Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine accumulates in glioma cells, resulting in a concentration-dependent inhibition of proliferation. We have shown that estramustine treatment results in a rapid inhibition of deoxyribonucleic acid synthesis (within 4 h) in human glioblastoma cells associated with an alteration of cell size and shape, consistent with its known antimicrotubule activity. To extend these findings, we performed an immunohistochemical analysis of microtubules with a monoclonal antibody to beta-tubulin, using a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to measure the antimitotic effects of estramustine on both human glioblastoma and astrocyte cultures. Within 4 hours, estramustine (10 mumol/L) caused a dramatic alteration in the tubulin staining in glioma cells, characterized by a disorganization in microtubules. Cell shape and microtubule staining in astrocytes were relatively preserved. Estramustine had a concentration-dependent cytotoxic effect in tumor cultures, whereas it had no effect on astrocyte viability at any concentration. Differences in the antimitotic effects do not appear to be related to variations in proliferation rates among these different types of cells. These data suggest that although estramustine is a potent inhibitor of proliferation in glioblastoma cells, it has modest antiproliferative effects on astrocytes and its selective activity is closely correlated with its antimicrotubule properties.
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PMID:Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes. 805 84

Three neuron-associated microtubule proteins, Class III beta-tubulin isotype, MAP-2, and tau, were evaluated in a comparative immunoblot and immunohistochemical study of the rat C-6 glioma cell line maintained for up to 31 days in vitro. Western blots on whole SDS extracts of cells grown: (i) as monolayers on plastic dishes (for 13 and 16 days); (ii) as monolayers on poly-D-lysine coated glass coverslips (for 3, 7, and 11 days); and (iii) as explants on Gelfoam matrices (for 10, 30, and 31 days) were probed with monoclonal antibodies (MoAb) specific for the above-mentioned microtubule proteins. For these and all other markers employed, immunoperoxidase histochemistry was performed only on the matrix cultures. The immunoblot experiments demonstrated that the Class III beta-tubulin isotype, MAP2, and tau were not expressed by the C-6 cell line in any of the culture conditions, nor were they found by immunohistochemistry. In contrast, explants from all culture conditions were positive for glial fibrillary acidic (GFA) protein and for a universal anti-beta-tubulin isotype MoAb by immunoblotting, as well as by immunohistochemistry in Gelfoam matrix cultures maintained in an organ culture system. Both sets of experiments indicate that these markers are not altered under three different conditions of growth over a one-month period in vitro. The expression of GFA protein and the absence of detectable levels of Class III beta-tubulin, MAP2, and tau are in keeping with the astrocytic phenotype of the C-6 cell line.
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PMID:Absence of neuron-associated microtubule proteins in the rat C-6 glioma cell line. A comparative immunoblot and immunohistochemical study. 823 55

Methylmercury (MeHg) specifically depolymerizes microtubules and inhibits cell proliferation in mouse glioma cells. The effect of microtubule depolymerization by MeHg on tubulin synthesis was studied. Tubulin synthesis analyzed by two-dimensional electrophoresis using [35S]methionine as a tracer was markedly inhibited in mouse glioma cells exposed to 5 x 10(-6)M MeHg for 3 hr, which completely depolymerized microtubules. Under this condition, density of the protein bands other than tubulin in autoradiogram remained unchanged on gradient urea-polyacrylamide gels. Furthermore, the decrease in tubulin mRNA level was relevant to that in tubulin synthesis, although actin mRNA levels remained unchanged. In addition, specific transcription rates of beta-tubulin genes appeared to be unaffected under the same experimental condition as above. Thus, it is concluded that the disruption of microtubules by MeHg resulted in the inhibition of the synthesis of tubulin itself through autoregulatory repression in post-transcriptional processes as in the case of colchicine treatment.
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PMID:Methylmercury-induced microtubule depolymerization leads to inhibition of tubulin synthesis. 992 40

C6.9 rat glioma cells undergo a cell death program when exposed to 1, 25-dihydroxyvitamin D3 (1,25-D3). As a global analytical approach, we have investigated gene expression in C6.9 engaged in this cell death program using differential screening of a rat brain cDNA library with probes derived from control and 1,25-D3-treated cells. Using this methodology we report the isolation of 61 differentially expressed cDNAs. Forty-seven cDNAs correspond to genes already characterized in rat cells or tissues. Seven cDNAs are homologous to yeast, mouse or human genes and seven are not related to known genes. Some of the characterized genes have been reported to be differentially expressed following induction of programmed cell death. These include PMP22/gas3, MGP and beta-tubulin. For the first time, we also show a cell death program induced up-regulation of the c-myc associated primary response gene CRP, and of the proteasome RN3 subunit and TCTP/mortalin genes. Another interesting feature of this 1,25-D3 induced-cell death program is the down-regulated expression of transcripts for the microtubule motor dynein heavy chain/MAP 1C and of the calcium-binding S100beta protein. Finally 15 upregulated cDNAs encode ribosomal proteins suggesting a possible involvement of the translational apparatus in this cell program. Alternatively, these ribosomal protein genes could be up-regulated in response to altered rates of cellular metabolism, as has been demonstrated for most of the other isolated genes which encode proteins involved in metabolic pathways. Thus, this study presents to our knowledge the first characterization of genes which are differentially expressed during a cell death program induced by 1, 25-D3. Therefore, this data provides new information on the fundamental mechanisms which participate in the antineoplastic effects of 1,25-D3 and on the machinery of a cell death program in a glioma cell line.
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PMID:Differentially expressed genes in C6.9 glioma cells during vitamin D-induced cell death program. 1020 Apr 52

In several neuropathological conditions, alphaB-crystallin and glial fibrillary acidic protein (GFAP) accumulate and form cytoplasmic inclusions in astrocytes. To explore the pathogenesis of the inclusions and the possible functions of the accumulated alphaB-crystallin, GFAP and alphaB-crystallin were overexpressed in cultured astrocytes by transient transfection. Human GFAP formed filamentous, cytoplasmic inclusions in mouse astrocytes, NIH3T3 cells, rat C6 glioma cells, and human U251 glioma cells. These human GFAP inclusions did not contain the endogenous vimentin or beta-tubulin, and the intermediate filament and microtubular networks of the transfected cells appeared normal. alphaB-crystallin and hsp25 were associated with the GFAP inclusions. Increasing intracellular alphaB-crystallin levels using recombinant adenoviruses, either before or after GFAP inclusions were formed, decreased the number of inclusion-bearing astrocytes and converted the human GFAP from an inclusion to a spread, filamentous form. These results suggest that alphaB-crystallin reorganizes abnormal intermediate filament aggregates into the normal filamentous network.
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PMID:Formation of GFAP cytoplasmic inclusions in astrocytes and their disaggregation by alphaB-crystallin. 1032 8

We have reported that the three serine residues in alphaB-crystallin are phosphorylated under various stress conditions. We prepared affinity-purified antibodies recognizing each of the phosphorylated serine residues (Ser-19, Ser-45, and Ser-59, respectively) in alphaB-crystallin with peptides (p19S, p45S, or p59S) that contained the corresponding phosphorylated serine residue. Immunocytochemically anti-p45S antibodies stained the cytoplasm of mitotic cells (J. Biol. Chem. 273, 28,346-28,354). We have now found that the anti-p59S antibodies recognize centrosomes and midbodies of dividing cells. alphaB-Crystallin was the only protein recognized by the anti-p59S antibodies in Western blot analyses of isolated centrosome fractions. alphaB-Crystallin phosphorylated at Ser-59 was localized at the microtubule organizing centers by means of double staining with anti-beta-tubulin antibody in aster formation analysis and was co-localized with gamma-tubulin in centrosomes. Gamma-Tubulin was co-immunoprecipitated with alphaB-crystallin in U373 glioma cell extracts. On the other hand, the location of the phosphorylated alphaB-crystallin deviated from that of alpha-tubulin or gamma-tubulin in the midbody region. Taken together with the evidences that several chaperones are distributed to centrosomes, these results suggest that alphaB-crystallin as a chaperone might be also involved in the quality control of proteins.
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PMID:AlphaB-crystallin phosphorylated at Ser-59 is localized in centrosomes and midbodies during mitosis. 1183 87

As the subunits of microtubules, alpha- and beta-tubulins have been thought to only exist in the cytoplasm where they are incorporated into microtubules. However, the beta(II) isotype of tubulin has recently been observed in the nuclei of rat kidney mesangial cells [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274-284]. In this study, we detected nuclear beta(II)-tubulin in rat C6 glioma cells, human T98G glioma cells, human MCF-7 breast carcinoma cells, human MDA-MB-435 breast carcinoma cells, and human Hela cervix carcinoma cells. In addition, nuclear beta(II)-tubulin in these cells was found to exist as alphabeta(II) dimers instead of assembled microtubules and appeared to be particularly concentrated in the nucleoli. Several anti-tubulin drugs were used to treat C6 cells to determine their influence on nuclear beta(II)-tubulin. Taxol, a tubulin drug with higher specificity for beta(II)-tubulin than for other beta-tubulin isotypes, irreversibly decreased nuclear beta(II) content in a concentration-dependent manner in C6 cells. Meanwhile, cells were found to be apoptotic as was suggested by the presence of multiple micronuclei and DNA fragmentation. On the other hand, no depletion of nuclear beta(II)-tubulin was observed when C6 cells were incubated with colchicine or nocodazole, two anti-tubulin drugs with higher specificity for the alphabeta(IV) isotype, supporting the hypothesis that drugs with higher specificity for beta(II)-tubulin deplete nuclear beta(II)-tubulin.
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PMID:Characterization of nuclear betaII-tubulin in tumor cells: a possible novel target for taxol. 1221 Nov 14

The expression of the cytoskeletal protein class III beta-tubulin isotype is reviewed in the context of human central nervous system development and neoplasia. Compared to systemic organs and tissues, class III beta-tubulin is abundant in the brain, where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar neurogenesis, the distribution of class III beta-tubulin is neuron associated, exhibiting different temporospatial gradients in the neuronal progeny of the external granule layer versus the neuroepithelial germinal matrix of the velum medullare. However, transient expression of this protein is also present in the telencephalic subventricular zones comprising putative neuronal and/or glial precursor cells. This temporospatially restricted, potentially non-neuronal expression of class III beta-tubulin may have implications in the accurate identification of presumptive neurons derived from transplanted embryonic stem cells. In the adult central nervous system, the distribution of class III beta-tubulin is almost exclusively neuron specific. Altered patterns of expression are noted in brain tumors. In "embryonal"-type neuronal/neuroblastic tumors of the central nervous system, such as the medulloblastomas, class III beta-tubulin expression is associated with neuronal differentiation and decreased cell proliferation. In contrast, the expression of class III beta-tubulin in gliomas is associated with an ascending grade of histologic malignancy and with correspondingly high proliferative indices. Thus, class III beta-tubulin expression in neuronal or neuroblastic tumors is differentiation dependent, whereas in glial tumors, it is aberrant and/or represents "dedifferentiation" associated with the acquisition of glial progenitor-like phenotype(s). From a diagnostic perspective, the detection of class III beta-tubulin immunostaining in neoplastic cells should not be construed as categorical evidence of divergent neuronal differentiation in tumors, which are otherwise phenotypically glial. Because class III beta-tubulin is present in neoplastic but not in normal differentiated glial cells, the elucidation of molecular mechanisms responsible for the altered expression of this isotype may provide critical insights into the dynamics of the microtubule cytoskeleton in the growth and progression of gliomas.
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PMID:Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. 1473 79

Elevation of the intracellular cAMP level induces morphological changes of astrocyte-like differentiation in C6 glioma cells. Such changes may be accompanied with expression of cytoskeletal protein genes. We therefore analyzed morphological changes after a treatment with dibutyryl cAMP (dbcAMP) and then assessed the expression of cytoskeletal protein genes by a quantitative real-time polymerase chain reaction. The cell number remained unaltered upon incubation with 1 mM dbcAMP in medium supplemented with 0.1% fetal bovine serum (FBS), whereas the number and lengths of processes increased, when compared with those of cells incubated in medium supplemented with 0.1% or 10% FBS only. The amounts of beta-actin, gamma-actin, and beta-tubulin mRNAs in C6 cells, but not alpha-tubulin mRNA, increased during the early proliferation in DMEM containing 10% FBS. The expression of cytoskeletal protein genes decreased when incubated with 0.1% FBS or 1 mM dbcAMP in 0.1% FBS, compared with those of cells cultured in 10% FBS. These results indicated that, during the early proliferation in normal culture condition, the expression of cytoskeletal protein genes in C6 cells, except alpha-tubulin, increased, while in differentiating or differentiated C6 glioma cells, cAMP-induced morphological changes were not accompanied with elevation of gene expression for cytoskeletal proteins, such as actin and tubulin.
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PMID:Change of morphology and cytoskeletal protein gene expression during dibutyryl cAMP-induced differentiation in C6 glioma cells. 1800 Jul 53

Malignant glioneuronal tumors (MGNT) are suggested to be a new entity of glioma defined morphologically as any malignant glioma showing immunohistoichemical evidence of neuronal differentiation. We encountered seven cases of MGNT with oligodendroglioma-like component and investigated alternations of chromosome 1p and 19q in these tumors. Seven patients ranged from 33 to 62 years of age, four females and three males. Immunohistochemical study of these tumors was performed using neuronal markers (synaptophysin, neurofilament, beta-tubulin, chromogranin A and NeuN), astrocytic marker (GFAP) and Ki-67. We undertook a molecular cytogenetic study of tumor specimens obtained from seven patients using fluorescence in situ hybridization (FISH) with DNA probes mapping to chromosome 1p36, 1q25, 19p13 and 19q13. Histologically, these tumors resembled anaplastic oligodendroglioma. Immunohistochemically, tumor cells were immunoreactive for synaptophysin (7/7), neurofilament (6/7), beta-tubulin (5/7), chromogranin A (4/7), NeuN (2/7) and GFAP (7/7). The Ki-67 labeling index ranged from 4.5% to 20.7%. FISH analysis demonstrated either 1p or 19q deletion in all seven cases (100%) and both 1p and 19q deletions in five cases (71%). The 1p deletion was detected in six of seven cases (86%) and 19q deletion was also detected in six (86%). 1p and 19q deletions were present in MGNT, especially those with oligodendroglial components. We suggest that the oligodendroglial-like feature was associated with not only 1p or 19q loss but also differentiation along neuronal cell lines as a factor of favorable prognosis in glial tumors. It is inappropriate to make a diagnosis of oligodendroglioma based only on morphological resemblance to oligodendroglia.
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PMID:Chromosome 1p and 19q deletions in malignant glioneuronal tumors with oligodendroglioma-like component. 1878 Dec 79


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