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)

We have derived sets of human monoclonal antibodies by fusing lymphocytes from cancer patients with a human lymphoid line, LICR-LON/HMy2. Two antibodies, LGL1.1D6 and LLU6.3A4, derived from patients with glioma and bronchial carcinoma respectively, were selected for clinical study on the basis of binding patterns in radioimmunoassays with tumour cell lines and localisation of human tumour xenografts. Highly purified monoclonal antibodies were prepared using bulk supernatants from hybridomas grown in serum free medium. After radiolabelling with 131I, 1 mg antibody was injected intravenously into patients with advanced glioma and carcinoma of the bronchus. Good localisation was obtained in five out of eight patients with glioma and five out of seven patients with carcinoma of the bronchus. Despite the technical difficulties inherent in the production of human monoclonal antibodies this study demonstrates their potential for the clinical localisation of solid tumours.
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PMID:Tumour localisation by human monoclonal antibodies. 390 70

This paper reviews the diagnostic role of monoclonal antibody immunohistochemistry in a series of 189 brain tumour biopsies and 22 cases of neoplastic meningitis. The diagnostic monoclonal antibody panel, which includes markers for glial, neural, epithelial and lymphoid differentiation antigens, was used to test a wide variety of cerebral and spinal tumours by indirect immunofluorescence and immunoperoxidase techniques on unfixed frozen sections. Gliomas, meningiomas, schwannomas, medulloblastomas, choroid plexus tumours, cerebral lymphomas and metastatic carcinomas could all be reliably differentiated by means of their characteristic antigenics profiles, as defined by their patterns of reactivity with the antibody panel. Confident diagnosis was possible even in very poorly differentiated tumours and in biopsies distorted by surgical squeeze artefact, where paucity of morphological clues made diagnosis by conventional histological methods difficult or impossible. It was estimated that use of the antibody panel was responsible for, or made a significant contribution towards the final diagnosis in approximately 20% of cases. The monoclonal reagents were also found to be of great value in the detection and characterisation of neoplastic cells in CSF specimens from patients with malignant meningitis. Malignant cells were detected in 73% of cases and characterised in 16% of cases by routine cytological techniques. Employing monoclonal immunocytology however, these figures were improved to 95% and 95% respectively. Our findings suggest that patients with neoplastic meningitis can be spared prolonged investigation and inappropriate management by the early detection and characterisation of malignant cells in CSF using panels of monoclonal antibodies.
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PMID:The role of monoclonal antibodies in brain tumour diagnosis and cerebrospinal fluid (CSF) cytology. 403 74

Monoclonal antibodies allow the precise definition of molecular components present on tumour cell surfaces. Some human monoclonal antibodies prepared by fusing intratumoral lymphocytes from patients undergoing craniotomy for malignant glioma with cells from a specially derived human lymphoid line (LICR-LON-HMy2) bind to glioma surface components. To study the feasibility of continuous administration of human monoclonal antibodies directed against glioma we designed a chamber which enables hybridoma cells to be cultured in the subcutaneous tissue. This chamber allows antibodies to diffuse out, and nutrients and oxygen necessary for continued cell viability to diffuse in. Cells are unable to traverse the membrane pores of the device, so there is no risk that malignant cells put in the chamber can metastasise. The chamber has now been inserted in one patient with recurrent glioma, in whom the kinetics of internally labelled antibody release has been monitored.
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PMID:Subcutaneous culture chamber for continuous infusion of monoclonal antibodies. 612 60

The angiogenic activity of various neoplastic and control tissues, cells and extracts has been tested on the chorioallantoic membrane of the chick (CAM). The vascular response was assessed macroscopically and also by histological examination. Angiogenesis was induced by a number of neoplastic implants the most potent being derived from Hodgkin's disease, histiocytic lymphoma or glioma tissue. Boiled tumour tissue was ineffective. Lymphocytes extracted from human lymphomas, activated normal peripheral blood lymphocytes and established lymphoid cell lines of neoplastic origin were generally effective in inducing neovascularisation through millipore membranes as were 90,000-100,000 MW fractions of human tumour tissue. In all cases examined histologically a mononuclear cell infiltrate in the CAM mesoderm accompanied a positive vascular response. These results implicate host monocytes in the generation of neovascularisation by neoplastic tissue.
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PMID:Mechanism of the induction of angiogenesis by human neoplastic lymphoid tissue: studies on the chorioallantoic membrane (CAM) of the chick embryo. 615 66

The distribution and localization of a glioma-associated antigen defined by monoclonal antibody 81C6 has been examined using human cultured cell lines and tissues. Monoclonal antibody 81C6 was selected from a hybridoma fusion of spleen cells of mice immunized with the glial fibrillary acidic protein-positive human glioma cell line U-251 MG. Results of cell surface radioimmunoassay and absorption analysis demonstrated that 81C6 defined a glioma-mesenchymal extracellular matrix (GMEM) antigen expressed by 14 of 16 gliomas, 1 of 3 neuroblastomas, 1 of 7 melanomas, 2 of 6 sarcoma cell lines, and 8 of 9 cultured fibroblast lines. GMEM was not expressed by carcinoma or by the myeloid-lymphoid cell lines examined. Within the central nervous system, GMEM was expressed in 10 of 11 glioblastomas but was undetected in 5 of 6 astrocytomas and in normal adult and fetal brain by peroxidase-antiperoxidase immunohistology. In glioblastomas, the GMEM antigen was localized to basement membranes of the distinctive glomeruloid endothelial proliferations and hyperplastic blood vessels. The GMEM antigen was also expressed in 3 of 3 glioblastoma cell lines and 6 of 8 glioblastoma biopsy xenografts in athymic nude mice. Among non-central nervous system tissues and tumors, GMEM was found by peroxidase-antiperoxidase immunohistology in normal liver sinusoids, spleen red pulp sinusoids, kidney medullary tubule interstitium, and glomerular mesangium and in association with vascular and stromal elements of several undifferentiated tumors. The GMEM antigen is distinct from previously described forms of fibronectin, laminin, collagen types I to V, hyaluronic acid, chondroitin sulfate, and heparin, as determined by absorption analysis and immunohistological localization in tissues. The expression of GMEM in glioblastoma but not normal brain, association with glioblastoma-proliferative endothelium basement membranes, and expression in glioblastoma cell lines and nude mouse xenografts suggest that GMEM may be a useful marker of gliomas in vivo and in vitro.
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PMID:Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. 634 60

Mononuclear cell infiltrates are found to varying degrees in 30% to 60% of primary human central nervous system (CNS) gliomas. To explore the immunological importance of this, six operative glial tumors, eight non-glial tumors, and three normal brain specimens were studied. Utilizing an immunoperoxidase method, the authors examined frozen sections for lymphoid infiltrates expressing suppressor/cytotoxic and helper phenotypes, as identified with the Leu-1,2,3 monoclonal antibodies. Four of six gliomas demonstrated lymphoid infiltrates: three tumors exhibited a predominant suppressor/cytotoxic cell phenotype and the fourth showed mixed staining of suppressor/cytotoxic and helper cell phenotypes. Varying degrees of lymphoid infiltration characterized four out of eight non-glial primary CNS tumors. Two cases exhibited a prevalence of suppressor/cytotoxic phenotype cells, while two cases demonstrated a more heterogeneous pattern of phenotype expression. Normal brain sections revealed little or no evidence of mononuclear infiltrates. The immunobiological significance of these findings is discussed in the context of tumor-host interaction within the CNS.
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PMID:Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors. Characterization of cell subsets with monoclonal antibodies. 637 63

A surface-associated sulphydryl (thiol) protein (SASP) constitutively present in most nucleated cells was purified from human THP-1 monocytes and rat C6 glioma cells. The human protein was similar in mass and isoelectric point and had the same N-terminal amino acid sequence to adult T-cell leukemia-derived factor (ADF), a growth factor secreted by human lymphoid cells which is able to induce increased expression of interleukin-2 receptors. A further internal amino acid sequence, determined following cleavage of human SASP with cyanogen bromide, was also identical to the corresponding sequence deduced for ADF. Samples of SASP were able to reductively depolymerize human immunoglobulin, a property shared with thioredoxin, a ubiquitous protein, almost identical to ADF, with an essential function in many thiol-dependent reducing reactions. Furthermore, SASP purified from rat C6 glioma cells had an identical N-terminal amino acid sequence to that deduced for rat liver thioredoxin, showing that they were both members of the same family of proteins. The use of membrane-impermeable thiol reagents indicated that SASP was predominantly a cell-surface protein, and was not normally secreted. This SASP protein appeared to be a surface-associated form of thioredoxin that was constitutively present in a wide range of cells and was related to ADF, a secreted form of the same protein.
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PMID:Characterization of a thioredoxin-related surface protein. 781 92

Human immunodeficiency virus type 1 (HIV-1) mRNAs encoding structural proteins contain multiple inhibitory/instability elements (INS), which decrease the efficiency of viral protein expression. We have previously identified a strong INS element (INS-1) within the p17(gag) coding region. Here we show that poly(A)-binding protein 1 (PABP1) binds preferentially to INS-1 within the p17(gag) mRNA, but not to a mutated mRNA in which INS-1 function is eliminated. Competition experiments performed in the presence of different nucleic acids and homoribopolymers demonstrated preferential binding of PABP1 to the INS-1-containing RNA. In contrast to HeLa cells and several lymphoid cell lines, certain human glioma cell lines exhibit high levels of gag expression in the absence of Rev upon transient transfection with wild type gag expression vectors. We analyzed extracts of different cell lines and found that the binding of PABP1 to INS-1 RNA is significantly diminished in glial cell extracts. The expression levels of gag correlate with the absence of binding of PABP1 to the INS-1 RNA in cellular extracts. These results suggest a role for PABP1 in the inhibition of gag expression mediated through INS-1.
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PMID:Preferential binding of poly(A)-binding protein 1 to an inhibitory RNA element in the human immunodeficiency virus type 1 gag mRNA. 899 38

Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes (CLN) in a number of experimental animals. To investigate the role of CLN in brain tumour immunity, temporal profiles of MHC class II molecule expression and T lymphocyte subsets in brain tumours, CLN and other lymphoid tissues were analysed by immunocytochemistry. A total of 64 Wistar rats weighing 250 g were used. Two weeks after the transplantation of C6 glioma cells (10(6) cells/1 microl) into a rat brain, expression of MHC class II molecules was induced in the brain and all systemic lymphoid tissues examined. However, the subsequent appearance of CD4 or CD8 positive cells was strictly confined to CLN, and coincided with the infiltration of such cells into the brain tumour 2 weeks after transplantation. In the group of animals in which cervical lymphadenectomy was followed by intracerebral transplantation of C6 glioma cells, infiltration of CD4 or CD8 positive cells into the brain tumour was delayed until 3 weeks after the transplantation, and the production of such cells was by the spleen. These results suggest that CLN act as regional lymph nodes in brain tumour immunity.
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PMID:Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats. 1021 99

The evaluation of peptide receptors in man is relevant to identifying the physiological target tissues of a given peptide and to selecting diseases with a sufficient receptor overexpression for diagnostic or therapeutic intervention. VIP/PACAP receptors have been evaluated in normal and diseased human non-neuronal tissues by using in vitro receptor autoradiography with 125I-VIP or 125I-PACAP in tissue sections. As assessed by subtype-selective VIP analogs, VIP receptors of the VPAC1 subtype are found in a wide variety of tissues including liver, breast, kidney, prostate, ureter, bladder, pancreatic ducts, gastrointestinal mucosa, lung, thyroid, adipose, and lymphoid tissues. VPAC2 receptors are predominantly found in vessels and smooth muscles, whereas PAC1 receptors are present in the adrenal medulla. VIP/PACAP receptors are expressed in the majority of the most frequently occurring human tumors, including breast, prostate, pancreas, lung, colon, stomach, liver, and bladder carcinomas, as well as lymphomas and meningiomas, predominantly as VPAC1 receptors, as do their tissues of origin. Although leiomyomas predominantly express VPAC2 receptors, glial tumors, pituitary adenomas, neuroblastomas, paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. The very wide distribution of VIP/PACAP receptors in the normal human body is indicative of the key role of these peptides in human physiology and pathophysiology. Moreover, the receptor expression in tumors is the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analog treatment for tumor growth inhibition.
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PMID:In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications. 1119 11


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