Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes a new fluorescent microcarrier cytostasis assay. Human glioma cell lines and primary cultures were attached to microcarrier tissue culture beads and treated with various chemotherapeutic drugs. After treatment, the cells were labelled with two vital fluorescent dyes in order to measure cellular viability. The uptake of hydroethidine and Hoechst 33342 was evaluated alone and in combination as probes for determining metabolic activity and cellular proliferation. Hydroethidine was found to be superior when compared to trypan blue and tritiated thymidine. The use of the microcarrier technique allows for the direct cellular measurement of fluorescence without the need of extensive extraction procedures. The fluorescent assay is a sensitive, rapid and an effective way to screen for potential antiproliferative compounds.
 ...
PMID:Chemosensitivity testing of human gliomas using a fluorescent microcarrier technique. 235 44

Malignant gliomas, especially glioblastoma multiforme, are composed of cells that contain various amounts of DNA. We characterized cells dissociated from biopsy specimen of human gliomas by sorting vital cell populations on the basis of DNA content, determined the sensitivity of sorted cells to BCNU, and did the follow-up study using subpopulations cultivated for a long time after sorting on both the DNA histogram and the BCNU response. Seven malignant human gliomas carried in monolayer culture which had three peaks on the DNA histogram were used for this study. To obtain each DNA distribution histogram, cells were stained with chromomycin A 3 and were analyzed with a modified FACS III flow cytometer. Vital DNA was stained with Hoechst 33342 by means of a modification of the procedure of Jovin et al, which involved negligible toxicity to cells. Cells were sorted on FACS III at each peak on the DNA histogram. The colony forming efficiency (CFE) of each population was determined after sorting and surviving fraction was determined after exposure to graded doses (2.5-10 micrograms/ml X 2 hr) of BCNU. Six subpopulations derived from two human glioma cells were cultivated for a long time and reevaluated by both the DNA histogram and the sensitivity to BCNU. The CFEs for each cell population of three peaks on DNA histograms of human glioma cells were similar, except that the CFE for the far left peak (peak 1) in each histogram appeared to be slightly lower in four specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clonogenicity and BCNU response of subpopulations of human glioma cells sorted according to DNA content]. 406 24

Malignant gliomas, especially glioblastoma multiforme, are composed of a considerable number of cells undergoing DNA synthesis and cells that contain various amounts of DNA. We have characterized cells dissociated from biopsy specimens of such tumors by sorting vital cell populations on the basis of DNA content and have determined the sensitivity of sorted cells to BCNU. Cultured human glioma cells from seven malignant gliomas were stained with Hoechst 33342 dye; the colony-forming efficiency (CFE) of stained tumor cells ranged from 2-50%. Stained cells were sorted on a fluorescence-activated cell sorter (FACS-III). The surviving fraction of each population was determined after exposure to graded doses (2.5-10 micrograms/ml X 2 h) of BCNU. Sorted populations of cells from 5 tumors had dose-response curves that were similar, although differences in cell kill of up to a half-log were commonly found between cells from different DNA peaks treated with the same BCNU dose. For two tumors, cells from the first peak (smallest DNA content) had distinct BCNU sensitivity compared to cells from the second and third peaks (largest DNA content); compared to other tumors in the series, cell kill differences were significant and greater than 1 log in magnitude for one anaplastic astrocytoma. This lack of uniformity in the response of cells within a tumor demonstrates the problem imposed by heterogeneity with regard to the interpretation of chemosensitivity testing of all cells within a single tumor.
 ...
PMID:Variable response to 1,3-bis(2-chloroethyl)-1-nitrosourea of human glioma cells sorted according to DNA content. 608 24

Malignant human gliomas have a highly variable distribution of cell nuclei, consisting of diploid and/or other populations in terms of nuclear DNA content. In order to study in vitro clonogenicity of each population, dissociated or cultured human glioma cells were stained with 20 microM/ml of Hoechst 33342 dye (which stains viable DNA with minimal cell kill), and were sorted sterile into separate populations, based on specific nuclear DNA content, for clonogenicity assay. The colony-forming efficiency (CFE) of tumor cells plated immediately after disaggregation of the biopsy specimens ranged from 0.0044 to 0.149%, and the CFEs increased dramatically with successive passages (to 5 to 40%). The CFEs of the individual populations sorted according to DNA content were similar within individual tumors. These results suggest not only that malignant gliomas are composed of multiple populations in terms of DNA content, but also that each of these populations contain clonogenic cells. The morphologic structure of cells within and among colonies did not appear to relate to DNA content.
 ...
PMID:Clonogenicity of multiple populations of human glioma cells in vitro sorted by DNA content. 617 1

Six human soft-tissue sarcoma and 14 glioma cell lines, exhibiting considerable differences in radioresponsiveness and histological grade of differentiation of the parental tumour, were examined with respect to apoptosis development after irradiation with 60Co gamma-rays. After test doses of 6 and 25 Gy, significant changes characteristic of apoptosis occurring within 6 to 30 hr were exhibited by only 2 differentiated sarcoma cell lines, EL7 and ESS2. The characteristic internucleosomal fragmentation of DNA was detected as early as 6 hr after exposure of subconfluent monolayer cultures to 6 Gy. It was limited to cells that had detached from the culture plate, whereas adherent cells showed random degradation of DNA, namely after higher doses (25Gy) or longer incubation times (30 hr). As assessed by fluorescence microscopy of unfixed cultures stained with Hoechst 33342 and propidium iodide, the proportion of cells showing apoptotic bodies in non-irradiated controls was < 0.1% and 0.3% for EL7 and ESS2, respectively. The dose-response relationship for apoptosis was determined at 9 hr post-irradiation. After 2 Gy, the percentage of apoptotic cells was elevated to 3.4% in EL7 and 4.5% in ESS2 cultures. Saturation was obtained above 6 Gy, with 8.4% apoptosis in EL7 and 15% in ESS2 after 25 Gy. Taken together, rapid ionizing-radiation-induced apoptosis seems to be limited to a subgroup of sarcomas and is unlikely to occur in gliomas.
 ...
PMID:Radiation-induced apoptosis in human sarcoma and glioma cell lines. 760 68

The vascularisation and perfusion of seven subcutaneously xenografted human glioma lines established from surgical specimens has been analysed using an anti-collagen type IV antibody to visualise the vascular walls in combination with a perfusion marker (Hoechst 33342). A computer-based digital image processing system was employed for quantitative analysis of the parameters. The vascular architecture of individual tumours belonging to the same tumour line showed a consistent similarity, while substantial differences occurred between the various tumour lines derived from different patients. Despite the presence of a large inter-tumour variation in vascular area as a proportion of the tumour area, this vascular parameter clearly showed tumour line-specific characteristics. The perfused fraction of the tumour vessels also showed a large inter-tumour variation for all tumour lines ranging from 20% to 85%, but the majority of tumours of all lines had perfusion fractions of more than 55%. Despite large variation, the perfused vascular area as a proportion of the tumour cross-sectional area exhibited clear tumour line-specific tendencies. These observations suggest that consistent differences in vascular parameters are present between glioma xenograft lines, although the tumour lines all originated from histologically similar human high-grade gliomas. These differences may have important consequences for treatment and clinical behaviour of this type of tumour.
 ...
PMID:Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse. 771 Sep 35

A semiautomatic method based on a computerized digital image analysis system was developed to quantitate the perfused fraction of blood vessels and the relative vascular area in cross-sections of human glioma xenografts, implanted subcutaneously in athymic mice or intracerebrally in nude rats. The fluorescent dye Hoechst 33342 was injected intravenously to detect perfused tumor vessels. An immunofluorescent staining of Collagen type IV visualized the vascular structures in the same tumor section. Whole tumor sections were automatically scanned twice on a computer-controlled motorized stage of a fluorescence microscope under two different settings of the image analysis system. At the beginning of a scanning session an interactive routine was used to determine the threshold value for segmentation of vascular structures from the darker background. After the first scan a composite image was created, from the individually processed microscopic images, containing the detected vascular structures. The second scan yielded another composite image with objects representing the perfused areas. When both composite images were combined the overlapping structures showed the perfused vessels. Differences in perfused fractions and relative vascular areas were found between different tumors. The reproducibility of this analysis system was tested and evaluated. The method developed here provides a fast and accurate technique for simultaneous quantitative analysis of tumor perfusion and vasculature.
 ...
PMID:Application of an image analysis system to the quantitation of tumor perfusion and vascularity in human glioma xenografts. 853 95

The effect of tissue site of implantation of four different human gliomas on tumor vascularity and perfusion was examined. Vascular parameters of gliomas implanted subcutaneously in the nude mouse and intracerebrally in the nude rat were analyzed. Tumor vessels were stained with an antibody to collagen type IV and perfusion was investigated with the perfusion marker Hoechst 33342. Characteristic vascular patterns were observed in both intracerebral and subcutaneous xenografts belonging to the same tumor line. Major differences in vascular architecture and in the degree of vascularization were noted in comparisons of the two implantation sites for the same tumor line. Tumor perfusion was highly variable for both locations of tumor growth. Distinct differences between the implantation sites of similar tumor lines in vascular perfusion, intervascular distance, and vascular density were present. Incomplete perfusion of vascular structures, as seen in this study, may result in reduced delivery of oxygen to tumor areas. Therefore, measurements of vascular density and intervascular distance alone, without knowledge of the perfusion status, may not be sufficient to estimate the degree of tumor oxygenation. Furthermore, differences in vascular parameters may have important consequences for treatment modalities such as radiotherapy and chemotherapy. Thus, the findings in our study suggest that care has to be taken in extrapolating therapy results obtained with subcutaneous glioma tumor models to the original growth location of gliomas, the brain, due to major differences in vasculature.
 ...
PMID:A quantitative analysis of vascularization and perfusion of human glioma xenografts at different implantation sites. 1032 51

Tissue oxygenation influences the radiation response of tumors. To further investigate the underlying mechanisms of tumor hypoxia, the spatial distribution of hypoxic cells in relation to the vasculature was studied. In a panel of three human glioma xenograft lines (E2, E102, E106) with different growth characteristics, tumor line-specific patterns of hypoxia (pimonidazole) and (functional) vasculature (Hoechst 33342) were observed. Two of the three glioma lines showed a more homogeneous distribution of perfused vessels (E102 and E106) than the third glioma line (E2). Although all tumors showed hypoxia, the distance at which the steepest part of the gradient of the hypoxia marker was found varied significantly among the different glioma lines. The faster-growing E102 tumors had the longest distance (>300 microm). These results indicate that tumor line-specific factors, rather than vascular geometry alone, may determine the oxygenation status of a tumor. As a consequence, vascular density cannot be used as a surrogate parameter for tumor hypoxia when comparing different tumors. Additional hypoxia and perfusion markers will further improve our understanding of changes in tumor physiology at the microregional level explaining the relationship between the low oxygen levels and the response of tumors to treatment.
 ...
PMID:Quantitative analysis of varying profiles of hypoxia in relation to functional vessels in different human glioma xenograft lines. 1200 40

In C6 rat brain glioma, we have investigated the relation between hypoxia and the presence of lipid droplets in the cytoplasm of viable cells adjacent to necrosis. For this purpose, rats were stereotaxically implanted with C6 cells. Experiments were carried out by the end of the tumour development. A multifluorescence staining protocol combined with digital image analysis was used to quantitatively study the spatial distribution of hypoxic cells (pimonidazole), blood perfusion (Hoechst 33342), total vascular bed (collagen type IV) and lipid droplets (Red Oil) in single frozen sections. All tumours (n=6) showed necrosis, pimonidazole binding and lipid droplets. Pimonidazole binding occurred at a mean distance of 114 microm from perfused vessels mainly around necrosis. Lipid droplets were principally located in the necrotic tissue. Some smaller droplets were also observed in part of the pimonidazole-binding cells surrounding necrosis. Hence, lipid droplets appeared only in hypoxic cells adjacent to necrosis, at an approximate distance of 181 microm from perfused vessels. In conclusion, our results show that severe hypoxic cells accumulated small lipid droplets. However, a 100% colocalisation of hypoxia and lipid droplets does not exist. Thus, lipid droplets cannot be considered as a surrogate marker of hypoxia, but rather of severe, prenecrotic hypoxia.
 ...
PMID:Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection. 1277 75


1 2 3 Next >>