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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes a method for purification of human myeloma cells. Mononuclear cells from six bone marrow samples and one pleural fluid sample from multiple myeloma patients were incubated with B-B4, a monoclonal antibody that is specific for plasma cells, and the B-B4+ cells were isolated using monosized magnetic beads coated with sheep anti-mouse Ig. With this positive selection method it was possible to achieve primary cultures with more than 99% myeloma cells. The average viability of these cultures was 81%. The B-B4 antibody did not alter proliferation or cytokine production of the myeloma cell lines U-266 and JJN-3. The B-B4+ myeloma cultures did not produce IL-1 and made only small amounts of IL-6 (< 93 pg/ml), whereas the cells remaining after extraction of the B-B4+ cells produced IL-1 (89-350 pg/ml) and large amounts of IL-6 (520-17,000 pg/ml). This indicates that the B-B4+ myeloma cells are not directly responsible for the overproduction of these cytokines in multiple myeloma. This separation technique gave higher purity of myeloma cells than has been previously reported for any negative selection method and is recommended when high culture purity is of critical interest.
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PMID:Lack of IL-1 secretion from human myeloma cells highly purified by immunomagnetic separation. 813 64

Interleukin-6 (IL-6) is a multifunctional cytokine postulated to play a central role as a growth factor for multiple myeloma (MM). We evaluated the spontaneous secretion of IL-6 in supernatants of Ficoll-Hypaque--enriched bone marrow (BM) cultures from 35 patients with MM. The levels of IL-6 were correlated with biological and clinical characteristics of the disease. High levels of IL-6 production defined a subgroup of patients with low tumor burden as determined by lower serum beta 2-microglobulin (B2M) (P = .02) and lower percentage of myeloma cells infiltrating the bone marrow (P = .003), higher synthetic rates of monoclonal protein (P = .006), and low proliferative compartments as measured by the percentage of Ki-67--positive myeloma cells. Patients with high proliferative fractions (Ki-67--positive myeloma cells > 20%) had significantly lower levels of IL-6 when compared with patients with low proliferative fractions (P = .005). Our findings do not support IL-6 as a major growth factor for MM, but demonstrate an association of high levels of IL-6 secretion with low tumor cell burden and low proliferative fraction.
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PMID:High levels of interleukin-6 are associated with low tumor burden and low growth fraction in multiple myeloma. 814 57

Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.
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PMID:Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130. 814 45

While multiple myeloma is an incurable disease for nearly all patients, current chemotherapy and supportive care can result in significant disease control and improved duration of survival and quality of life. With the average age of patients about 70, most of the high-dose curative strategies exclude the bulk of patients affected by the disease. Recent advances in understanding the biology and pathophysiology of myeloma have led to novel therapies aimed at altering drug resistance, improving duration of the plateau phase, interrupting the cytokine growth stimulation, and improving management of common complications including infections, anemia, and bone lesions. These latter approaches are not restricted to younger patients, and early evidence indicates that elderly patients are also likely to benefit.
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PMID:Multiple myeloma in the elderly. 820 Nov 52

In multiple myeloma the duration of plateau is an important clinical and biological determinant of quality of life and survival. During plateau phase, the tumour is in an indolent state, as manifested by a low labelling index of plasma cells and other proliferative markers, e.g. the thymidine kinase level. The mechanism by which plasma cells escape from this indolent phase to a more aggressive phase of this disease is unknown, but a number of possible mechanisms have been postulated. These include loss of immunoregulation, clonal evolution, cytokine dysfunction and oncogene activation or tumour suppressor gene dysfunction. As current chemotherapy protocols do not appear to be able to eradicate the malignant clone, understanding the nature of the indolent phase of the malignant clone and the reasons for its escape from this phase are very important and may provide new options for disease control.
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PMID:Mechanisms of the escape phase of myeloma. 820 6

Cytokines play a key-role in the immune response. The best known of them is interleukin-2 and its specific receptors. Monoclonal antibodies directed against the interleukin-2 receptor have initially enabled this receptor to be characterized; then they served to confirm the major role played by this cytokine in immune responses, where it proved effective in many animal models such as allograft reaction, delayed hypersensitivity reaction and some experimental auto-immune diseases. These results have been confirmed in man, particularly in kidney transplantation (but also in bone marrow transplantation), and they encourage to develop new bioreagents (chimeral antibodies, "humanized" antibodies, fusion proteins). Some of these reagents are now undergoing evaluation in renal transplantation. The principles of these bioreagents, issued from molecular biology, can be applied to other cytokines involved in the immunopathological mechanisms of certain diseases such as, for example, IL-6 and its role in the development of myeloma. Data from immune intervention directed against other cytokines are, for the moment, preliminary, but many potential targets (IL-1, IL-4, TNF alpha, INF gamma) are emerging.
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PMID:[Anti-cytokines and anti-cytokine receptors]. 834 28

The present study evaluated the effect of a novel anti-lipid A monoclonal antibody, termed SdJ5, on the in vitro production of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta by endotoxin- or lipopolysaccharide (LPS)-challenged human peripheral blood mononuclear cells (hPBMC). In addition, the present study determined whether SdJ5 could neutralize the in vivo toxicity of LPS. SdJ5, at a concentration equal to or greater than 3 micrograms/ml, specifically inhibited TNF-alpha and interleukin-1 beta production by hPBMC stimulated with every type of LPS and lipid A assessed. SdJ5 also showed a significantly greater inhibition of cytokine production than a nonrelevant human immunoglobulin M myeloma control. The SdJ5-mediated inhibition of TNF-alpha production was rapid, as the simultaneous addition of the SdJ5 and LPS still resulted in a marked decrease in hPBMC cytokine synthesis. The ability of SdJ5 to neutralize in vivo toxicity was also determined by using LPS from four different strains of gram-negative bacteria. LPS, when preincubated with SdJ5, resulted in a significant decrease in the 24-h mortality rate compared with that for the control. These studies show that the anti-lipid A monoclonal antibody SdJ5 can modulate LPS-induced cytokine production in vitro and increase the survival rate of rats challenged with lethal doses of LPS.
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PMID:Inhibition of lipopolysaccharide-associated endotoxin activities in vitro and in vivo by the human anti-lipid A monoclonal antibody SdJ5-1.17.15. 835 8

To study the effects of cytokines on human IgE antibody forming cells (AFCs), log phase U266 myeloma cells (3 x 10(3)/ml), which secrete immunoglobulin E (IgE), were cultured for 0-24 h with and without cytokine or with or without antibodies against various cytokines. The numbers of IgE AFCs were determined in ELISPOT assay. We found that interleukin-6 (IL-6) suppressed (to 95%) whereas anti-IL-6 increased (to 148%) the numbers of IgE AFCs and that both worked in a dose-dependent fashion. IL-4 and interferon-gamma (IFN-gamma) also suppressed IgE AFC responses in a dose-dependent fashion. However, antibodies to these cytokines had no effect. In contrast, IFN-alpha increased (to fourfold) the numbers of IgE AFCs in a dose-dependent fashion. The data are the first to show a suppressive effect of IL-6 on human IgE responses and may also suggest a role for IL-6 in the treatment of atopic disease.
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PMID:Suppression of human IgE antibody forming cell responses by IL-6. 836 May 95

Communication between cells is essential for a wide variety of biological functions. One way cells interact in immune and hemopoietic systems is through soluble mediators called interleukins or cytokines. Many cytokines and their receptors have been identified and characterized at the molecular level. These studies have observed that most cytokines function in a pleiotropic and redundant manner. Receptor studies have shown that many cytokine receptors consist of two polypeptide chains, a ligand-binding receptor, and a nonbinding signal transducer. This arrangement may explain the pleiotropic and redundant effects of cytokines. For example, leukemia inhibitory factor (LIF) and IL-6 share many biological activities including platelet production, and the receptors of these cytokines utilize gp130 as a common signal transducer. IL-6 is multifunctional and produces both favorable and unfavorable effects on human health. Dysregulation of IL-6 expression is linked to the occurrence of cancer and autoimmune diseases, such as multiple myeloma, Castleman's disease, mesangial proliferative glomerulonephritis, and rheumatoid arthritis. Studies in transgenic mice in which the IL-6 gene was overexpressed have confirmed these pathogenic actions of IL-6. The pathogenesis of these diseases and therapies to treat them are discussed here based on insights derived from cytokine research.
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PMID:[Diseases associated with cytokine dysregulation]. 837 Oct 4

We have recently shown that peripheral blood T cells of multiple myeloma (MM) patients are very susceptible to stimulation of the T-cell receptor/CD3 complex with anti-CD3 monoclonal antibodies (MoAbs). CD3 stimulation is currently under clinical investigation as a nonspecific approach to boost antitumor effector mechanisms. The aim of this study was to determine whether the hyperreactivity of MM T cells to CD3 stimulation could be exploited to generate antitumor activity. Bone marrow mononuclear cells (BMMCs) from 65 MM patients were stimulated with the anti-CD3 MoAb OKT3 and the effect of this stimulation on autologous T cells and plasma cells was evaluated. The number of CD3+ CD25+ cells on day 6 was significantly higher in MM than the controls (30 normal individuals) (P = .001). Kinetic studies showed that 3H-thymidine incorporation peaked on day 3 and that the T-cell expansion peaked on days 5 and 6. In MM, T-cell activation markedly affected the survival of autologous plasma cells; their number in OKT3-treated cultures was significantly lower than in unstimulated cultures (P < .0001). T-cell activation and plasma cell decrease were not observed when T cells were removed from BMMC preparations. MM produced significantly higher levels of interferon-gamma (P = .005) and tumor necrosis factor-beta (P = .001), but lower levels of tumor necrosis factor-alpha (P < .001) than normal individuals. Interferon-gamma only was partially involved in CD3-induced plasma cell killing. Transwell cultures showed that the main mechanism by which CD3+ CD25+ cells affected plasma cells was direct cell-to-cell contact rather than cytokines. In conclusion, T cells in MM BMMCs possess distinct features in terms of susceptibility to CD3 stimulation and cytokine production compared with normal bone marrow T cells that can be exploited to generate antiplasma cell activity.
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PMID:Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells. 840 Feb 33


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