Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new murine monoclonal antibodies were prepared by hybridoma technique after immunization with the immature pluripotent leukemia cell line K562. The monoclonal antibody Bra10G (IgG2b) reacted in a non-lineage pattern with all examined hematopoietic neoplastic cell lines and peripheral blood cells (granulocytes, lymphocytes, erythrocytes) of healthy donors, with the exception of monoblastoid cell line U-937 and B lymphoma cell line Daudi. This monoclonal antibody immunoprecipitated an 18-20 kDa cell surface protein expressed also on the cell surface of examined non-hematopoietic (malignant glioma, melanoma and breast carcinoma) cell lines. These properties and the efficient inhibition of Bra10G binding to the cell surface of K562 cells by the reference CD59 monoclonal antibody (MEM-43) indicated that Bra10G belongs to the CD59 cluster of monoclonal antibodies which identify the human protectin molecule. The monoclonal antibody Bra7G (IgM) reacted with a 95 kDa cell surface protein expressed on hematopoietic cells (with the exception of erythrocytes) and was absent on the examined non-hematopoietic neoplastic cell lines. These data together with a partial inhibition of Bra7G binding by the reference CD-43 monoclonal antibody suggested the CD43 (leukosialin, sialophorin) specificity of this monoclonal antibody.
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PMID:Monoclonal antibodies to two adhesive cell surface antigens (CD43 and CD59) with different distribution on hematopoietic and non-hematopoietic tumor cell lines. 128 43

We developed a culture system for the rapid generation of CD4+ T cells that have both helper and killer functions. CD4+ T cells isolated from human PBL did not proliferate or develop significant cytotoxicity when treated with rIL-2 because of the lack of p75 IL-2R expression. However, culture of isolated CD4+ T cells with immobilized anti-CD3 mAb plus rIL-2 resulted in a marked proliferation (500-fold increase in 14 days) of CD4+ T cells. The proliferating CD4+ T cells produced IL-2 (92 U/ml) and showed strong cytotoxicity against OKT3 hybridoma cells and Daudi, K562, and U937 tumor cells in an anti-CD3 mAb-dependent manner. The CD4+ T cells contained significant amounts of cytolytic granule-related proteins such as serine esterase and perforin. Activated CD4+ helper/killer cells can be generated from both healthy donors and tumor patients and can be propagated in vitro for 14 to 35 days by biweekly restimulation with immobilized anti-CD3 mAb plus rIL-2. This culture yielded about 20,000-fold increase in cell number after a 21-day culture. Bispecific antibody containing anti-CD3 and anti-glioma Fab components enhanced the cytotoxicity of activated CD4+ helper/killer cells against IMR32 glioma cells. Moreover, the activated CD4+ helper/killer cells showed both helper and antitumor activity in vivo and prevented growth of anti-CD3 hybridoma cells in nude mice whether or not IL-2 was administered. These results indicate that anti-CD3 mAb plus IL-2-activated CD4+ helper/killer cells may provide an effective strategy for adoptive tumor immunotherapy of cancer.
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PMID:Generation propagation, and targeting of human CD4+ helper/killer T cells induced by anti-CD3 monoclonal antibody plus recombinant IL-2. An efficient strategy for adoptive tumor immunotherapy. 134 87

This study investigated the secretion of a tumor necrosis factor (TNF) and lymphotoxin (LT) from lymphokine-activated killer (LAK) cells during co-culture with glioblastoma cell lines, autologous glioma cells, and other non-gliomatous tumor cell lines (K562 and Daudi). Cytokine secretion from peripheral blood mononuclear cells (PBMC) was also examined. The TNF activity of culture supernatants was measured by L cell cytotoxic assay, and a neutralization test using anti-TNF and/or anti-LT antibodies determined whether the cytotoxic activity was due to TNF or LT. The results show that LAK cells secrete both TNF and LT during monoculture and release increased amounts of TNF and LT with non-gliomatous tumor cell stimulation, but PBMC secrete only TNF with tumor cell stimulation. Glioblastoma or anaplastic astrocytoma cells, however, did not stimulate cytokine secretion from either LAK cells or PBMC. This indicates a discrepancy between the capability of LAK cells to lyse malignant glioma cells and cytokine secretion from LAK cells, and suggests that malignant glioma cells may produce some factors which inhibit cytokine secretion from LAK cells.
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PMID:Analysis of tumor necrosis factor and lymphotoxin secreted by incubation of lymphokine-activated killer cells with tumor cells. 137 61

Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells.
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PMID:Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells. 150 88

The effects of interferon (IFN) on the expression of the nuclear antigen Ki-67 were studied in the two IFN-sensitive tumour cell lines Daudi and 251 MG, known to be arrested in the cell cycle in separate stages. The GO/G1-arrested Burkitt's lymphoma cell line Daudi displayed an increasing fraction of Ki-67 negative cells with time, concomitant with an increasing proportion of growth arrested cells. A small fraction of Ki-67 positive cells were found mainly arrested in G2/M. In contrast, no effect on Ki-67 expression was seen in IFN-resistant Namalwa cells, nor in the sensitive glioma cell line 251 MG, which is blocked in the S phase of the cell cycle. Agents blocking the cells in other phases of the cycle did not affect Ki-67 expression. However, after serum deprivation, no Ki-67 expression was found in the glioma cell line, while restimulation initiated expression after 12 hours as cells entered the S phase. We conclude that the Ki-67 antigen was not down regulated in all cells inhibited by IFN and thus does not seem to be useful to monitor clinical effects of IFN treatment.
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PMID:Ki-67 as a marker for cell cycle regulation by interferon. 172 63

A high density cell culture system has been developed for large-scale production of lymphokine-activated killer (LAK) cells from peripheral blood lymphocytes (PBLs) of malignant tumor patients. The system consists of a culture bag, which has two compartments separated by a semipermeable membrane, and an external rotator. The system allows for a long-term, at least 4 weeks, culture of LAK cells at high cell density in the inner compartment. The collected PBLs were first divided between the two culture bags and cultured without harvesting for 7-10 days to obtain LAK cells. Half of the LAK cells from each bag was administered to patients twice a week for clinical trials. Culture of the remaining half was continued following addition of a fresh culture medium. LAK cells were transferred to patients alternatively from each bag for the following 2-3 weeks. The total number of LAK cells administered amounted to 3.9-9.8 (mean 5.8) times more than the PBLs collected by leukapheresis (n = 10). The 5 x 10(6)/ml of PBLS of the initial concentration reached a maximum of 2 x 10(7)/ml. Our system does not need for a CO2 incubator. Cytotoxicity of the LAK cells was evaluated in 4 hr 51Cr release assays. Mean cytotoxicity at maximum cell density was 95.4 +/- 3.2% against ONS-12 (a human glioma cell) and 84.8 +/- 3.0% against Daudi cells (n = 10), but gradually decreased to about 50% at the end of fourth week of the culture period. Cell viability of the LAK cells was normally over 80% through the entire culture period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A high density cell culture system for generation of human lymphokine-activated killer (LAK) cells for clinical use in adoptive immunotherapy. 196 36

Human glioblastoma cells secrete factors, such as prostaglandin E (PGE) and transforming growth factor beta type 2, which are capable of suppressing several immune functions. The present study investigated the effect of PGE2 and agents known to increase intracellular cyclic adenosine monophosphate (cAMP) levels on 1) the induction of lymphokine-activated killer (LAK) cell activity from the peripheral blood lymphocytes (PBL) of both normal and glioma patients and on 2) the cytolytic activities of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). Cytolytic activity was measured against autologous and allogeneic tumor cells and the natural killer-resistant Daudi cell line. The results demonstrate that PGE2 and agents known to increase intracellular cAMP levels can significantly suppress the IL-2-dependent generation of cytolytic activity from the PBL of normal and glioma patients and from glioblastoma-derived TIL's. The inhibitory effects of these agents could not be reduced by higher concentrations of IL-2 or by cyclic guanosine monophosphate. Although the suppressive effect of PGE2 was most significant during the early stages of LAK cell generation, an inhibitory effect was still evident when PGE2 was added directly to the cytotoxicity assay. Secretion of PGE2 by glioblastoma cells in vivo may regulate both the generation of an immune response and the effectiveness of adoptively transferred immune cells.
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PMID:Influence of PGE2- and cAMP-modulating agents on human glioblastoma cell killing by interleukin-2-activated lymphocytes. 196 67

In phase-I clinical trials of adoptive immunotherapy using lymphokine-activated killer (LAK) cells plus recombinant interleukin-2 (rIL-2) (Cetus) for the treatment of malignant glioma, we observed that blood mononuclear cells (MNC) from patients dependent on dexamethasone for management of cerebral edema produced substantially less LAK activity as compared to MNC of normal blood donors or glioma patients not receiving steroid therapy. Therefore, we examined the in vitro effects, brought about by therapeutically attainable concentrations of various corticosteroids, on the proliferative response, production of gamma interferon (IFN-gamma), and induction of LAK activity from blood MNC of normal donors. Incubation in media containing rIL-2 (1000 U/ml) with either dexamethasone, hydrocortisone, methylprednisolone, or prednisolone profoundly affected all of these parameters. First, while 0.01 micrograms/ml of either dexamethasone or hydrocortisone caused a slight enhancement of the mitogenic response of lymphocytes to phytohemagglutinin, a dose-dependent decline occurred as concentrations increased to 10 micrograms/ml. The addition of prednisolone and methylprednisolone elicited a dose-dependent inhibition of lymphocyte proliferation over the entire concentration range tested. At 0.1 microgram/ml or higher, dexamethasone, hydrocortisone, methylprednisolone and prednisolone significantly (P less than 0.02) inhibited the production of IFN-gamma: respectively 18.9%, 4.4%, 2.2%, and 12.3% of the IFN-gamma produced by MNC in the absence of steroids. All four corticosteroids inhibited the induction of LAK activity. Compared to MNC that had been incubated with 1000 U/ml rIL-2 alone, MNC cultured with rIL-2 and 10 micrograms/ml either dexamethasone or prednisolone demonstrated significantly lower cytotoxicity (P less than 0.05) for the natural-killer-cell-resistant cell line, Daudi. Culturing MNC with hydrocortisone had a more dramatic result, causing a significant decline (P less than 0.01) in lytic activity at both 1.0 micrograms/ml and 10 micrograms/ml, while incubation with methylprednisolone produced a significant drop (P less than 0.02) in LAK-mediated cytotoxicity at 0.1 micrograms/ml as well as 1.0 micrograms/ml and 10 micrograms/ml. When cytotoxicity was expressed as lytic units per million effectors, a dose-response decline in lytic activity was once again apparent, with hydrocortisone, methylprednisolone and prednisolone showing significant inhibition (P less than 0.05) at both 1.0 micrograms/ml and 10 micrograms/ml and dexamethasone at 10 micrograms/ml (P less than 0.01). These results indicate that corticosteroids commonly used in the management of cere
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PMID:Corticosteroids inhibit the generation of lymphokine-activated killer activity in vitro. 249 21

Tumor-infiltrating lymphocytes (TIL's) were isolated from human glioma biopsy specimens by immunomagnetic separation using T cell-specific monoclonal antibodies coupled to paramagnetic beads, and were expanded in culture with feeder cells and interleukin-2 (IL-2). The infiltrating cells from five of seven patients proliferated in culture. When tested after 2 to 3 weeks of culture, virtually all of the cells stained with antibodies against the CD2 and CD3 antigens. Most cells also expressed human leukocyte antigen class II molecules, while varying percentages of cells stained with antibodies against the IL-2 receptor and the CD4 and CD8 antigens. The cytotoxicity of the cultured TIL's against autologous and allogeneic glioma cells and the K562 and Daudi cell lines was measured and compared with that of lymphokine-activated killer (LAK) cells from the same patients. None of the TIL's showed significant cytotoxicity against these targets, whereas LAK cells lysed all of the targets.
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PMID:Immunomagnetic separation of infiltrating T lymphocytes from brain tumors. 266 96

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


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