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

In a patient with cerebral glioblastoma, metabolic disturbances were detected within the tumor and in the surrounding brain. Within the volume occupied by the tumor, phosphocreatine (PCr)/adenosine triphosphate was reduced and inorganic phosphate/PCr elevated, indicative of tissue necrosis. Loss of total 31P signal was consistent with reduced metabolite content within the area of tumor defined by CT and magnetic resonance (MR). These studies were accomplished with 31P MR spectroscopy at 2 T, using a volume head coil and the technique of two-dimensional phase-encoding to map regional metabolism across the entire cerebral cortex in voxels of 30 cm3. Using the same method, only minor variations in 31P metabolism were noted in six normal controls. Treatment with locally placed Interleukin-2 activated lymphocytes resulted in changes in both MR and 31P MR spectroscopy in the region of the tumor.
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PMID:Metabolic response of glioblastoma to adoptive immunotherapy: detection by phosphorus MR spectroscopy. 292 4

A procedure for enrichment in recombinant interleukin-2 (rIL2)-activated natural killer (NK) cells was developed and used for in vitro generation of antitumor effector cells from the peripheral blood of 20 patients with central nervous system (CNS) tumors. In comparison to the patients' unseparated mononuclear cells and nonadherent lymphocytes cultured in the presence of 1000 U/ml of rIL2 for up to 3 weeks, interleukin-2-stimulated lymphoid cells, when purified by adherence to plastic, proliferated better (up to 6,720-fold expansion) and achieved up to five times higher levels of antitumor activity against K562 cell targets and NK-resistant glioblastoma cell targets. Two-color flow cytometry analysis showed that cultures of cells purified by adherence to plastic which had the best proliferation contained 10% or less of CD3+Leu19- T-lymphocytes, while the unseparated lymphokine-activated killer cell cultures which proliferated poorly contained up to 85% of CD3+Leu19- T-cells. Cultures of adherent lymphocytes which reached the highest antitumor cytotoxicity were enriched in CD3+Leu19+ effectors (60-80%); the proportion of CD3-Leu19+ NK-cells was not greater than 25% in these cultures. Thus, using the technique of 24- or 48-h activation in rIL2 and adherence to plastic, and in contrast to the results obtained with cells from normal donors, it was not possible to enrich in activated NK cells from the blood of patients with CNS tumors. Instead of activated NK cells, a population enriched in non-major histocompatibility complex-restricted cytotoxic T-cells (CD3+Leu19+) was obtained in cultures from most but not all patients. Low NK cell activity and elevated numbers of circulating CD3+Leu11+ cells seen in the blood of these patients, previously treated by surgery/radiation/chemotherapy and maintained on steroids, could be responsible for the preferential adherence and subsequent expansion to plastic of IL2-activated non-major histocompatibility complex restricted cytotoxic T-lymphocytes.
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PMID:In vitro generation and antitumor activity of adherent lymphokine-activated killer cells from the blood of patients with brain tumors. 297 33

Culture of peripheral blood lymphocytes (PBL) from brain-tumor patients with recombinant interleukin-2 (IL-2) results in the activation of lymphokine-activated killer cells (LAK) with the capacity to lyse autologous and allogeneic glioblastoma. In this study, PBL obtained from brain-tumor patients were cultured with or without IL-2 for 3 to 7 days and then tested for their ability to lyse target cells in a 4-hour chromium release cytotoxicity assay. The PBL were drawn 1 to 2 weeks following operative tumor debulking. Cells used as targets included fresh brain-tumor cells obtained at the time of craniotomy, fresh brain-tumor cells grown from 1 to 3 weeks in tissue culture, fresh autologous PBL, and allogeneic glioblastoma cells grown in tissue culture. Peripheral blood lymphocytes from brain-tumor patients that were cultured without IL-2 did not significantly lyse autologous or allogeneic glioblastoma. However, when these PBL were cultured with IL-2, LAK were generated which produced marked lysis of autologous as well as allogeneic tissue-culture glioblastoma in all of eight cases. Significant lysis of autologous fresh tumor by patient LAK was observed in four of five experiments. By contrast, patient LAK did not kill autologous normal PBL. The ability to generate LAK was not influenced by the patient's age, previous therapy, or the administration of steroids.
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PMID:In vitro killing of human glioblastoma by interleukin-2-activated autologous lymphocytes. 300 Dec 47

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

Peripheral blood mononuclear cells from 11 glioma patients and 11 healthy control subjects were cultured in medium containing recombinant interleukin-2 for a period of 5 days. The cytotoxicity of these lymphokine-activated killer (LAK) cells was tested on chromium-51-labeled freshly prepared allogeneic glioblastoma cells, and on the cell lines K562 (natural killer cell (NK)-sensitive) and Daudi (NK-resistant). Peripheral blood mononuclear cells from all subjects showed high levels of cytotoxicity against these targets. There was no significant difference between the patients and the control group when LAK cytotoxicity was compared. Thus, although glioma patients are known to have depressed immunological reactivity, the cytotoxic capacity of LAK cells derived from glioma patients is similar to that of LAK cells from healthy control subjects. However, the glioma patients had significantly reduced numbers of mononuclear cells in their peripheral blood, possibly due to steroid treatment. Therefore, the volume of blood required to generate the same number of LAK cells was approximately three times larger from the glioma patients than from control subjects.
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PMID:Comparison of in vitro glioma cell cytotoxicity of LAK cells from glioma patients and healthy subjects. 326 Jun 22

We have cultured peripheral blood lymphocytes (PBL) from glioblastoma patients in recombinant interleukin-2 (IL-2) containing medium for a period of 5 days. The cytotoxicity of these cells was tested on 51Cr-labelled autologous dissociated glioblastoma cells which had not been cultured. Significant cytotoxicity against glioma cells was observed in seven out of nine cases. IL-2 activated PBL from normal donors were equally cytotoxic against these glioma cells. Autologous lymphocytes activated by phytohaemagglutinin were also lysed in most cases, and the erythroleukemia cell line K562 was highly susceptible to the cytotoxic capability of the IL-2 activated PBL. In cold target inhibition experiments, K562 inhibited the cytotoxicity against both autologous and allogenic glioma cells, and glioma cells inhibited the cytotoxicity against K562. Following immunomagnetic separation, the IL-2 activated cells demonstrated cytotoxicity against glioma cells, K562 cells, and PHA blasts in both the CD8+ and the CD8- subsets.
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PMID:Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro. 326 Sep 42

Human glioblastoma cells secrete a peptide, termed glioblastoma-derived T cell suppressor factor (G-TsF), which has suppressive effects on interleukin-2-dependent T cell growth. As shown here, complementary DNA for G-TsF reveals that G-TsF shares 71% amino acid homology with transforming growth factor-beta (TGF-beta). In analogy to TGF-beta it is apparently synthesized as the carboxy-terminal end of a precursor polypeptide which undergoes proteolytic cleavage to yield the 112 amino-acid-long mature form of G-TsF. Comparison of the amino-terminal sequence of G-TsF with that of porcine TGF-beta 2 and bovine cartilage-inducing factor B shows complete homology, which indicates that we have cloned the human analogue of these factors. It is tempting to consider a role for G-TsF in tumor growth where it may enhance tumor cell proliferation in an autocrine way and/or reduce immunosurveillance of tumor development.
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PMID:Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. 332 13

T cell suppressor factor produced by human glioblastoma cells inhibits T cell proliferation in vitro and more specifically interferes with interleukin-2 (IL-2)-dependent T cell growth. Here we report the purification of this factor from conditioned medium of the human glioblastoma cell line 308. Amino-terminal sequence analysis of the 12.5-kd protein demonstrates that eight out of the first 20 amino acids are identical to human transforming growth factor-beta. Purified glioblastoma-derived T cell suppressor factor and transforming growth factor-beta from porcine platelets inhibit both IL-2-induced proliferation of ovalbumin-specific T helper cells and lectin-induced thymocyte proliferation with similar specific activities. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.
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PMID:T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. 349 30

Nine patients with recurrent glioblastoma were given autologous adherent lymphokine-activated killer (A-LAK) cells and interleukin-2 (IL-2) administered directly into the tumor cavity through an Ommaya tube placed during surgery/biopsy. The immunotherapy was well tolerated and the response rate was 33% (one complete response, two partial responses, four with stable disease and two with progressive disease). However, survival 18 months from initial diagnosis did not differ from that reported in the literature for patients treated conventionally. Serial determinations of IL-2 in the tumor cavity during the course of treatment revealed that IL-2 concentrations were sufficient to maintain lymphocyte activation. Since steroid medication was discontinued during treatment and A-LAK cells have greater antitumor activity than standard LAK cells, other factors are discussed that might explain the limited results.
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PMID:Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients. 792 50

The effects of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleukin-2 (IL-2). The administration of IL-2 to dogs resulted in hypotension within 3 days of treatment. The development of hypotension correlated with accumulation in the serum of nitrate, which is a stable breakdown product of nitric oxide. Administration of L-NMA decreased serum nitrate levels and increased the mean arterial pressure. The antihypotensive effect was dose dependent with a maximum effect observed at a dose of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 mg.kg-1.h-1) maintained the mean arterial pressure for 48 h with concurrent administration of IL-2. Evaluation of IL-2-induced lymphokine-activated killer cell proliferation and tumoricidal activity toward a canine glioblastoma target cell line was unaffected by L-NMA. These studies imply that L-NMA may effectively ameliorate the dose-limiting hypotension associated with administration of IL-2 without adversely affecting the antitumor effects.
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PMID:NG-methyl-L-arginine, an inhibitor of nitric oxide formation, reverses IL-2-mediated hypotension in dogs. 800 55


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