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 purpose of these studies was to examine the antiproliferative properties of 16 recombinant human IFN-alpha B/D hybrids against various human tumor lines of different histological origin and to determine whether any of the hybrid molecules possessed immunomodulating activity that could active antitumor properties in peripheral blood monocytes of normal donors. Hybrids with the B domain at the NH2 terminal end exhibited higher activity for antiviral activity and a higher level of direct antitumor antiproliferative activities as compared with hybrids with the D domain at the NH2 terminal end. The positive hybrids were directly cytostatic to melanoma, glioblastoma, renal carcinoma, colon carcinoma, and prostatic carcinoma cells. Tumor cell sensitivity to IFN-alpha hybrids was independent of sensitivity to IFN-gamma or to Adriamycin. The growth of a normal cell line (human embryo fibroblast) was unaffected by IFN-alpha hybrids but was completely arrested by Adriamycin. Some of the IFN-alpha hybrids were also cytostatic to mouse melanoma, lung carcinoma, and fibrosarcoma cell lines, albeit at lower levels than they were to human cells. The incubation of monocytes with IFN-alpha hybrids with the B domain at the NH2 terminal end was also associated with marked antitumor cytotoxicity. Kinetic studies, however, indicated that this activity was attributable to IFN-alpha carried on monocytes and acting directly on tumor cells. We conclude that recombinant human IFN-alpha B/D hybrids possess potent direct antiproliferative activity against a large variety of human tumor lines.
 ...
PMID:Direct antiproliferative effects of recombinant human interferon-alpha B/D hybrids on human tumor cell lines. 382 90

In a patient with glioblastoma treated with interferon (IFN-alpha) for a long period of time, a high titer of IFN-neutralizing antibody was detected in the serum during and after IFN therapy. Computerized tomography findings and neurological symptoms in this patient were unchanged during IFN therapy. General malaise, fever, anorexia, nausea, and decrease of leukocytes, platelets, erythrocytes, hemoglobin, and hematocrit were recognized transiently as side effects of IFN administration. These side effects were not serious and resolved spontaneously without discontinuation of therapy. The appearance of IFN-neutralizing antibody is clinically important because the antibody probably neutralizes the effect of systemically administered IFN before it reaches the site of action.
 ...
PMID:High titer of interferon (IFN)-neutralizing antibody in a patient with glioblastoma treated with IFN-alpha. Case report. 608 59

Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
 ...
PMID:Interferon therapy in neoplastic diseases. 618 85

Four patients with glioblastoma and one patient with astrocytoma (grade III) were treated with recombinant IFN ( rIFN -alpha A, Ro 22-8181) and the effect of IFN on clinical symptoms, CT findings and side effects of IFN were studied. Neurological symptoms were improved in one patient, stable in one patient and worsened in three patients. In all cases, there was no remarkable change of CT findings but in one case a slight decrease in tumor size was recognized. With regards to IFN side effects general malaise, anorexia, fever, nausea and vomiting were observed clinically, decrease of leukocytes, platelets, erythrocytes, hematocrit, hemoglobin and increase of GOT, GPT, LDH, AL-P were noted in the laboratory findings. These symptoms and change in laboratory findings were not serious, and they recovered spontaneously during or after IFN therapy. In one patient, an increase in IFN neutralizing antibody titer was detected. Since the biological activity of IFN may be diminished and anti-tumor effect cannot be expected in such a patient, the appearance of IFN neutralizing antibody may indicate an important problem in IFN therapy.
 ...
PMID:[rInterferon-alpha A (Ro 22-8181) therapy for patients with malignant brain tumors]. 632 84

Since 1980, phase 1 and 2 clinical trials of Hu-IFN-beta have been done in the field of neurosurgery. In the present study, (1) the results of in vivo experiments of Hu-IFN-beta are reported and (2) the effectiveness of Hu-IFN-beta in patients with malignant brain tumors is also evaluated. (1) The antitumor activities of beta-IFN and poly ICLC in nude mice receiving subcutaneous transplants of human brain tumors (2 strains) were compared with those of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, beta-IFN and poly ICLC, tumor reduction rates were evaluated by the method of Battelle. The effectiveness of beta-IFN and poly ICLC was slightly inferior to that of ACNU and vincristine, although tumor reduction rates (treated/control values) of 43% and 39% were respectively obtained with beta-IFN and poly ICLC against one strain of glioblastoma. (2) Clinically, 7 patients with malignant brain tumors were given beta-IFN (4 by intratumor administration and 3 by intravenous injection) in a dose of 3 X 10(6) to 9 X 10(6) IU/day for 2 to 6 months to study the efficiency and side effects of IFN treatment. One of four patients given IFN intratumorally showed a reduction in tumor size (partial response) by CT scan; the three patients injected IFN intravenously were unchanged. There were no noteworthy side effects in the cases treated intratumorally except for fever occurring in one patient. In the patients treated intravenously, however, fever, general malaise, leukopenia and thrombocytopenia were noted.
 ...
PMID:[Effect of human fibroblast interferon on malignant brain tumors]. 665 89

Cytokines regulate the expression of specific sets of proteins which mediate their biological effects. We have comprehensively delineated the regulation of the human tryptophanyl-tRNA synthetase (hWRS) by eight different cytokines (including IFNs) and poly(I).poly(C) in several cell lines. Six non-lymphoid cell lines were tested, and all of these produced human, IFN inducible hWRS (gamma 2) mRNA upon stimulation with IFN-gamma. In all these cell lines the level of gamma 2 mRNA increased 2-4 h after induction reaching a stable plateau after 8-12 h. The IFN-gamma induction of gamma 2 mRNA could be blocked by cycloheximide in human amniotic (AMA) cells, epithelial HeLa cells and HT1080 fibroblasts, but not in T98G glioblastoma cells. IFN-alpha and poly(I).poly(C) elicited small, transient gamma 2 responses in a few of the non-lymphoid cell lines, whereas none of the other six cytokines tested elicited a response. The six lymphoid cell lines tested did not show the same induction pattern. In the monocytic cells, THP-1, gamma 2 mRNA was highly induced by IFN-gamma, whereas in the B-cell line, Daudi, gamma 2 mRNA was transiently induced by IFN-alpha and poly(I).poly(C), and not by IFN-gamma. Altered mRNA turnover rate as a consequence of IFN-gamma treatment did not appear to play a significant role in the accumulation of gamma 2 transcript, since the stability essentially was the same in induced versus non-induced cells. We conclude that the hWRS gene is induced preferentially by IFN-gamma, and that the induction pattern resembles the one reported for the IFN induced enzyme, indoleamine 2,3-dioxygenase (IDO).
 ...
PMID:Differential regulation of the human, interferon inducible tryptophanyl-tRNA synthetase by various cytokines in cell lines. 774 68

The purpose of our study was to investigate the susceptibility of human glioblastoma multiforme (GBM) cells to lysis by human peripheral-blood monocytes following activation with biological response modifiers (BRM) and to lysis by various BRMs directly. Cytotoxic effects were determined using a monocyte-/BRM-mediated tumor cytotoxicity assay. Human peripheral-blood monocytes from healthy donors were activated in vitro by incubation for 24 h with different BRMs such as gamma- and beta-interferon (gamma, beta-IFN), lipopolysaccharide (LPS), muramyldipeptide (MDP) and tumor necrosis factor-alpha (TNF-alpha) in varying concentrations and combinations. Seven human GBM cell lines as well as an adenocarcinoma brain metastasis cell line and a malignant melanoma cell line served as target cells. Radiolabeled target cells were cocultivated with activated monocytes or with BRMs directly. Cytotoxicity was calculated after 72 h of cocultivation. High levels of cytotoxicity were mediated by monocytes activated with beta-IFN in six out of eight brain tumor cell lines and with TNF-alpha in five cell lines. The combination of two BRMs, in particular the combination of gamma-IFN + beta-IFN and gamma-IFN + TNF-alpha, was associated with an enhanced monocyte mediated lysis exceeding LPS control, whereas the combination of gamma-IFN + MDP was very effective against the metastasis cell line. Monocyte-mediated cytotoxicity against tumor target cells was up to ten fold higher than direct cytotoxicity of soluble BRMs. Our data indicate that BRM-stimulated peripheral-blood monocytes exert cytotoxic properties against human glioblastoma cells in vitro, which exceed those of BRMs alone up to ten fold. The higher tumoricidal activities observed after stimulation with combined BRMs suggest mutual promoting mechanisms of BRMs acting on the stimulation of lyctic activity in human peripheral blood monocytes.
 ...
PMID:Activated monocytes kill malignant brain tumor cells in vitro. 780 82

The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.
 ...
PMID:Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF. 798 57

The cell-surface expression of major histocompatibility (MHC) antigens and the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) is essential for target cell recognition by T lymphocytes. The expression of both classes of molecule is induced by various cytokines, notably interferon gamma (IFN gamma). Since transforming growth factor beta (TGF beta) has been recently reported to antagonise HLA-DR induction by IFN gamma we have examined, using a number of murine and human cell lines, the effect of TGF beta on IFN gamma-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFN gamma treatment. Class II MHC induction was seen on most but not all of the cells, the exceptions being among a panel of human colorectal carcinoma cell lines. A striking difference between cells of different origin was noted in the response to TGF beta. TGF beta was found to antagonise IFN gamma-induced class I and class II MHC expression on C3H 10T1/2 murine fibroblasts, early-passage BALB/c mouse embryo fibroblasts, a murine oligodendroglioma cell line, and on MRC5 human fibroblasts and two human glioblastoma cell lines. Class II MHC was much more strongly inhibited (sometimes completely) than class I MHC. TGF beta also inhibited induction of class I MHC expression by IFN alpha. However, TGF beta did not inhibit class I or class II MHC induction by IFN gamma in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGF beta. On the other hand, human ICAM-1 induction by IFN gamma was not affected by simultaneous treatment with TGF beta in any of the cell lines. The down-regulation of IFN gamma-induced MHC antigens by TGF beta is not, therefore, the result of a general antagonism of IFN gamma. Retinoic acid has recently been reported to induce ICAM-1 expression on human tumour cells. We have confirmed this observation on MRC5, and the two human glioblastoma cell lines, however six colorectal carcinoma cell lines tested did not respond. In contrast to IFN gamma-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGF beta on two of the three responsive lines.
 ...
PMID:Interactions between interferon gamma and retinoic acid with transforming growth factor beta in the induction of immune recognition molecules. 810 Apr 85

IFN-gamma induces the production of N-formyl-kynurenine from L-tryptophan in various cell types by the induction of the enzyme indoleamine 2,3-dioxygenase (IDO). The IFN-gamma induced IDO activity in the glioblastoma cell line 86HG39 and cells of clone 2D9 derived from this cell line was found to be greater than that in Hela cells and U373MG cells. Consequently 2D9 cells were used in all subsequent experiments. The determination of kynurenine in the supernatant of IFN-gamma activated cells was performed photometrically using a microplate reader. It was found that the amount of kynurenine produced was directly proportional to the amount of IFN-gamma used to activate cells. The detection limit for IFN-gamma of this assay was 20 U/ml. The induction of L-tryptophan degradation was specific for IFN-gamma since neither IFN-alpha, IFN-beta, IL-1, IL-2, IL-6, GM-CSF nor TNF alpha induced the production of detectable amounts of kynurenine by 86HG39 and 2D9 cells. Furthermore, a mab directed against IFN-gamma was able to completely block the IFN-gamma induced IDO activation. This bioassay was used to determine the IFN-gamma content of supernatants harvested from toxoplasma antigen specific human T cell lines and clones. This assay gave reproducible results which correlated well with the IFN-gamma content detected in the same samples using a commercially available ELISA kit. Furthermore in the case of T cell supernatant stimulated 2D9 cells a mab directed against IFN-gamma was able to completely block IDO induction. We conclude that the measurement of kynurenine production induced by IFN-gamma can be used to determinate IFN-gamma content. This is a simple bioassay which can be performed with standard laboratory equipment.
 ...
PMID:A new, simple, bioassay for human IFN-gamma. 828 93


<< Previous 1 2 3 4 5 6 7 8 9 Next >>