Disease relevance of Astrocytoma

• This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss [1].
• We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1 [2].
• Specifically, in human astrocytoma cells (U373-MG) transfected with the US11 gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are significantly destabilized [3].
• Nitrosotrimethylurea, given for 47 weeks, gave rise to astrocytomas of the brain and tumors of the forestomach; nitrosotriethylurea induced a high incidence of adenocarcinomas of the breast and uterus and tumors of the forestomach [4].
• Cell surface glycoproteins of human tumor cell lines (melanomas and astrocytomas, and ovarian, bladder, stomach, cervical, laryngeal, and renal cancers) were studied by labelling with 1) neuraminidase-galactose oxidase-[3H]borohydride, 2) galactose oxidase-[3H]borohydride, and 3) dilute periodate-[3H]borohydride [5].

Psychiatry related information on Astrocytoma

• Impaired neurofibromin function in these nervous system cells contributes to the development of astrocytomas, learning disabilities, and radiographic abnormalities of the brain [6].

High impact information on Astrocytoma

• Diagnosis of recurrent astrocytoma with fludeoxyglucose F18 PET scanning [7].
• Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells [8].
• Inhibiting protein synthesis by incubating C6-2B rat astrocytoma cells with cycloheximide or emetine for periods up to 24 hours caused a progressive decrease in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) when the cells were challenged for 30 minutes with 100 microM forskolin [9].
• Incubation of astrocytoma cells with catecholamines results in a decrease in catecholamine-stimulated adenylate cyclase activity and a concomitant alteration in the sedimentation properties of particulate beta-adrenergic receptors [10].
• We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas [11].

Chemical compound and disease context of Astrocytoma

• Nitrosomethyldiethylurea induced almost exclusively a high incidence of both astrocytomas of the brain and tumors of the spinal cord [4].
• Nine children were cured; in one case infection (with a different organism) recurred but a further course of cefotaxime was successful; one child died, with sterile CSF; one child died from his underlying disease (astrocytoma); and one child was cured with sequelae (hydrocephalus) [12].
• C6 astrocytoma cells contain beta-adrenergic receptors coupled to adenylate cyclase [13].
• Our results show that human astrocytoma cells contain mRNAs coding for functional acetylcholine and glutamate receptors that have properties similar to those of neurons [14].
• Calcium and microtubule dependence for increased ornithine decarboxylase activity stimulated by beta-adrenergic agonists, dibutyryl cyclic AMP, or serum in a rat astrocytoma cell line [15].
• Using 4',6-diamidino-2-phenylindole and Annexin V, we showed that astrocytoma cell death induced by oleanolic acid or maslinic acid were mainly due to apoptotic events [16].

Biological context of Astrocytoma

• The earliest genetic alteration in human astrocytoma progression is mutation of the p53 tumour suppressor gene, while one of the earliest phenotypic changes is the stimulation of neovascularization [17].
• Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system [18].
• Through analysis of F1 progeny, we demonstrate that susceptibility to astrocytoma is linked to chromosome 11, and that the modifier gene(s) responsible for differences in susceptibility is closely linked to Nf1 and Trp53 [19].
• The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate [20].
• The clonal progression of human astrocytomas to a more malignant phenotype often involves the amplification and overexpression of the epidermal growth factor receptor (EGFr) gene [21].

Anatomical context of Astrocytoma

• From these results, it is clear that the glial specific intermediate filament protein, GFAP, is required for process extension of these astrocytoma cells in response to granule neurons [22].
• In the present study, we examined the structural determinants governing recognition and translocation of substrates by the anandamide transporter constitutively expressed in a human astrocytoma cell line [23].
• An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein [20].
• Based on ongoing gene expression profiling experiments on human astrocytoma tumors, we demonstrate increased expression of two proteins implicated in cell attachment, spreading and motility (GAP43 and T-cadherin) in Nf1+/- and Nf1-/- astrocytes [24].
• Here we report the first evidence of loss of heterozygosity at the TSC1 critical region in a giant cell astrocytoma of a familial tuberous sclerosis case [25].

Gene context of Astrocytoma

• We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53 [1].
• Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8-binding receptors in astrocytoma [26].
• PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme [27].
• Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34) [27].
• Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance [28].
• IL-13R alpha 2, EphA2, and Fra-1 are attractive therapeutic targets representing molecular denominators of high-grade astrocytomas [29].

Analytical, diagnostic and therapeutic context of Astrocytoma

• Northern blot analysis demonstrated the coexpression of the c-sis/PDGF-2 protooncogene and the PDGF-R gene in all astrocytomas examined [28].
• In situ hybridization of astrocytoma tissue localized the expression of the c-sis and PDGF-R mRNA's in tumor cells [28].
• Furthermore, PAb 1801 immunohistochemistry may not be an adequate method of screening astrocytomas for p53 mutations [30].
• CONCLUSIONS: There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone [31].
• PATIENTS AND METHODS: We correlated the MGMT level in malignant astrocytoma tissues, obtained from patients treated with radiotherapy and bis-chloroethylnitrosourea (BCNU) on a prior prospective trial (Southwest Oncology Group [SWOG] 8737), with overall and failure-free survival [32].

References