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)

The purpose of this work was to analyze cDNA encoding human monocyte chemoattractant protein-1 (MCP-1), previously isolated from glioma cell line culture fluid. Screening of a cDNA library from total poly(A) RNA of glioma cell line U-105MG yielded a clone that coded for the entire MCP-1. Nucleotide sequence analysis and comparison with the amino acid sequence of purified MCP-1 showed that the cDNA clone comprises a 53-nucleotide 5'-non-coding region, an open reading frame coding for a 99-residue protein of which the last 76 residues correspond exactly to pure MCP-1, and a 389-nucleotide 3'-untranslated region. The hydrophobicity of the first 23 residues is typical of a signal peptide. Southern blot analysis of human and animal genomic DNA showed that there is a single MCP-1 gene, which is conserved in several primates. MCP-1 mRNA was induced in human peripheral blood mononuclear leukocytes (PBMNLs) by PHA, LPS and IL-1, but not by IL-2, TNF, or IFN-gamma. Among proteins with similar sequences, the coding regions of MCP-1 and mouse JE show 68% identity. This suggest that MCP-1 is the human homologue of the mouse competence gene JE.
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PMID:Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. 246 24

Physicochemical characteristics of monocyte chemotactic activity in the culture fluid of PHA-stimulated human mononuclear leukocytes (MNL) were investigated. Among several chemotactic activity peaks eluted from a TSK-2000 gel filtration column, one peak, corresponding to a molecular mass of 17 kDa, accounted for about 40% of total chemotactic activity. On a chromatofocusing column, most of the 17-kDa activity eluted in a pH range of 9.4 to 7.9. It could bind to Orange-A Sepharose. These three characteristics--molecular mass, basic isoelectric point, and dye column binding--were similar to those of human glioma-derived monocyte chemotactic factor (GDCF), recently purified in our laboratory. Therefore, the MNL-derived chemoattractant was purified by the same procedures used for purification of GDCF, namely Orange-A Sepharose chromatography, carboxymethyl (CM)-HPLC, and reverse phase (RP) HPLC. About 50% of the culture fluid chemotactic activity bound to Orange-A Sepharose and was eluted in a single peak by a NaCl gradient. The active pool from the Orange-A column was separated into two sharp peaks by CM-HPLC, each of which eluted at identical acetonitrile concentrations from a RP HPLC column. By SDS-PAGE, the peptides had apparent molecular masses of 15 and 13 kDa and appeared homogeneous. Amino acid analysis showed that the composition of the two peptides was almost identical; and the N terminus of each peptide was apparently blocked. Shared characteristics of these peptides and the GDCF peptides include identical elution patterns from CM- and RP HPLC columns, identical SDS-PAGE migration, almost identical amino acid composition, and blocked N terminus. This suggests that the monocyte attractants isolated from culture fluid of PHA-stimulated MNL are identical to those derived from human glioma cells.
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PMID:Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. 292 21

It has recently been shown that human T-cell subpopulation can be identified functionally via surface receptors for Fc fragment of immunoglobulins. We detected peripheral blood T-cells bearing the Fc receptor for IgG molecules (T gamma cell) in patients with brain tumors who manifested a variety of immunological abnormalities. We also analyzed immunological values of T gamma cells which were thought to be suppressor and/or a part of killer T cells, comparing with other immunological parameters. The percentage of T gamma cells was significantly higher in patients with malignant brain tumors than in normal controls (6.54 +/- 1.6%). The values of T gamma cells in patients with glioma, metastatic brain tumor, benign brain tumor were 15.4 +/- 4.8%, 14.9 +/- 3.2%, and 8.1 +/- 3.7%, respectively. In the patients with glioma, the values increased in the uncontrolled group compared with the well-controlled group. Furthermore, the values were decreased by surgical removal of the tumor. On immunological study of T gamma cells in the patients with glioma, there was a definite correlation between the values of T gamma cells and ADCC activity. Furthermore, the T gamma cells in the patients showed higher ADCC activity than in normal controls. The values of T gamma cells also correlated with blastogenesis of the peripheral blood lymphocytes by PHA (r = -0.742, p less than 0.001) and Con A (r = -0.662, p less than 0.001). These results suggest that T gamma cells are playing two important roles in patients with glioma such as suppressor function and ADCC activity, and that these cells may change according to the tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinicoimmunological values of measurement of IgG-Fc receptor positive T cells in the patients with malignant brain tumors]. 293 80

In considering immunological approaches to treatment of the patients with malignant brain tumors, it seems very important to enhance the tumor specific immunity. Then, to ascertain whether tumor specific immune response occurs in these patients with malignant brain tumors, lymphocyte blastogenetic responses to tumor cells were examined in 18 patients with malignant brain tumors. Furthermore, to compare the systemic immunological responses with the local responses in the brain tumor tissues, both peripheral blood lymphocyte (PBL) and tumor infiltrating lymphocyte (TIL) were used as blastogenetic stimulators to the tumor cells. The PBL from the patients with malignant gliomas showed any positive blastogenetic response to their own glioma cells in 7 or 12 cases (about 58%). But, TIL from these patients showed a positive response in the only 3 cases (25%). In 6 cases of metastatic brain tumors, otherwise, their PBL showed any positive blastogenetic response to their own tumor cells in 4 of 6 cases (about 67%), and their TIL showed any positive blastogenetic responses in these same 4 cases. So, the tumor specific immunological responses may be stronger in the patient with metastatic brain tumors than in the patient with malignant gliomas. These immunological responses were, furthermore, more weak in the brain tumor tissues than in the systemic immunity. Then, this lymphocyte blastogenetic response to tumor cells were compared with other lymphocyte stimulating examination such as rectine or allogenetic lymphocyte stimulation. Our studies revealed that this lymphocyte blastogenetic response to tumor cells were at lower level compared with rectine such as PHA, PWM, and Con A, or allogenetic lymphocyte stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Analysis of tumor specific immunological response in the patients with malignant brain tumors by the mixed lymphocyte-tumor cell reaction]. 297 95

We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma]. 308 95

We have cultured peripheral blood lymphocytes (PBL) from glioblastoma patients in recombinant interleukin-2 (IL-2) containing medium for a period of 5 days. The cytotoxicity of these cells was tested on 51Cr-labelled autologous dissociated glioblastoma cells which had not been cultured. Significant cytotoxicity against glioma cells was observed in seven out of nine cases. IL-2 activated PBL from normal donors were equally cytotoxic against these glioma cells. Autologous lymphocytes activated by phytohaemagglutinin were also lysed in most cases, and the erythroleukemia cell line K562 was highly susceptible to the cytotoxic capability of the IL-2 activated PBL. In cold target inhibition experiments, K562 inhibited the cytotoxicity against both autologous and allogenic glioma cells, and glioma cells inhibited the cytotoxicity against K562. Following immunomagnetic separation, the IL-2 activated cells demonstrated cytotoxicity against glioma cells, K562 cells, and PHA blasts in both the CD8+ and the CD8- subsets.
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PMID:Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro. 326 Sep 42

Effects of 5-bromo-2-deoxy-uridine (BrdU) and 2-deoxy-D-glucose (2-DG) on 60-Co-gamma-ray induced damage were studied in monolayer cultures of glioma (BMG-1) cells, and PHA-stimulated peripheral leukocytes from normal donors. Micronuclei formation was used as an index of cytogenetic damage. BrdU and 2-DG treatments did not induce micronuclei formation in unirradiated cultures. Presence of BrdU (0.8 microM) for more than one cell cycle (24 hr) significantly increased gamma-ray (1-4 Gy) induced micronuclei formation in exponentially growing BMG-1 cells. Incubation of irradiated cells under sub-optimal growth conditions (DMEM with 1% serum) for 3 hr, instead of growth medium, significantly decreased micronuclei formation. Post-irradiation presence of 2-DG (5 mM; 3 hr, in DMEM + 1% serum) significantly increased radiation damage. In BrdU sensitized cells also, 2-DG significantly increased radiation damage further. In PHA-stimulated leukocytes from normal donors, 2-DG (5mM, equimolar with glucose; for 2 hr) did not increase gamma-ray (2-Gy, 42 hr after PHA-stimulation) induced micronuclei formation. Pre-irradiation presence of BrdU (1.6 microM) significantly increased micronuclei. On the contrary, 2-DG treatment reduced radiation induced micronuclei formation in BrdU sensitized leukocyte cultures. These results suggest that (i) radiation induced lesions leading to micronuclei formation in proliferating tumour cells, are, at least, partly repairable; (ii) combination of 2-DG could reduce BrdU doses required for radiosensitization of proliferating tumour cells; and (iii) 2-DG could differentially increase radiation damage in BrdU sensitized proliferating tumour cells, while reducing manifestation of damage in normal proliferating cells.
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PMID:Differential modification of radiation damage in 5-bromo-2-deoxy-uridine sensitized human glioma cells and PHA-stimulated peripheral leukocytes by 2-deoxy-D-glucose. 781 43

In 16 patients with primary supratentorial and in 1 with cerebellar tumor among them 5 multiforme glioblastomas, 3 malignant astrocytomas, 6 astrocytomas of other subtypes and 1 mixed glioma (oligo-astrocytoma) the peripheral blood was drawn and lymphocytes were separated from it. Out of the removed part of the tumors about 10 cultures in each case were prepared and cultivated at least 14 days. When the growth zone was well developed the cultures were used for further studies. All samples of the separated lymphocytes activated with PHA were cultivated for 72 h. So prepared lymphocytes were added to the tumor culture in vitro and observed for 24 h. After that time the not adhered lymphocytes were removed and the remaining tissue cultures with adhered lymphocytes were fixed and stained and the number of lymphocytes was counted. It was found that 1 h after the addition of lymphocytes the number of lymphocytes was very high, though a great part of them did not adhere to the tumor tissue. After 24 h the number of adhered lymphocytes was small or minute. Taking into consideration the results obtained it seems that the low efficiency of therapy of gliomas with autologous lymphocytes in vivo can result from the very weak direct contact with tumor cells. The influence of lymphocytes can be very limited so more as the tumor cells can secret biological active substances like PGE2, which counteract the cytotoxic activity of lymphocytes. For that reason the number of lymphocytes can be of significant value as counterbalance to that properties of the tumor cells. Taking into account even secretion of tumor cells of the same biological active substances such as PGE2 which counteract the cytotoxic activity of lymphocytes for the efficient activity of lymphocytes the number of them may be of significant value.
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PMID:Some remarks on adherence reactivity of autologous PHA--transformed lymphocytes on human glial tumor cells in vitro. 792 99

Little is known about the role of the N-linked oligosaccharides in the function of the epidermal growth factor (EGF) receptor (EGF-R). In a human glioma cell line, U373 MG, EGF-Rs contain the bisecting N-linked oligosaccharide sequence recognized by erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris (E-PHA). Incubation of E-PHA with cultured U373 MG cells results in inhibition of EGF binding to its receptor and consequently inhibition of EGF-induced autophosphorylation of the receptor. Consistent with the inhibitory effects on the EGF-R, phenotypic events that depend on EGF-R signaling, such as cell spreading and proliferation, were also found to be modified. The effect of this lectin seems to be specific because leukoagglutinating phytohemagglutinin lectin from P. vulgaris (L-PHA), an isolectin of E-PHA, had no effect on EGF-R activity or the biological functions of these cells even though L-PHA was able to bind to the EGF-R. These findings suggest the presence of an important bisecting N-linked oligosaccharide structure in close proximity to the EGF binding site on the receptor. Furthermore, these results suggest the possibility that E-PHA lectin binding may provide an additional approach to blocking EGF-dependent glioma cell growth.
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PMID:Binding of erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris to the epidermal growth factor receptor inhibits receptor function in the human glioma cell line, U373 MG. 893 57

It has been well established that patients with malignant glioblastomas exhibit T cell anergy. In this report, we further investigate the nature of this T cell anergy. The results demonstrate that tumor size but not location correlates with decreased mitogen or anti-CD3 mAb responsiveness of T cells obtained from patients. Stimulation of the TCR/CD3 complex on these patients' T cells revealed defects in early transmembrane signaling. Both PHA and anti-CD3 mAb activated PBL and T cells obtained from patients exhibited a marked decrease in the tyrosine phosphorylation of a number of proteins. In particular, decreased phosphorylation of pp100 and phospholipase Cgamma1 (PLCgamma1) was observed. In addition, PLCgamma1 and p56(lck) protein levels were dramatically reduced in T cells obtained from patients harboring a glioma. In contrast, the protein levels of p59(fyn) were normal or only slightly reduced in T cells obtained from patients with gliomas. Quantitation of free intracellular calcium concentrations ([Ca2+]i) after mitogen (PHA) stimulation or ionomycin treatment of T cells obtained from patients revealed that they mobilize less calcium than do T cells obtained from normal subjects. Stimulation of T cells obtained from patients with PMA and ionomycin, which should bypass the requirement for PLCgamma1 activation as well as directly activate the p21(ras) signaling pathway, did not restore the proliferative capacity of these T cells to normal levels. These results indicate that the anergy observed in T cells obtained from these patients is a consequence of one or more defects in the early transmembrane signaling events associated with TCR/CD3 stimulation.
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PMID:T cell receptor-mediated signaling is defective in T cells obtained from patients with primary intracranial tumors. 937 40


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