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)

In the present study, antitumor activity of glioma-infiltrating lymphocytes (GILs) was compared to that of lymphokine-activated killer (LAK) cells. Results suggested that killing activity of GILs against autologous glioma cells was significantly higher than that of LAK cells (P less than 0.05), but their activity against allogeneic glioma cells was not different from that of LAK cells (P greater than 0.05). Analysis of cell surface phenotypes showed that CD4+ cells were a main portion of LAK cells, and CD8+ were predominant in the GILs. In the beginning, growth of GILs was slower than that of LAK cells. As time went on, generation of GILs was faster than that of LAK cells. The results suggested that GILs were superior to LAK cells for adoptive immunotherapy in patients with brain glioma.
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PMID:[Experimental studies on the antitumor activity of glioma-infiltrating lymphocytes against autologous glioma]. 132 62

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

The use of adjuvant immunotherapy for the treatment of primary malignant brain tumors dates to studies performed in the 1960's and 1970's using non-specific immune stimulators. Although the theoretical designs have remained similar, recent advances in molecular biotechnology have produced a new group of recombinant cytokines, spawning a new generation of immunotherapy-based clinical trials. In contrast to other published Phase I/II studies, we have had highly encouraging preliminary results using lymphokine-activated killer (LAK) cells and recombinant human Interleukin-2 (rIL-2; Cetus, Emeryville, CA), when the patients' use of corticosteroids could be restricted while on study. Patients with recurrent grade 3/3 glioma received multiple cycles of autologous LAK cells and rIL-2, post-operatively, via an Ommaya reservoir implanted into the tumor cavity following re-operation. The overall median survival for 13 patients with grade 3/3 glioma has not yet been reached at 55 weeks following second surgery, [mean +/- SEM, 64.7 +/- 10.5 weeks], with 5 patients still alive. Three patients have had partial responses (PR) demonstrated by CT scanning. In addition, one patient with grade 2/3 glioma has had a complete response (CR), with the disappearance of all residual CT-documented enhancement and mass effect.
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PMID:The cellular immunotherapy of primary brain tumors. 144 66

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

Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL-6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:[An analysis of lymphokine gene expression within astrocytoma]. 163 May 67

It is well documented that drug delivery into experimental and human brain tumors is limited by the variably intact blood-brain barrier (BBB) at the growing edge. The aim of the present investigation was to examine the histopathological changes that occur after a single intralesional injection of human recombinant interleukin-2 (rIL-2) into a growing glioma and determine whether the injection improved delivery of cytotoxic drug into the neuropil surrounding the site of lymphokine injection. Because an intracerebral injection of rIL-2 causes a temporary breakdown in the BBB, we hoped to enhance drug penetration into peritumoral areas of brain with an intact BBB by using the novel biomodulating effect of rIL-2 on the cerebral endothelial cells. The results demonstrated that an intralesional injection of 7.2 x 10(4) National Units rIL-2 on Day 7 after tumor inoculation did not accentuate the already increased cerebrovascular permeability produced by the glioma nor did rIL-2 trigger additional or aggravate neurological deficits in glioma-bearing rats. Before the administration of chemotherapy in vivo, the RT-2 glioma cells were tested for in vitro sensitivity by colorimetric assay. At 24 hours after exposure to either methotrexate (MTX), vincristine (VIN), or doxorubicin (DOX), no significant inhibition of metabolic activity was observed. In contrast, a timed pulsed of any drug for 5 minutes caused significant dose-dependent inhibition of RT-2 glioma cells at 48 hours to 5 days after drug administration. Animal models receiving an intralesional injection of rIL-2 followed 3 days later by an intravenous dose of 30 mg/kg MTX, 0.23 mg/kg VIN, or 10 mg/kg DOX demonstrated that only MTX combined with intralesional rIL-2 significantly inhibited intracranial proliferation of RT-2 glioma cells. Use of intralesional rIL-2 and intravenous chemotherapy, however, did not significantly increase survival in this animal model of glioma. These results show that the combination of cytotoxic drugs with intralesional rIL-2 can be safely applied in the management of glioma and may form a rational basis for additional pharmacological investigations of a wider assortment of chemotherapies in combination with rIL-2 for intracranial malignancies.
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PMID:Cerebrovascular effects and tumor kinetics after a single intratumoral injection of human recombinant interleukin-2 alone or in combination with intravenous chemotherapy in a rat model of glioma. 164 Nov 14

Tumor-infiltrating lymphocytes (TIL) were generated from 10 glioma specimens by using recombinant interleukin-2 and an anti-CD3 antibody (CD3 + TILs). We obtained more than 1 x 10(9) cells in 5 cases, more than 5 x 10(8) cells in 2 cases, and about 1 x 10(8) cells in 3 cases during three weeks of incubation from small specimens ranging in weight from 0.5 to 2.0 g. In 4 cases, TILs were expanded following stimulation with only rIL-2 (CD3-TILs). The growth rate of CD3-TILs was less than that of CD3 + TILs. Cytotoxicity of CD3 + TILs was lower than that of lymphokine-activated killer (LAK) cells in a standard 4h 51Cr release assay. Cold target inhibition was undertaken in three cases and specific cytotoxicity could be shown in only one case. CD3 + TILs mainly consisted of CD3-positive cells, ranging from 63.2 to 99.9%. The ratio of CD4-positive cells to CD8-positive cells was not constant. The expression of Leu 7 and CD16 was low. The present study did not confirm previous findings that TILs were more tumor-selective and potent than LAK cells. Furthermore, the results on in vitro antitumor activity of those cells were not necessarily consistent with the results on their clinical activity. Further careful work is necessary on the preparation of immunocytes and the subsequent adoptive immunotherapy.
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PMID:Cytological characteristics of human glioma-infiltrating lymphocytes stimulated with recombinant interleukin 2 and an anti-CD3 antibody. 182 92

The homing characteristics and infiltrative capacity of interleukin-2 activated human peripheral blood lymphocytes, the lymphokine activated killer (LAK) cells, were studied. In vitro stimulated 111In-oxine labeled lymphocytes were injected into the hypogastric artery during hysterectomy, performed because of endometrial carcinoma. Scintigrams demonstrated clear homing of the lymphocytes into the area of the malignant tumor. No selective homing was detectable when labeled red blood cells were injected in a similar fashion. To analyze the infiltrative capacity of the activated lymphocytes, they were incubated in vitro with tumor spheroids grown from cultured glioma cell lines. As revealed by antibodies against the leukocyte common antigen and immunoperoxidase techniques, the activated lymphocytes infiltrated the three-dimensional tumor tissue slowly as a frontier. These results show that, in addition to their previously suggested potential role in cancer therapy, interleukin-2 activated lymphocytes may possibly also be useful as tumor tracers.
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PMID:Interleukin-2 activated lymphocytes (LAK cells) as potential tumor tracers. 196 55

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

The results of specific targeting therapy by use of lymphokine-activated killer (LAK) cells treated with bispecific antibody in 10 patients with malignant glioma were compared with the results of therapy with untreated LAK cells in 10 other patients. Both treated and untreated cells were given locally. The bispecific antibody was an anti-CD3 monoclonal antibody (mAb) chemically conjugated to anti-glioma mAb. Of the 10 patients given specific targeting therapy, 4 showed regression of tumour, and in another 4 patients computed tomography and histology suggested eradication of the glioma cells left behind after surgery. No recurrence was detected in the 10 to 18 months of follow-up. Patients receiving untreated LAK cells had recurrences within 1 year except in 1 case, and 8 patients died within 4 years. So far specific targeting therapy seems to be a new useful form of adoptive immunotherapy.
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PMID:Preliminary trial of specific targeting therapy against malignant glioma. 196 15


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