droplets and the approximately 1.3 ppm lipid proton concentration by 1H MRS. Droplet sizes ranged from 1 to 10 microm in diameter, and the size distribution was constant independent of tumour grade. In the non-necrotic biopsy samples, the number of lipid droplets correlated with cell density, whereas in the necrotic samples, there were greater numbers of droplets that showed a positive correlation with percentage necrosis. The correlation between 1H MRS lipid signals and number of Nile Red-stained droplets, and the presence of lipid droplets in the non-necrotic biopsy specimens provide good evidence that the in vivo NMR-visible lipid signals are cytoplasmic in origin and that formation of lipid droplets precedes necrosis.
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PMID:An investigation of human brain tumour lipids by high-resolution magic angle spinning 1H MRS and histological analysis. 1818 27

As for the surgical treatment of glioma, the recent employment of fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) or high-dose fluorescein sodium has increased the rate of radical tumor resection. On the other hand, there is no specific technique for metastatic brain tumor surgery. We have used a fluorescence-guided tumor resection procedure with the aid of high-dose fluorescein sodium in surgery for metastatic brain tumor. Fluorescein sodium has been used in 13 cases, and achieved effective stainability in all cases. Fluorescein sodium is inexpensive, highly safe, and comparatively easy to use, and does not require any special equipment. We believe that the use of fluorescein sodium is beneficial for resection of the metastatic brain tumor.
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PMID:Metastatic brain tumor surgery using fluorescein sodium: technical note. 1821 Mar 65

Fluorescent agents, e.g. 5-aminolevulinic acid (5-ALA), fluorescein and indocyanine green (ICG) are in common use in neurosurgery for tumor resection and neurovascular surgery. Protoporphyrine IX (PPIX) as major metabolite of 5-ALA is a strong fluorescent substance accumulated within malignant glioma tissue and a very sensitive and specific tool for visualizing high grade glioma tissue during surgery. Furthermore, 5-ALA or rather PPIX also offers an intratumoral therapeutic option stimulated by laser light in specific wavelength. Fluorescein was demonstrated to show similar fluorescent reactions in neurosurgery, but is controversial in its use, especially in high grade tumor surgery. Intraoperative angiography during resection of arterio-venous malformations, extracranial-intracranial-bypass or aneurysm surgery is supported by ICG fluorescence. Generally ICG will provide beneficial information for both, exposure of the pathology and illustration of healthy structures. This manuscript shows an overview of the literature focussing fluorescence in neurosurgery.
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PMID:Fluorescence in neurosurgery: Its diagnostic and therapeutic use. Review of the literature. 2600 Jul 42

OBJECTIVE Fluorescence guidance with 5-aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue. METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System). RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection. CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.
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PMID:Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note. 2833 32


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