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 regulation and expression of protein kinase C (PKC) and phosphomyristin C (PMC) (a principal substrate of PKC which is the major myristylated protein in lymphocyte and glioma lines that express it) in murine B and T lymphocytes were investigated. Both PMC and PKC are differentially regulated during T-cell development. The level of PMC expression is highest in CD4-8-, intermediate in CD4+8+, and lowest in J11d-, CD4, or CD8 single-positive thymocytes. PKC is equally expressed by all three thymic populations. In striking contrast to thymocytes, resting peripheral lymph node T cells and T-cell clones express little if any PMC and reduced levels of PKC. Neither PKC nor PMC is significantly induced upon the activation of lymph node T cells: treatment with anti-CD3 antibodies or anti-CD3 and interleukin-2 fails to induce PKC, whereas PMC is not induced by anti-CD3 alone and is only slightly induced by anti-CD3 and interleukin-2. In contrast to the situation with T cells, PMC and PKC are constitutively expressed at moderate levels in mature B cells. PMC is greatly increased in B-cell blasts generated by cross-linking the antigen receptor with anti-immunoglobulin. These results demonstrate that PMC and PKC are differentially regulated during the development and activation of B and T cells, suggesting that cellular events that rely upon PKC and PMC may differ during ontogeny and activation of different lymphocyte subsets.
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PMID:A major myristylated substrate of protein kinase C and protein kinase C itself are differentially regulated during murine B- and T-lymphocyte development and activation. 278 36

We investigated the ability of glioma cells to respond to T cell-derived lymphokines. The growth of astrocytoma and mixed glioblastoma cell lines, as assessed by DNA synthesis, was inhibited in the presence of supernatants derived from mitogen-stimulated human T cells, an HTLV-II-transformed human T cell line, Mo, and human interleukin-2 (IL-2). The mixed glioblastoma cell line, 138-MG-C, was subjected to limiting dilution analysis, and two cell lines (5D7, 5C5) were derived which were homogeneous with respect to staining for galactocerebroside (GalC) (100%). These two GalC+ glioblastoma cell lines proliferated in the presence of high concentrations of recombinant human interleukin-2 (RIL-2). Additionally, these cell lines bear receptors for the IL-2 molecule as determined by immunofluorescent staining with various anti-IL-2 receptor antibodies.
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PMID:Response of human glioblastoma cells to recombinant interleukin-2. 282 24

The phenomenon of glioma killing by lymphokine activated killer cells (LAK) was studied. We demonstrate that LAK cells generated by culturing the lymphokine interleukin-2 (IL-2) with peripheral blood lymphocytes from brain tumour patients destroys autologous glioma. The rat 9L glioma model was used to show that LAK killing was tumour-selective as glioma but not syngeneic normal brain tissue was destroyed. The susceptibility of both human and 9L rat glioma to LAK cell killing was markedly diminished by pretreating glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with neuraminidase, glycosidases, sodium periodate or hydrocortisone. These results suggest that the cell surface determinant on glioma cells responsible for its tumour selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin. The tumour-selective killing of glioma by LAK in vitro prompted the initiation of a Phase I study in which ten patients with malignant glioma have been treated with direct intracerebral injection of IL-2 or LAK without evidence of systemic or brain toxicity.
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PMID:Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies. 287 9

The killing of human glioma by lymphokine activated killer (LAK) cells was studied. LAK cells generated by culturing recombinant interleukin-2 (IL-2) with human peripheral blood lymphocytes (PBL) obtained from normal volunteers markedly lysed allogeneic glioma grown in tissue culture. Susceptibility of glioma to lysis by LAK cells was abrogated by pretreating the glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with hydrocortisone, neuraminidase, glycosidases or sodium periodate. These results suggest that the cell surface determinant on human glioma cells responsible for its tumor selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.
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PMID:Lymphokine activated killer (LAK) cell mediated killing of human glioma: effect of pretreating glioma with various membrane modifying agents. 303 36

The present investigation was conducted in order to examine the feasibility of isolating and growing glioma-infiltrating lymphocytes in vitro as possible effector cells for use in new adoptive immunotherapy. Eight surgical specimens obtained from patients with malignant astrocytomas were treated by enzyme dispersion; the cells were separated on a density gradient and grown in the presence of human recombinant interleukin-2. The cultured lymphocytes were tested for cell-surface markers by using monoclonal antibodies in a flow cytometric analysis. In all cases the glioma-derived lymphocytes were grown in culture for several weeks with substantial increases in cell numbers (at least 5 X 10(8) cells). The mature T cell population (CD3, 89%) was found to have an increased proportion of the cytotoxic/suppressor phenotype CD8 (55%) as compared to peripheral blood lymphocytes (PBL's). Eighty-six percent of the cultivated lymphocytes expressed HLA-DR. The IL-2 receptor was predominantly expressed on the helper subset (CD4-positive). Otherwise, anti-CD16, which specifically reacts with natural killer (NK) cells, did not stain significantly more of the cultured gliomaderived lymphocytes compared with lymphocyte-activated PBL's. These results corroborate the observations made with conventional immunohistochemical examination. It has been demonstrated that T lymphocytes isolated from human cancers are enriched for specific reactivity to their autochthonous tumor cells. These experiments support the possible use of glioma-infiltrating lymphocytes as a new treatment for patients with malignant glioma.
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PMID:Isolation and in vitro growth of glioma-infiltrating lymphocytes, and an analysis of their surface phenotypes. 305 14

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with a glucomannan-protein antigen of Candida albicans (GMP) or Interleukin-2 (IL-2), then assayed for proliferation and production of Interferon gamma. PBMC of healthy, age and sex matched subjects were the controls. PBMC from glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a definitely lesser ability to produce IFN. The results are discussed in the framework of the impairment of immune responses known to affect glioma-bearing patients.
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PMID:The response of peripheral blood mononuclear cells of glioma-bearing patients to stimulation with microbial antigen and IL-2: proliferation and IFN-gamma production. 314 74

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (IL-2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells. PBMC of healthy, age and sex-matched subjects were the controls. PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation. PBMC of glioma patients were fully responsive to IL-2 in cytotoxicity generation, as were the PBMC from normal subjects. The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors. This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.
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PMID:Cell-mediated cytotoxicity in glioma-bearing patients: differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen. 314 18

Type beta transforming growth factor (beta-TGF) is a potent regulator of cell growth and differentiation. The human glioblastoma cell line, T-MGI, was growth inhibited by beta-TGF under anchorage independent conditions. The antiproliferative effect of beta-TGF was potentiated to nearly total arrest by low doses of retinoic acid (RA) or tumor necrosis factor (TNF), while epidermal growth factor, platelet-derived growth factor, interleukin-2, and gamma interferon did not have this potentiating effect. The potentiation of the beta-TGF effect by RA and TNF could not be explained by modulation of the epidermal growth factor receptor, the beta-TGF receptor, or the TNF receptor. beta-TGF alone and in combination with RA or TNF were further tested on primary cultures from freshly resected human glioma biopsies (n = 13). There was great individual variation in sensitivity to beta-TGF, RA, or TNF. The astrocytoma and oligodendroglioma cells were inhibited to various degrees by beta-TGF or TNF, while most of the glioblastomas were not sensitive to these agents. Most of the biopsies were stimulated by RA. RA or TNF did not potentiate the growth inhibitory effect of beta-TGF on biopsy cells. We therefore think it unlikely that beta-TGF in combination with RA or TNF will be effective agents in the treatment of gliomas.
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PMID:Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors. 316 58

Mononuclear cells infiltrating human brain tumors were isolated from seven of nine surgical biopsy specimens. These cells were small T11+, T3+ lymphocytes that did not express DR antigens or the receptor for interleukin-2. In addition, large granular lymphocytes were recovered from two of these tumors. The clonogenic potential of tumor-infiltrating lymphocytes (TIL's) was assessed by limiting-dilution analysis (LDA) using a microculture system that permits proliferation of virtually 100% of normal peripheral blood T lymphocytes (PBL-T's). In comparison to normal and autologous PBL-T's, TIL's had a strikingly reduced proliferative potential revealed by a decrease in the frequency of proliferating T lymphocyte precursors calculated by LDA. On average, only one of every 100 T cells from TIL's was able to proliferate, as compared to one of every two or all of the T cells from the patient's peripheral blood or from normal donors. Furthermore, the TIL populations showed depressed proliferative responses to the lectins phytohemagglutinin and concanavalin A and to the phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate. Clonal analysis performed on the proliferating microcultures from three tumors demonstrated that the majority of these clones possessed cytolytic activity against various tumor cell targets. Among clones tested for cytolytic activities with glioma cells, four lysed cultured autologous tumor cells, and the specific lysis was greater than 50% in all cases. Numerous clones with natural killer (NK)-like activity were obtained from two TIL preparations, and the frequency of cytolytic T lymphocyte precursors with NK-like activity was determined for one of these preparations and was found to be higher than that in the patient's peripheral blood. Glioma cells grown in culture and then mixed with normal peripheral blood lymphocytes (PBL's) were capable of inhibiting the PBL's response to lectins. This inhibitory property may account in part for the observed poor clonogenicity of TIL's from brain tumors. Nevertheless, nearly all proliferating clones displayed cytotoxicity against either autologous or allogeneic tumor cell targets and may imply selective accumulation of cytolytic effector cells at the tumor site.
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PMID:In situ characterization, clonogenic potential, and antitumor cytolytic activity of T lymphocytes infiltrating human brain cancers. 325 92

This is the first morphological study of interleukin-2-stimulated human peripheral blood mononuclear (PBM) cells resulting in lymphokine-activated killer (LAK) cell activity against human glioma-derived tumor cells in vitro, in which high-resolution differential interference video light microscopy, scanning electron microscopy, and transmission electron microscopy were used. A subset of cells within the LAK cell population are the effector cells and have an asymmetric cellular architecture characteristic of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Upon binding to target cells, the LAK effector cell nucleus is positioned away from the target cell, whereas the granules, Golgi apparatus, and microtubules orient toward the target cell. These LAK-glioma cell conjugates form very tight plasma membrane bonds with numerous interdigitations, and vesicles were found in the small extracellular spaces between the cells. This morphology was not observed in unstimulated PBM-glioma cell co-cultures. Glioma-derived cells react to LAK effector cells by blebbing, becoming round, and rapidly detaching from the substrate. The injured glioma-derived cells had a highly condensed cytoplasm and chromatin, lobular nucleus, and severe plasma membrane blebs, which are consistent with an apoptotic rather than an osmotic lysis mechanism of cell death. This study provides morphological evidence that supports a common cytotoxic mechanism for CTLs, NK cells, and LAK effector cells. The cytotoxic mechanism is based on the local exocytosis of vesicles by the effector cell into the small extracellular space between the effector-target cell conjugate. Granules found in CTLs, NK cells, and LAK cells contain a pore-forming protein that inserts holes in the target cell's plasma membrane through which a lethal substance(s) not yet identified is thought to enter the cell.
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PMID:Morphology of interleukin-2-stimulated human peripheral blood mononuclear effector cells killing glioma-derived tumor cells in vitro. 325 38


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