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

To study human monocyte functions, we attempted to immortalize human monocytes by producing somatic cell hybrids between such monocytes and the mouse myeloma cell line NSI. In this study we report the successful establishment of eight hybrid cell lines that have been grown in culture for more than a year, and some of them retained part of the human chromosome complement, as well as monocyte markers and activities. Karyotype analysis of these hybrid lines revealed that cells of seven out of eight of the lines contained one to 16 human chromosomes and in four of them, more than nine human chromosomes were observed. Several of the cell lines expressed monocytic markers and functions. Thus, in two of the hybrid lines nonspecific esterase could be demonstrated in 10 to 29% of the cells, and Fc receptors were demonstrated in three of the hybrid cell lines. Significant levels of human ferritin were detected in one of the lines, and two other cell lines secreted interleukin 1-like substance into the culture medium. These results encourage us to use human-mouse somatic cell hybridization as an approach for the establishment of human monocyte cell lines, which will preserve their functions and produce monocyte-derived factors.
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PMID:Establishment of cell lines from somatic cell hybrids between human monocytes and mouse myeloma cells. 660 77

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89

The etiology and pathophysiology of bone lesions in multiple myeloma (MM) and the new treatment for bone lesions in MM are mentioned in this report. The osteoclastic activating factors (OAF) include lymphotoxin (TNF-beta), interleukin 1, tumor necrosis factor (TNF-alpha) and several other cytokines. MM patients with multiple bone lesions have low bone density and low serum 1,25-hydroxyvitamin D level. The measurement of bone mineral density using dual-energy X-ray absorptiometry is useful to evaluate the bone lesions in MM. New diphosphates, which strongly inhibit the activity of osteoclasts, are now expected to be effective in the treatment of bone lesions in MM.
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PMID:[Bone lesions in multiple myeloma]. 769 4

The authors review contemporary findings on the role of different components of the cytokine network from the aspect of development, prognosis and treatment of multiple myeloma. Greatest attention was devoted to the main growth factor of myeloma elements IL-6, but also to the real or so far sparsely elucidated role of other cytokines (IL-1, IL-2, GM-CSF, G-CSF, IL-3, IL-4, IL-5, IL-10, TNF, interferon alpha and gamma) under conditions in vitro and in vivo. For completeness sake the authors did not omit the problem of the soluble receptor of IL-2 and the role of TNF, TNF beta and in particular IL-1 beta in the pathogenesis of osteolytic lesions and the potential therapeutic role of antibodies against IL-6 (anti IL-6 mab) and interferon alpha and gamma.
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PMID:[The cytokine network in multiple myeloma]. 794 39

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

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 uniformly fatal plasma cell malignancy, multiple myeloma (MM), currently represents 10-15% of hematologic neoplasms in the USA and has been steadily increasing in incidence for several decades. Therapeutic alternatives have lagged significantly behind insights into the biology and pathogenesis of this entity. Traditionally felt to be a neoplasm of fully differentiated plasma cells, evidence has been mounting that the self renewing population consist of cells derived from a much earlier compartment; perhaps prior to B-cell lineage commitment or even at the level of an earlier 'stem cell'. Bcl-2 protein overexpression has been almost uniformly seen in both clinical myeloma specimens as well as in myeloma cell lines. The failure to consistently identify the t(14;18) translocation, normally found in follicular lymphomas and characteristically associated with overexpression of bcl-2, implies a unique mechanism in MM. A number of cytokines, including TNF alpha, IL-1 and IL-6 have been found to play a central role not only in the biology of the malignant clone but also in the bony and other systemic manifestations of this disease. Since both IL-6 and bcl-2 protein have been shown to prevent programmed cell death, this may be the unifying event in MM. Standard therapy for MM has been an alkylating agent and corticosteroid. Combination chemotherapy provides more prompt palliation but no clear survival advantage. In advanced stages, adriamycin may offer some survival advantage. High dose chemotherapy with or without stem cell support offers a potentially curative therapeutic approach. New interventions directed at the complex cytokine networks pertinent to the pathogenesis of MM are an exciting new area of investigation. Identification of new prognostic parameters as well as new active agents remains the central theme in clinical myeloma research.
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PMID:Biology and treatment of multiple myeloma. 846 29

By analogy with the model of pristane-induced mouse plasmacytomas, we have wondered about the putative role of prostaglandin E2 (PGE2) in the human multiple myeloma (MM) cytokine network, involving interleukin 6 (IL-6) and interleukin 1 (IL-1) as essential myeloma cell growth factors and inducing cofactors respectively. We show that PGE2 is produced in short-term cultures of bone marrow cells of patients with MM, concomitantly with both IL-6 and IL-1. Indomethacin, a potent inhibitor of cyclo-oxygenase and of PGE2 synthesis, significantly inhibits IL-6 production (but not IL-1 production) by 35% to 90% depending on the different MM patients studied and concurrently to that of PGE2. Exogenous PGE2 reverses this inhibition or even stimulates IL-6 production. An IL-1 receptor antagonist (IL-1RA) also significantly inhibits PGE2, IL-6 production and myeloma cell growth. The inhibition of IL-6 production is reversed by adding exogenous PGE2. These results show that induction of IL-6 by IL-1 is related to PGE2 in the bone marrow of patients with MM. Inhibition of PGE2 synthesis (as obtained with indomethacin and the IL-1RA) might be helpful to inhibit myeloma cell proliferation by reducing IL-1-induced endogenous IL-6 production not only in vitro (as demonstrated here) but also in vivo.
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PMID:An interleukin 1 receptor antagonist blocks the IL-1-induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma. 852 May 8

In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate.
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PMID:Erythropoiesis and erythropoietin in multiple myeloma. 852 47

Eight species of murine monoclonal antibodies against human ST2 protein, which is highly similar in protein sequence to the interleukin 1 receptor, were produced. The fusion was carried out between the murine myeloma cell line PAI and murine lymph node or spleen cells from mice immunized with the recombinant ST2 protein produced in Escherichia coli. Characterization of these monoclonal antibodies by immunoblot analysis revealed that they all reacted with recombinant, N-glycosylated ST2 protein that was secreted from COS7 cells transiently transfected with a mammalian expression vector carrying ST2 cDNA. The recombinant N-glycosylated ST2 protein could be immunoprecipitated by 5 out of 6 species of the IgG class monoclonal antibodies. Furthermore, these antibodies were also able to detect, by immunofluorescence, the membrane-bound chimeric molecule possessing an extracellular portion of human ST2 and a transmembrane and cytoplasmic portion of murine receptor type ST2L expressed on COS7 cells, indicating that these monoclonal antibodies were useful for detecting the natural membrane-bound ST2 in human cells. Combining immunoprecipitation and immunofluorescence with the aid of these monoclonal antibodies, together with the reverse transcriptase-polymerase chain reaction method, the human leukemic cell line UT-7 was demonstrated to express human ST2 mRNA and protein. The identification of the ST2 gene product in UT-7 cells may help investigators elucidate the function of the human ST2 gene.
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PMID:Studies on natural ST2 gene products in the human leukemic cell line UT-7 using monoclonal antihuman ST2 antibodies. 857 90


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