Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.
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PMID:Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. 171 Jun 8

Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, as de novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.
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PMID:Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line. 171 85

Three autotumor-reactive T-cell clones have been established from tumor-infiltrating lymphocytes isolated from a metastatic lesion of human gastric carcinoma in the liver. The clones all were shown to be CD3+, CD8+, CD4-, CD16-, T-cell receptor alpha/beta +, and T-cell receptor gamma/delta-, and they have retained both their autotumor reactivity and the same phenotype for over a year in culture. Each clone had a different rearrangement of the T-cell receptor gamma chain genes as indicated by Southern blot analysis. Tested against a panel of 18 tumor cell targets, the clones preferentially lysed autologous tumor (AuTu) cells, but each clone also showed weak cytotoxicity against one allogeneic cholangiocarcinoma cell line. At the same time, each clone showed appreciable cytotoxicity against K562 targets. In blocking experiments, anti-CD3, anti-WT31, anti-CD8, or anti-HLA class I monoclonal antibodies blocked AuTu cytotoxicity but not cytotoxicity against K562. In contrast, allocytotoxicity against the cholangiocarcinoma was blocked only by anti-CD3 monoclonal antibody. All 10 subclones of one T-cell clone had high levels of AuTu cytotoxicity but variable levels of anti-K562 cytotoxic activity. Proliferation of the T-cell clones was significantly stimulated by the addition of irradiated autologous but not allogeneic tumor cells. Preincubation of cultured AuTu cells with tumor necrosis factor alpha or gamma-interferon (IFN-gamma), but not with IFN-alpha, increased their susceptibility to lysis by the T-cell clones; however, it increased resistance of AuTu to lysis by interleukin 2-activated natural killer cells. The expression of an adhesion molecule, intercellular adhesion molecule 1, on the surface of AuTu was also up-regulated by tumor necrosis factor alpha or IFN-gamma, but not by IFN-alpha. All three cytokines up-regulated HLA-class-I antigens on AuTu. Pretreatment of K562 targets or allogeneic cholangiocarcinoma cells with the same cytokines increased their resistance to lysis by the T-cell clones. Overall, the results indicate that these T-cell clones show specificity for AuTu but also independently recognize a limited number of allogeneic tumor targets and lyse K562 targets. The mechanisms involved in the recognition by the T-cell clones of autologous, allogeneic, and K562 tumor targets appeared to be distinct.
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PMID:Characterization of human autotumor-reactive T-cell clones obtained from tumor-infiltrating lymphocytes in liver metastasis of gastric carcinoma. 171 96

In this study we demonstrate a differential transcription of H-2K and H-2D class-I genes in two different tumor cell clones; one is highly metastatic (IE-7) and the other is not metastatic (IC-9), both derived from the same fibrosarcoma, T-10, induced in an (H-2b x H-2k)F1 mouse. The expression of the two parental H-2K alleles is transcriptionally suppressed in both of these clones. In addition the IC-9 clone does not transcribe also the H-2Dk allele. Our data rule out the possibility that this suppression results from enhanced RNA degradation, impaired polyadenylation, DNA rearrangement, or changes in DNA methylation within these genes. Interferons (IFN) are known to enhance MHC expression by acting on a consensus IFN responsive element present in the promoter region of MHC genes. However, IFN-gamma, which is the most potent IFN in this respect, failed to activate the expression of the silent MHC genes in our cells. This finding may reflect a defect within the promoter region of these genes or changes in their chromatin structure.
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PMID:Differential transcriptional control of the H-2K and H-2D loci of the major histocompatibility complex in fibrosarcoma cells. 172 30

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


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