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)

The determination and comparison of genotypic combinations at genomic loci in normal and tumour tissues from patients with various types of cancer have defined the chromosomal locations of loci at which recessive mutations play a role in disease. The predisposing nature of some of these mutant alleles is exemplified in studies of retinoblastoma and osteogenic sarcoma. These two clinically associated diseases share a pathogenetically causal predisposition that maps to chromosome position 13q14. A similar mechanism at 11p15.5 is involved in the development of the embryonal variant of rhabdomyo-sarcoma, Wilms' tumour and hepatoblastoma. Finally, genomic alteration of chromosome 10 is apparent in glioblastomas and mixed tumours of glioblastoma/astrocytoma grade III but not in homogenous astrocytoma grades II or III, suggesting the definition of a locus involved in tumour progression and, perhaps, an approach to molecular genetic staging of tumours.
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PMID:Loss of genetic information in cancer. 274 36

Clinical and pathomorphological findings in 2 stillborn and 15 lifeborn children with primary intracranial tumors are reported. All infants died within the first year of life and the tumors were confirmed histologically. In 6 children the tumors (3 intracranial teratomas, 1 glioblastoma, 1 hemangioblastoma, 1 choroid plexus papilloma) were present at birth. All 6 were born with pathologically enlarged heads. Another child exhibited symptoms of brain tumor at the age of three weeks. The tumor was probably present at birth as well. In the remaining infants the signs and symptoms of tumor development became evident some months after birth. These tumors might have occurred postnatally. In a girl aged 9 months, a nephroblastoma of the right kidney and a malignant cerebral tumor, probably a glioma, were present. An incidental coexistence of both tumors is considered, however, a common etiology cannot be excluded. 8 of the 17 intracranial tumors were supratentorially situated. This supports the view that the proportion of supratentorial tumors is higher in early life than in older children.
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PMID:[Primary intracranial tumors as cause of death in the fetus and infant]. 632 94

In 1955, Collins made the observation that tumor recurrence in children with Wilms' tumor was correlated with the child's age plus 9 months. This concept of a period of risk for recurrence was later applied to a variety of tumors in children and became known as Collins' Law (CL). The law has been a successful predictor of survival for some children with neural tumors within the central nervous system and a poor predictor for others. We tested Collins' concept of a period of risk for recurrence and extended it to survival for 14 childhood neural tumors described in the Childhood Brain Tumor Consortium (CBTC) database. The CBTC data describe clinical, surgical, and histological details (over a 49-year period in 10 institutions) from 3921 patients under the age of 21 years at the time of their first surgical procedure for a brain tumor. CL was considered to be a good predictor of survival if fewer than 10% of patients who die survive beyond the expiration of the period of risk for that child. We found that CL applied to tumors such as anaplastic astrocytoma, glioblastoma, pineoblastoma, medulloblastoma or "primitive neuroectodermal tumor," teratoma, and germinoma, as well as ependymoma, papilloma, and tumors that could not be classified; it had no predictive value in craniopharyngioma, oligodendroglioma, or plain, fibrillary, pilocytic, or protoplasmic astrocytoma. We had sufficient follow-up data to determine adherence to CL when the child's age at diagnosis was less than 8 years; it is likely that CL applies to older children with these tumors, but we did not have the data to show this unequivocally.
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PMID:The applicability of Collins' Law to childhood brain tumors and its usefulness as a predictor of survival. 764 86

Eukaryotic chromosomes contain specialized structures at the termini called telomeres. This region of DNA is required for replication and stability of the chromosome. Telomere reduction can contribute to genetic instability and has been described in certain malignancies (e.g., colon, leukemia, giant cell tumor of bone). To determine whether telomere reduction is a generalized phenomenon in malignancies, the telomere integrity of genomic DNA isolated from tumor cells was determined from 39 individuals with 15 different malignancies categorized as musculoskeletal, epithelial, cranial, or other, and peripheral blood leukocytes from the same patient, when possible, or age-matched controls. Significant telomere reduction occurred randomly across histopathologic groups including giant cell tumor of bone, glioblastoma, colon cancer, and Wilms' tumor while telomere elongation occurred in chordoma. The other remaining 10 malignancies do not show significant differences in telomere lengths compared with controls.
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PMID:Chromosome telomere integrity of human solid neoplasms. 861 86

The Wilms' tumor gene (WT1) encodes a transcriptional regulator involved in growth and differentiation of various tissue types. A continuous over-expression of WT1 was found in leukemic blasts, thus suggesting an oncogenic function. Solid cancer entities have also been described as expressing WT1. We systematically analyzed WT1 expression in small-cell and non-small-cell lung cancer, colon cancer and glioblastoma patients and in the respective tumor cell lines. Using reverse transcription/polymerase chain reaction, we found WT1 expression in glioblastoma (5 of 8), lung (5 of 11), and colon cancer (5 of 15) cell lines. While WT1 was expressed in only 1 of 12 lung cancer and 1 of 5 glioblastoma specimens, it was not detected in colon cancer or macroscopically tumor-free colon and lung tissue. In addition, HT29 colon cancer cells showed a loss of WT1 expression when grown to confluence or induced to differentiate by sodium butyrate. From this evidence, testing for WT1 expression is not clinically relevant for colon cancer, lung cancer, or glioblastoma patients. WT1 expression in cancer cell lines can probably be attributed to optimized in vitro growth conditions.
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PMID:Wilms' tumor gene (WT1) expression in lung cancer, colon cancer and glioblastoma cell lines compared to freshly isolated tumor specimens. 1078 96

Nephroblastoma overexpressed gene (NOV) is highly expressed in the nervous system. We investigated its biological activity by expressing the human NOV gene (NOVH) in a human glioblastoma cell line that is negative for NOVH and by analyzing four clones with different levels of NOVH expression. There was no difference in cell proliferation between the NOVH-expressing cell lines, but there was increased cell adhesion and migration that correlated with increasing NOVH expression. Gene expression profiling was used to investigate the mechanisms by which NOVH expression regulated cell activity. We identified two induced genes in NOVH-expressing cells that are involved in cell migration: matrix metalloprotease (MMP)3 and platelet-derived growth factor receptor (PDGFR)-alpha. Our studies show that PDGFR-alpha induced MMP3 gene expression and increased cell proliferation and cell migration upon stimulation by platelet-derived growth factor (PDGF)-AA. We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB. Thus, expression of NOVH in glioblastoma cells triggers a cascade of gene expression resulting in increased cell adhesion and migration.
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PMID:NOVH increases MMP3 expression and cell migration in glioblastoma cells via a PDGFR-alpha-dependent mechanism. 1451 68

The Wilms' tumor gene WT1 was first identified as the gene responsible for a childhood renal tumor, Wilms' tumor. This gene encodes for a zinc finger-containing transcription factor. Although originally identified as a tumor suppressor gene, WT1 is overexpressed in a variety of hematologic malignancies and solid tumors. Recently, WT1 protein has been considered as a new molecular target of cancer immunotherapy for several solid tumors. In the present study, we investigated the expression of WT1 protein and WT1 mRNA in glioblastomas and medulloblastomas. Forty-eight of 51 glioblastoma samples (94%) showed immunohistochemically positive staining of WT1 protein, whereas all 10 medulloblastomas examined were negative. According to the immunohistochemical expression of WT1 protein, WT1 mRNA was also highly expressed in the same glioblastoma tissue. Our results suggest that the WT1 gene may play an important role in the tumorigenesis of glioblastoma, in contrast to medulloblastoma, and be integral in the development of the immunotherapy targeting WT1 protein in patients with glioblastoma.
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PMID:Expression of the Wilms' tumor gene product WT1 in glioblastomas and medulloblastomas. 1569 71

WT1 was first identified as a tumor suppressor involved in the development of Wilms' tumor. Recently, oncogenic properties of WT1 have been demonstrated in various hematological malignancies and solid tumors. Because WT1 has been identified as a molecular target for cancer immunotherapy, immunohistochemical detection of WT1 in tumor cells has become an essential part of routine practice. In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. Staining for C-19 and 6F-H2 was found in 35-100 and 5-88% of the cases of each kind of tumor, respectively. WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. Immunohistochemical detection with routinely processed histologic sections could provide meaningful information on the expression of WT1 in cancer cells.
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PMID:Immunohistochemical detection of WT1 protein in a variety of cancer cells. 1654 68

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

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


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