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)

In a study of 29 patients who were receiving or had received interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, antibodies were detected in 58% (17/29) of patients measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). Only 7/17 patients who were positive for antibody in the ELISA had neutralising antibody to IFN-alpha 2b, measured by virus growth inhibition. These patients comprised six who were receiving IFN-alpha 2b at the time of assessment and one who had finished treatment. Among patients who were receiving the cytokine, four had progressive disease, one was in complete remission and one in partial remission. Neutralising activity was also detected to natural human leucocyte IFN-alpha in the same patients. Two patients who were positive for neutralising antibody remain in remission and are continuing to receive IFN-alpha 2b. These two patients have since lost their neutralising titre. No neutralising antibody to IFN-alpha 2b or natural human leucocyte IFN-alpha was detected in serum from six normal donors. The data suggest that neutralising antibody formation in patients with multiple myeloma is not responsible for relapse in patients receiving IFN-alpha 2b. The transient nature of neutralising antibody production in patients who remain in remission suggests that this response to IFN-alpha 2b is not associated with memory B cells.
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PMID:Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b. 791 11

Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.
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PMID:Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells. 791 64

Cytokines play an essential role in normal and malignant B-cell proliferation and isotype-switching. Therefore we determined serum levels of different B-cell activating cytokines including IFN gamma, IL-4 and IL-10, IgG subclasses, further immunoglobulins and the soluble B-cell activation marker sCD23 in 68 patients with recently diagnosed and previously untreated IgG myelomas in comparison with age- and sex-matched healthy controls. Our results demonstrated that 16% of the myeloma patients had elevated IL-10 levels up to 1000 pg/ml and 8% showed increased IFN gamma serum concentrations. By contrast, only 7% of the controls showed detectable IL-10 levels and 3% had measurable IFN gamma levels. While in men 67% of the paraproteins were of the kappa light chain type, we found an equal occurrence of kappa and lambda light chains in women. In addition, the distribution of IgG subclasses differed in men and women. In comparison with the controls, no alteration of sCD23 was detected in myeloma patients. We found an apparent correlation of elevated IL-10 levels and the IgG1 subclass.
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PMID:[Cytokines, immunoglobulins, and IgG subclasses in patients with IgG plasmacytomas]. 792 79

IL-6 is an autocrine growth factor for U266 myeloma cells and their growth is inhibited by IFN-alpha or IL-6 mAb. We asked, therefore, whether IFN-alpha-induced growth inhibition involved IL-6. IFN-alpha and mAb against IL-6, the IL-6R alpha-(gp80) or beta-chain (gp130) potently inhibited U266 cells. Remarkably, this effect occurred despite IFN-alpha-augmented secretion of endogenous IL-6. However, examining the IL-6R revealed that IFN-alpha drastically curtailed expression of the IL-6R alpha- and beta-chain. This effect occurred on two different levels (protein and mRNA) and by two different mechanisms (directly and indirectly through IL-6). First, IFN-alpha, but not IL-6, greatly decreased gp80 and, to a lesser extent, gp130 mRNA levels which resulted in a loss of IL-6 binding sites. Second, IFN-alpha-induced IL-6 predominantly down-regulated membrane-bound gp130. IFN-alpha-mediated decrease of gp80 levels was not detected on IL-6-independent myeloma (RPMI 8226) or myeloid cells (U937). We conclude that IFN-alpha inhibited IL-6-dependent myeloma cell growth by depriving U266 cells of an essential component of their autocrine growth loop, a functional IL-6R.
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PMID:Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6-dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha- and beta-chains. 798 87

Interferon-alfa (IFN-alpha) has been evaluated in non-Hodgkin's lymphoma and multiple myeloma. The preclinical evidence that IFN-alpha has antitumor activity against non-Hodgkin's lymphoma includes genetic deficits in IFN-alpha production in patients with non-Hodgkin's lymphoma, direct antiproliferative effects of IFN-alpha in stem cell assays, and beneficial effects of combined IFN-alpha and chemotherapy in experimental models. Interferon-alfa was active in phase I and II studies of patients receiving prior chemotherapy for non-Hodgkin's lymphoma, particularly those with low- to intermediate-grade lymphoma. The results of randomized studies suggest that adding IFN-alpha to chemotherapy as either induction or maintenance therapy may improve the outcome in patients with previously untreated non-Hodgkin's lymphoma. Interferon-alfa also appears to have activity as a single agent in patients with multiple myeloma, and eventually may have a role as maintenance therapy in patients with multiple myeloma. Collectively, these studies reveal a trend toward using IFN-alpha in patients with smaller hematologic tumor burden instead of reserving it as a last-resort measure.
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PMID:Innovative treatment strategies for non-Hodgkin's lymphoma and multiple myeloma. 799 95

Interleukin-6 (IL-6) mediates pleiotropic functions through specific receptors (IL-6R) composed of an 80-kDa binding protein, associated with a non-ligand binding protein (gp130) which transduces the signal. Because IL-6 is the major tumor growth factor in multiple myeloma, we investigated the regulation of IL-6R in two human multiple myeloma cell lines. Binding experiments with 125I-labeled IL-6 showed that IL-6R were expressed at a high density on RPMI-8226 cells (15 000 receptors/cell), but no specific binding was detected on XG-1 cells, whose growth depends on the presence of exogenous IL-6. However, when IL-6 was removed from the culture medium, high-affinity IL-6R appeared on the surface of XG-1 cells (5300 sites/cell). Treatment of RPMI-8226 cells with IL-6 reduced the number of IL-6R without changing their affinity. This reduction was dose dependent and was not affected by acid treatment which dissociates ligand-receptor complexes. Cross-linking experiments showed that the formation of one IL-6/receptor complex of 160 kDa markedly decreased upon IL-6 treatment, while the other complex of 190 kDa became undetectable. These data provide evidence for ligand-induced down-regulation of membrane IL-6R expression in myeloma cells. Treatment of RPMI-8226 cells with interferon-alpha (IFN-alpha), which inhibits the growth of these cells, stimulated IL-6R expression and increased the formation of the 160-kDa IL-6/receptor complex. This stimulation was specific for IFN-alpha, since IFN-gamma reduced the number of IL-6R. These data indicate that, in myeloma cells, IL-6R are differentially regulated by IL-6 and IFN-alpha.
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PMID:Differential regulation of interleukin-6 receptors by interleukin-6 and interferons in multiple myeloma cell lines. 802 May 47

The mts1 gene, encoding small Ca(2+)-binding protein of the S100-family, is considered as a gene whose activity correlates with the manifestation of a metastatic phenotype of tumor cells. It was shown before that the mts1 is expressed not only in metastatic tumor cells but also in some normal tissues, namely in so-called "lymphoid" organs: spleen, thymus, bone marrow. In this work we analyzed in more detail the expression of mts1 in human and mouse hematopoietic cells and cell lines. A high level of mts1 RNA was observed in T-lymphocytes, neutrophils, monocytes/macrophages and in corresponding cell lines. Controversially, the mts1 gene was silent in B-lymphocytes as well as in myeloma and erythroleukemia cell lines. The possibility of modulating the mts1 gene expression by the action of different agents was demonstrated. Mitogens, such as lipopolysaccharides (LPS), interferon (IFN gamma), and concanavalin A (Con A), modulate the level of the mts1 gene expression in hematopoietic cells differently. Calcium ionophore, A23187, can also be regarded as a modulator of the mts1 gene expression, since its addition to the cells results in a substantial decrease of the mts1 RNA level. It was shown that the mts1 RNA's half-life is relatively long, more than 24 h. We therefore believe that calcium ionophore can activate some ribonucleases which degrade the mts1 RNA. Cycloheximide prevents the effect of A23187 and stabilizes the mts1 RNA, probably by blocking the synthesis of these nucleases. Thus, the obtained data indicate that the agents which are capable of changing the physiological status of the cells also modulate the mts1 gene expression.
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PMID:Modulation of mts1 expression in mouse and human normal and tumor cells. 805 72

Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy. The protocol was generally well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment-related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN-alpha 2b in refractory myeloma.
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PMID:Recombinant interferon-alpha 2b and high dose methyl prednisolone in relapsed and resistant multiple myeloma. 814 32

A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.
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PMID:[Aggressive myeloma with subcutaneous tumor and pericardial involvement]. 815 51

Therapeutic use of interferon-alpha (IFN-alpha) has been associated with the development of a variety of autoimmune disorders. We describe a patient who received chronic treatment with IFN-alpha following autologous bone marrow transplantation for multiple myeloma. The patient developed an antibody inhibitor directed against factor VIII coagulant protein (FVIIIC) leading to a fatal hemorrhagic diathesis. The association between IFN-alpha therapy and autoimmune complications deserves wider recognition and further study.
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PMID:Acquired factor VIII inhibitor associated with chronic interferon-alpha therapy. 818 49


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