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)

Oligoastrocytomas form a poorly defined subgroup of glial tumors, and few clinical series have been reported. We performed a retrospective study to elucidate the histopathological features of these tumors and to relate the clinical signs and symptoms and proliferative potential to survival. Oligoastrocytomas were defined as glial tumors with at least 10% neoplastic astrocytes and 10% neoplastic oligodendrocytes; tumors were graded with the St. Anne-Mayo criteria for astrocytomas and oligodendrogliomas. Proliferative potential was estimated with antibodies against proliferating cell nuclear antigen (PCNA). Median survival of 52 patients (median age, 42 years) was 75 weeks (range 2-703 weeks). Actuarial 1-, 2-, 3-, and 5-year survival rates were 67%, 43%, 40%, and 29%, respectively. For 15 patients with grade 3 and 33 with grade 4 lesions (St. Anne-Mayo astrocytoma classification), median survival was 217 and 55 weeks, respectively. For 19 patients with grade 2 and 33 with grade 3 lesions (St. Anne-Mayo oligodendroglioma classification), median survival was 305 and 55 weeks, respectively. Interobserver agreement between three experienced neuropathologists on identification of astrocytes, oligodendrocytes, and unclassifiable cells was low, indicating considerable subjectivity in the histopathological diagnosis. Median PCNA labeling indices correlated with tumor grade, but individual values varied so widely within grades that they had no predictive value for survival. In a multivariate analysis, symptoms of increased intracranial pressure and microvascular proliferation were independently associated with poor prognosis. The biological behavior of subgroups appeared to be distinctly less aggressive than that of 'pure' astrocytomas of similar grade. Better histopathological definition of oligoastrocytomas and improved assessment of percentages of constituent cell types may allow more accurate prognosis.
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PMID:Oligoastrocytomas: a clinicopathological study of 52 cases. 919 94

p21WAF1/CIP1 is a downstream mediator of p53 and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Since cellular differentiation is frequently characterized by G1 arrest, we examined whether p21WAF1/CIP1 overexpression would induce growth suppression and differentiation in p53-defective human glioma cells. Overexpression of p21WAF1/CIP1 resulted in an accumulation of cells in G1, altered morphology, growth arrest and cell differentiation. The extent of cell differentiation correlated with the level of p21WAF1/CIP1 as well as of proliferating cell nuclear antigen, cyclin E, and cdk 2, which associates with p21WAF1/CIP1. Our data suggest that gene transfer of p21WAF1/CIP1 may arrest glioma cell growth in vivo by committing malignant glioma cells to a pathway of terminal differentiation.
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PMID:Overexpression of p21WAF1/CIP1 induces cell differentiation and growth inhibition in a human glioma cell line. 946 69

To evaluate the hypothesis that co-implantation of different rodent glioma cell lines might result in experimental brain tumours that more closely resemble human gliomas the neuropathology and immunocytochemical features of implantation gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admixed 50:50 prior to implantation (C6 + F98 and C6 + A15A5) and three cell lines equally admixed (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours grew consistently following implantation of the single and the two admixed cell lines, however tumour growth following triple mix implantation was considerably and consistently impaired. The tumours derived from admixed cell lines showed regional heterogeneity with areas characteristic of both the primary cell lines. Foci of lymphocytic infiltrates, tumoural necrosis, often with pseudopallisading, and peritumoural edema were consistent features of all tumours. Limited parenchymal and more extensive perivascular tumoural invasion was seen predominantly in tumours containing the C6 cell line. There were no significant differences in GFAP, vimentin and HSP70 staining between the mixed tumours, although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100 negative. Using PCNA expression as a measure of the tumour proliferation all except the tumours derived from the three cell lines mix, which had a staining index of 7-10%, had focal staining indices in viable tumour of between 40-80%. There was focal positive staining in both perilesional brain and in regions of all tumours for the macrophage markers ED-1 and ED-2. None of the three cell lines stained in vitro for either ED1 and ED2 but all were constitutively positive in vitro for OX-6, a proposed marker for antigen presenting cells. The macrophage and lymphocytic response suggest a vigorous but largely ineffective immunological response had been mounted against all tumours. The consistent failure of the triple mix tumours to grow is unexplained. This work has shown the feasibility of producing 'mixed' cell line experimental gliomas by combining two cell lines at the time of innoculation. However, the relative failure to produce (i) mixed tumours that have properties not inherent to either parent cell line and (ii) implantation glioma with three cell lines suggest there are limits to this approach. Admixture of cell lines at the time of implantation therefore does not make experimental glioma models that more closely resemble natural gliomas, and also has some particular disadvantages. This experimental approach is therefore not recommended for use in the study of tumour biology and in evaluating the effectiveness of novel therapies.
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PMID:Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours. 952 1

Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.
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PMID:Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers. 960 6

Ribonucleotide reductase (RR) is a cytoplasmatic enzyme catalyzing the reduction of all four ribonucleotides to their corresponding deoxyribonucleotides. Its activity strongly correlates to the rate of DNA synthesis. By using a specific monoclonal antibody against the large M1 subunit of RR, we assessed the expression of M1-RR versus DNA content by dual-parameter flow cytometry. The aim of this paper was to compare the variations in the immunopositivity for M1-RR during the cell cycle to the positivity for other cell cycle markers identifying either proliferating cells (Ki-67 and PCNA) or quiescent cells (statin). To do this, normal human embryonic fibroblasts in different growth conditions as well as several other mammalian cell lines (rat C6 glioma cells; mouse 3T3 fibroblasts and B16 melanoma cells; human epithelial EUE cells and mammary carcinoma MCF-7 cells) were used. The expression of M1-RR antigen was found to correlate positively with the expression of Ki-67 and PCNA, and negatively with the expression of statin. During early G1 phase, M1-RR becomes detectable by specific antibodies relatively later compared to PCNA and Ki-67; therefore, the lack of immunopositivity for M1-RR cannot be taken as an absolute indication of cell quiescence in G0.
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PMID:Bivariate flow cytometric analysis of DNA content versus immunopositivity for ribonucleotide reductase M1 subunit in the cell cycle. 962 20

The present study analyzed the combined immunostaining for proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGFR) with the aim of obtaining an objective method for the evaluation of the growth fraction in human glial tumors. A retrospective study was undertaken on 157 gliomas employing MoAb PC10 and MoAb 108, recognizing a 36 Kd nuclear protein associated with the cell cycle and the extracellular domain of the EGFR, respectively. The results of this immunohistochemical analysis showed that the rate of PCNA positive cell is directly associated to EGFR expression and significantly (P < 0.0001) correlates with tumor morphological grading, this was also the case in patients submitted to multiple surgical treatments for recurrent tumors. PCNA and/or EGFR are expressed by a minority of low grade astrocytoma, while anaplastic astrocytoma and glioblastoma displayed an intense immunoreactivity for the two antigens in more than 85% of tested cases. These findings indicate that the combined evaluation of PCNA and EGFR could allow a more definite biopathological grading of neuroepithelial brain tumours.
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PMID:Comparative analysis of proliferating cell nuclear antigen and epidermal growth factor receptor expression in glial tumours: correlation with histological grading. 967 49

Leflunomide, a novel immunomodulatory drug, has two biochemical activities: inhibition of tyrosine phosphorylation and inhibition of pyrimidine nucleotide synthesis. In the present study, we first showed that A77 1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], the active metabolite of leflunomide, was more effective at inhibiting the tyrosine kinase activity of platelet-derived growth factor (PDGF) receptor than that of epidermal growth factor (EGF) receptor, and had no effect on the tyrosine kinase activity of the fibroblast growth factor receptor. In the presence of exogenous uridine, A77 1726 was more effective at inhibiting the PDGF-stimulated proliferation of PDGF receptor-overexpressing C6 glioma than the EGF-stimulated proliferation of EGF receptor-overexpressing A431 cells. In vivo studies demonstrated that leflunomide treatment strongly inhibited the growth of the C6 glioma but had only a modest effect on the growth of the A431 tumor. Uridine co-administered with leflunomide did not reverse the antitumor activity of leflunomide on C6 and A431 tumors significantly. Quantitation of nucleotide levels in the tumor tissue revealed that leflunomide treatment significantly reduced pyrimidine nucleotide levels in the fast-growing C6 glioma but had no effect on the relatively slow-growing A431 tumor. Whereas uridine co-administration normalized pyrimidine nucleotide levels, it had minimal effects on the antitumor activity of leflunomide in both tumor models. Immunohistochemical analysis revealed that leflunomide treatment significantly reduced the number of proliferating cell nuclear antigen-positive cells in C6 glioma, and that uridine only partially reversed this inhibition. These results collectively suggest that the in vivo antitumor effect of leflunomide is largely independent of its inhibitory effect on pyrimidine nucleotide synthesis. The possibility that leflunomide exerts its antitumor activity by inhibition of tyrosine phosphorylation or by a yet unidentified mode of action is discussed.
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PMID:In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide: mechanisms of action. 1051 84

C6 glioma - Ca2+ depletion - proliferation arrest morphology change - CDK inhibitor In this study, we investigated the role of the intracellular calcium store in modulating the cellular proliferation and the expression of cell cycle regulatory proteins in cultured C6 glioma cells. By means of microspectrofluorimetry and Ca(2+)-sensitive indicator fura-2, we found that the intracellular Ca2+ pump inhibitors, thapsigargin (TG) irreversibly and 2,5-ditert-butyl-hydroquinone (DBHQ) reversibly depleted the Ca(2+)-store accompanied with the induction of G0/G1 arrest, an increase in glial fibrillary acidic protein (GFAP) expression and morphological changes from a round flat shape to a differentiated spindle-shaped cell. The machinery underlying these changes induced by Ca(2+)-store depletion was investigated. The results indicated that Ca(2+)-store depletion caused an increased expression of p21 and p27 proteins (cyclin-dependent kinase inhibitors), with unchanged mutant p53 protein of C6 cells but reduced amounts of the cell cycle regulators: cyclin-dependent kinase 2 (CDK2), cdc2, cyclin C, cyclin D1, cyclin D3 and proliferating cell nuclear antigen (PCNA) in a time-dependent manner. These findings indicate a new function of the endoplasmic reticulum (ER) Ca2+ store in regulating cellular proliferation rate through altering the expression of p21 and p27 proteins. Moreover, cellular differentiation as revealed by spindle-shaped morphology and induced GFAP expression were also modulated by the ER Ca2+ store. The implication of this finding is that the abnormal growth of cancer cells such as C6 glioma cells may be derived from a signalling of the ER which can be manipulated by depleting the Ca2+ store.
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PMID:Proliferation arrest and induction of CDK inhibitors p21 and p27 by depleting the calcium store in cultured C6 glioma cells. 1060 59

11C-methionine positron emission tomography (PET) and proliferating cell nuclear antigen (PCNA) staining were performed in 13 cases of glioma to investigate the relationship between the uptake of L-[methyl]-11C-methionine and the degree of malignancy and proliferative potential. The 11C-methionine uptake was significantly greater in high-grade gliomas compared to low-grade gliomas (P<0.05). The PCNA indexes were also significantly higher in the high-grade cases (P<0.05). Moreover, a strong positive correlation was found between the 11C-methionine values and the PCNA indexes (P<0.005), demonstrating that higher 11C-methionine uptake was associated with greater proliferative potential and greater malignancy. 11C-methionine PET is a potentially useful preoperative method to discriminate the malignancy of glioma.
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PMID:Evaluation of the malignancy of glioma using 11C-methionine positron emission tomography and proliferating cell nuclear antigen staining. 1068 29

The aim of this study was to assess the correlation between thallium-201 (201Tl) uptake and proliferative activity measured using the proliferating cell nuclear antigen labelling index (PCNA-LI) in brain tumours. Twenty-nine patients with brain tumours were included in this study. Of these, seven were diagnosed with meningioma, 13 had high grade glioma (HGG) and nine had low grade glioma (LGG). A 210Tl single photon emission computed tomography study was performed on all patients before operation, and 201Tl uptake index (UI) and retention index (RI) values were calculated. Cell proliferation was determined by PCNA. While all of the HGGs and meningiomas showed intense 201Tl accumulation on visual interpretation, eight of the nine LGGs did not show accumulation of 210Tl at the tumour site. 201Tl UI values were 3.23+/-0.89 and 2.67+/-0.66 in HGG, 1.27+/-0.18 and 1.23+/-0.09 in LGG, and 4.35+/-1.60 and 2.52+/-0.78 in meningioma on early and delay images, respectively. There was a statistical difference between the 201Tl UI in HGG and LGG. PCNA-LI values were 16.72+/-6.15%, 1.63+/-0.81% and 2.00+/-1.88% in HGG, LGG and meningioma, respectively. The PCNA-LI in HGG was significantly higher than in LGG and meningioma. While the correlation coefficient between the 201Tl UI and the PCNA-LI was 0.94 in gliomas (n=22), there was no correlation in meningiomas. No statistically significant correlation was found between the RI and the PCNA-LI in gliomas. The presence of a strong positive correlation between 201Tl uptake and PCNA-LI indicates that 201Tl uptake can predict the proliferative activity of the glioma.
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PMID:Correlation of thallium-201 uptake with proliferating cell nuclear antigen in brain tumours. 1106 52


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