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 combination of the cytokines interferon-alpha 2b and rIL-2, at doses of 10 x 10(6) IU and 9 x 10(6) IU, respectively, in a 1.5 cc solution, can be safely injected into cystic glioblastoma without any evidence of side effects or increase in surrounding tumoral oedema. Nevertheless, an immunotherapeutic protocol in ten glioblastoma patients with tumour growth, that consisted of one intralesional injection per week, over 4 weeks of this combination of cytokines, had no effect on tumour progression.
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PMID:Intratumoral immunotherapy with interferon-alpha and interleukin-2 in glioblastoma. 133 9

It is known that natural killer (NK) cells are involved in immunosurveillance against tumours. This study examines the NK activity of mononuclear cells (MNC) from the peripheral blood of patients with glioblastoma. The cytotoxic inducer effect of interferon-alpha (IFN-alpha) upon these MNC has also been studied. A marked decrease in NK activity mediated by MNC from these patients was found. This functional defected in MNC is not due to a decrease in phenotypically defined NK cells. After long-term (5-day) incubation with IFN-alpha, MNC from 5 out of 14 patients showed strong lytic activity against NK-sensitive target cells. In this system, IFN-alpha failed to induce cytotoxic activity against NK-resistant target cells in MNC from all the patients studied. This in vitro induction of cytotoxic activity in MNC from some patients with glioblastoma by IFN-alpha suggests a potential immunotherapeutic use of the lymphokine in these subjects.
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PMID:Modulation by interferon alpha of the decreased natural killer activity in patients with glioblastoma. 185 28

Interferon-gamma-induced tryptophan metabolism of human macrophages was compared to ten human neoplastic cell lines of various tissue origin and to normal dermal human fibroblasts. Tryptophan and metabolites were determined in supernatants of cultures, after incubation for 48 h, by high-performance liquid chromatography with ultraviolet and fluorescence detection. With the exception of two cell lines (Hep G 2, hepatoma and CaCo 2, colon adenocarcinoma) in all of the ten other cells and cell lines tryptophan degradation was induced by interferon-gamma. Five of these ten formed only kynurenine (SK-N-SH, neuroblastoma; T 24, J 82, bladder carcinoma; A 431, epidermoid carcinoma; normal dermal fibroblasts), three formed kynurenine and anthranilic acid (U 138 MG, glioblastoma; SK-HEP-1, hepatoma; A 549, lung carcinoma). Only one line, A 498 (kidney carcinoma) showed the same pattern of metabolites as macrophages (kynurenine, anthranilic acid and 3-hydroxyanthranilic acid). Interferon-gamma regulated only the activity of indoleamine 2,3-dioxygenase. All other enzyme activities detected were independent of interferon-gamma, as shown by the capacity of the cells to metabolize L-kynurenine or N-formyl-L-kynurenine. Increasing the extracellular L-tryptophan concentration resulted in a marked induction of tryptophan degradation by macrophages. Contrarily, a significant decrease of the tryptophan degrading activity was observed when the extracellular L-tryptophan concentration was increased 2-fold with SK-N-SH, T 24 and J 82, 4-fold with A 431 and A 549 and 10-fold with U 138 MG and SK-HEP-1. The activity was unaffected by extracellular L-tryptophan with dermal fibroblasts and A 498. Though interferon-gamma was the most potent inducer of tryptophan metabolism, interferon-alpha and/or -beta showed small but distinct action on some of the cells. In all cells which reacted to interferon-gamma by enhanced expression of class I and/or class II major histocompatibility complex antigens tryptophan degradation was also inducible. These results demonstrate that induction of indoleamine 2,3-dioxygenase is a common feature of interferon-gamma action, that the extent of this induction is influenced by extracellular L-tryptophan concentrations and that indoleamine 2,3-dioxygenase is the only enzyme in the formation of 3-hydroxyanthranilic acid from tryptophan which is regulated by interferon-gamma.
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PMID:Characteristics of interferon induced tryptophan metabolism in human cells in vitro. 250 Sep 76

The combined effects of Acyclovir [9-(2'-hydroxyethoxymethyl)guanine; ACV] and human interferon-alpha (IFN-alpha) on replication of the herpes simplex virus type I (HSV-1) were determined in human neural cell lines, neuroblastoma (IMR), glioblastoma (118MGC), and glioma (U251MG). HSV-1 grew well in all these cells, with final yields of more than 1 x 10(6) PFU/ml. In terms of virus-yield reduction, ACV was found to be highly effective in IMR, moderately effective in U251MG, but ineffective in 118MGC. By contrast, IFN-alpha reduced the virus yield significantly in 118MGC and in U251MG, but did not in IMR. Combined application of ACV and IFN-alpha strongly inhibited the virus replication in all three cell lines with various degrees of synergism or additive effect. These results were also confirmed by immunofluorescent examinations. The sensitivity of HSV-1 to ACV or IFN-alpha was found to be different among the three different cell types. By combining the two agents, the virus growth was strongly suppressed in all the cells. These results suggest the importance of combination therapy for severe type of herpes simplex encephalitis in clinical practice.
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PMID:Combined effects of acyclovir and human interferon-alpha on herpes simplex virus replication in cultured neural cells. 255 47

The effects of human lymphoblastoid interferon-alpha (MOR-22) on the growth of xenografted human tumors in nude mice were examined. IFN-alpha was administered subcutaneously to mice with renal tumor (ACHN), intratumorally for glioblastoma (U-373MG) or intravenously with uterine cervical tumor (HeLa S3). The dosages of IFN-alpha were 2 X 10(4)-5 X 10(5) IU/mouse for ACHN tumor, 1 X 10(5)-5 X 10(5) IU/mouse for U-373MG tumor and 3 X 10(4)-1 X 10(5) IU/mouse for HeLa S3 tumor. IFN-alpha inhibited the growth of these tumors in a dose-dependent manner.
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PMID:[Study on human lymphoblastoid interferon-alpha (MOR-22): Part III. Antitumor effect on nude mouse-transplanted human tumors]. 375 41

This report presents the results of a phase I trial of the value of human leucocyte interferon-alpha in the treatment of glioblastoma. Twelve patients entered the trial. In one case we believe that the patient benefitted from the interferon treatment. CT scans of patients on interferon did not reveal the true extent of the tumorous tissue.
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PMID:The effect of systemic human interferon-alpha administration to patients with glioblastoma multiforme. 630 69

The effect of interferon-alpha or beta on platinum analogues [cisplatin (CDDP) and carboplatin] cytotoxicity was studied in four glioblastoma cell lines (U373MG, T98G, A172 and U118Mg). All cell lines were strongly resistant to the cytotoxic effect of CDDP or carboplatin. Although both interferons were not cytotoxic in all cell lines, they were able to significantly increase the cell platinum-sensitivity. Specifically interferon-alpha increased the magnitude of CDDP-induced DNA interstrand crosslinks. Our findings suggest that interferons are able to induce a very strong potentiation of platinum analogues cytotoxicity in drug-resistant human glioma cell lines.
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PMID:Interferon-alpha or beta potentiate platinum analogous in human glioblastoma cell lines. 852 65

It has previously been reported that de novo infection of primary rabbit brain cells with Borna disease virus (BDV) can be blocked with interferon-alpha/beta (IFN), whereas this cytokine has no inhibitory effect on BDV in persistently infected rat lung cells [v. Rheinbaben et al., J. Gen. Virol. (1985) 66: 2,777-2,780]. It remained unclear, however, whether these results indicated that IFN exclusively targets early steps of the BDV replication cycle or whether they simply reflected cell line differences. We now show that BDV replication was effectively inhibited by IFN in both acutely and persistently infected monkey Vero cells. By contrast, IFN had no clear protective effect on either de novo or persistent BDV infections of rat C6 glioblastoma cells. IFN protected C6 cells from the cytopathic effects of vesicular stomatitis virus, excluding the possibility that these cells are devoid of a functional IFN system. In primary rat fibroblasts and in a human oligodendroglial cell line, IFN induced an efficient antiviral state against BDV. These results indicate that BDV is highly susceptible to the antiviral effect of IFN in some cell lines, while others seem to lack undefined components of the IFN system which mediate protection against BDV.
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PMID:Inhibition of Borna disease virus multiplication by interferon: cell line differences in susceptibility. 1044 54

Cancer recurrence post surgical resection is of considerable challenge especially in glioblastoma (GBM) therapy. Herein, we demonstrate that interferon-alpha (IFN) fused to a body temperature-sensitive elastin-like polypeptide (IFN-ELP(V)) formed a depot in situ when injected into GBM resection cavity in a mouse brain orthotopic model of GBM. Notably, IFN-ELP(V) in the depot showed a zero-order release kinetics, resulting in dramatically improved pharmacokinetics and biodistribution, and thus inhibited GBM recurrence by stimulating antitumor immunoresponse as compared to IFN. More importantly, when combined with subsequent intraperitoneal injection of temozolomide (TMZ), IFN-ELP(V) could much more effectively suppress post-surgical GBM recurrence than IFN, leading to a remarkably enhanced GBM-free survival rate (60%) over IFN (12.5%). Our findings implicate that the spatiotemporally-programmed combination of IFN-ELP(V) and TMZ leads to the synergy of post-surgical GBM immunochemotherapy, thereby providing a new and effective strategy for cancer therapy.
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PMID:Spatiotemporal combination of thermosensitive polypeptide fused interferon and temozolomide for post-surgical glioblastoma immunochemotherapy. 3306 37