Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.
 ...
PMID:Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis. 142 4

The capacity of three different human glioblastoma cell lines to activate human T cells was analysed by measuring major histocompatibility complex (MHC) antigen expression, monokine secretion and lectin, mAb OKT3 and antigen-driven T cell proliferation. All glioblastoma cells tested were able to induce PHA and concanavalin A (ConA)-driven T cell proliferation in a dose-dependent fashion, while all failed to induce T cell activation with mAb OKT3. In addition, the glioblastoma cell line 86HG39 was able to induce tetanus toxoid and toxoplasma lysate antigen-specific T cell proliferation. The responding T cell lines originated from only one out of five different donors. This foreign antigen-specific T cell proliferation induced by 86HG39 cells could be inhibited with mAb L243 directed against HLA-DR molecules. The study of monokine secretion by 86HG39 cells showed a strong interleukin (IL)-6 secretion after lipopolysaccharide (LPS) treatment, whilst no IL-1 secretion was observed. Furthermore, only 86HG39 cells were positive for HLA-DR molecules, whereas interferon (IFN) gamma treatment of 87HG28 and 87HG31 cells was necessary for the induction of class II antigen expression. Thus, cell line 86HG39 shows many features of an antigen presenting cell and the interaction of these cells with MHC compatible human T cells might be a useful model to study cellular immune reactions within the central nervous system.
 ...
PMID:Human glioblastoma cell line 86HG39 activates T cells in an antigen specific major histocompatibility complex class II-dependent manner. 146 90

Interferon-gamma (IFN-gamma) regulates a variety of immunoregulatory functions through the induction of a specific set of IFN-gamma response genes. This includes the invariant chain associated with the major histocompatibility complex class II molecules. To investigate the mechanism involved in the invariant chain (In) response to IFN-gamma we constructed chloramphenicol acetyltransferase (CAT) hybrid genes in which the CAT gene is under the control of the In promoter. The glioblastoma cell line, U-373 MG, transfected with a CAT construct having the In promoter sequence -790 to +1 bp showed over 3-fold increased CAT activity when treated with IFN-gamma indicating that this region confers IFN-gamma responsiveness to the CAT gene. The IFN-gamma response element in the promoter was further sublocalized to the region -120 to -61 base pairs (bp). This region contains homology to the interferon-stimulated response elements identified in other IFN responsive genes. By gel shift analyses, an IFN-gamma-induced sequence-specific DNA-binding factor was identified. This induced complex binds to an oligonucleotide corresponding to -107 to -79 bp of the In promoter. Mutations of this binding site at -94 and -92 bp drastically decreased binding of the constitutive and IFN-gamma-induced complexes. This IFN-gamma induced factor also binds to an oligonucleotide corresponding to -91 to -62 bp of the interferon-beta (IFN-beta) gene promoter, a region necessary for the induction of the IFN-beta gene by virus and double-stranded RNA. This binding specificity is characteristic of a family of DNA binding factors that bind both the interferon-stimulated response elements and the IFN-beta gene promoter.
 ...
PMID:Interferon-gamma-inducible regulation of the human invariant chain gene. 189 64

The cooperative study on the beta-interferon (IFN) therapy for glioblastoma and malignant astrocytoma reported the response rate as 14.0%. Continuing study resulted the response rate of 24.0% to low grade astrocytoma and 20.0% to medulloblastoma. Totally, effectiveness of 19.2% to gliomas was confirmed in 120 evaluated cases. A randomized study was conducted on combination therapy with beta-interferon and chemoradiotherapy. The response rate of 41.2% (21/51) in the group treated with IFN, ACNU and Radiation was significantly higher than the rate of 19.6% (10/51) in the group treated with ACNU and radiation only. Application of IFN to a maintenance therapy is also on going. Adoptive immunotherapy has been developed as potential therapeutic method of malignant glioma. Lymphokine activated killer cells (LAK) and Tumor infiltrating lymphocytes (TIL) are put to clinical use. Clinical application of human monoclonal antibody (MAb) CLN-IgG was conducted to recurrent malignant glioma. 131I labeled MAb was administered intratumorously and the specific incorporation was confirmed by gamma-scintigraphy. Concomitant administration of interferon enhanced the efficacy of the therapy. This radio-immunotherapy holds future promise as a new therapeutic approach to gliomas.
 ...
PMID:[Advances of BRM therapy of malignant brain tumors]. 199 12

We have applied restriction fragment length polymorphism analysis to a 30-member panel of primary glioma DNAs, which had been previously examined for loss of genetic information (C. D. James, E. Carlbom, J. P. Dumanski, M. Hansen, M. Nordenskjold, V. P. Collins, and W. K. Cavenee, Cancer Res., 48:5546-5551, 1988), to determine the frequency and sublocalization of loss of genetic information from chromosome 9. We have also utilized scanning densitometry for dosage determination of the 9p-localized interferon alpha and interferon beta-1 genes among these same tumors. Our results reveal the following: (a) for those cases in which loss has occurred, the region of common loss lies on the short (p) arm of the chromosome; (b) loss of genetic information from the short arm of chromosome 9 occurs frequently in glial tumors of intermediate (anaplastic, grade III) and high (glioblastoma, grade IV) histological malignancy (10 of 20 cases) but not in tumors of low (grade II) histological malignancy (0 of 10 cases); (c) tumors with 9p deletions are hemi- or nullizygous for interferon beta-1 and the interferon alpha gene cluster; (d) cases of interferon nullizygosity occur exclusively among tumors of highest histological malignancy (glioblastoma). These data, especially the determination of a region of nullizygosity, suggest proximity to or residence within a gene(s) whose function(s) is (are) critical to the suppression of the malignant evolution of glial tumors.
 ...
PMID:Chromosome 9 deletion mapping reveals interferon alpha and interferon beta-1 gene deletions in human glial tumors. 199 58

A clinical trial of an immunotherapy which consisted of intratumoural injections of autologous lymphocytes with human lymphoblastoid interferon was evaluated in 31 patients with intracranial glioblastoma. Immunotherapy was performed after stereotactic biopsy or surgical resection. The treatment was tolerated well by all patients. Three patients showed positive response to immunotherapy as documented by transient regression or stabilization of the tumour size on computed tomography. Nevertheless, there is no significant difference in the survival time of the patients treated with immunotherapy and those not treated. We conclude that this immunotherapeutic regimen is not beneficial in patients with glioblastoma when used as single treatment after tumoural biopsy or resection.
 ...
PMID:Immunotherapy of glioblastoma with intratumoural administration of autologous lymphocytes and human lymphoblastoid interferon. A further clinical study. 206 65

Seven glioblastomas were studied between 1 and 6 months after intratumoral injection of autologous lymphocytes and human lymphoblastoid interferon. Morphological study showed a great number of lymphocytes within the tumor tissue, and interactions between lymphocytes and glioblastoma cells, suggesting a killing phenomenon. These data support the potential usefulness of adoptive immunotherapy in patients with glioblastoma by means of intratumoral administration of activated lymphoid cells.
 ...
PMID:Histological changes in glioblastoma after intratumoral injection of autologous lymphocytes and human lymphoblastoid interferon. 216 27

In an attempt to clarify the role of beta interferon in vitro cell systems, the metabolic expression of dihydrofolate reductase (DHFR), succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH), by histochemical methods was studied. DHFR was also quantified by flow cytometry. Glioblastoma cell line with or without beta interferon was used. Three days after the treatment the DHFR reaction was much less intense than in the control. Quantitative data confirmed these results. Immediately afterwards, most cells exhibited much more intense reaction. These facts underlined that, in this biological model in vitro, beta interferon could reduce the synthesis of these enzymes only for a short period.
 ...
PMID:[Qualitative and quantitative histochemical evaluation of the dehydrogenase activity in human glioblastoma cells treated with beta-interferon]. 237 36

The enzyme 2-5A synthetase is induced in cultured cells in response to interferon (IFN) treatment. A lambda gt10 cDNA library of mRNA from IFN-induced Daudi lymphoblastoid cells was screened with oligonucleotide probes. Several overlapping cDNAs were isolated and shown to be derived from the human synthetase gene using filter selection and oocyte microinjection assays. The nucleotide sequence of one of these, cDNA 8-2, extended the 2-5A synthetase sequence already described 72 bp in the 5' direction but was found to differ significantly in coding sequence at the 3' end. The longest cDNA isolated (6-2) was approximately 1.4 kb. By Northern hybridization analysis single mRNAs of 1.7 kb were detected in Daudi and T98G (glioblastoma) cells. However, in HeLa cells, four mRNAs ranging in size from 1.5 to 3.5 kb were found, one of which differed at the 3' end. Analysis of both phage and cosmid genomic clones and comparison with genomic DNA indicate that there is a single gene for 2-5A synthetase, comprising at least six exons and five introns, which can undergo a novel form of alternative RNA processing depending on cell type.
 ...
PMID:Human 2-5A synthetase: characterization of a novel cDNA and corresponding gene structure. 241 47

Preliminary experience with a clinical trial of immunotherapy for glioblastoma, by means of intratumoural injection of autologous lymphocytes (AL) mixed with low doses of human lymphoblastoid interferon (HLI) is presented. In two of twelve patients, a transient reduction of tumoural volume was obtained. Morphological studies showed that injected lymphocytes remain within the tumour, and suggest tumoural lysis due to activity of natural killer (NK) cells. Clinically no significant prolongation of survival time could be achieved and, as in other series, patients with additional radiation therapy survived longer. But the morphological findings suggest that immunotherapy carrying NK-cells to contact with tumoural cells might be useful in some patients with glioblastoma. Actually no explanation can be given why only two of our cases responded positively. Regarding the otherwise poor prognosis it seems justified to continue these studies.
 ...
PMID:Intratumoural injection of autologous lymphocytes plus human lymphoblastoid interferon for the treatment of glioblastoma. 247 37


1 2 3 4 5 6 7 8 9 10 Next >>