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)

Tumor growth depends on cell division and cell death. To investigate the role of apoptosis in tumor cell death, we examined 83 cases of glial tumors using in situ nonradioactive tailing of DNA breaks. In addition, since p53 protein may participate in the regulation of apoptosis in glioblastoma, we compared the apoptosis ratio (AR) with the labeling index (LI) of p53 protein immunopositivity. The AR in glial tumor parenchyma ranged from 0 to 1.4%: mean AR +/- standard deviation was 0.4 +/- 0.4% (range, 0-1.4) for glioblastoma, 0.3 +/- 0.3% (range, 0.01-0.83) for anaplastic astrocytoma, 0.1 +/- 0.1% (range, 0-0.41) for low-grade astrocytoma, 0.006 +/- 0.008% (range, 0-0.02) for pilocytic astrocytoma, 0.2 +/- 0.2% (range, 0-0.62) for oligodendroglioma and 0.003 +/- 0.004% (range, 0-0.01) for ependymoma. ARs were significantly higher in higher-grade astrocytic tumors than in lower-grade tumors (Mann-Whitney U test: P = 0.0003), although wide variability in each group resulted in overlapping between the groups. p53 protein immunopositivity (more than 25% of nuclei) was found in 15 of 32 glioblastoma cases, while in the remaining 17 none or only a low percentage (up to 6%) of the nuclei were positive. In p53 protein-positive cases mean AR (0.51 +/- 0.47%) was not significantly higher than that in p53 protein-negative cases (0.22 +/- 0.23%; P = 0.1681).
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PMID:Apoptosis in glial tumors as determined by in situ nonradioactive labeling of DNA breaks. 877 55

At the time of recurrence, the majority of low-grade cerebral gliomas transform to a higher grade of histologic malignancy. The purpose of this study was to determine the survival outcome for patients whose anaplastic gliomas began as low-grade tumors compared with patients with de novo high-grade gliomas. Seventy-seven (11.5%) of 667 patients with anaplastic gliomas consecutively treated at the University of Alabama at Birmingham had histologically proven prior low-grade tumors. As a group, the patients with prior low-grade tumors would be expected to have a relatively favorable outcome, as they were younger and had a lower proportion of glioblastoma multiforme than the patients with de novo anaplastic gliomas. The provide a valid comparison, we performed a matched case-control study. We matched 68 patients from the prior low-grade group one-to-one with patients from de novo group for tumor histology, age, Karnofsky performance scores, and type of surgery, without knowledge of outcome. The two groups received comparable radiotherapy and chemotherapy. For the 68 patients with prior low-grade tumor, median actuarial survival from the time of diagnosis of malignant degeneration was 19.7 months and the 5-year survival rate was 22%, compared with 22.0 months and 28% for the 68 matched de novo patients. Kaplan-Meier survival curves for the two group did not significantly differ (p = 0.24 by logrank test). There were no significant survival differences between the patient subsets of prior low-grade versus de novo with glioblastoma, anaplastic astrocytoma, or anaplastic oligodendroglioma/mixed anaplastic glioma. The data indicate that the currently available treatment options, the survival outlook for patients with anaplastic gliomas, whose tumors arose from transformation of low-grade gliomas, is equivalent to the prognosis for patients with de novo anaplastic gliomas.
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PMID:The prognostic impact of prior low grade histology in patients with anaplastic gliomas: a case-control study. 879 65

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.
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PMID:Human astrocytoma cells express a unique chloride current. 880 32

Glioblastoma multiforme, the most malignant human brain tumor, may develop de novo (primary glioblastoma) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). We present further evidence that primary and secondary glioblastomas constitute distinct disease entities which develop through the acquisition of different genetic alterations. We analyzed p53 mutations, p53 protein accumulation and epidermal growth factor receptor (EGFR) overexpression in 49 biopsies classified as primary or secondary glioblastoma according to clinical and histopathologic criteria. Patients with primary glioblastoma were selected on the basis of a clinical history of less than 3 months and histopathologic features of glioblastoma at the first biopsy (19 cases; mean age, 55 years). The diagnosis of secondary glioblastomas required at least two biopsies and clinical as well as histologic evidence of progression from low grade or anaplastic astrocytoma (30 cases; mean age, 39 years). DNA sequence analysis showed that p53 mutations were rare in primary glioblastomas (11%) while secondary glioblastomas had a high incidence of p53 mutations (67%), of which 90% were already present in the first biopsy. The incidence of p53 protein accumulation (nuclear immunoreactivity to PAb 1801) was also lower in primary (37%) than in secondary glioblastomas (97%). In contrast, immunoreactivity for the EGF receptor prevailed in primary glioblastomas (63%) but was rare in secondary glioblastomas (10%). Only one out of 49 glioblastomas showed EGFR overexpression and a p53 mutation. These data indicate that overexpression of the EGF receptor and mutations of the p53 tumor suppressor gene are mutually exclusive events defining two different genetic pathways in the evolution of glioblastoma as the common phenotypic endpoint.
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PMID:Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. 886 78

Forty-eight astrocytic tumours were stained immunohistochemically with antibodies to the cell cycle-regulating protein, cyclin D1, and to the proliferation marker MIB1 (Ki-67) using formalin fixed paraffin embedded tissue and a microwave antigen retrieval system. Cases were classified by the WHO system (1993). The labelling indices (LI) for both antibodies were compared with each other and with the tumour type. The mean labelling indices for both antibodies increased with the degree of malignancy, and a significant difference was seen between the pilocytic astrocytoma and diffuse astrocytoma together vs anaplastic astrocytoma and glioblastoma together. However, within each tumour type there was considerable variation in the labelling indices and a clear cut off value could not be demonstrated. There was a strong positive correlation between labelling indices for cyclin D1 and MIB1 in diffuse astrocytoma, but this correlation broke down increasingly in anaplastic astrocytoma and glioblastoma. There was poor correlation between cyclin D1 and MIB1 in pilocytic astrocytoma, a feature which appeared to separate them from the diffuse astrocytoma. Average labelling indices for cyclin D1 were higher than those of MIB1, which suggests that cyclin D1 positive cells represent a pool of cells from which proliferation and hence MIB1 expression can take place. In conclusion, cyclin D1 is overexpressed in astrocytic tumours, more so with increasing grade of malignancy and in a way which approximately correlates with MIB1 expression.
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PMID:Cyclin D1 in astrocytic tumours: an immunohistochemical study. 887 65

Increased levels of human cysteine proteases have been implicated in the progression of tumors from the premalignant to the malignant state. The physiological activities of these proteases are regulated by their interactions with specific inhibitors. To our knowledge there have been no previous reports about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study reported here, we determined CPI activity during glioma progression and compared that with normal human brain tissue. We also determined CPI activities in meningioma and glioblastoma cell lines in vitro. This activity was significantly higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma and glioblastoma. CPI activity was significantly higher in benign and atypical meningioma cell extracts in comparison with those from malignant meningiomas and with those from glioblastoma cell lines. After several passages, one benign meningioma cell line showed reduced levels of CPI and increased levels of cathepsin. Our results suggest that decreases in the activities of CPI may contribute to the malignant properties of brain tumors.
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PMID:Expression of cysteine protease inhibitors in human gliomas and meningiomas. 887 8

To elucidate the morphological characteristics of glioma in children, we investigated 83 tumors that occurred in patients under the age of 20 years old. Seven of 20 histologically malignant tumors were adult-type anaplastic astrocytoma and glioblastoma. Eleven tumors were composed of small undifferentiated or poorly differentiated cells. The tumors usually had no fibrillary stroma or if present, the stroma was scanty. A few tumors exhibited ependymal differentiation. One tumor showed rhabdoid features. In 63 benign tumors, including 28 pilocytic astrocytomas and 15 ependymomas, there were 6 plemorphic tumors. Four were regarded as pleomorphic xanthoastrocytoma (PXA), and contained a few neurofilament-positive cells. Further-more, an unclassified glioma composed of eosinophilic plump cells coexpressed glial fibrillary acidic protein and neurofilament protein in identical cells. There were 6 tumors associated with desmoplasia including PXA and desmoplastic infantile astrocytoma (DIA). Characteristics of gliomas in children were considered to be the presence of tumors showing insufficient expression of glial phenotype, expression of neurofilament in some types of gliomas, and the presence of a special type of glioma with conspicuous desmoplasia, including PXA and DIA.
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PMID:Morphological features of gliomas in children. 891 25

The benefit of cytoreductive surgery in the management of glioma remains speculative. We therefore reviewed all confirmed deaths in our Neuro-Oncology Program and examined various clinical factors related to survival. There were 63 patients (34 males/29 females), with an average age of 57.6 years. The pathology was glioblastoma in 44 and anaplastic astrocytoma in 19; median survival was 12 months. Forty patients underwent at least one craniotomy, following which 22.5% achieved a gross total resection, 23 had biopsy only. Only age and gross total resection of tumor as judged by postoperative MR (CT in 2 cases) correlated significantly with outcome. The subtotal craniotomy group and biopsy only cohort were indistinguishable (median survival 11 vs. 10 months, respectively). Although craniotomy associated with gross total resection results in enhanced survival (median 27 months), subtotal tumor excision offers little beyond a diagnosis. Therefore, careful and realistic preoperative assessment of glioma patients ought to be performed to determine optimal surgical management.
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PMID:Value of surgical intervention in the treatment of glioma. 891 49

Tumor fragment spheroids (TFS) represent an organotypic in vitro model with preserved cytoarchitecture and matrix components of the native tumor in situ. In order to determine whether DNA amplifications within gliomas remain stable in spheroid culture, tumor fragment spheroids were established from 15 human gliomas including 14 glioblastoma and one anaplastic astrocytoma. Native tumor tissue, monolayers as well as TFS were evaluated for DNA amplification using reverse chromosome painting (RCP). A modified protocol for DNA isolation from TFS was established. Amplifications in the original tumor tissue were found on chromosomes 12q13-15, tel, 4q12-13 and 11p12-13, an amplification on 11p12-13 is reported for the first time. By RCP we could demonstrate that amplified domains on 12q13-15 and 4q12-13 in three tumors were maintained in TFS whereas the amplification on 11p12-13 could not be confirmed in TFS. In monolayer cultures, all amplifications which were detected in primary culture were lost until passage 5. The results of this first comparative study of DNA amplification in glioma by analyzing native tumor tissue and tumor fragment spheroids enables us to conclude that TFS seems to be a promising in vitro model for the study of DNA amplification under cell culture conditions.
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PMID:Comparative amplification analysis of human glioma tissue and glioma derived fragment spheroids using reverse chromosome painting (RCP). 891 57

Glioblastoma multiforme (WHO Grade IV), the most malignant neoplasm of the human nervous system, develops rapidly de novo (primary glioblastoma) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). We recently reported that mutations of the p53 gene are present in more than two-thirds of secondary glioblastomas but rarely occur in primary glioblastomas, suggesting the presence of different genetic pathways (Watanabe et al, Brain Pathol 1996:6:217-24). In the present study, primary and secondary glioblastomas were screened by immunohistochemistry for MDM2 overexpression and by differential PCR for gene amplification. Tumor cells immunoreactive to MDM2 were found in 15 of 29 primary glioblastomas (52%), but in only 3 of 27 secondary glioblastomas (11%; P=0.0015). MDM2 amplification occurred in 2 primary (7%) glioblastomas but in none of the secondary glioblastomas. Only one out of 15 primary glioblastomas overexpressing MDM2 contained a p53 mutation. These results suggest that MDM2 overexpression with or without gene amplification constitutes a molecular mechanism of escape from p53-regulated growth control, operative in the evolution of primary glioblastomas that typically lack p53 mutations.
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PMID:Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. 903 72


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