Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0017638 (glioma)
30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastomas are highly invasive intracerebral tumors that are known to express the CD44 cell adhesion molecule. Human glioma cell adhesion and invasion in vitro may in part be mediated by the interaction of CD44 with extracellular matrix proteins. To suppress the growth and invasive effects of CD44 expression on primary brain tumors we have designed two hammerhead ribozymes as potential gene therapeutic agents. Both ribozymes designed to target exon 2 of CD44 exhibited in vitro cleavage of in vitro transcribed CD44s and CD44R1 RNAs. The anti-CD44 effect of these ribozymes results from directed RNA cleavage, requiring both a target sequence and an appropriate catalytic center. Further, following transient transfection of one of these ribozymes into the SNB-19 glioma cell line, significant in vivo cleavage activity against cellular CD44 transcripts was demonstrated by flow cytometrical analysis. These preliminary results suggest that CD44-directed hammerhead ribozymes may be useful as gene therapeutic agents.
...
PMID:Gene therapeutic approaches to primary and metastatic brain tumors: II. ribozyme-mediated suppression of CD44 expression. 875 Jan 91

CD44 is a major receptor for hyaluronic acid, which is the most frequent route of malignant glioma invasion. Multiple isoforms of CD44 are generated by alternative mRNA splicing. We have examined differential expression of CD44 variant isoforms (CD44vs) during dibutyryl cyclic AMP (dbcAMP)/theophylline-induced differentiation of human glioma A172 cells using reverse transcriptase-polymerase chain reaction (RT-PCR). Treatment of cells with dbcAMP and theophylline caused decreased expression of all CD44 isoforms after 24 h. The CD44 standard form was observed to return to the unstimulated level after 72 h, whereas the variant isoforms, CD44 8v-10v and 10v, remained at the low level after 24-72 h. Changes of CD44vs were correlated with the level of expression of c-jun. These results suggested that the expression patterns of CD44vs might correlate with cellular differentiation in human glioma cells.).
...
PMID:Suppressed expression of CD44 variant isoforms during human glioma A172 cell differentiation induced by cyclic AMP. 880 27

The use of whole immunoglobulin G (IgG) and F(ab')2 of the G-22 monoclonal antibody associated with cationic liposomes (immunoliposomes) and the effect of repeated exposure were investigated for the transfection of the LacZ gene to various glioma cell lines. Immunoliposomes associated with either whole IgG or F(ab')2 monoclonal antibody caused an about 2-fold increase in beta-galactosidase activity compared with liposomes associated with no antibody in glioma cell lines expressing the CD44 antigen. beta-Galactosidase activity was further increased by about 2-fold by repeated exposure compared with single exposure. A glioma cell line not expressing the CD44 antigen showed no such increase in beta-galactosidase activity. These results indicate that repeated exposure of cationic immunoliposomes achieves a higher transfection efficiency and is a potentially effective method of gene therapy for patients with malignant glioma.
...
PMID:Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells. 886 48

Glial cells express three splicing variants of a receptor-type protein tyrosine phosphatase called RPTP beta. Two are receptor forms that differ in a large extracellular domain. The third is a secreted proteoglycan called phosphacan that lacks the cytoplasmic phosphatase domains. We have now identified, by immunoblotting, proteins corresponding to these three forms of RPTP beta in rat C6 glioma cells and brain. The short receptor form is much more prevalent than the full-length receptor in C6 glioma cells. Phosphacan is much more abundant than either of the receptor forms in rat brain, and its expression increases progressively during embryonic development, while the receptor forms show only moderate changes. In contrast to the long form and phosphacan that were detected as proteoglycans, the short receptor form, lacking the large alternatively spliced domain, was not detected as a chondroitin sulfate proteoglycan. We recently showed that phosphacan binds to the neuron-glia cell adhesion molecule, Ng-CAM, and we now report that glia expressing RPTP beta adhere and extend processes on substrates coated with Ng-CAM. After one day in culture, however, the glia retract their processes and often lift off the substrate. Conditioned medium from glial cells, which contains large amounts of phosphacan, inhibits glial adhesion to Ng-CAM, and depletion of phosphacan from the conditioned medium by immunoadsorption reduces the inhibitory activity. The results show that phosphacan increases dramatically during development, and indicate that secreted forms of RPTP beta can modulate glial cell adhesion and behavior.
...
PMID:Expression of polypeptide variants of receptor-type protein tyrosine phosphatase beta: the secreted form, phosphacan, increases dramatically during embryonic development and modulates glial cell behavior in vitro. 898 99

In this report we focus on the characterization of appican, the chondroitin sulfate proteoglycan form of amyloid precursor protein (APP), and the role that it and other proteoglycans may play in AD. Appican is expressed by certain transformed cell lines of neural origin, namely C6 cells and N2a neuroblastomas. It is detected in both human and rat brain and in primary cultures is expressed by astrocytes, but not neurons. The core protein of appican has been shown to be an alternatively spliced isoform of APP, lacking exon 15 of the APP gene, originally identified in leukocytes (L-APP). Splicing out of exon 15 results in the joining of exons 14 and 16, and formation of an Asp-Xaa-Ser-Gly consensus sequence for chondroitin sulfate chain attachment to serine 619 of L-APP, which lies 16 amino acids upstream of the A beta peptide sequence. Mutation of this serine residue to an alanine prevented chondroitin sulfate chain addition to the core protein. Levels of appican expression could be regulated by growth conditions independently of APP, suggesting that these molecules may serve distinct physiological roles within the cell. Morphological changes were also observed in both astrocytic and transformed cell cultures, that appeared to reflect changes in levels of appican expression. Preliminary data suggest that appican may be a strong cell adhesion molecule. Transfected C6 glioma cells overexpressing appican remained attached to tissue culture dishes markedly better than either C6 cells over-expressing exon-15 containing APP or WT C6 cells. Appican-enriched extracellular matrix (ECM) was also observed to serve as a much better substrate for attachment of N2a neuroblastomas, pheocromocytoma PC12 cells and primary astrocytes compared to APP enriched ECM.
...
PMID:Characterization of appican, the chondroitin sulfate proteoglycan form of the Alzheimer amyloid precursor protein. 911 61

The adoptive transfer of tumor-reactive T lymphocytes has recently been demonstrated to be an effective means for mediating the regression of experimental intracranial fibrosarcomas. In this study, mice bearing syngeneic intracranial GL261 gliomas were cured by the combination of sublethal whole body irradiation followed by the intravenous transfer of tumor-draining lymph node (LN) T cells activated with anti-CD3 or staphylococcal enterotoxin C2 (SEC2). To further identify the functional effector T cel population in the adoptive immunotherapy, LN T cells were separated into two subsets, based on the level of expression of the cell adhesion molecule CD62L (L-selectin). As few as 5 x 10(5) CD62Llow cells could cure the majority of animals, whereas 2 x 10(6) CD62Lhigh cells were completely ineffective. Moreover, T cells isolated from advanced intracranial tumors were identified to be predominantly CD62Llow. In contrast, spleens contained a mixture of CD62L low and high cells similar to the transferred cell population. T cells in the glioma site were more actively proliferating than those isolated from the spleen. Mice cured of GL261 tumors demonstrated long-term immunologic memory by rejecting intracranial challenges of the original tumor but not an immunologically distinct tumor. Furthermore, despite infiltration of transferred cells into the intracranial tumors, cured mice did not exhibit any apparent neurologic abnormalities during treatment, prolonged follow-up, or after intracranial tumor rechallenge. This study demonstrates the effective treatment of an intracranial murine glioma by the systemic adoptive transfer of activated tumor-draining LN T cells and selective tumor infiltration by the therapeutically active CD62Llow T cells.
...
PMID:Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells. 922

Cell adhesion is a critical factor in the multistep process of tumour invasion. CD44 is one of the cell surface adhesion molecules responsible for interaction with hyaluronic acid, a component of the CNS extracellular matrix. The aim of the present study was to demonstrate whether alterations in the CD44 gene might account for different invasive behaviour. EcoRI restriction analysis by Southern blot hybridization revealed several additional hybridization signals in tissue specimens of two out of 16 patients with glioblastoma, indicating DNA rearrangements or point mutations, respectively, within the region of the CD44 gene. Expression patterns of CD44 isoforms in these two rearranged gliomas and in 28 other patients with malignant gliomas were analysed by RT-PCR. All cases displayed only the splice variant CD44H, which acts as hyaluronic acid receptor in glioma tumour cells. Tumour cell invasion was studied with Boyden chamber assays using hyaluronic acid as ligand and functional CD44H blocking antibody. Invasion of cells derived from those gliomas carrying the rearranged CD44 gene locus was decreased by about 50% compared with gliomas without rearrangement, indicating that the altered hybridization patterns in the two glioma samples influenced CD44H mediated glioma cell invasion through hyaluronic acid in vitro. Our results on CD44 isoform expression suggest that, in contrast to other solid tumours, gliomas seem to express only the CD44 variant. Genetic alterations within the CD44 gene might alter the binding domain of the receptor and thus account for different invasive behaviour in glioblastomas.
...
PMID:Effect of changes in the CD44 gene on tumour cell invasion in gliomas. 936 62

The cell adhesion molecule melonoma cell adhesion molecule (MCAM)/MUC18/CD146 is specifically up-regulated on tumors of neuroectodermal origin and in animal models confers metastatic capacity to human melanoma cells. To identify critical regions regulating MCAM expression in melanomas, 1 kilobase of the MCAM 5' region was analyzed for promoter activity and transcription factor binding in 1 glioma, 1 carcinoma, and 4 melanoma cell lines. The minimal MCAM promoter (-106/+22 base pair (bp)) consists of 4 Sp-1 sites, two AP-2 elements, one cAMP responsive element, and the initiator surrounding the transcriptional start site. Analysis of mutated constructs indicated that the cAMP-responsive element is a major transcriptional activator in the majority of cell lines. Site-directed mutagenesis revealed that, in AP-2 expressing cells, the AP-2 site within the core promoter (-23 bp) has an inhibitory influence on MCAM expression while the AP-2 sites at -131 and -302 bp are activating. Functional AP-2 was observed in both MCAM positive and MCAM negative melanoma cell lines indicating that expression of MCAM does not require loss of this transcription factor. Furthermore, all MCAM constructs were strongly expressed in MCAM negative as well as MCAM positive cells, indicating that the expression of this gene is not controlled solely by the presence of transactivating factors binding to the investigated region.
...
PMID:Identification of the elements regulating the expression of the cell adhesion molecule MCAM/MUC18. Loss of AP-2 is not required for MCAM expression in melanoma cell lines. 1093 73

The purpose of this study is to investigate the efficacy of dendritic cell-mediated immunotherapy against intracranial gliomas. Cloned DC2.4 dendritic cells originating from C57BL/6 mice were pulsed with glioma GL261 cell extracts and administered i.p. to C57BL/6 mice with intracranial GL261 gliomas. The survival of mice with and without pulsed dendritic cells was monitored after intracranial implantation of the GL261 glioma cells. Fluorescence activated cell sorting (FACS) analysis showed that DC2.4 cells express high levels of MHC class I and class II molecules, costimulatory molecules B7-1 and B7-2, and the cell adhesion molecule ICAM-1. Antigen-presenting capabilities in these dendritic cells were initially characterized in vitro by a mixed lymphocyte reaction, showing that Balb/c CD4+ and CD8+ T cells were able to generate allogeneic responses to DC2.4 cells. Tumor extract-pulsed DC2.4 dendritic cells were then used for the treatment of C57BL/6 mice with syngeneic GL261 gliomas. Animals with intracranial GL261 gliomas and vaccinated i.p. with pulsed DC2.4 dendritic cells exhibited significantly enhanced survival, relative to animals treated with saline or non-pulsed DC2.4 cells alone. In addition, cured animals showed an increased delayed-type hypersensitivity response to GL261 cells and survived when rechallenged with intracranial GL261 gliomas. In summary these results indicate that dendritic cells pulsed with tumor extract can enhance immune responses to tumor antigen and therefore represent a potential immunotherapeutic approach for treating patients with intracranial gliomas.
...
PMID:Immunization with dendritic cells pulsed with tumor extract increases survival of mice bearing intracranial gliomas. 1134 74

Protein tyrosine phosphatase (PTPase) dephosphorylation and protein tyrosine kinase (PTKs) phosphorylation of key signal transduction proteins may be regulated by extracellular signals, making PTPases important in the regulation of cell proliferation. Leucocyte common antigen (LAR), a receptor-like PTPase, consists of E-subunit, containing the cell adhesion molecule-like receptor region, and P-subunit specific for a short segment of the extracellular region, the transmembrane peptide, and two cytoplasmic PTPase domains. We produced a monoclonal antibody against the LAR P-subunit for immunohistochemical screening of LAR expression in normal and tumourous tissues. Gliomas and gastric, colorectal, lung, breast and prostate cancers showed weak and relatively infrequent expression. Intense and diffuse expression, however, was detected in 95% (227 out of 239) of thyroid carcinomas, but only 12% (22 out of 128) of adenomas and no cases of benign thyroid disease were immunopositive. In contrast to broad staining in carcinomas, LAR expression in thyroid adenomas was often found in small focal or locally invasive areas. Western blot analysis similarly detected LAR P-subunit protein in thyroid carcinomas, but not in normal tissues. We believe this to be the first demonstration of LAR overexpression in thyroid carcinoma and may help to elucidate the role of PTPases in the development of malignancy.
...
PMID:Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas. 1269 88


<< Previous 1 2 3 4 5 Next >>

---