Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aims-(1) To investigate the expression in human derived glioblastoma cell lines of two structurally related genes, novH (nephroblastoma overexpressed gene) and CTGF (connective tissue growth factor), which encode putative insulin-like growth factor binding proteins of a novel type. (2) To investigate whether the same transcription factors regulate CTGF and novH expression.Methods-Expression of novH and CTGF was analysed in 24 glioblastoma derived cell lines by northern blotting. The CTGF promoter region was characterised by nucleotide sequencing, RNase protection experiments, by transient transfections, and CAT assays.Results-CTGF and novH mRNA levels differed in the glioma cell lines studied. NovH and CTGF genes were not co-expressed in all cell lines. The CTGF promoter region was highly conserved compared with the corresponding region in the mouse (FISP12) and exhibited in vitro transcriptional activity.Conclusions-Although the coding regions of novH and CTGF are highly homologous, their promoter regions are substantially different, suggesting that these two genes may be regulated by different mechanisms. Considering that novH and CTGF are likely to be, respectively, negative and positive regulators of growth and that some glioma cell lines expressing novH are not tumorigenic, expression of these two genes might represent a key element in determining the stage of differentiation or the malignant potential, or both, of some tumour cell lines.
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PMID:Differential expression of novH and CTGF in human glioma cell lines. 1669 57

Gefitinib (ZD1839, Iressa), a member of the 4-anilinoquinazoline class of compounds, has the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib often is referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor (EGFR). EGFR expression has been noted in neuroblastoma and rhabdomyosarcoma cell lines and in tumor specimens from children with Wilms tumor, osteosarcoma, and glioma. Thus, gefitinib, the first marketed EGFR tyrosine kinase inhibitor, was chosen for study in children with refractory solid tumors and central nervous system (CNS) malignancies. This review discusses findings from 3 clinical trials of gefitinib in children with refractory solid tumors and CNS malignancies, focusing on the clinical pharmacology of the compound. To date, gefitinib has been studied in children as a single agent and in combination with irinotecan. Overall, the compound has been well tolerated in children and has a safety profile similar to that observed in adults. The clinical pharmacokinetics of gefitinib in children are similar to those observed in adults. Finally, the future for the use of gefitinib in pediatrics is similar to that of other molecularly targeted agents and awaits definition of tumors and patient populations in which it will be most advantageous.
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PMID:Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients. 1680 60

The Wilms' tumor 1 (WT1) gene is overexpressed in human glioblastoma and correlates with wild-type p53 status. In other cell types, WT1 inhibits p53-mediated apoptosis in response to DNA damaging agents. However, neither this interaction nor the relationship between WT1 and radiosensitivity has been studied in glioblastoma. To study this interaction, we generated LN-229 glioma cell lines (p53 mutant) stably expressing WT1 isoforms and induced apoptosis by transfecting with different doses of wild-type p53 plasmid expression vector. Constitutive expression of WT1 did not protect against exogenous p53-mediated apoptosis. Likewise, WT1 expression did not protect against endogenous p53-mediated cell death induced by radiotherapy in U87MG cells, which contain functional wild-type p53. We then tested the efficacy of WT1 siRNA in inhibiting WT1 expression and its effect on radiosensitivity. In T98G and LN-18 glioma cells, which possess p53 mutations, WT1 siRNA decreased WT1 protein to almost undetectable levels by 96-h post-transfection. Furthermore, WT1 siRNA transfection caused a significantly larger decrease in viability following irradiation than was seen in untransfected cells in both cell lines after treatment with ED50 of ionizing radiation. In conclusion, WT1 overexpression did not protect against p53-mediated apoptosis or ionizing radiation induced cell death. WT1 siRNA increased the radiosensitivity of two human glioma cell lines independently of p53. Anti-WT1 strategies may, therefore, prove useful in improving the response of glioblastoma to radiotherapy, thus potentially improving patient survival.
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PMID:Down-regulation of Wilms' tumor 1 expression in glioblastoma cells increases radiosensitivity independently of p53. 1720 72

Adolescence, spanning 15-19 years of age, is a time of developmental transition from childhood to adult life. The spectrum of cancers affecting this age group reflects a similar transition. The common malignant diseases of childhood - leukemias, lymphomas, tumors of the central nervous system and embryonal solid tumors (such as nephroblastoma and neuroblastoma) - are replaced in relative frequency by sarcomas of bone and soft tissue, and tumors of the male and female genital tracts. Moreover, the epithelial tumors (carcinomas), so prevalent in adults, occur (albeit at much lower frequencies) in adolescents. Within individual tumor types, biological features may be distinctive in this age group. Examples are the high prevalence of poor prognostic determinants in acute lymphoblastic leukemia and histologically higher grade forms of astrocytic/glial tumors. Particular challenges in addressing the common tumors of adolescence include the development of better categorization, especially of soft tissue sarcomas, and exploring these diseases in this age group within the developing world where most adolescents reside.
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PMID:Common cancers in adolescents. 1722 81

Layer hens (310 days old) affected with subcutaneous tumours were investigated pathologically. Basopholic intracytoplasmic viral matrix inclusions (MIs) were widely distributed in the chickens affected with subcutaneous myxoma rhabdomyosarcoma, perineuroma, glioma, intra-abdominal adenocarcinoma, and nephroblastoma. MIs were observed in the myocardial cells and the impulse-conducting-system cells. They were also present in the smooth muscle cells of the arteries in the spleen and lungs, in the smooth muscle of the digestive tract muscular layer (crop, oesophagus, proventriculus, gizzard, duodenum, jejunum, ileum, caecum, and large intestine), and in the smooth muscle of the capsule in the ovary and pancreas. They were also observed in the podocytes of glomeruli and renal epithelium in the kidneys, tumour cells of nephroblastoma, chondrocytes of the trachea, squamous-epithelial cells of the pharynx, and nerve cells of the cerebrum and tumour cells of the glioma in the cerebellum. Histochemically, MIs were stained with RNA, but not with DNA. MIs in the various tissues were strongly positive for the avian leukosis virus (ALV) antigen. Ultrastracturally, MIs were found in the cytoplasm of myocardial cells and podocytes of renal glomeruli. They consisted of electron-dense small granules and ring-shaped particles. Viral particles were observed in the vesicles of the cytoplasm of myocardial cells and glomerular podocytes. The gene product specific for subgroup A of ALV was detected in the livers or tumours by reverse transcription-polymerase chain reaction. This result suggests that MIs can be formed in organs rather than muscular systems in the chickens naturally affected with ALV-associated tumours.
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PMID:Basophilic intracytoplasmic viral matrix inclusions distributed widely in layer hens affected with avian-leukosis-virus-associated tumours. 1736 10

The expression of Wilms' tumor gene WT1 protein was investigated immunohistochemically in 73 glial tumors, including 60 astrocytic tumors, eight oligodendroglial tumors, and five ependymal tumors. WT1 protein was detected in 70 of the 73 glial tumors (95.9%) examined. Almost all glioblastomas, anaplastic astrocytomas, anaplastic ependymomas, and anaplastic oligodendrogliomas expressed high levels of WT1 protein. A significant (p < 0.001) correlation was found between WT1 protein expression and MIB-1 staining index. Histological examination found that WT1 protein was strongly expressed in the anaplastic portions and areas with perivascular proliferation and high cellularity, implying that WT1 gene might be important in glial tumor cell proliferation. WT1 gene is overexpressed in various types of solid tumors and WT1 protein is a target antigen for cancer immunotherapy. This study indicates that many malignant glial tumors are good candidates for cancer immunotherapy targeting WT1 protein and that WT1 protein expression could be used as a proliferation marker in glial tumors.
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PMID:Expression of WT1 protein and correlation with cellular proliferation in glial tumors. 1745 20

Gap junctions form channels that allow exchange of materials between cells and are composed of transmembrane protein subunits called connexins. While connexins are believed to mediate cellular signaling by permitting intercellular communication to occur, there is also increasing evidence that suggest connexins may mediate growth control via a junction-independent mechanism. Connexin43 (Cx43) is the most abundant gap junction protein found in astrocytes, and gliomas exhibit reduced Cx43 expression. We have previously observed that restoration of Cx43 levels in glioma cells led to increased expression of CCN3 (NOV) proteins. We now report that overexpression of Cx43 in C6-glioma cells (C6-Cx43) also upregulates the expression of CCN1 (Cyr61). Both CCN1 and CCN3 belong to the Cyr61/Connective tissue growth factor/Nephroblastoma-overexpressed (CCN) family of secretory proteins. The CCN proteins are tightly associated with the extracellular matrix and have important roles in cell proliferation and migration. CCN1 promotes growth in glioma cells, as shown by the increased proliferation rate of CCN1-overexpressing C6 cells. In addition to its effect on cell growth, CCN1 also increased the motility of glioma cells in the presence of extracellular substrates such as fibronectin. Gliomas expressing high levels of Cx43 preferentially upregulated CCN3 which resulted in reduced growth rate. CCN3 could also be observed in Cx43 gap junction plaques in confluent C6-Cx43H culture at the stationary phase of their growth. Our results suggest that the dissimilar growth characteristics between high and low Cx43 expressors may be due to differential regulation of CCN3 by varying levels of Cx43.
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PMID:Dose-dependent differential upregulation of CCN1/Cyr61 and CCN3/NOV by the gap junction protein Connexin43 in glioma cells. 1800 27

Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5'-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs.
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PMID:Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors. 1803 Mar 65

Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/CTGF/nephroblastoma-overexpressed gene] family. These proteins have been implicated in various biological processes, including stimulation of cell proliferation, migration, angiogenesis and tumorigenesis. In a previous study, we found that CTGF mRNA was elevated in primary gliomas, and a significant correlation existed between CTGF mRNA levels versus tumor grade, histology and patient survival. In this study, the role of CTGF in glioma tumorigenesis was explored. Forced expression of CTGF in glioblastoma multiforme (GBM) cells accelerated their growth in liquid culture and soft agar, stimulated cells migration in Boyden chamber assays and significantly increased their ability to form large, vascularized tumors in nude mice. CTGF induced the expression of the antiapoptotic proteins, Bcl-xl, Survivin and Flip. Overexpression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist antitumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand, VELCADE (bortezomib, proteasome inhibitor) and temozolomide. Our data suggest that CTGF plays an important role in glioma progression, by supporting tumor cells survival and drug resistance.
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PMID:Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme. 2016 79

A diagnostic difficulty in neuropathology practice is distinguishing reactive from neoplastic astrocyte populations. This is particularly true in small biopsy samples that lack evidence of increased cellularity or mitotic activity, microvascular proliferation, or necrosis. We performed the current study to validate the previously reported finding that in the central nervous system, the expression of WT1 is limited to neoplastic astrocytes. We retrospectively studied WT1 protein expression by immunohistochemistry (IHC) in 100 formalin-fixed, paraffin-embedded brain tissue samples consisting of 3 normal control tissues, 44 cases of reactive gliosis, 49 gliomas and 4 lesions suspicious for glioma. In normal human cortex, WT1 staining was restricted to vascular endothelium. Most cases of reactive gliosis (82%) showed at least focal WT1 positivity, and analysis of specimens with electrode monitoring lesions showed an inverse relationship between WT1 expression intensity and the number of days from electrode placement to tissue resection. All glioma samples (100%) and all cases suspicious for glioma (100%) showed at least focal WT1 positivity. Our results likely differ from those in the prior report because of differences in tissue fixation and IHC methodology. Thus, our findings indicate that WT1 expression alone is not a reliable feature to distinguish reactive from neoplastic astrocytes.
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PMID:WT1 is not a reliable marker to distinguish reactive from neoplastic astrocyte populations in the central nervous system. 2057 27


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