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)

To characterize some of the genetic events underlying the development of glioblastoma multiforme, the authors analyzed 65 astrocytic tumors (seven pilocytic astrocytomas, eight astrocytomas, 16 anaplastic astrocytomas, and 34 glioblastomas multiforme) for loss of heterozygosity for chromosome 17p, loss of heterozygosity for chromosomes 10p and 10q, amplification of the epidermal growth factor receptor (EGFR) gene, and amplification of the oncogenes N-myc, c-myc, and N-ras using Southern blot analysis. Alterations of the p53 gene (positive immunostaining for p53 protein in tumors with or without p53 gene mutations) in these 65 tumors were analyzed previously. None of the 65 tumors showed amplification or rearrangement of N-myc, c-myc, or N-ras oncogenes. The molecular analysis presented here demonstrates distinct variants of astrocytic tumors, with at least three genetic pathways leading to glioblastoma multiforme. One pathway was characterized by 43 astrocytomas with alterations in p53. Glioblastomas with p53 alterations may represent tumors that progress from lower-grade astrocytomas. This variant was more likely to show loss of chromosome 17p than tumors without p53 alterations (p < 0.04). Seventy-five percent of tumors with loss of one 17p allele demonstrated mutations in the p53 gene. Loss of chromosome 10 was associated with progression from anaplastic astrocytoma (13%) to glioblastoma (38%) (p < 0.04). Amplification of the EGFR gene was a rare (7%) but late event in tumor progression (p < 0.03). A second pathway was characterized by six astrocytomas without p53 alterations and may represent clinically de novo high-grade tumors. These tumors were more likely to show amplification of the EGFR gene (83%) than tumors with p53 alterations. Sixty percent of tumors with EGFR amplification also showed loss of chromosome 10; loss of chromosome 17p was infrequent in this variant. One or more alternative pathways were characterized by 16 astrocytomas without p53 alterations and with none of the genetic changes analyzed in this study. Glioblastomas are a heterogeneous group of tumors that may arise via multiple genetic pathways.
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PMID:Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. 805 51

We performed intraoperative radiotherapy (IORT) in 19 patients with various brain tumors. IORT was given for primary tumors in 2 patients with malignant glioma, but was used for treating recurrent tumors in the other 17 patients. The former 2 patients respectively received 33 Gy by IORT alone and 30 Gy by IORT in combination with 50 Gy of external beam radiotherapy (EBRT), and survived for 12 and 9 months. The latter 17 patients had received EBRT at 4 to 112 months before IORT. In this group, single doses of 23-40 Gy were delivered by IORT after removing as much tumor as possible. The median survival time after IORT was 12 months for 9 patients with glioblastoma or anaplastic astrocytoma, while it was 51 months for 8 patients with less infiltrative tumors (ependymoma, anaplastic ependymoma, and anaplastic oligodendroglioma). One patient with ependymoma and another with anaplastic ependymoma are currently alive with no evidence of disease at 7 and 11 years after IORT, respectively. Symptomatic brain necrosis occurred in 3 patients following IORT, but the symptoms were relieved in 2 of them by the removal of necrotic brain tissue. It is concluded that IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors.
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PMID:Intraoperative radiation therapy for brain tumors with emphasis on retreatment for recurrence following full-dose external beam irradiation. 809 10

Although intracranial gliomas carry a poor long-term prognosis, retreatment at the time of tumor progression may prolong survival and maintain or improve the quality of life. Thirty-three patients who underwent retreatment with surgery, radiotherapy, and chemotherapy were reviewed retrospectively. Median survival after initiation of retreatment was 8 months for glioblastoma, 13 months for anaplastic astrocytoma, 22 months for astrocytoma, and 47 months for oligodendroglioma/mixed glioma. Survival was significantly better for younger patients and for those with better functional status. One third of patients were neurologically improved by surgery. Surgical morbidity was minimal (2.1%); there was no surgical mortality. Chemotherapy and radiotherapy produced expected adverse reactions. Retreatment of intracranial gliomas carries acceptable risk and is beneficial in selected patients. Decisions regarding retreatment must be carefully individualized with consideration of the quality of life and the wishes of the patient and family.
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PMID:Retreatment of intracranial gliomas. 811 86

We investigated the expression and production of the interleukin-1 receptor antagonist (IL-1ra) in three human glioblastoma cell lines (LN443, LN444, LN859). Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated the expression of IL-1ra mRNA transcripts in the three cell lines. These three cell lines also expressed mRNA for IL-1 alpha, IL-1 beta, as well as IL-1 receptor type I and type II, suggesting the presence of an IL-1 autocrine loop in these cell lines. Northern blot analysis demonstrated that the IL-1ra mRNA expression increased with IL-1 beta or tumor necrosis factor (TNF)-alpha but not with GM-CSF stimulation in both LN443 and LN444 cell lines. PMA stimulation increased the mRNA expression in LN444 but not in LN443 cells. Immunocytochemical staining showed IL-1ra immunoreactivity in these three cell lines. ELISA on culture supernatants demonstrated that the IL-1ra was secreted from the cell lines in agreement with the mRNA expression. RT-PCR with isoform-specific primers showed that both intracellular and secreted forms of IL-1ra were expressed by the three cell lines, with a predominance of the intracellular form. In vivo study with RT-PCR and Northern blot analysis demonstrated IL-1ra mRNA in six out of 12 human glioblastoma and two out of five anaplastic astrocytoma tissues, although the expression level was not high in some cases. Immunohistochemistry demonstrated the presence of IL-1ra within the cytoplasm of tumor cells in six out of 10 glioblastomas in vivo. These results suggest a potential role of IL-1ra in regulation of the IL-1 autocrine loop in glioblastomas.
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PMID:Production of interleukin-1 receptor antagonist by human glioblastoma cells in vitro and in vivo. 812 Jan 40

The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.
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PMID:Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. 820 29

We reported a multicentric glioma having three separate lesions in the cerebrum. A 75-year old man was hospitalized with progressive disorientation. Computed tomography demonstrated two lesions in the left temporal lobe and the right frontal lobe. Magnetic resonance image disclosed one more lesion in the right occipital lobe. 2-staged operative procedures were performed for the left temporal and the right frontal tumors. It was histologically proven that one was glioblastoma and the other was anaplastic astrocytoma. The patient subsequently underwent radiotherapy and chemotherapy. Most multicentric gliomas are diagnosed in autopsy. Therefore it should be stressed that diagnosis is best made by biopsy or surgery. We discussed what therapy we should use for this fatal disease.
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PMID:[A multicentric glioma exhibiting three supratentorial lesions]. 829 8

We report clinical and pathological data of 419 image-guided stereotactic biopsies. In the present series the diagnostic yield, estimated by comparing the original histological diagnoses with follow-up data, was found to be approximately 94% in gliomas. As it has been suggested that malignancy of astrocytic gliomas may be considerably underestimated in the small tissue samples obtained by stereotactic biopsy, we have reviewed 160 adult, diffuse supratentorial astrocytic tumours, correlating the original Kernohan tumour grades with survival. In this grading system, although there was generally a good correlation between histological grade and survival probability (P < 0.0001), no distinction could be made between the grade 3 (anaplastic astrocytoma) and grade 4 (glioblastoma) groups. Tumour grades obtained by applying the criteria of the more recent Daumas-Duport grading system were also determined and correlated with survival. These latter tumour grades not only correlated well with survival (P < 0.0001), but also enabled us to identify a group of patients with intermediate grade malignancy (grade 3, anaplastic astrocytoma), surviving longer than those with grade 4 tumours. Image-guided stereotactic biopsy is a useful means of providing tissue samples for histological diagnosis of brain neoplasms, including gliomas. Histological grading of adult, diffuse supratentorial astrocytic gliomas diagnosed by this technique is possible and should be carried out using an appropriate grading system.
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PMID:Reliability of histological diagnosis including grading in gliomas biopsied by image-guided stereotactic technique. 835 8

Expression of the human placental form of glutathione S-transferase (GST-pi) in pediatric gliomas, consisting of three pilocytic astrocytomas (grade 1), two fibrillary astrocytomas (grade 2), three anaplastic astrocytomas (grade 3), and one glioblastoma multiforme (grade 4), were investigated by immunohistochemical methods. Western blot analysis for GST-pi using proteins extracted from formalin-fixed and paraffin-embedded glioma specimens was performed and compared with the results of immunohistochemistry. Both the immunohistochemical examination and the Western blot analysis of pediatric gliomas revealed that malignant gliomas such as anaplastic astrocytoma and glioblastoma had strong expression of GST-pi while benign gliomas showed weak GST-pi expression.
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PMID:Expression of the placental form of glutathione S-transferase in pediatric gliomas. 839 67

Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.
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PMID:Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue. 850 40

Expression of the glial fibrillary acidic protein (GFAP) and S-100 protein was examined in 76 astrocytic gliomas (AG) with different degree of malignancy, which were subdivided into 4 groups: pilocytic astrocytoma, mixed astrocytoma, anaplastic astrocytoma and glioblastoma. Combined light-microscopical and immunohistochemical investigation detected several variants among different kinds of malignant AG that were distinguished by cytological composition and immunomorphology. Gemistocytic and polymorphic nuclear types were distinguished among anaplastic astrocytoma. Glioblastomas were subdivided into multiforme, isomorphic and gemistocytic variants. It was established that fractions of GFAP-negative cells occur in benign and malignant AG. Thus, the presence of population of immunonegative cells in AG is not a sign of high-grade tumor anaplasia. Groups of GFAP-positive cells around tumor vessels were found in malignant AG only.
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PMID:[Expression of glial fibrillary acidic protein and protein S-100 in cerebral astrocytic gliomas of varying degrees of malignancy (immunohistochemical study)]. 852 53


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