UMLS:C0027651 - FACTA Search

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

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV-positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV-negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV-positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.
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PMID:Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. 842 93

A majority of SJL mice develop spontaneous reticulum cell sarcomas (RCS) at about 1 year of age which can be transplanted into young SJL recipients. Previous studies have shown that RCS tumors are of B cell lineage, and that the development of these lymphomas and their subsequent growth depends upon host-derived T helper cell factors. In vivo treatment of SJL mice with anti-CD4 monoclonal antibody (mAb) prevents the development of the characteristic B lymphomas. Most of the mAb-treated animals were tumor free and had a significantly prolonged life span. However, one such CD4 mAb-treated mouse developed a transplantable IgM+ CD5+ B cell lymphoma (designated NJ101), which has not previously been described in SJL/J mice. NJ101 is clonal on the basis of a discrete non-germ line Ig heavy chain gene rearrangement by Southern blot analysis. Unlike the sIg- CD5- transplantable RCS-X cell line, the IgM+ CD5+ NJ101 lymphoma cells will grow in immuno-compromised hosts, such as irradiated recipients or in recipients treated with CD4 mAb in vivo. The RCS (B cell) lymphoma requires CD4+ T cells for progressive growth, whereas the growth of the CD5+ B lymphoma cells is enhanced by the removal of such cells. Thus, CD5+ B cell clonal development may be aided by the removal of regulatory T cells and/or the malignant CD5+ B cells may produce their own growth factors in an autocrine manner. Examination of IL-10 message by quantitative polymerase chain reaction techniques indicate that the CD5+ B lymphoma cells produce increased levels of IL-10 relative to normal LN cells or purified RCS lymphoma cells. These results suggest that two different types of B cell tumors, both of which can develop in SJL mice, have different growth requirements. Furthermore, treatment to prevent the occurrence of the characteristic RCS malignancy of SJL mice may lead to the development of another form of B cell neoplasia.
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PMID:IL-10 production in a CD5+ B cell lymphoma arising in a CD4 monoclonal antibody-treated SJL mouse. 138 8

We have reported that in irradiated, long-term surviving RFM strain of mice there is enhanced kinetics of tumor development upon challenge with RFM lymphoma cells. We reported that we cloned splenic oncofetal (OFA)-specific, noncytotoxic CD8+ T cells from such mice. These noncytotoxic CD8+ T cell clones secrete a factor upon Ag stimulation that inhibits the ability of OFA-specific RFM cytotoxic T (TC) cell clones from killing 5T RFM lymphoma cells in vitro. These supernatants do not inhibit the tumor cell-induced proliferation of the TC cell clones however. We report here that OFA-stimulated, RFM-noncytotoxic CD8 T cell clone culture supernatants also inhibit IFN-gamma-secretion by stimulated CD4 and CD8 RFM anti-OFA effector T cell clones in a dose-dependent manner. The inhibitor in those culture supernatants acts in neither an Ag-specific nor MHC-restricted manner. We find that the culture supernatants of OFA-stimulated, noncytotoxic CD8 T cell clones contain IL-10, while those from OFA-stimulated, RFM OFA-specific TC cell clones do not. We show that monoclonal anti-IL-10 Ab specifically blocks the inhibition of cytotoxic activity and IFN-gamma secretion by OFA-specific CD8 and CD4 effector T cell clones in a dose-dependent manner in vitro. Incorporation of anti-IL-10 Ab into the cytotoxicity assays of the OFA-specific, noncytotoxic CD8+ T cell clones against 5T tumor cells restores their cytotoxic activity. This may suggest that one way of inducing anergic T cells is by induction of IL-10 secretion.
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PMID:CD8 T cell clones inhibit antitumor T cell function by secreting IL-10. 749 59

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
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PMID:Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. 750 78

Localization of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and of their ligands, lymphocyte function-associated antigen-1 and very late activation antigen-4, was determined in non-small cell lung carcinomas and tumor-free lung. Messenger RNA expression for interleukins (IL) IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma, granulocyte-macrophages colony stimulating factor, and human perforin-1 was assessed by in situ hybridization on the same tissues. Intercellular adhesion molecule-1 was expressed in all blood vessels, whereas only a low number of vessels displayed vascular cell adhesion molecule-1 immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of lymphocyte function-associated antigen-1-positive cells and of a lower number of very late activation antigen-4-positive cells. All squamous cell carcinomas consisted of intercellular adhesion molecule-1-positive neoplastic cells infiltrated by lymphocyte function-associated antigen-1-positive tumor infiltrating lymphomononuclear and CD-la-positive Langerhans cells, whereas only a minor number of adenocarcinomas displayed a consistent number of intercellular adhesion molecule-1-positive neoplastic cells. Tumor infiltrating lymphomononuclear cells showed a wider production of cytokines when compared to bronchus-associated lymphoid tissue of tumor-free lung. Moreover, cells producing interferon-gamma, IL-4, and IL-5 were more numerous in squamous cell carcinomas than in adenocarcinomas. These findings indicate that the lung squamous cell carcinoma might represent a neoplastic microenvironment able to induce activation of tumor infiltrating lymphomononuclear cells more efficiently than the adenocarcinoma.
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PMID:Cytokine production and expression of adhesion molecules and integrins in tumor infiltrating lymphomononuclear cells of non-small cell carcinomas of the lung. 751 25

Interleukin 10 (Il-10) was initially discovered on the basis of its ability to suppress cytokine synthesis. Additionally, it can exert immunosuppressive effects on a variety of cell types. Since patients with malignant gliomas present with a general impairment of the immune system, we sought to investigate if IL-10 is expressed in the glioma tissue. Using RT-PCR, IL-10 mRNA levels were determined in 37 glial tumors of different grades including 2 recurrencies, 3 specimens from normal brain tissue and 3 glioblastoma cell lines. Expression of IL-10 mRNA was demonstrable in all tumors as well as in normal brain. High grade tumors and recurrent cases expressed significantly higher amounts of IL-10 specific mRNA compared to low grade tumors, while 2 out of 3 cell lines showed only weak constitutive expression. We suggest, that IL-10 may contribute to the progression of astrocytomas by allowing the tumor cells to attenuate the T-cell immune response and evade immune detection.
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PMID:[Increased amounts of IL-10 mRNA in anaplastic astrocytomas and glioblastoma multiforme]. 753 12

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.
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PMID:Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis. 753 75

A variety of tumors are potentially immunogenic but do not stimulate an effective antitumor immune response in vivo. Tumors may be capable of delivering antigen-specific signals to T cells, but may not deliver the costimulatory signals necessary for full activation of T cells. In this regard, we recently reported that a human melanoma cell line (sMC) expressing MHC class II, was able to induce clonal anergy in a specific, MHC-restricted CD-4+ T cell clone (sTC3). We used this system to investigate the influence of interleukin (IL)-12 on induction of this T cell unresponsiveness. The presence of 10 to 100 U IL-12 during the induction phase of anergy leads to a primary proliferative response of sTC3, which was significantly higher than that induced by IL-12 alone; however, in the absence of IL-12 no proliferation was seen during the induction of anergy. Subsequent optimal stimulation of IL-12 treated cells, but not of those cultured without IL-12, led to substantial IL-2 production and cell proliferation. This indicates that induction of the unresponsive state could be inhibited by IL-12. In addition, we have recently demonstrated that anergic T cell clones can produce high amounts of IL-10 and that this event was correlated with their impaired ability to produce IL-2. This marked induction of IL-10 can be suppressed if IL-12 is present during initiation of unresponsiveness. However, IL-12 was not able to prime the T cell clone, sTC3, to become resistant against the anergizing stimulus, as this cytokine was only effective when present at the time of anergy induction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of anergy induction in cloned T cells by interleukin 12. 753 8

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.
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PMID:The functional characterization of interleukin-10 receptor expression on human natural killer cells. 754 68

We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon gamma (IFN gamma), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF alpha), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFN gamma (5/8), IL-4 (4/8) or both (3/8), and for TNF alpha (4/7). In contrast, IFN gamma mRNA was detected in only 1/17 and TNF alpha mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
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PMID:Expression of cytokine mRNA in human melanoma tissues. 755 83

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