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

Two new murine monoclonal antibodies were prepared by hybridoma technique after immunization with the immature pluripotent leukemia cell line K562. The monoclonal antibody Bra10G (IgG2b) reacted in a non-lineage pattern with all examined hematopoietic neoplastic cell lines and peripheral blood cells (granulocytes, lymphocytes, erythrocytes) of healthy donors, with the exception of monoblastoid cell line U-937 and B lymphoma cell line Daudi. This monoclonal antibody immunoprecipitated an 18-20 kDa cell surface protein expressed also on the cell surface of examined non-hematopoietic (malignant glioma, melanoma and breast carcinoma) cell lines. These properties and the efficient inhibition of Bra10G binding to the cell surface of K562 cells by the reference CD59 monoclonal antibody (MEM-43) indicated that Bra10G belongs to the CD59 cluster of monoclonal antibodies which identify the human protectin molecule. The monoclonal antibody Bra7G (IgM) reacted with a 95 kDa cell surface protein expressed on hematopoietic cells (with the exception of erythrocytes) and was absent on the examined non-hematopoietic neoplastic cell lines. These data together with a partial inhibition of Bra7G binding by the reference CD-43 monoclonal antibody suggested the CD43 (leukosialin, sialophorin) specificity of this monoclonal antibody.
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PMID:Monoclonal antibodies to two adhesive cell surface antigens (CD43 and CD59) with different distribution on hematopoietic and non-hematopoietic tumor cell lines. 128 43

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (uCi) of tumor activity per gram per 100 uCi injected activity compared to 4.5 uCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. Tumor dose found in normal organs is less than 20% of the tumor dose, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibodies QCI054 and ZME018, which define a tumor-associated and a second melanoma-associated antigen, respectively, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5, QCI054, and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Average absorbed doses of 3770 +/- 445 (mean +/- SEM), 2043 +/- 134, and 645 +/- 48 cGy in tumor, 353 +/- 41, 243 +/- 22, and 222 +/- 13 cGy in a contralateral control intramuscular site, 980 +/- 127, 815 +/- 41, and 651 +/- 63 cGy in liver, and 275 +/- 14, 263 +/- 11, and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 uCi 90Y-radiolabeled P96.5, QCI054, and ZME018, respectively. To test the therapeutic potential, tumor-bearing nude mice were given intracardiac injections of either buffer or 90Y-radiolabeled P96.5, QCI054, or ZME018. Striking tumor regression and prolonged survival were measured following administration of 90Y-labeled P96.5. Average maximal decreases in tumor volume were 42.7 +/- 11.9 and 94.2 +/- 3.3 percent 28 and 58 days following 100 and 200 uCi 90Y-radiolabeled P96.5 administration, respectively. The time required to achieve four times the initial tumor volume was 6.1 +/- 0.9 days for buffer; 43 +/- 12 and 63 +/- 10 days for 50 and 100 uCi 90Y-radiolabeled P96.5; 7 +/- 2, 20 +/- 1, and 53 +/- 4 for 50, 100, and 200 uCi 90Y-radiolabeled QCI054; and 9 +/- 1, 13 +/- 1, and 29 +/- 3 days for 50, 100, and 200 uCi 90Y-radiolabeled ZME018, respectively. Average tumor regrowth failed to occur 180 days following administration of 200 uCi 90Y-labeled P96.5.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Targeting and therapy of human glioma xenografts in vivo using radiolabeled antibodies. 217 Mar 1

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively. Shared cell surface antigens among neuroectodermally derived neoplasms provide a basis for exploration of human glioma radioimmunotherapy.
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PMID:Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies. 237 Jan 86

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. IIIIn-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCi of tumor activity/g/100 microCi injected activity compared to 4.5 microCi following administration of 100 microCi radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate the deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The dose found in normal organs is less than 20% of that in the tumor, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, demonstrates positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5 and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters. Average absorbed doses of 3770 +/- 445 (SEM) and 645 +/- 48 cGy in tumor, 353 +/- 41 and 222 +/- 13 cGy in a contralateral control i.m. site, 980 +/- 127 and 651 +/- 63 cGy in liver, and 275 +/- 14 and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 microCi 90Y-radiolabeled P96.5 and ZME018, respectively. Calculations of absorbed dose by the medical internal radiation dose method confirmed thermoluminescent dosimeter absorbed dose measurements. To test the therapeutic potential, tumor-bearing nude mice were given intracardiac injections of either buffer or 90Y-radiolabeled P96.5 or ZME018. Tumor regression was measured in 1 of 12, 9 of 10, and 12 of 12 compared to 0 of 10, 1 of 10, and 2 of 10 animals following administration of 50, 100, or 200 microCi 90Y-labeled P96.5 and ZME018, respectively. Average maximal decreases in tumor volume were 42.7 +/- 11.9 and 94.2 +/- 3.3% 28 and 58 days following 100 and 200 microCi 90Y-radiolabeled P96.5 administration, respectively. In contrast, no average decrease in tumor volume was noted following 50, 100, or 200 microCi 90Y-labeled ZME018.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Targeting and therapy of human glioma xenografts in vivo utilizing radiolabeled antibodies. 240 87

Tenascin is an extracellular matrix glycoprotein expressed in association with mesenchymal-epithelial interactions during development and in the neovasculature and stroma of undifferentiated tumors. This selective expression of tenascin indicates a specific role in cell matrix interactions. We now show that tenascin can support the adhesion of a variety of cell types, including various human tumor cells, normal fibroblasts, and endothelial cells, all of which can attach to a substrate coated with tenascin. Detailed studies on the mechanism of the tenascin-promoted cell attachment were carried out with the human glioma cell line U251MG. The attachment of these cells and others to tenascin were inhibited specifically by peptides containing the RGD cell attachment signal. Affinity chromatography procedures similar to those that have been used to isolate other adhesion receptors yielded a heterodimeric cell surface protein which bound to a tenascin affinity matrix in an RGD-dependent fashion. One of the subunits of this putative tenascin receptor comigrates with the beta subunit of the fibronectin receptor in SDS-PAGE and cross reacts with antibodies prepared against the fibronectin receptor in immunoblotting. These results identify the tenascin receptor as a member of the fibronectin receptor family within the integrin superfamily of receptors. The cell attachment response on tenascin is distinctly different from that seen on fibronectin, suggesting that cell adhesion and motility may be modulated at those sites where tenascin is expressed in the extracellular matrix.
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PMID:Tenascin mediates cell attachment through an RGD-dependent receptor. 246 38

We have isolated a monoclonal antibody, clone betaE11, which recognizes an antigen that is highly abundant on the surface of mitotic vascular endothelial cells and tumor cells. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, expression of this 190-kd antigen is approximately threefold higher in mitotic versus interphase endothelial cells. Treatment of tumor cells with an antibody to the betaE11 antigen inhibits their growth in a dose-dependent manner in vitro with maximal inhibition at an antibody concentration of 1 microg/ml. Different tumor cell lines demonstrate varying sensitivities to anti-betaE11 with the following order of growth inhibition: colon > prostate = glioma > melanoma = fibroblast > breast > liver. Furthermore, the betaE11 antigen localizes to regions of prostatic intraductal neoplasia in paraffin-embedded sections. Mass spectrometry of the cell-derived betaE11 protein and V8-protease fingerprint analysis indicate that the betaE11 antigen is nearly identical to the 4F2 heavy chain antigen, a cell surface protein that has been implicated in cell activation and proliferation. Expression of the betaE11 antigen during mitosis functionally links it to a fundamental aspect of cell proliferation, and its spatial localization on the surface of both proliferating endothelium and tumor cells demonstrates its potential for tumor immunotherapy.
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PMID:Controlling tumor-derived and vascular endothelial cell growth: role of the 4Ff2 cell surface antigen. 1143 64

The neuronal glutamate transporter, EAAC1, appears to both limit spillover between excitatory synapses and provide precursor for the synthesis of the inhibitory neurotransmitter, gamma-aminobutyric acid. There is evidence for a large intracellular pool of EAAC1 from which transporter is redistributed to the cell surface following activation of protein kinase C (PKC) or platelet-derived growth factor (PDGF) receptor by seemingly independent pathways. A variety of biotinylation strategies were employed to measure trafficking of EAAC1 to and from the plasma membrane and to examine the effects of phorbol ester and PDGF on these events. Biotinylation of cell surface protein under trafficking-permissive conditions (37 degrees C) resulted in a 2-fold increase in the amount of biotinylated EAAC1 within 15 min in C6 glioma and in primary neuronal cultures, suggesting that EAAC1 has a half-life of approximately 5-7 min for residence at the plasma membrane. Both phorbol ester and PDGF increased the amount of transporter labeled under these conditions. Using a reversible biotinylation strategy, a similarly rapid internalization of EAAC1 was observed in C6 glioma. Phorbol ester, but not PDGF, blocked this measure of internalization. Incubation at 18 degrees C, which blocks some forms of intracellular membrane trafficking, inhibited PKC- and PDGF-dependent redistribution of EAAC1 but had no effect on basal trafficking of EAAC1. These studies suggest that both PKC and PDGF accelerate delivery of EAAC1 to the cell surface and that PKC has an additional effect on endocytosis. The data also suggest that basal and regulated pools of EAAC1 exist in distinct compartments.
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PMID:Rapid trafficking of the neuronal glutamate transporter, EAAC1: evidence for distinct trafficking pathways differentially regulated by protein kinase C and platelet-derived growth factor. 1519 83

Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis with largely unknown mechanisms. Posttranslational processing of proteins by glycosylation could have multiple regulating roles in the process of apoptosis. Here, we found that the expression of beta1,6-linked GlcNAc-bearing N-glycans on cell surface protein was gradually decreased after induction of apoptosis by As2O3-treatment. And, As2O3 significantly decreased the protein expression level of beta1,4GalT V, which effectively galactosylates the beta1,6-GlcNAc branch of N-glycans and functions as a positive regulator in glioma development. Furthermore, interfering with the expression of beta1,4GalT V in human glioma cell markedly promoted As2O3-induced cell apoptosis and beta1,4GalT V overexpression significantly reduced As2O3-induced glioma cell apoptosis. Taken together, our results suggested that down-regulation of beta1,4GalT V expression plays an important role in As2O3-induced apoptosis, providing a new mechanism of As2O3-induced cell apoptosis and indicating that inhibitors of beta1,4GalT V may enhance the therapeutic efficiency of As2O3 for malignant glioma.
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PMID:Down-regulation of beta1,4GalT V at protein level contributes to arsenic trioxide-induced glioma cell apoptosis. 1843 52

Brain tumor-initiating cells (BTICs) have been enriched using antibodies against the cell surface protein CD133; however, the biological relevance and the regulatory mechanism of CD133 expression in human gliomas are not yet understood. In this study, we initially demonstrated that CD133 was overexpressed in high-grade human glioblastomas where CD133-positive cells were focally observed as a micro-cluster. In addition, CD133 transcripts with exon 1A, 1B, or 1C were predominantly expressed in glioblastomas. To elucidate the mechanism regulating this aberrant expression of CD133, three proximal promoters (P1, P2, and P3) containing a CpG island were isolated. In U251MG and T98G glioblastoma cells, the P1 region flanking exon 1A exhibited the highest activity among the three promoters, and this activity was significantly inactivated by in vitro methylation. After treatment with the demethylating agent 5-azacytidine and/or the histone deacetylase inhibitor valproic acid, the expression level of CD133 mRNA was significantly restored in glioma cells. Importantly, hypomethylation of CpG sites within the P1, P2, and P3 regions was observed by bisulfite sequencing in human glioblastoma tissues with abundant CD133 mRNA. Taken together, our results indicate that DNA hypomethylation is an important determinant of CD133 expression in glioblastomas, and this epigenetic event may be associated with the development of BTICs expressing CD133.
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PMID:Promoter hypomethylation regulates CD133 expression in human gliomas. 1867 14

Gliomas of WHO grades III-IV are malignant brain tumors mostly resistant to conventional therapies. Therefore, novel strategies for the treatment of gliomas are warranted. Although immunotherapy is gaining increased attention for the treatment of malignant gliomas and in particular of glioblastoma multiforme (GBM), this approach requires the identification of appropriate antigens. Our aim was to investigate the expression of the prostate stem cell antigen (PSCA), a highly N-glycosylated phosphatidylinositol (GPI)-anchored cell surface protein, in gliomas of different WHO grades in order to evaluate its potential as a diagnostic marker and as a target for immunotherapy. Tumor specimens and controls were assessed by quantitative RT-PCR, Western blotting and immunohistochemistry. The samples investigated in the study consisted of 210 human glial tumors, among which 31 were oligodendrogliomas, 9 ependymomas and 170 were astrocytomas (including 134 glioblastomas). PSCA was absent in normal brain tissue, but was detected in WHO grade III-IV gliomas. Weak PSCA protein expression was also recognized in some WHO grade I and WHO grade II tumors. The difference between WHO grade I-II tumors and WHO grade III-IV tumors was statistically significant (p<0.001). Our results suggest that increased PSCA expression levels are linked to gliomas of WHO grades III and IV, and may represent a suitable additional target for immunotherapy of gliomas.
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PMID:The prostate stem cell antigen represents a novel glioma-associated antigen. 2150 83


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