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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of gamma-interferon (IFN-gamma) on immune parameters in the 9L gliosarcoma model were examined. IFN-gamma increased class I major histocompatibility complex (MHC) expression in 9L cells in vitro. In vivo, intratumor injections of IFN-gamma led to increased numbers of inflammatory cells within the tumor and class II+ mononuclear phagocytes at its periphery, and increased MHC class I or II expression by endothelial and ependymal cells. Class I expression in 9L cells themselves was not increased. This suggests that there may be inhibition of class I induction in vivo for certain cell types, for which immunotherapies based on non-MHC restricted mechanisms may be more effective.
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PMID:Effects of gamma-interferon on major histocompatibility complex antigen expression and lymphocytic infiltration in the 9L gliosarcoma brain tumor model: implications for strategies of immunotherapy. 173 69

The line 1 lung carcinoma is a spontaneous BALB/c tumor deficient in class I Ag expression at the protein and mRNA levels. Exposure of line 1 cells to 3% DMSO or IFN-gamma increases class I Ag protein and mRNA dramatically. We have examined the regulation of class I Ag induction by DMSO in line 1 cells. We found DMSO induces class I Ag expression in line 1 cells by a mechanism distinct from IFN, because the kinetics of class I Ag induction by these agents were dramatically different, 7 days vs 3 days, and DMSO did not act through an IFN second messenger. At the molecular level, class I H chain transcription in line 1 cells was low. Treatment with 3% DMSO or IFN-gamma increased H chain transcription four-fold and sevenfold, respectively, indicating that class I H chain expression is regulated at the level of transcription in line 1 cells. Using reporter gene constructs, we mapped the regions in the Dd H chain promoter that increase H chain expression after DMSO treatment of line 1 cells. Two regions of the Dd promoter, D1, from -210 to -133 bp, and D2, from -125 to -61 bp, were found to be independently responsive to DMSO. These regions were also responsive to IFN-gamma in line 1 cells. However, consistent with our cellular results, DMSO and IFN induction of class I H chain expression differed at the molecular level as determined by D1 point mutations that diminished IFN-gamma responsiveness but did not alter induction by DMSO. Thus, DMSO appears to regulate class I transcription through multiple regions of the class I H chain promoter in line 1 cells by a mechanism distinct from IFN-gamma.
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PMID:Two regions of the H-2 Dd promoter are responsive to dimethylsulfoxide in line 1 cells by a mechanism distinct from IFN-gamma. 173 36

The L-arginine-dependent tumor cell cytotoxicity produced by activated macrophages (M phi) may be mediated either directly by production of nitric oxide (NO), or by induction of NO synthesis in the tumor cell. The influence of M phi NO synthesis on the release of soluble cytotoxic mediators was investigated in this study. The synthesis of M phi NO, measured as nitrite, was detected 6 h after lipopolysaccharide (LPS)-triggering and reached a peak level by 44 h. A concurrent decrease in M phi viability beginning at 18 h after triggering was detected during a period of 72 h in culture. Both the production of NO and loss of viability correlated with the presence of L-arginine in the incubation media and was inhibited by NG-monomethyl-L-arginine (NMA). The medium in which LPS-triggered adherent peritoneal exudate cells were incubated was examined for the presence of tumor necrosis factor (TNF), gamma interferon (IFN-gamma), and the soluble mediators that induce mitochondrial respiratory inhibition in tumor cells. All of these effector molecules were released at peak levels into the conditioned supernatants within 12 h after LPS-triggering. The peak level obtained for each effector molecule was influenced by the media in which the M phi was incubated; however, no correlation was detected between the level of cytokines produced and the synthesis of nitrite by the M phi indicating that NO synthesis has no inhibiting effect on the initial burst of cytotoxic factors released.
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PMID:Independence of the pattern of early cytokine release from autoregulation by nitric oxide. 174 44

We compared the regulatory effects of interferon (IFN)-beta and IFN-gamma on the susceptibility of a human gliosarcoma line GI-1 to the attack of autologous cloned tumor-specific cytotoxic T-lymphocytes (CTL) and lymphokine-activated killer (LAK) cells. Preincubation of GI-1 cells with IFN-gamma caused augmented susceptibility to the cytotoxic attack of two autologous CTL clones, whereas IFN-beta exhibited no such marked effect. On the other hand, preincubation with either IFN-beta or IFN-gamma made the GI-1 cells resistant to the attack of autologous LAK cells. Both IFNs augmented the surface expression of HLA class-I molecules on GI-1 cells. A monoclonal anti-HLA class-I antibody blocked the cytolysis by one CTL clone, but not by the other one. These results suggest that IFN-gamma exerts some different effect (s) from that of IFN-beta on the target GI-1 cells in their susceptibility to the CTL-mediated cytolysis, and that recognition mechanisms of target cells by the CTL are different from those by LAK cells. This draws our attention to IFN administration in adoptive immunotherapy against brain tumors using CTLs and LAK cells.
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PMID:[Immunomodulatory effects of interferons on target human gliosarcoma cells in the tumor-specific CTL- and LAK-mediated cytolysis]. 176 55

Morphological and biochemical studies were performed using tissue culture methods in 14 cases of giant cell tumor of bone. Primary cultures consisted of three types of cells, multinucleated giant cells, mononuclear round cells and spindle-shaped cells. The round cells were considered to be infiltrating macrophages, not neoplastic cells, according to the results obtained by morphological and immunohistochemical studies. The spindle-shaped cells were apparently neoplastic since they extensively proliferated and showed chromosomal abnormalities. Western blotting analysis of the supernatant fluid from the culture of the spindle-shaped cells showed the presence of several cytokines; M-CSF, IFN-gamma, TNF-alpha, which were known to show chemotactic, differentiation-inducing and activating effects on macrophages. When the conditioned mediums of cultured spindle-shaped cells were added to the culture of U-937 macrophage cell line, U-937 cells were induced to differentiate and became multinucleated giant cells. The results indicate that the spindle-shaped cells which could be passaged are neoplastic elements and that the cytokines produced by these cells have a significant role in clinicopathological status of the giant cell tumor of bone.
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PMID:[Identification of cytokines produced by cells cultured from human giant cell tumors of bone]. 177 Feb 61

DMN exposure has been shown to increase macrophage cytotoxic activity against tumor targets both in vitro and in vivo. Since the production and expression of the macrophage-derived cytokine tumor necrosis factor-alpha (TNF-alpha) is associated with such anti-tumor activity, studies were performed to determine whether changes in TNF-alpha gene transcription and biosynthesis resulted following DMN exposure. Thioglycollate-elicited macrophages obtained from DMN-exposed animals displayed enhanced levels of constitutively expressed TNF-alpha transcripts compared to vehicle controls. Northern blot analysis of the time course expression of TNF-alpha following endotoxin (1 microgram/ml) stimulation in vitro showed a significantly greater induction of TNF-alpha transcripts in macrophages from DMN-exposed than control animals, with peak levels detected between 30 and 120 min. Maximum endotoxin-induced TNF-alpha secretion occurred later than the accumulation of the transcripts, with greater secretion observed between 120 and 360 min. In contrast to endotoxin, stimulation with IFN-gamma (100 U/ml) produced no changes in the level of TNF-alpha transcripts. However, stimulation of macrophages with IFN-gamma did greatly enhance the surface expression of membrane-bound TNF-alpha in cells from the DMN-treated animals. Supernatants from media and endotoxin stimulated macrophage were tested for TNF-alpha activity against WEHI-164 cells. In media alone, a five-fold increase in TNF-alpha activity was observed at 6 h in supernatants from macrophage obtained from DMN-exposed animals compared to the vehicle group. Treatment of supernatants with either superoxide dismutase (SOD) or catalase to remove reactive oxygen products did not alter their lytic capacity. However, addition of a neutralizing murine-anti-TNF-alpha antibody reduced the lytic capacity of the supernatants by 90% in both treatment groups. Accumulation of IL-1 beta transcripts gradually increased over the 6 h with a concomitant increase in secreted IL-1 beta that was identical in both DMN and vehicle groups. These results demonstrate that DMN exposure: (1) enhances the expression of TNF-alpha in peripheral macrophages by transcriptional regulatory mechanism(s) and, (2) does not alter the expression or secretion of IL-1 beta.
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PMID:Transcriptional changes in macrophage TNF-alpha expression following dimethylnitrosamine exposure in vivo. 179 Nov 40

Expression of the Cytokine genes in human astroglial cell lineage was studied. Primers for 5 different human cytokine, TNF-alpha, -beta, IFN-gamma, G-CSF and GM-CSF, were used to analyze messenger RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell lines and fresh brain specimens by polymerase chain reaction (PCR). Three out of 5 unstimulated astrocytomas, U138, U251, U373 MG and IMR32 neuroblastoma cells expressed TNF-alpha genes. After stimulation with IL-1 beta (1000 U/ml) all these cell lines expressed TNF-alpha genes. TNF-beta genes could not be detected in these cell lines even in the presence of any cytokine stimuli. We were able to detect expression of IFN-gamma genes within 2 astrocytoma cell lines (U87MG and A172), which interestingly did not show TNF-alpha activity. Constitutive expression of mRNA transcripts of GM -CSF could be detected in all astrocytoma and two out of 5 unstimulated astrocytomas, U87MG and U138MG, expressed G-CSF genes. After stimulation with IL-1 beta, all cell lines expressed G-CSF. In addition, we also examined gene expression of these cytokines within 4 human malignant astrocytoma specimens, 2 peritumoral brain and 2 autopsied normal brains. The results show that tumor and surrounding lesions express TNF-alpha (4 of 6), TNF-beta (1/6), IFN-gamma (4/6), G-CSF (3/6) and GM-CSF (5/6) but not normal brains. One tumor specimen also expresses TNF-beta as well as TNF-alpha genes (case 2). From these results, it is suspected that astroglial cell-derived cytokines may participate in local immune reactions accompanying glioma in the brain.
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PMID:[Expression of cytokine genes within astrocytoma cell lines and brain specimens]. 179 21

We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti-CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross-linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound.
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PMID:Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth. 182 9

C57BL/6N mice bearing Lewis lung tumours were treated with anti-gamma-interferon (IFN-gamma) monoclonal antibodies. Early, but not late, treatment inhibited tumour growth, suggesting that endogenous IFN-gamma promotes initial tumour cell proliferation. Tumour development was associated with failure to gain weight or with progressive weight loss. Anti-IFN-gamma given early or late counteracted this wasting syndrome, which indicates that IFN-gamma production subsists during tumour growth and is directly or indirectly responsible for tumour-associated cachexia. Studies of body composition in cachectic mice revealed fat tissue to be particularly affected. Fat loss was enhanced by IFN-gamma and antagonised by anti-IFN-gamma. Tumour-bearing mice were also hypersensitive to the lethal effect of endotoxin; anti-IFN-gamma was unable to mitigate this sensitisation, suggesting that IFN-gamma does not exert its cachexia-inducing effect through augmentation of the host response to an endogenous endotoxin source.
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PMID:Anti-interferon-gamma antibody treatment, growth of Lewis lung tumours in mice and tumour-associated cachexia. 182 86

The biologic effects of IFN-gamma are mediated through a receptor that is expressed in relatively low abundance on normal mammalian cells. As a consequence, investigations of the physicochemical and ligand-binding properties of the purified receptor have been limited. The work reported here characterizes a secreted form of the receptor for mouse IFN-gamma, made by deletion of the nucleotides that code for the anchoring domain from a cDNA that encodes the receptor binding protein and its related signal peptide. When transfected into rat XC cells, this construct produced up to approximately 1 mg/liter of a secreted protein that had the characteristics of the native receptor. Both the secreted protein and its mRNA were of sizes that were consistent with loss of the transmembrane region. The protein was detectable by a mAb that is specific for an epitope that is found in the ligand binding site of the receptor for mouse IFN-gamma, as well as by a goat polyclonal IgG that is monospecific for the mouse IFN-gamma R. Supernates that contained the secreted protein blocked binding of IFN-gamma to mouse IFN-gamma R and inhibited in a dose-dependent manner the IFN-gamma-mediated priming of mouse bone marrow culture-derived macrophages for tumor cell killing. Availability of relatively large amounts of a secreted protein that retains ligand-binding activity should facilitate purification and basic studies of the receptor binding protein and could provide new approaches to the treatment/prevention of diseases that arise due to inappropriate response of cells to IFN-gamma. In addition, because this secreted receptor, unlike others, consists of both the extracellular and intracellular domains, it is likely that it will be useful in determining how the cytoplasmic portion of the receptor is involved in receptor function.
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PMID:Stable expression of a secreted form of the mouse IFN-gamma receptor by rat cells. 183 66


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