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)

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.
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PMID:Induction of tumor degeneration by sodium benzylideneascorbate. 174 10

A novel antitumor antibiotic, 11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1, 11-diazatetracyclo [7.4.1.0(2,7).0(10,12] tetradeca-2,4,6-trien-6,9-diyl diacetate, FK973, was obtained as a fermentation product from Streptomyces sandaensis. This drug showed excellent cytotoxic effects on human glioblastoma and medulloblastoma and murine glioma (203 glioma) cells. The antitumor effects were also observed in ACNU-resistant glioma cells. The median survival time (MST) of MG models was 15 days. When they were treated with FK973, their MST was prolonged to 21 days. FK973 showed no apparent damage to murine brain cells.
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PMID:Cytotoxic effects of a new antitumor antibiotic, FK973, in malignant glioma. 177 43

Three cell lines established from human gliomas were found to differ in the capacity to phosphorylate the glycolytic enzyme pyruvate kinase in vitro. Phosphorylation in the glioblastoma cell line U-138 was more pronounced than in the glioma cell line Hs 683 and in the glioblastoma cell line A-172. All 3 cell lines showed similar pyruvate kinase isozyme patterns and expressed about 90% K-type and 10% M-type subunits. So, differences in pyruvate kinase phosphorylation could not be explained by differences in the availability of the appropriate substrate, being pyruvate kinase type K. As in gliomas, phosphorylation could specifically and almost completely be inhibited by fructose-1,6-bisphosphate. In order to investigate a potential physiological significance of the phosphorylation of pyruvate kinase, we have characterized these cell lines for several glycolytic parameters. In U-138 cells, the production of lactate appeared to be 2 times higher as compared with A-172 and Hs 683 cells under normal growth conditions and even 4 times higher under low glucose culture regime. The efflux of lactate correlated with the pyruvate kinase phosphorylation pattern in the cell lines. In none of the cell lines could the lactate production be stimulated by glutamine as additional energy source under low glucose culture conditions. The higher glycolytic flux in U-138 cells was not accompanied by higher glycolytic enzyme activities. The isozyme patterns of hexokinase, pyruvate kinase, aldolase, enolase and lactate dehydrogenase in the cell lines were nearly identical and resembled the patterns previously described for solid gliomas. However, the isozyme composition of phosphofructokinase in the cell lines differed from the situation in gliomas. While in gliomas the expression of L-type phosphofructokinase is favored, in the glioma cell lines, we found an increase in the expression of C-type subunits.
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PMID:Phosphorylation of pyruvate kinase and glycolytic metabolism in three human glioma cell lines. 179 9

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary's criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month follow-up examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disabled. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.
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PMID:Direct surgery for brainstem tumours. 180 73

Changes in the fibrinolytic and coagulation values measured preoperatively in brain tumor patients have not been done systematically using individual rather than global assays. Such measurements can provide meaningful information on the status of tumor-host interactions and could potentially help in predicting thromboembolic and hemorrhagic tendencies. A complete fibrinolytic profile including total fibrinolytic activity (TFA), tissue plasminogen activator (t-PA), plasmin inhibitor (PI), plasminogen activator inhibitor (PAI), protein C (PC) and plasminogen (PLG) was obtained preoperatively in 114 brain tumor patients. PLG and PI did not show much variation among the groups. TFA was slightly reduced (15%) in patients with malignant brain tumors. t-PA, however, was abnormally low in several patients and in almost 40% of patients with brain metastasis. PAI was above the upper limit of normal in approximately 50% of the patients but particularly in glioma, glioblastoma and metastasis patients. Finally, mean PC was abnormally increased in the glioblastoma and metastasis groups (p less than 0.001). This is the first study that has measured protein C in brain tumor patients. In conclusion, plasma fibrinolytic levels show marked changes in a substantial number of brain tumor patients prior to surgery--suggesting an ongoing tumor-host interaction.
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PMID:Plasma fibrinolytic profile in patients with brain tumors. 182 14

The expression of CD10/CALLA is associated primarily with childhood leukemia of pre-B lymphocyte phenotype. We have compared the hybridization pattern of the CALLA gene from leukemic and normal cells digested with several restriction enzymes. No alterations were noticed with Eco RI, Sac I, Pvu II, Eco RV, Hind III, and Msp I. Since CALLA is also found on other malignancies, we analyzed DNA samples prepared from cell lines derived from leukemia, lymphoma, glioblastoma, retinoblastoma, and neuroblastoma. Normal restriction patterns were observed for all the lines regardless of their CALLA phenotype. Having demonstrated previously that CALLA was structurally identical to neutral endopeptidase 3.4.24.11 (NEP), we have now established a correlation between surface expression of CALLA and NEP activity on leukemia samples and on several cell lines. Malignant cells tested expressed a functionally active enzyme and no gross alteration was present in the CALLA gene. The CD44 gene is expressed on most cells of hemopoietic origin and on greater than 95% of cases of acute lymphoblastic leukemia and acute myeloblastic leukemia studied. It is also expressed on normal astrocytes and on malignant cells of glioma/astrocytoma types. We now report that a similar pattern of hybridization was observed with Sac I, Pvu II, and Eco RI for leukemic samples, normal cells, and malignant cell lines. A polymorphism was recently detected for CD44 using Hind III; leukemic cells and malignant lines also showed this normal polymorphism. Thus no deletion or insertion could be detected in the CD44 gene of leukemic cells and malignant lines, suggesting that no gross DNA alterations were involved. The correlation between surface expression and enzymatic activity of CD10/CALLA and the expression of CD44 on a variety of malignant cells would suggest that the structure and function of these two gene products are probably not altered by the process of transformation.
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PMID:CD10 and CD44 genes of leukemic cells and malignant cell lines show no evidence of transformation-related alterations. 183 12

Glial fibrillary acidic protein (GFAP) is a constituent of intermediate filaments of glial cells of the astrocyte lineage. We cloned a human GFAP complementary DNA, deduced the amino acid sequence, and established the chromosomal location (17q21) of the GFAP gene by Southern blot hybridization of somatic cell hybrids and by in situ hybridization. The authenticity of the complementary DNA was proven by expressing it in glioma cells lacking endogenous GFAP; after microinjection of the complementary DNA, such cells became positive for staining with GFAP antibodies. The levels of fibronectin (FN) and GFAP mRNA of ten human glioblastoma cell lines, determined by Northern blot hybridization of RNA, were related to other phenotypic characteristics [cell morphology and expression of the genes encoding platelet-derived growth factor (PDGF) receptors]. A high expression of GFAP mRNA was found only in cells lacking fibronectin mRNA and protein. Glioma cells with a fibroblastic phenotype (bipolar, FN+/GFAP-) were found to express both types of PDGF receptors (alpha and beta). Relatively high levels of PDGF alpha-receptor mRNA, in the absence of beta-receptor expression, were found in cell lines that express GFAP and lack detectable levels of fibronectin mRNA. The findings are compatible with the idea that the genes encoding PDGF receptors in glioma cells are regulated in concert with other genes, the expression of which may reflect the developmental program of normal glia cell lineages.
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PMID:Human glial fibrillary acidic protein: complementary DNA cloning, chromosome localization, and messenger RNA expression in human glioma cell lines of various phenotypes. 184 65

We report a case of association of a brain tumor with multiple intestinal polyposis (Turcot's syndrome) and offer a critical analysis of the relevant literature with a view to revising the classification of the syndrome in relation to familial multiple polyposis and Gardner's syndrome. For this purpose, we considered only cases of intestinal polyposis associated with a primary neuroepithelial tumor (medulloblastoma, glioma, or glioblastoma) as originally described by Turcot. Differences emerged, depending on the central nervous system tumor type, which suggests that this neoplastic association may be classified as two distinct syndromes.
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PMID:Association between neuroepithelial tumor and multiple intestinal polyposis (Turcot's syndrome): report of a case and critical analysis of the literature. 184 39

The immunohistochemical distribution of alpha and beta subunits of S-100 protein (S-100 alpha, S-100 beta, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 alpha (+) and/or S-100 beta (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 alpha (+) and S-100 beta (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 alpha (-) and S-100 beta (+)]; acoustic Schwannoma. Group 4 [S-100 alpha (-) and S-100 beta (-)]; medulloblastoma malignant lymphoma, germinoma. The S-100 beta immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 beta than for S-100 alpha with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 beta immunoreactivity decreased according to degree of malignancy, while that of S-100 alpha varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 alpha and S-100 beta might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.
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PMID:Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in brain tumors. 188 40

This audit of clinical management confirmed the poor prognosis for patients (n = 80) aged over 60 years with a diagnosis of supratentorial glioma. The median survival time after diagnosis was 9 weeks following steroids and 7 weeks after biopsy and steroids. Cytoreductive surgery and radiotherapy improved median survival time by a maximum of 16 weeks, but there was significant morbidity in some patients undergoing craniotomy. Although 92% of the biopsied lesions were either glioblastoma or anaplastic astrocytoma, the median survival of these patients was similar to the 8% of patients confirmed as having intermediate grade astrocytoma. Patients presenting with minimal functional deficit (WHO grade I or II) had longer median survival times than those presenting in poor condition (WHO grade III or IV). In this series there was no relationship between management undertaken and clinical status of the patient. The 9% of the cohort that survived 1 year were treated in a variety of ways. This audit, together with results from other studies, suggests that a prospective clinical trial of different management regimes in elderly patients with supratentorial gliomas is needed. Since median survival time in the most intensively treated patients will be around 6 months, treatment evaluation must consider the quality of life provided.
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PMID:Management of patients aged over 60 years with supratentorial glioma: lessons from an audit. 189 54


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