Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human glioblastoma multiforme (M27) tested in early cell cultures by indirect immunofluorescence staining showed SV40-related tumor (T)-antigen, 95% of the cells being positive. SV40-related viral capsid (V)-antigen was absent in all cells tested. Experiments to rescue this virus were performed by fusing M27 cells with CV-I monkey cells, which were permissive for SV40, using polyethylene glycol (PEG) as fusion factor. We succeeded in isolating virus particles SV40-GBM which electron microscopy showed to correspond in size and morphology to papovaviruses. Serological tests (hemagglutination, neutralization, fluorescent antibody) revealed that the virus is indistinguishable from SV40. Despite this apparent antigenic identity SV40-GBM differs slightly from SV40 wild type. This virus can propagate and produce CPE in both CV-I cells and primary fetal human kidney cells. Furthermore digestion of SV40-GBM DNA with the HindII/III restriction endonucleases revealed minor differences compared with the SV40 DNA. Therefore the virus SV40-GBM obtained from glioblastoma cells seems to be closely related to the SV40-PML viruses described earlier.
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PMID:Isolation of a SV40-like Papovavirus from a human glioblastoma. 9 81

A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling time in monolayer cultures. Expression of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high gamma-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.
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PMID:Characterization of an established human, malignant, glioblastoma cell line (GBM) and its response to conventional drugs. 792 29

P53 immunohistochemistry in astrocytic tumors has usually been evaluated by the percentage of positive cells. However, in this study we analyzed the P53 immunopositive cells by their patterns of distribution. Formalin-fixed and paraffin-embedded sections from 38 patients with astrocytic tumors were examined. The distribution pattern of P53 immunostaining cells was divided into 3 types: negative, locally scattered, and diffuse clustering. There were 2 positive stains in 5 astrocytomas (40%), 12 positive in 24 anaplastic astrocytomas (50%), and 7 positive in 9 glioblastoma multiformes (78%). In astrocytomas, the positive cells were locally scattered. In anaplastic astrocytoma and GBM, the positive cells appeared locally scattered or as diffuse clustering. For the variant immunoreactive expression, the mean ages for patients with negative, locally scattered and diffusely clustered P53 immunostaining were as follows: 51.4, 52.6, and 28.4 years (P < 0.01), respectively. In anaplastic astrocytoma and GBM, the diffusely clustered pattern was more common in younger patients, whereas elderly patients in same groups tended to have few or no P53 immunopositive cells. Thus, our results implicate that clonal expansion of P53 immunopositive cells is associated with brain tumor progression.
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PMID:Immunohistochemical pattern of P53 protein in human astrocytic tumors. 867 33

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.
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PMID:Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel. 1077 76

Bcl-2 protein plays an important role in inhibiting apoptosis and protecting normal and neoplastic cells from toxicity. Bcl-2 overexpression in malignant tumors, on the other hand, may cause resistance against adjuvant treatment. Since there are subpopulations of patients with glioma that differ considerably in their treatment benefit, it is important to identify prognostic factors for outcome and to tailor adjuvant protocols in accordance with specific biological features of the respective tumor. The present study aimed at investigating the role of bcl-2 expression in higher-grade glioma (WHO grade III and IV). Bcl-2 expression was correlated with clinical and paraclinical parameters, and evaluated in univariate and multivariate statistical models. In addition, bcl-2-overexpressing human glioma cells in culture were used for modeling the in vivo findings and for investigating the importance of bcl-2 for tumor resistance against cytotoxic treatment. A group of 86 patients with higher-grade glioma were investigated. Anaplastic astrocytoma (AA; WHO G III, n = 29) showed bcl-2 expression in 48% of the cases, and immunohistochemical positivity was associated with a significantly shorter survival time (p = 0.0068). In glioblastoma patients (GBM; WHO G IV, n = 57), 51% of tumors were bcl-2 positive, but bcl-2 expression did not correlate significantly with survival (p = 0.39). In a Cox proportional hazards regression model, bcl-2 positivity was confirmed as a negative prognostic parameter in AA, but not in GBM. Bcl-2 overexpressing and control human glioma cell clones (T98MG line) were treated in culture with the cytotoxic drugs carmustine (BCNU), paclitaxel, vincristine, and doxorubicin. In addition, bcl-2-overexpressing and control cells were infected with a retrovirus carrying the herpes-simplex-virus thymidine kinase gene (HSV-tk), and then treated with ganciclovir (GCV). Bcl-2 overexpression significantly increased tumor cell resistance against all of the above cytotoxic drugs, and also against HSV-TK/GCV mediated gene therapy.
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PMID:Bcl-2 expression in higher-grade human glioma: a clinical and experimental study. 1110 Aug 18

Increased expression of gamma-glutamyltransferase (GGT) has been detected in a range of human malignancies and is thought to be involved in neoplastic proliferation and treatment resistance. Since GGT expression and its role in malignant glioma biology remain largely unknown, we investigated this phenomenon by immunostaining 26 higher-grade human astrocytic gliomas (WHO grades III and IV) with a monoclonal anti-GGT-antibody (138H11). Further, human pancreatic GGT cDNA was used for liposome-mediated transfection of 9L gliosarcoma cells. GGT-expressing and control 9L cells were cultured in media containing different amounts of essential amino acids and/or cytotoxic agents. Cell viability was evaluated by microplate MTT assay. Immunohistochemical staining of tumor specimens demonstrated that GGT expression is a frequent feature of higher-grade human astrocytic gliomas, but not of normal brain tissue. Human tumors were strongly GGT-positive in 6 of 7 cases of grade III astrocytoma, and in 12 of 19 grade IV astrocytoma (glioblastoma multiforme, GBM) cases. In the cell culture model, 9L-GGT cells had a growth advantage over control cells in cysteine-deficient medium. but not in standard or glutamine-free medium. No significant difference in numbers of viable cells of either clone was found in media containing the alkylating drug BCNU (5-200 microg/ml). In conclusion, GGT is expressed in a high percentage of human WHO grade III astrocytomas and GBM, but not in normal brain tissue. This molecule seems to give neoplastic cells a moderate growth advantage under in vivo conditions.
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PMID:Gamma-glutamyl transferase expression in higher-grade astrocytic glioma. 1150 14

Intrinsic chemoresistance constitutes a major problem in the therapy of malignant gliomas. In vitro experiments with four astrocytoma/glioblastoma (AC/GBM) cell lines revealed that the chemoresistance of two cell lines, A172 and T98G, to cisplatin and etoposide was due to resistance to drug-induced apoptosis. In contrast, all the AC/GBM cell lines tested were sensitive to treatment with the lipophilic ether lipid erucylphosphocholine, ErPC. ErPC-induced apoptosis was independent of wild-type p53-signaling and triggering of the CD95/CD95 ligand (CD95L) system. Inhibition of protein and RNA synthesis by cycloheximide and actinomycin D did not abrogate ErPC-induced apoptosis. However, expression of members of the bcl-2 protein family was modulated during ErPC treatment. Activation of caspase 3 and mitochondrial alterations were central to ErPC-induced apoptosis. We conclude that ErPC-induced activation of the mitochondrial pathway enables cell death in the chemoresistant AC/GBM cells.
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PMID:Erucylphosphocholine-induced apoptosis in chemoresistant glioblastoma cell lines: involvement of caspase activation and mitochondrial alterations. 1184 99

Erucylphosphocholine (ErPC) is a promising candidate for the treatment of human brain tumors. The aim of the present study was to investigate whether structural modifications of ErPC would improve its antineoplastic activity in vitro. The novel alkylphosphocholine (APC) derivatives docosenyl-( cis-10,11)-phosphocholine, tricosenyl-( cis-12,13)-phosphocholine, heneicosenyl-( cis-12,13)-phosphocholine and erucyl- N, N, N-trimethylpropanolaminophosphate all reduced cell growth and viability of rat and human astrocytoma/glioblastoma (AC/GBM) cell lines (C6, T98G, U87MG, A172) and had improved antineoplastic activity when compared to the prototypical APC hexadecylphosphocholine (HePC). However, the four cell lines differed in their sensitivity to the APC derivatives. A172 cells were most sensitive to their cytostatic action and T98G cells to their cytotoxic action. The LC(50) values for T98G cells after a 72-h exposure to the novel derivatives varied between 25 and 54 microM compared to 45+/-8.1 microM for ErPC. Complete killing of T98G cells was obtained with all derivatives at 90 microM. Structural modifications of the chain length of the alcohol moiety as well as changing the position of the double bond within the alkyl chain improved cytotoxicity of the APC in C6 and A172 cells and to a lesser extent in T98G cells, whereas U87MG cells showed almost similar sensitivities to the novel drugs and ErPC. Increasing the distance between the phosphorus and nitrogen atoms within the polar phosphocholine group did not alter antineoplastic activity but modified physicochemical characteristics, e.g. increased the solubility in water. In a similar manner to ErPC, all derivatives induced growth arrest in the G(2)/M phase of the cell cycle and apoptotic cell death. Importantly, none of the derivatives showed hemolytic activity. As there was no clear superiority of any of the novel derivatives, ErPC remains the leading APC derivative for future clinical trials in brain tumor chemotherapy.
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PMID:Structure-activity relationships of alkylphosphocholine derivatives: antineoplastic action on brain tumor cell lines in vitro. 1211 Nov 15

An in-frame deletion of 801 bp in exons 2-7 (type III mutation) of the epidermal growth factor receptor (EGFR) is detected at high incidence in primary glioblastoma tumors. A proteomic approach was used to generate differential protein expression maps of fetal human astrocytes (FHA), human glioblastoma cell lines U87MG and U87MG expressing type III EGFR deletion (U87MGdeltaEGFR) that confers high malignancy to tumor cells. Two-dimensional gel electrophoresis followed by in-gel digestion of separated spots and protein identification by LC-MS-MS and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identified 23 proteins expressed at higher levels or exclusively in FHA and 29 proteins expressed at higher levels or exclusively in U87MG cells. Three proteins, ubiquitin, cystatin B, and tissue transglutaminase (TTG), were upregulated in U87MGdeltaEGFR relative to U87MG. Four proteins highly expressed by U87MG cells, Hsp27, major vault protein, TTG, and cystatin B, were analyzed by Western blot, ELISA, or RT-PCR in cell extracts and in tissue samples of glioblastoma multiforme (GBM; grade IV), low-grade astrocytomas (grades I and II), and nonmalignant brain lesions. All four proteins were highly expressed in GBM tissues compared to nonmalignant brain. These proteins may be used as diagnostic or functional (e.g., multiple drug resistance, invasiveness) markers for glioblastoma tumors.
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PMID:Identification of differentially expressed proteins in human glioblastoma cell lines and tumors. 1265 3

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.
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PMID:The importance of genomic copy number changes in the prognosis of glioblastoma multiforme. 1284 40


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