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)

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

This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C. A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.
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PMID:Antifibrinolytic therapy of experimentally grown malignant brain tumors. 300 64

A monoclonal antibody against a 52,000 dalton human plasminogen activating enzyme (HPA52) was used for immunofluorescence staining of cultured glioblastoma cells. The fluorescence was located in the cytoplasm of the cells. A pronounced variation in the staining intensity was observed between the individual cells. The specificity of the fluorescent stain was supported by the findings that 1) no staining was obtained with a monoclonal antibody of the same subclass, but with irrelevant specificity (anti-2,4,6-trinitrophenyl); 2) adsorption with HPA52 purified to homogeneity removed the ability of anti-HPA52 to mediate staining; 3) the glioblastoma cells contained HPA52, as measured by enzymatic assay, while melanoma cells that were not stained did not contain HPA52 activity; 4) dexamethasone reduced both the enzymatically determined HPA52 content and the immunofluorescence in parallel, while progesterone affected none of these parameters; 5) we have previously found that culture fluid conditioned by the glioblastoma cells apart from HPA52 does not contain detectable amounts of any protein that binds to anti-HPA52. Several advantages of immunohistochemical detection of plasminogen activators compared with enzyme histochemical methods are discussed, among these that the immunohistochemical method distinguishes between plasminogen activators of different types.
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PMID:Plasminogen activating enzyme in cultured glioblastoma cells. An immunofluorescence study with monoclonal antibody. 618 13

We cloned a previously characterized glioblastoma-derived parent cell line (12-18) in order to obtain a relatively homogenous population of human neural cells of neoplastic origin. These cells reach high densities in culture (over 100,000 cells/cm2) and have a high mean DNA content per cell of 18.1 +/- 0.9 pg. A histogram of the cloned cells' chromosome numbers revealed one peak and a modal near diploid number of 52, whereas the parent cell line had expressed polyploidy, with several peaks (including 52) at population doubling level 16. Several consistent results were obtained by Giemsa staining. A persistent structural alteration was the duplication of the long arm of chromosome #9 on to another arm of #9, and the translocation of the short arm of #9 to chromosome #21. We further observed that these cloned cells secrete a specific protease, a plasminogen activator (PA), into serum-free medium (SFM). This enzyme was assayed by the conversion of purified plasminogen to plasmin and the subsequent degradation by plasmin of 125I-labelled fibrin. Glioblastoma-derived cells had higher levels of cell-associated PA activity (2.9-fold) and released more PA activity into SFM (22-fold) than human fetal neural cells. The presence of this protease suggests a mechanism for the invasive character of these neoplasms (glioblastoma multiforme) in vivo.
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PMID:Properties of cloned human glioblastoma cells. Release of a specific protease. 676 10

Incorporation of the serine protease active site reagent diisopropyl fluorophosphate (DFP) into a plasminogen activator with an Mr of approximately 52000 released from cultured human glioblastoma cells was strongly enhanced by incubation with plasmin. This observation led to the isolation of an inactive form of the enzyme from serum-free conditioned culture fluid by affinity chromatography on a column of a Sepharose-bound monoclonal antibody raised against urokinase. An 831-fold purification was obtained with a yield of 41%. The purified molecule was homogeneous as evaluated by polyacrylamide gel electrophoresis with sodium dodecyl sulfate (NaDodSO4), having one stainable band under nonreducing as well as reducing conditions with an Mr of approximately 52000. It was unable to activate plasminogen, but catalytic amounts of plasmin converted it into active enzyme. After NaDodSO4-polyacrylamide gel electrophoresis, the active enzyme showed one band under nonreducing conditions, but after reduction, two bands with Mr values of approximately 20000 and 32000 were observed. The active enzyme incorporated [3H]DFP into the approximately Mr 32000 band, while no incorporation was observed into the inactive form. These findings show that the Mr 52000 human plasminogen activator exists in a proenzyme form consisting of a single polypeptide chain that by proteolysis between half-cystine residues is converted into the active enzyme consisting of two chains with molecular weights of approximately 20000 and 32000, the active site being on the latter chain. The results are consistent with the active form of the enzyme being identical with the higher molecular weight form of urokinase, and together with recent observations that a murine plasminogen activator is released from sarcoma virus transformed cells as an inactive proenzyme, they suggest that zymogens to plasminogen activators are of more general occurrence.
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PMID:Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. 689 Dec 64

A survey of 56 normal and neoplastic tissues has shown that plasminogen activators were released by cultured human cells in several molecular weights and their susceptibility to inhibition by antibodies to the normal urinary enzyme, urokinase. Melanoma cells characteristically secreted plasminogen activators which were immunochemically distinct from urokinase and which migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a prominent, closely spaced doublet with an apparent molecular weight of approximately 70,000 and a minor molecular weight component of approximately 60,000. Enzymes with similar characteristics have been observed in serum-free harvest fluids collected from other neoplastic tissue (a breast carcinoma, a glioblastoma, a malignant teratoma, a uterine sarcoma, and a carcinoma of the renal pelvis) and from normal tissue (8-week embryo fibroblasts, normal esophageal fibroblasts, and one culture of normal adult bladder epithelium). Plasminogen activators released by cells derived from most normal adult tissues, or from a 26-week-old embryo, and from other tumors of ectodermal or mesenchymal origin were inhibited by anti-urokinase antibody and showed a closely spaced doublet with a molecular weight of 60,000 as the most abundant molecular species with no evidence of the enzyme with a molecular weight of 70,000.
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PMID:Molecular species of plasminogen activators secreted by normal and neoplastic human cells. 719 17

Our previous studies have shown that some human cancer cell lines produce pancreatic trypsinogen, plasminogen, and tissue-type kallikrein. To understand the regulatory mechanism of these proteinases, serine proteinase inhibitors secreted by human glioblastoma cell line T98G were analyzed by gelatin reverse zymography with trypsin. The serum-free conditioned medium of T98G cells showed more than ten trypsin inhibitor bands ranging from 16 to 150 kDa in the reverse zymography. Major trypsin inhibitors were purified by trypsin-affinity chromatography. Analysis of their N-terminal amino acid sequences demonstrated that the purified inhibitors were identical to the secreted forms of amyloid protein precursors (APPs), tissue factor pathway inhibitor (TFPI), placental protein 5 (PP5)/TFPI-2, and secretory leukocyte proteinase inhibitor (SLPI). In addition, a novel 25-kDa trypsin-binding protein, tentatively named p25TI, was identified. p25TI showed weak inhibitory activity against trypsin in reverse zymography as compared with the other inhibitors. The secretion of multiple forms of serine proteinase inhibitors by human cancer cells raises the possibility that they might be involved in the abnormal growth of cancer cells.
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PMID:Purification and identification of a novel and four known serine proteinase inhibitors secreted by human glioblastoma cells. 888 27

Experimental and clinical evidence reveals that the growth of solid tumors is dependent on angiogenesis. Proteolytic enzymes such as plasminogen activators and matrix metalloproteinases have been implicated in this neovascularization. The role of lysosomal proteases in this process has yet to be explored. Increased expression of the lysosomal cysteine protease cathepsin B has been observed in many etiologically different tumors, including human brain, prostate, breast, and gastrointestinal cancers. Immunohistochemical and in situ histochemical studies have demonstrated expression of cathepsin B in neovessels induced during malignant progression of human glioblastoma and prostate carcinomas. In these two tumor types, neovessels stain strongly for cathepsin B compared with the normal microvasculature. As an initial point to elucidate whether cathepsin B is an important component of the angiogenic response in tumours, we analyzed expression of cathepsin B in endothelial cells during neovessel formation. We present evidence for strong immunostaining of cathepsin B in rat brain microvascular endothelial cells as they form capillary tubes in vitro. This finding is discussed within the general framework of the role of proteolytic enzymes in tumor invasion and angiogenesis.
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PMID:Tumor progression and angiogenesis: cathepsin B & Co. 916 49

The cell surface urokinase-type plasminogen activator receptor (uPAR) has been shown to be a key molecule in regulating plasminogen-mediated extracellular proteolysis. To investigate the role of uPAR in invasion of brain tumors, human glioblastoma cell line SNB19 was stably transfected with a vector capable of expressing an antisense transcript complementary to the 300 base pair of the 5' end of the uPAR mRNA. Parental and stably transfected (vector, sense, and antisense) cell lines were analysed for uPAR mRNA transcript by Northern blot analysis, and receptor protein levels were measured by radioreceptor assays and Western blotting. Significant reduction of uPAR sites was observed in the antisense transfected cell lines. The levels of uPAR mRNA were significantly decreased in antisense clones compared to control, vector and sense clones. The invasive potential of the cell lines in vitro was measured by Matrigel invasion assay and migration of cells from spheroids to monolayers. The antisense transfected cells showed a markedly lower level of invasion and migration than the controls. The antisense clones were more adhesive to the ECM components compared to parental, vector and sense clones. All transfected (vector, sense and antisense) clones and parental cells produced similar levels of uPA activity without any significant difference however, MMP-2 activity was decreased in antisense clones compared to controls. These results demonstrate that uPAR expression is critical for the invasiveness of human gliomas and down regulation of uPAR expression may be a feasible approach to decrease invasiveness.
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PMID:In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA receptor. 917 95

The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in the regulation of cell-surface plasminogen activation in several physiological and pathological conditions. Recent evidence suggests that the uPAR is also involved in processes that are not related to plasminogen activation, including cell adhesion and transmission of extracellular signals across the plasma membrane. The uPAR influences cell migration and spreading both in vivo and in vitro through the cell-surface activation of plasminogen. The uPAR can bind to vitronectin, an adhesive extracellular matrix protein that contains the Arg-gly-Asp (RGD) cell adhesion domain and that serves as a ligand for several integrin receptors. uPAR also forms complexes with (1, (2, and (3 integrins, thereby allowing mutual interactions and regulation between cell adhesion and proteolysis. Recently, uPAR has been shown to have strong prognostic value for predicting disease recurrence and overall survival in certain types of cancer. We discuss here the biological significance of uPAR in the glioblastoma invasion process. Strong correlations found between elevated uPAR levels in glioblastoma cells and tumor invasiveness have led to uPAR being selected as a target for therapy in experimental animal models. Using antisense vectors to down regulate uPAR expression at the level of the mRNA and protein in glioblastoma cells, has been shown to inhibit tumor formation in nude mice. These results provide a potential basis from which to develop novel therapeutic strategies to direct the expression of antisense uPAR and to evaluate the efficiency of this technique for cancer gene therapy in patients with brain tumor.
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PMID:Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors. 998 51


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