Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 47-year-old male case of IgG-kappa type multiple myeloma was treated with VMCP and recombinant human alpha-interferon (IFN-alpha 2a). The direct Coombs test was positive before treatment. Hemolytic anemia associated with massive hematuria was observed during the administration of 9 million IU IFN-alpha 2a per day for 2 weeks. The hemolytic symptoms rapidly improved after withdrawal of IFN-alpha 2a. This clinical course suggests that IFN-alpha as an immunomodulator was responsible for the progression of autoimmune hemolytic anemia in a case of multiple myeloma.
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PMID:[Autoimmune hemolytic anemia induced by alpha-interferon therapy in a case of IgG-kappa type multiple myeloma]. 143 29

Three efficient mouse interferon gamma (MoIFN gamma) inhibitors were constructed, which consist of the MoIFN gamma receptor (MoIFN gamma R) extracellular portion and constant domains of immunoglobulin (Ig) molecules. These are: 1) the constant domain of the mouse kappa chain, 2) the hinge region and the constant domains 2 and 3 of the mouse gamma 2a chain, and 3) the hinge region and the constant domains 2 and 3 of the human gamma 3 chain. The hybrid molecules were expressed in the mouse myeloma cell line J558L and recovered from the supernatants of cell cultures in one purification step. The proteins MoIFN gamma R-M gamma 2a and MoIFN gamma R-H gamma 3 form homodimers, whereas MoIFN gamma R-M kappa is a monomer. All three constructs inhibit the binding of radiolabeled MoIFN gamma to its receptor on L1210 cells. They are biologically active in vitro, neutralizing the action of MoIFN gamma in an antiviral activity assay. The fusions of Ig regions to the soluble MoIFN gamma R do not decrease the affinity of the binding site for the ligand. MoIFN gamma R-M kappa has about the same affinity as the soluble MoIFN gamma R and the cell surface receptor of L1210 cells in situ, which are also monomers, whereas the dimers MoIFN gamma R-M gamma 2a and MoIFN gamma R-H gamma 3 display a 5-10-fold higher affinity for MoIFN gamma than the monomeric molecules. This is best documented in the efficacy of the inhibitors to antagonize the antiviral activity of MoIFN gamma, as the dimeric constructs are about 10 times more active than MoIFN gamma R-M kappa and the soluble MoIFN gamma R. The hybrid constructs can be used as high efficiency MoIFN gamma inhibitors in mouse models of several pathological states in humans, where IFN gamma is thought to play a disease-promoting role.
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PMID:Construction, purification, and characterization of new interferon gamma (IFN gamma) inhibitor proteins. Three IFN gamma receptor-immunoglobulin hybrid molecules. 153 30

In multiple myeloma (MM), an overproduction of IL-6, indicated by increased plasma C-reactive protein levels, is found in 37% of MM patients at diagnosis and is associated with disease aggressiveness, myeloma-cell proliferation, and poor prognosis. IL-6 is produced by the tumoral environment mainly and not by myeloma cells themselves. IL-6 is a major growth factor for malignant plasmablastic cells in vitro, and it is possible to reproducibly obtain IL-6-dependent myeloma-cell lines. Moreover, anti-IL-6 therapies in patients with terminal disease block myeloma-cell proliferation in vivo. The myeloma-cell growth factor activity of IL-6 is probably the consequence of IL-6 being a growth factor for normal plasmablastic cells. Hematopoietic cytokines (GM-CSF, IL-3, IL-5, G-CSF) synergize with IL-6 to support myeloma-cell proliferation. IFN-alpha and TNF induce an autocrine production of IL-6 in myeloma-cell lines and make possible the autonomous growth of these cell lines. On the contrary, IFN-gamma completely inhibits the IL-6-mediated myeloma-cell proliferation. The identification of some major cytokines involved in the control of the myeloma clone has immediate therapeutic implications, because some of these cytokines are, or might be, used in the treatment of patients with MM.
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PMID:Cytokine network in human multiple myeloma. 158 74

The data provided in the medical literature suggest that alpha-IFN is a useful agent in the management of myelomatosis. In particular, its combination with conventional induction therapies of previously untreated MM patients may improve the overall response rate and probably increase the number of complete responders. On the other hand, even though alpha-IFN alone, in some patients with previously untreated MM, may induce good objective responses, it certainly remains less effective than conventional chemotherapy. Moreover, in a small proportion of advanced MM patients, alpha-IFN alone has induced objective responses. It is therefore possible that alpha-IFN should be combined with other therapeutic modalities to improve the observed response rate in these patients. Finally, alpha-IFN maintenance treatment seems to be one of the most promising therapies for patients with myelomatosis. However, the achievement of a "true" plateau phase after the induction treatment is certainly necessary to permit alpha-IFN maintenance treatment to prolong the response duration. As for the prolongation of survival duration observed in the Italian study, it requires confirmation by the other ongoing randomized studies. In the future, a better understanding of the mechanisms of action of alpha-IFN, as well as the increasing use of other biologic response modifiers, will improve the therapeutic modalities utilized to treat myelomatosis and therefore lead to better control of this so-far-incurable disease.
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PMID:The role of interferon-alpha in the management of myelomatosis. 158 81

An approach to obtain monoclonal antibodies directed against cell surface proteins induced by interferon has been developed in order to characterize such proteins and determine their role. Hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice immunized with interferon-alpha-treated Daudi cells were screened for the production of antibodies reacting differentially with interferon-alpha-treated and untreated Daudi cells. One such hybridoma, 2D5, produced an antibody reacting with a 28/32 kDa homodimeric protein (p28/32) expressed at the surface of Daudi cells in response to IFN-alpha treatment. IFN-alpha treatment also increased the basal level of p28/32 detected on peripheral blood leukocytes (PBL). 2D5 Antibody was used to probe the expression of p28/32 on different cells and in response to various inducers. It appears that 2D5 reacted in fact with CD69, a marker of leukocyte activation and that, following IFN-alpha treatment, CD69 was not induced on all cultured cell lines tested. Interestingly, IFN-gamma was also able to induce CD69 expression on a restricted number of cell lines but the induction pattern only partially overlapped that of IFN-alpha. As expected, activation of cells with phorbol myristate acetate (PMA) resulted in a notable increase in the level of CD69 on all cell lines considered except for the epithelial and fibroblastic types.
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PMID:CD69 is expressed on Daudi cells in response to interferon-alpha. 161 56

Untreated twenty patients of multiple myeloma were treated with the chemotherapy protocol as follows: Initial induction therapy;MP continuous or MP intermittent----IFN alpha----steroid pulse. Maintenance therapy;alkylating agents which have no cross resistance were used ((V) MP----(MP)----(V) EP----MCNU). Remission rate (CR+PR) after the initial MP therapy was 45%, and that after including IFN alpha and steroid pulse therapy was 50%, Fifty percent survival rate was almost as same as those reported previously (34M). Our protocol presented here was based on the idea that, initially, myeloma cells with proliferative activity could be affected by MP therapy, and subsequent IFN alpha therapy would have effect even on the residual myeloma cells. Serial checks of 3H-TdR uptake of myeloma cells during the therapy supported this idea. During the maintenance therapy, clinical responses to the initial induction therapy were not aggravated in the responded cases when evaluated by the variation of serum M-protein level. We propose that considering from a point of proliferative activity of myeloma cells is important for designing therapeutic protocols for multiple myeloma.
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PMID:[Study on the therapy of multiple myelomas--initial induction therapy (MP, IFN alpha, steroid pulse) and maintenance therapy (VMP, MP continuous, VEP, MCNU)]. 163 17

Several important new agents are effecting the management of non-Hodgkin lymphoma (NHL) and multiple myeloma. The two selected for review in this article include a biologic-response modifier and a new chemotherapeutic agent. The biologic-response modifiers offer entirely new approaches to these diseases. The most extensively tested agent currently has been recombinant alpha-interferon (alpha-IFN). The IFN are active, albeit weak, remission-induction agents for low-grade NHL and some T-cell lymphomas, but they appear to be ineffective as single agents in most intermediate-grade or high-grade NHL and myeloma. However, an emerging pattern in follicular lymphomas and myeloma is that alpha-IFN in combination with chemotherapy may lead to more complete and durable clinical responses and the increased prospect of prolonged disease control. Fludarabine, a new chemotherapeutic agent, is a promising drug with demonstrated activity in low-grade lymphomas that parallels its impressive activity in chronic lymphocytic leukemia.
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PMID:New agents for the treatment of multiple myeloma and non-Hodgkin lymphoma. 163 66

An IgE-binding factor(s) (IgE-BF(s] was partially purified from the supernatant of human HTLV-II carrying T-cell line MO. This IgE-BF(s) was shown to increase the IgE synthesis in the human myeloma cell line U-266, but did not affect its viability or growth. The effect of the IgE-BF(s) was dose-dependent and selective for IgE protein synthesis as beta 2-microglobulin synthesis in the U-266 and the immunoglobulin production in the U-1958 IgG-secreting human myeloma cell line were unaffected. The IgE-BF(s) increased the production of the epsilon heavy chain but not the lambda light chain production. The IgE-BF(s) was distinct from IL-1 beta, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, -beta, -gamma, M-CSF, and fragments of CD23.
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PMID:Enhancement of IgE synthesis in the human myeloma cell line U-266 with an IgE binding factor from a human T-cell line. 174 21

IL-6 is a major tumor growth factor in human multiple myeloma. Myeloma cell lines, which have the same phenotypic characteristics and Ig gene rearrangements as the original fresh myeloma cells and whose growth is strictly dependent on exogenous IL-6 similar to fresh myeloma cells, have been reproducibly established. We show here that IFN-alpha stimulated the growth of five of six of these human myeloma cell lines by inducing an autocrine production of IL-6 in myeloma cells. Indeed, IFN-alpha induced IL-6 mRNA accumulation and IL-6 production in myeloma cells and the IFN-alpha-induced growth of these cells was inhibited by anti-IL-6 mAb. Moreover, IFN-alpha made possible the rapid emergence of autonomously growing myeloma cell sublines, which produced IL-6 as an autocrine growth factor. As IFN-alpha has a potential therapeutical interest for multiple myeloma, the present study opens up new directions for studying its effects on the myeloma clone in vivo.
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PMID:IFN-alpha induces autocrine production of IL-6 in myeloma cell lines. 175 8

A successful induction of remission in two patients with resistant multiple myeloma using a new combination therapy of modified M-2 protocol and interferon-alpha (IFN-alpha) is described. The first case was a 32-year-old man with K type urinary Bence-Jones protein who became resistant after treatment with melphalan and prednisone (MP protocol). IFN-alpha alone had a marginal response. The modified M-2 protocol proved insufficient. Therefore, IFN-alpha was administered in the interval of M-2 protocol. This combination therapy showed remarkable responses. The second case was a 59-year-old woman with advanced IgA myeloma who was treated with M-2 protocol and became resistant. IFN-alpha alone resulted in a slight response. After addition of IFN-alpha to the modified M-2 protocol, a rapid reduction in the level of serum IgA was found and clinical symptoms including bone pain, anaemia and so on were dramatically improved. No infection and/or intolerable side effects were observed in either case. This combination treatment appears worthy to try in cases of resistant or relapsing myeloma patients.
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PMID:Combination therapy of M2-protocol and interferon-alpha as remission induction in refractory multiple myeloma. 181 63


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