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)

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.
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PMID:Multiple myeloma. 208 Oct 91

Administration of recombinant interleukin-6 (IL-6) was found to induce in vivo generation of cytotoxic T lymphocytes (CTL) against syngeneic transplantable erythroleukemia (FBL-3) in lymph node cells and peritoneal exudate cells (PEC) in C57BL/6 mice. Furthermore, 15 out of 16 C57BL/6 mice injected with 5 x 10(6) viable FBL-3 cells survived on day 100 when they were treated with 5 x 10(4) U of recombinant IL-6 three times a day on days 1, 2, 3, 5, 7 and 9 after the inoculation of tumor cells (the cure rate was 94%). Cured mice could reject the tumor cells rapidly after the re-inoculation of a large number of live FBL-3 cells. In contrast, all normal mice died of tumor development by day 10. In these cured mice, FBL-3-specific CD4-8+ CTL cells were found to be generated in PEC, spleen and lymph node cells by either in vivo or in vitro re-stimulation with FBL-3 cells, but lymphokine-activated killer cells never developed. The results suggested that the anti-tumor effect of IL-6 was mediated by in vivo induction of tumor-specific CTL.
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PMID:The in vivo anti-tumor effect of human recombinant interleukin-6. 212 76

IL6-PE40 is a chimeric toxin composed of human interleukin-6 (IL6) linked by a peptide bond to PE40, a form of Pseudomonas exotoxin (PE) devoid of its cell recognition domain. To identify cancer cell lines with high numbers of IL6 receptors and to assess the usefulness of IL6-PE40 as a possible anticancer agent, we evaluated the toxicity of IL6-PE40 on a variety of tumor cell lines and demonstrated that certain human myeloma and hepatoma cell lines were particularly sensitive. IL6 binding to selected hepatoma and myeloma cell lines were determined by using [125I]IL6. IL6 receptor mRNA levels were measured by polymerase chain reactions. When comparisons were made among different hepatoma cell lines, the sensitivity to IL6-PE40 correlated with the number of IL6 receptors. However, the hepatoma line PLC/PRF/5, which contains 2,300 IL6 receptors, was more sensitive to IL6-PE40 (amount of protein required to inhibit protein synthesis by 50% was 5 ng/ml) than both the myeloma cell lines U266 and H929 (for both cell lines, the 50% inhibitory dose was 8 ng/ml), which contain 15,500 and 16,500 IL6 receptors, respectively. RNA analysis confirmed that the sensitivity of these cells to IL6-PE40 and the amount of IL6 receptor RNA detected did not correlate. These data suggest that factors in addition to the number of IL6-binding sites contribute to the sensitivity of cells to IL6-PE40.
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PMID:Cell-specific toxicity of a chimeric protein composed of interleukin-6 and Pseudomonas exotoxin (IL6-PE40) on tumor cells. 216 May 79

The cytokine which is now called interleukin-6 (IL-6) has emerged as a major systemic alarm signal produced by essentially every injured tissue in response to almost every kind of damage. The hallmark of IL-6 gene regulation is its induction in many different tissues by inflammation-associated cytokines, bacterial products, virus infection and by activation of any of the three major signal transduction pathways (diacylglycerol, cAMP and Ca2(+)-activated). Many of these inducers act largely through a 23 base-pair "multi-response element" in the IL-6 promoter. Different tissues secrete multiple post-translationally modified forms of IL-6 (six protein species in the size range 23 to 30 kDa, and additional forms of size greater than or equal to 45 kDa). IL-6 plays a key role in activating a variety of host defence mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiological and immunological status of the host (e.g. the "acute phase" plasma protein response). IL-6 enhances plasma protein gene expression not only in hepatocytes but also in monocytes, fibroblasts and lymphocytes. Elevated levels of IL-6 are observed in body fluids during acute and chronic infections, neoplasia and autoimmune diseases. The nature of the IL-6 receptor in hepatic and non-hepatic cells, the different signal transduction pathways involved in the regulation of particular liver genes by IL-6, the association between IL-6 levels in body fluids and clinical outcome and between IL-6 haplotypes and specific disease states remain to be explored in detail.
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PMID:Interleukin-6: a regulator of plasma protein gene expression in hepatic and non-hepatic tissues. 218 60

The cytokine interleukin-6 (IL-6) has emerged as a major systemic alarm signal which appears to be produced by essentially every injured tissue. Recent evidence points to the skin, particularly the injured skin, as one of the major sites of IL-6 production. The hallmark of IL-6 gene regulation is its induction by inflammation-associated cytokines, bacterial products, virus infection, and activation of any of the three major signal transduction pathways (diacylglycerol-, cAMP-, and Ca(++)-activated). Many of these inducers act largely through a 23-bp "multiple-response element" in the IL-6 promoter. Different cell types, including keratinocytes, secrete multiple post-translationally modified forms of IL-6. This cytokine, in turn, plays a key role in activating a variety of local and systemic host defense mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiologic, and immunologic status of the host (e.g., the "acute phase" plasma protein response; activation of B, T, and NK-cell function). IL-6 enhances the proliferation of human keratinocytes and of many B-cell lines but inhibits that of certain carcinoma cell lines; nevertheless, IL-6 can enhance the motility of these carcinoma cells. Elevated levels of IL-6 are observed in human body fluids during acute and chronic infections, neoplasia, autoimmune diseases, and psoriasis and following third-degree burns. It is likely that IL-6 produced by cellular elements in the skin represents an important means of communication between the external environment and the millieu interieur.
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PMID:Interleukin-6: molecular pathophysiology. 219 Oct 52

Two glioma tumor lines and specimens from five patients with gliomas were analyzed to determine genic expression of four growth factors found in human brain. Messenger RNA encoding for interleukin-1 beta, interleukin-6, and basic fibroblast growth factor was found to be expressed in significant amounts in some of these tumors, while mRNA for interleukin-3 was found in small quantities in only the tumor lines. Multiple species of mRNA for basic fibroblast growth factor were found. Expression of growth factor genes may play a role in the growth of human gliomas.
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PMID:Cytokine gene expression by human gliomas. 219 Dec 39

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytotoxic for certain tumor cells but have a proliferative effect on normal cells. Here we show that interferon-gamma (IFN-gamma) can be cytotoxic for normal cells, in particular mouse embryonic fibroblasts. The cytotoxicity effect is observed with immuno-purified recombinant mouse IFN-gamma (MuIFN-gamma) at concentrations of 1,000 I.U./ml and can be neutralized by anti-MuIFN-gamma monoclonal antibodies. The effect appears 48 h after initial contact with IFN-gamma and is not influenced by infection of the target cells with mengovirus. Although TNF and IL-1 are not toxic for mouse fibroblasts, they can strongly enhance the IFN-gamma-induced cytotoxicity. Interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and interleukin-6 (IL-6) neither are cytotoxic themselves nor have any influence on the IFN-gamma-induced cytotoxicity. The cytotoxicity of IFN-gamma, in contrast to that of TNF is inhibited by actinomycin or cycloheximide. These data suggest that the cytotoxic effect of IFN-gamma requires active cooperation of target cells and that the mechanism of action is different from that of the TNF-induced cytotoxicity.
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PMID:Interferon-gamma is cytotoxic for normal mouse fibroblasts: enhancement by tumor necrosis factor and interleukin 1. 249 77

This review focuses on describing the specific role of interleukin-6 within the network of inflammatory mediators in man. Sites of interleukin-6 synthesis, regulation of its expression, and the biological functions of this molecule are here outlined. The potential role of interleukin-6 as a diagnostic monitor is discussed. Particular attention is paid to experimental evidence that interleukin-6 and its receptor may be involved in the pathogenesis of autocrine tumor growth. A recently proposed therapeutical use of cytotoxic interleukin-6 fusion proteins in order to selectively, destroy certain interleukin-6 receptor bearing tumor cells is discussed in the light of the finding, that not only hepatocytes, but also normal peripheral blood monocytes express the interleukin-6 receptor.
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PMID:Interleukin-6 and its receptor during homeostasis, inflammation, and tumor growth. 250 90

Our study was designed to investigate the production of interleukin-1 (IL-1) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-1 was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line. TAM did not release appreciable levels of IL-1 spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity, blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-1 and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy.
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PMID:IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. 258 59

The cytokine, interleukin-6 (IL-6), has emerged as a likely mediator of many of the systemic alterations observed in patients with cancer (fever, increased erythrocyte sedimentation rate, and alterations in plasma protein composition) and may also mediate local effects such as alteration in proliferation of tumor cells, increased tumor cell motility, and decreased intercellular adhesions between tumor cells. The distribution of IL-6 immunoreactivity in different human tumors was studied. IL-6 immunoreactivity was detected by the avidin-biotin-complex (ABC) procedure using a polyclonal rabbit antiserum raised against an E coli-derived human IL-6 (rIL-6). Preimmune rabbit serum used as a control did not yield specific staining and preadsorption of the IL-6 antiserum with rIL-6 abolished specific staining. Strong-to-moderate IL-6 immunoreactivity was observed in the neoplastic elements present in primary squamous cell carcinomas, in adenocarcinomas of mammary, colonic, ovarian, and endometrial origin, in various adenocarcinomas metastatic to lymph nodes, and in soft tissue tumors including leiomyosarcoma and neurofibrosarcoma. Weak-to-moderate IL-6 immunostaining was observed in Hodgkin's and non-Hodgkin's lymphomas. This study demonstrates that most human tumors stain positively for IL-6, adding weight to the hypothesis that IL-6 is a key cytokine that participates in the host-tumor interaction.
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PMID:Interleukin-6 immunoreactivity in human tumors. 267 20


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