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)

Monocyte chemoattractant protein-1 (MCP-1) belongs to the newly recognized "chemokine" superfamily of activation-inducible cytokines. We report here that MCP-1 gene-transferred mouse myeloma cells modulate tumor necrosis in myeloma-bearing nude mice. We established an MCP-1-producing myeloma cell line (X63-MCP-1) by transfection with human MCP-1 cDNA as well as interleukin-8-producing X63 cells (X63 IL-8). Each cell line showed the same growth characteristics in vitro, and 1 x 10(7) cells per mouse were injected into the peritoneal cavity resulting in the formation of tumors. Hematologic studies, including peripheral white blood cell counts and differentiation, showed no differences among the groups. They formed tumors in the same manner, which we observed from weeks 2.5 to 9. MCP-1 mice showed more tumor necrosis and infiltration of the macrophages into the tissue surrounding the tumor. In situ hybridization, using a partial cDNA as a probe, showed that macrophages contained MCP-1 mRNA. Bone marrow cell colony-forming assay showed a greater number of both granulocyte and macrophage colonies in MCP-1 mouse femur than in those of controls or interleukin-8 mice. MCP-1 has no direct stimulatory activity on stem cells, but longer exposure to MCP-1 in vivo might stimulate both granulocyte and macrophage progenitors and recruitment of macrophages into tumors, and it might explain the antitumor activity of macrophages in tumor-bearing nude mice.
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PMID:Monocyte chemoattractant protein-1 stimulates tumor necrosis and recruitment of macrophages into tumors in tumor-bearing nude mice: increased granulocyte and macrophage progenitors in murine bone marrow. 763 82

In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.
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PMID:An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines. 766 28

The pleiotropic nature of malignant fibrous histiocytomas (MFH) is manifested as mixed cellular infiltrates consisting of myofibroblasts, histiomonocytes, and neutrophils. We detail in this report the phenotypic characteristics of the human fibrous histiocytoma giant cell tumor (GCT) cell line that establish its mesenchymal origin. The latter is underscored by the ability of GCT cells to express mRNA for transforming growth factor beta (TGF-beta) as well as both A and B chains of platelet-derived growth factor (PDGF). GCT cells also support the binding of CD34+ cells, but less efficiently than do normal marrow stromal cells. Since cytokines elaborated by MFH may mediate in part the recruitment of monocytes and neutrophils into tumor-infiltrated tissues, we have determined the cytokine repertoire of the GCT cell line, already known for its ability to elaborate colony-stimulating factors (CSFs) and interleukin-1 (IL-1). GCT cells express IL-1 alpha, IL-1 beta, IL-6, macrophage colony-stimulating factor (M-CSF or CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-8. No detectable mRNA for IL-3, IL-4, IL-7, and tumor necrosis factor-alpha (TNF-alpha) was detected in GCT cells by polymerase chain reaction (PCR). Expression of cytokine mRNAs was responsive to agents such as dexamethasone (dex), 12-O-tetradecanoyl phorbol 13-acetate (phorbol diester or TPA), and TNF-alpha. Thus, this cell line provides a useful model for understanding the pathobiology of MFH and hematopoietic progenitor interactions with mesenchymal/stromal cells.
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PMID:Phenotypic characterization of the human fibrous histiocytoma giant cell tumor (GCT) cell line and its cytokine repertoire. 768 82

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN-gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL-3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.
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PMID:Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction. 769 Dec 45

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the human T-lymphotropic virus type I pX gene, undifferentiated mammary carcinomas developed predominantly in females starting at about 5 months of age, and there was massive infiltration of granulocytes in the tumor tissue. The incidence of the tumor reached about 40% when the rats were 12 months old. mRNAs of both pX and host genes Gro and MIP-2, which are granulocyte chemoattractants of the interleukin 8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and the antioncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats.
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PMID:Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I. 778 Sep 62

A newly synthesized demethylpodophyllotoxin derivative, 4-O-butanoyl-4'-demethylpodophyllotoxin (BDPT) or BN58705, has recently been shown to exert a potent cytotoxic activity in vitro against a variety of drug-resistant human tumor cell lines. The effect of this agent on effector cells of the immune system, however, has not been examined. The present study investigated the effect of BDPT on the response of activated human peripheral blood derived monocytes (PBM) to secrete cytokines. Activation of PBM overnight with LPS, IFN-gamma, or PMA resulted in secretion into the supernatant of TNF-alpha, IL-1 beta, IL-6, and IL-8 as assessed by ELISA. The addition of BDPT to the stimulated cultures resulted in significant inhibition of TNF-alpha and IL-1 beta secretion, whereas the secretion of IL-6 and IL-8 was not affected. The selective inhibition of TNF-alpha and IL-1 beta secretion by BDPT-treated PBM was observed with all three stimuli tested. The inhibitory effect mediated by BDPT was concentration dependent and was optimal at 6-20 microM. Time kinetic analysis indicated that the inhibition of secretion was rapid and detected as soon as 2 hr following stimulation of the PBM and lasted for as long as 24 hr. A comparison was made between BDPT and pentoxyfilline, a xanthine-derived phosphodisterase inhibitor that was reported to inhibit TNF-alpha and IL-1 beta secretion by PBM. Both BDPT and PTX showed similar time kinetics and patterns of inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by a new synthetic demethylpodophyllotoxin derivative. 781 57

The present study was aimed at characterizing the effects of in vitro exposure to GM-CSF on blood monocytes and tumor-associated macrophages (TAM) in human ovarian cancer. Purified populations of TAM from ovarian cancer patients were studied in terms of expression of surface molecules, cytokine production and tumor cytotoxicity after overnight incubation with GM-CSF or IFN gamma and LPS, used as reference activators. GM-CSF augmented the surface expression of ICAM-I and CD18 in TAM and in blood monocytes. Stimulation was more prominent in monocytes than in TAM, which showed higher baseline expression of this adhesion molecule. ICAM-3 was not influenced by GM-CSF or by IFN gamma/LPS. GM-CSF-augmented ICAM-I expression was associated with higher levels of mRNA transcripts. The protein synthesis inhibitor cycloheximide super-induced basal and GM-CSF-induced ICAM-I transcripts, thus excluding a role for secondary polypeptide mediators. In the absence of stimuli, TAM produced higher levels, compared to monocytes, of IL-6 and IL-8 but not of IL-1 and TNF. GM-CSF augmented the production of IL-6 and IL-8 (but not that of IL-1 and TNF) in TAM, whereas it had little effect on blood monocyte. Tumoricidal activity was tested against two ovarian tumor cell lines (OVCAR3 and SW626). GM-CSF more prominently augmented monocyte cytotoxicity, while only 2 of 6 TAM preparations were stimulated by GM-CSF. These results suggest that GM-CSF selectively regulates the function of blood monocytes and TAM, the effect of this cytokine varying with the parameter and cell population examined. These data provide a rational and biological endpoint for further studies with GM-CSF as an activator of mononuclear phagocyte function in ovarian cancer.
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PMID:Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression of adhesion molecules and production of cytokines in blood monocytes and ovarian cancer-associated macrophages. 782 34

A replication-defective recombinant retrovirus containing the human papilloma virus E6/E7 genes (LXSN-16 E6E7) was used to immortalize stromal cells from human marrow. The E6/E7 gene products interfere with the function of tumor-suppressor proteins p53 and Rb, respectively, thereby preventing cell cycle arrest without causing significant transformation. Twenty-seven immortalized clones designated HS-1 to HS-27 were isolated, four of which are characterized in this report. Two cell lines, HS-5 and HS-21, appear to be fibroblastoid and secrete significant levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (M-CSF), Kit ligand (KL), macrophage-inhibitory protein-1 alpha, interleukin-6 (IL-6), IL-8, and IL-11. However, only HS-5 supports proliferation of hematopoietic progenitor cells when cocultured in serum-deprived media with no exogenous factors. Conditioned media (CM) from HS-5 promotes growth of myeloid colonies to significantly greater extent than a cocktail of recombinant factors containing 10 ng/mL of IL-1, IL-3, IL-6, G-CSF, GM-CSF, and KL and 3 U of erythropoietin (Epo). Two additional clones, HS-23 and HS-27, resemble "blanket" cells, with an epithelioid morphology, and are much larger, broader, and flatter when compared with HS-5 and HS-21. These lines secrete low levels of growth factors and do not support proliferation of isolated progenitor cells in cocultures. CM from HS-23 and HS-27 also fail to support growth of myeloid colonies. Both HS-23 and HS-27 express relatively high levels of VCAM-1, yet HS-27 is the only line that supports the formation of "cobblestone" areas by isolated CD34+38lo cells. We hypothesize that HS-5, HS-21, HS-23, and HS-27 represent functionally distinct components of the marrow microenvironment.
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PMID:Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. 784 21

We previously found that an increased number of mucosal mast cells accumulated in the tumor site of nasal inverted papilloma as well as in the epithelial layer of the allergic nasal mucosa. However, the mechanism of accumulation of mucosal mast cells has not yet been clarified. The purpose of this study was to evaluate the cytokines produced by inverted papilloma cells, which would be important for the accumulation of mucosal mast cells. We found that the supernatant of the monolayer of cultured inverted papilloma cells contained GM-CSF, IL-6 and IL-8. IL-2, IL-3, IL-4 and IL-5 were not detected. Contrary to the quantities of cytokines detected in the supernatant of cultured allergic nasal epithelial cells, the quantities of IL-6 and IL-8 were greater in the supernatant of cultured inverted papilloma, whereas that of GM-CSF was less. Immunohistochemical study revealed the distribution of cytokines: GM-CSF was detected near the basement membrane of the tumor site, while IL-6 and IL-8 were detected in the superficial layer of nasal inverted papilloma. Interestingly, the tumor site near the basement membrane is also the site of accumulation of mucosal mast cells, suggesting that GM-CSF produced by nasal inverted papilloma cells may be one of the most important factors in the accumulation of mucosal mast cells.
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PMID:[Cytokines of nasal inverted papilloma: quantification and distribution]. 789 76

CD4+ and CD8+ cytotoxic T-cell (CTL) clones, selected for T-cell-receptor (TcR)-dependent lysis of the autologous tumor and isolated from peripheral-blood lymphocytes (PBL) or tumor-infiltrating lymphocytes (TIL) of 3 melanoma patients, were characterized for the pattern of 13 different cytokines released by antibody- or tumor-mediated triggering. Induction or enhancement of cytokine release by anti-CD3 monoclonal antibody (MAb) led to the identification of 2 major sub-sets of CD8+ CTL clones on the basis of production of IL-4. Within the 2 groups of IL-4-producing or non-producing clones, further sub-sets could be identified on the basis of differential production of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF-alpha, TNF beta and IFN-gamma. A similar analysis performed on a panel of CD4+ CTL clones indicated multiple patterns consistent with at least 4 major sub-sets, but further complexity was evident in each sub-set on the basis of differential production of IL-1, IL2, IL-6, IL-10 and G-CSF. The cytokine profile of CD4+ and CD8+ clones, as determined after anti-CD3 stimulation, was different from the pattern seen after co-culture with autologous tumor, since many clones released cytokines such as IL-4, IL-10, IFN-alpha and -gamma, TNF-alpha and GM-CSF after activation with only 1 of the 2 stimuli. These results indicate that CD4+ and CD8+ CTL clones reacting to human melanoma belong to a highly complex repertoire of functional subsets characterized by distinct cytokine profiles. In addition, the cytokine pattern of each T-cell sub-set can be modulated by changing the activation signals delivered to the T cell.
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PMID:Multiple sub-sets of CD4+ and CD8+ cytotoxic T-cell clones directed to autologous human melanoma identified by cytokine profiles. 790 59


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