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

We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro ("BT-cell lines"). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors ("V-cell lines"), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system-specific protein S-100, a "marker" not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development.
 ...
PMID:Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. 19 83

Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct "primary" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.
 ...
PMID:Glioblastoma multiforme: morphology and biology. 21 8

We used 2-parameter flow cytometry (FCM) to investigate the relationship between the cell cycle phases and 3 proteins whose expression is known to increase in proliferating cells: the surface antigen transferrin receptor (Trf-r), the "cyclin" (a proliferating cell nuclear antigen, PCNA), and the nuclear antigen recognized by the monoclonal antibody (MoAb) Ki-67. FITC-labeled antibodies against Trf-r, PCNA, and the Ki-67-reactive antigen, as well as propidium iodide-DNA distribution, were simultaneously measured on human leukemia HL-60 and K562, and breast carcinoma MCF-7 cell lines and on fresh human leukemic and glioblastoma cells. The 70% ethanol fixation for Trf-r and PCNA and the 95% acetone fixation for Ki-67 plus permeabilization (with 0.1% and 1% Triton X100, respectively, for the surface and the nuclear antigens) produced cell suspensions with negligible cell clumping, high-quality DNA profiles, and bright specific immunofluorescent staining. The investigated proteins have different relationships with the proliferative state of the cell. Trf-r is expressed mainly at the transition from G0/G1 to S-phase. PCNA expression is prominent in late G1 and through S-phase and decreases in G2-M. The Ki-67-reactive antigen is widely distributed in G1, S, and G2-M phases. Knowledge regarding the relationships between proliferation-associated antigens and cell cycle phase in normal and neoplastic cells could improve our understanding of the mechanisms underlying growth regulation and neoplastic transformation. Bivariate FCM is an easy method for obtaining these data from large numbers of cells.
 ...
PMID:Cell cycle-related proteins: a flow cytofluorometric study in human tumors. 290 62

Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic tendency for progression to anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). This change is due to the sequential acquisition of genetic alterations, several of which have recently been identified. In low-grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principal detectable change. Anaplastic astrocytomas contain p53 mutations at an overall incidence of 34% and, in addition, loss of heterozygosity on chromosome 19q and frequent homozygous deletion of the p16 tumor suppressor (MTS-1) gene. The most malignant astrocytic neoplasms, the glioblastoma, further shows loss of chromosome 10 and amplification of the epidermal growth factor receptor (EGF-R) gene at overall incidences of 66% and 34%, respectively. The type and distribution of p53 mutations in astrocytic brain tumours are not suggestive of specific environmental carcinogens operative in their aetiology. Analysis of 91 families with p53 germline mutations reported to date show that tumours of the nervous system account to 12% of all neoplasms. Of a total of 57 brain tumours reported, 30 were classified histologically and of these, 73% were of astrocytic origin. The observation that somatic p53 mutations in sporadic brain tumours are largely restricted to those of astrocytic origin and that astrocytomas also prevail among CNS neoplasms associated with p53 germline mutation strongly suggests, that p53 mutations are capable of initiating neoplastic transformation in astrocytes of the human nervous system.
 ...
PMID:Genetic alterations associated with the evolution and progression of astrocytic brain tumours. 758 39

Recently tau immunoreactivity has been observed in astrocytes in Alzheimer's disease and other neurological diseases. We examined the immunohistochemical localization of tau in 110 human brain tumors. Tau was widely distributed in the glial neoplastic cells and the reactive astrocytes in tumor tissues. In human surgical specimens positive immunostaining for tau was frequently observed in astrocytic tumors, oligodendroglial tumors, and glioblastoma, as well as neuronal tumors. The astrocytic neoplastic cells in medulloblastoma and other poorly differentiated tumors were also stained. In contrast, no immunoreactivity was observed in meningiomas and schwannomas. The expression of tau in brain tumors was mainly restricted to those cells with astrocytic features rather than small immature cells. The expression of tau mRNA was also demonstrated in astrocytic tumors. In conjunction with the findings of tau-positive astrocytes in some degenerative disorders, astrocytes are considered to have a potential to express tau through neoplastic transformation and reactive processes.
 ...
PMID:Widespread distribution of tau in the astrocytic elements of glial tumors. 821 81

Activation of protein synthesis is necessary for the transition of cells from quiescence to proliferation, while withdrawal of growth factors leads to decrease in protein synthesis and transition of normal cells into the resting period. It is shown in this paper that serum growth factors are required for activation of expression of gene encoding translation initiation factor 4E (eIF-4E) in non-transformed NIH 3T3 and Rat-1 fibroblasts but this requirement is lost in C6 glioblastoma, A431 carcinoma and N-myc transformed Rat-1 cells. These data raise the possibility that neoplastic transformation leads to growth factor-independent expression of eIF-4E, thus facilitating continuous growth and replication of transformed cells.
 ...
PMID:Growth factor-independent expression of the gene encoding eukaryotic translation initiation factor 4E in transformed cell lines. 852 9

Alternative RNA processing of the human fibroblast growth factor receptor-1 transcript results in receptor forms that vary in their affinity for fibroblast growth factor. An alternative RNA processing event involving recognition of the alpha-exon is deregulated during neoplastic transformation of glial cells. We have previously established a splicing reporter/transfection cell culture model system to identify sequences involved in recognition of this exon. In this study, the system was used to identify two sequence elements that differentially function to regulate splicing of this exon. Exclusion of the alpha-exon in glioblastoma cells specifically required the downstream intron sequence comprising the 5'-splice site. Replacement or mutation of this sequence increasing complementarity to U1 RNA resulted in enhanced exon recognition in SNB-19 glioblastoma cells. Sequences within the exon were found to be required for alpha-exon inclusion. Deletion and gain-of-function experiments identified a 69-nucleotide exon sequence that was specifically required for alpha-exon inclusion. These studies indicate that multiple sequences are required for the regulated recognition of the alpha-exon.
 ...
PMID:Exon sequence is required for regulated RNA splicing of the human fibroblast growth factor receptor-1 alpha-exon. 963 72

Over the past few years, although much has been learned about the molecular genetics of central nervous system (CNS) tumors, researchers and pathologists are only beginning to understand the scientific basis of the development of these tumors. Data accumulated so far support the division of glioblastoma into two clinical and molecular subsets. Primary or de novo glioblastomas occur in older patients, are clinically aggressive and exhibit epidermal growth factor receptor amplification or overexpression. Secondary glioblastomas develop from pre-existing low-grade astrocytomas, have a more protracted clinical course, and frequently contain p53 mutations. Both types of tumors show deletions of chromosome 10 and possibly mutations of the PTEN/MMAC1 gene as an endstage event. Oligodendrogliomas have been shown to have genetic abnormalities distinct from those of the astrocytic tumors, commonly involving chromosomes 1p and 19q. As regards meningiomas, loss of chromosome 22q and mutations of the neurofibromatosis type 2 gene are frequent events and loss of chromosome 14q and 10q may be seen in atypical or malignant transformation. Such genetic findings, apart from providing a better understanding of neoplastic transformation in brain tumors, are beginning to form the basis of a new approach to neuro-oncology.
 ...
PMID:The molecular genetics of central nervous system tumors. 964 6

The fibroblast growth factor receptor-1 (FGFR-1) primary transcript is alternatively processed to produce receptors that vary in their ligand affinity and specificity. A high affinity form of this receptor--FGFR-1beta--that lacks the alpha exon is observed on the neoplastic transformation of glial cells. In this study, we have identified a 62-bp sequence located 97 bp downstream from the alpha exon that is required for the exclusion of this exon in a human glioblastoma cell line. Deletion or mutation of this sequence is sufficient to allow enhanced inclusion of the alpha exon or a heterologous exon in glioblastoma cells. Therefore, it would appear that this sequence element plays a key role in the glioblastoma-specific splicing to form FGFR-1beta mRNA.
 ...
PMID:Glioblastoma cell-specific expression of fibroblast growth factor receptor-1beta requires an intronic repressor of RNA splicing. 992 39

The human fibroblast growth factor receptor-1 primary transcript is alternatively processed to produce receptor forms that vary in their affinity for fibroblast growth factor. The inclusion of a single exon (alpha) in normal brain glial cells produces a low affinity form of the receptor. Recognition of the alpha-exon is dysregulated during neoplastic transformation of glial cells to produce a high affinity receptor form. In this study, we have identified a second intronic repressor of RNA splicing located approximately 250 nucleotides upstream of the alpha-exon. Deletion or mutation of this sequence resulted in a significant increase in exon recognition in glioblastoma cells. This intronic repressor was found to share significant sequence homology with an intronic repressor element located downstream of the alpha-exon. The two repressor elements are functionally redundant in that they are capable of inhibiting alpha-exon recognition when positioned upstream or downstream of the exon. Finally, the elements were found to mediate enhanced exclusion of an unrelated exon, but only the repressors were placed flanking the exon. However, under these conditions, the cell-specific exon exclusion was no longer maintained. These results suggest that although the alpha-exon inclusion is actively repressed in glioblastomas, the absence of trans-activators appears to be key to the production of the high affinity form of fibroblast growth factor receptor-1 in glioblastomas.
 ...
PMID:Redundant intronic repressors function to inhibit fibroblast growth factor receptor-1 alpha-exon recognition in glioblastoma cells. 1048 55


1 2 3 Next >>