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)

The antitumour effect of recombinant human interferon (rh-IFN) alpha-2b was studied in 22 patients with advanced multiple myeloma (MM). Nine of 14 evaluable cases were refractory to cytostatic therapy; five were in relapse. rh-IFN was administered s.c. three times per week, in escalating doses starting with 2 x 10(6) IU m-2 and if possible up to 15 x 10(6) IU m-2. Two patients (one refractory, one relapsing) showed a partial response, defined as a 50% reduction of the serum M-component. Three further patients had a minor, significant but short-lived response. Subjective side-effects grade 1-2 were noted during rh-IFN therapy in all patients. In three cases thrombocytopenia necessitating platelet transfusions occurred. Although a fraction of patients with advanced MM obviously respond to rh-IFN, this type of therapy may be more effective, alone or in addition to chemotherapy, in patients with a low tumour cell burden.
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PMID:Effect of interferon alpha-2b in advanced multiple myeloma. 229 97

In a 59-year-old man with multiple myeloma (kappa-light chain paraproteinaemia) in stage IIIB, bone marrow infiltration with atypical plasma cells was reduced by five cytostatic treatment courses with vincristine, melphalan, cyclophosphamide and prednisone (VMCP protocol), but anaemia requiring blood transfusion persisted (haemoglobin concentration 5.3 g/dl). Even administration of interferon alpha-2b (5 million units s.c. every other day) failed to alter this. Only a combination of interferon and erythropoietin (150 U/kg i.v. every other day) achieved lasting regression of the anaemia (haemoglobin concentration up to 14 g/dl). In four other anaemic patients with multiple myeloma, stage III, treated according to the VMCP protocol but without additional interferon, erythropoietin did not improve erythropoiesis.
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PMID:[Erythropoietin in multiple myeloma]. 237 40

Human macrophages obtained from circulating monocytes matured in vitro by culture for seven days in hydrophobic flexible teflon bags were successfully fused with murine myeloma NS1 cells. Six of 20 clones, selected for their adherence properties, were further studied. All possessed human chromosomes (mean number ranging from 4 to 14 depending on the clones studied), exhibited non-specific esterases (but no peroxidase activity) and expressed CD14 antigen and C3 receptors (but no MAX-1 antigen). Moreover, the hybridomas retained phagocytic activity and high interferon plus lipopolysaccharide-activable cytolytic activity against tumor cells.
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PMID:Establishment and characterization of somatic hybrids between human differentiated macrophages and mouse myeloma NS1 cells. 240 83

Balbc/c mice were immunized with purified recombinant E. coli-derived human gamma-interferon (HuIFN-gamma). Their spleen cells were fused with a mouse myeloma cell line (Sp2/0). Hybridomas producing antibodies reacting with HuIFN-gamma were screened by a soluble-phase radioimmunoassay using pure 125I-labeled cloned IFN-gamma as antigen, and tested for their ability to neutralize the antiviral activity of IFN. Three hybridomas S1-1, S1-2, and S1-3, were cloned and subcloned and remained stable. Although the antibodies produced by clones S1-1 and S1-2 were both able to neutralize specifically the antiviral activity of natural and recombinant HuIFN-gamma, they appeared to recognize different epitopes on the HuIFN-gamma molecule. The antibodies produced by the S1-3 clone failed to neutralize the antiviral activity of either interferon. The antibodies from all three clones were characterized as IgG1 subclass. Their affinity constants were determined from competitive inhibition curves and ranged from 1 to 4.3 X 10(8) M-1.
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PMID:Characterization of antibodies against recombinant HuIFN-gamma produced by hybridoma cells. 241 75

The in vitro effect of IgA on natural killer (NK) activities of human peripheral blood mononuclear cells was investigated. Purified myeloma polymeric IgA2 (pIgA2) and secretory IgA (S-IgA) from human colostrum inhibited NK activity, while myeloma polymeric IgA1 (pIgA1), monomeric IgA1 (mIgA1), IgG, and IgM were ineffective. Inhibition was proportional to the concentration of pIgA2 (0.125-1 mg/ml) and was observed after as little as 1 hr of incubation at various effector to K562 target cell ratios. pIgA2 and S-IgA also inhibited NK activity of NK cell-enriched lymphoid cells and gamma-interferon-treated effector cells, but did not interfere with effector-target cell binding. The inhibitory effect was slightly diminished after 24 hr culture in pIgA2-free medium. Inhibition of cytotoxicity was not due to direct toxicity on lymphoid cells by IgA because PBL treated with pokeweed mitogen in the presence of pIgA2 or S-IgA differentiated into immunoglobulin-producing cells. Viability after 24 hr of preculture with pIgA2 and S-IgA was comparable to that of untreated control cells. Morphological examination of effector cells cultured with pIgA2 or S-IgA showed a decrease in the number of granules, and the formation of cytoplasmic vacuoles. These morphological changes appeared to coincide with the depressed cytotoxicity of NK cells. The results demonstrate that purified pIgA2 and S-IgA have significant immunomodulatory effects on human NK activity.
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PMID:Inhibition of natural killer cell activity by IgA. 242 7

Two types of hybridomas secreting monoclonal antibodies (MAB) with neutralizing activity against human interferon-r (HuIFN-r) were obtained by somatic cell hybridization between mouse myeloma P3UI cells and spleen cells from BALB/c mice immunized with purified recombinant HuIFN-r and a conjugate of a synthetic amino-terminal peptide (residues 4-21) of HuIFN-r and bovine thyroglobulin. One of these MAB recognized the amino-terminal region (residues 4-21) of HuIFN-r, and the other recognized some region in the internal part (residues 22-130) of the molecule. These results suggest that another region, in addition to the amino-terminal region, contributed to the biological activity of rHuIFN-r. A combination of one of these MAB and a previously described MAB directed to the carboxyl-terminal region (residues 131-146) of HuIFN-r enables a quantitative and sensitive assay method of biologically active rHuIFN-r.
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PMID:Monoclonal antibodies to human interferon-gamma. II: Antibodies with neutralizing activity. 243 10

Since the late 1970s, 18 clinical studies have been conducted in Japan with various types of human interferon (IFN) for their possible anti-tumor efficacy under the control of the Special Committee for Clinical Application of IFN of the Ministry of Health and Welfare. Objective antitumor effects have been observed in renal cell carcinoma, brain tumor, multiple myeloma, malignant lymphoma, adult T cell leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and by local injections in skin cancer such as malignant melanoma and cutaneous lymphoma. In this paper, updated results of clinical studies of the 3 types of IFNson various malignant tumors in Japan was reviewed, and the potential usefulness of IFNs as the first cytokine introduced into a clinical trial of the treatment of cancer was discussed.
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PMID:[Clinical studies on interferon in cancer therapy in Japan]. 243 62

This article reviews the diagnostic approach to a patient with suspected multiple myeloma. Studies of chemotherapeutic regimens are reviewed and the alternative therapeutic options available at different stages of disease progression are discussed. These include newer modalities of treatment such as hemi-body irradiation as second-line therapy, bone marrow transplantation in plateau-phase and the role of alpha interferon.
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PMID:Management of multiple myeloma. 243 86

A review of the clinical studies in which interferons have been involved has shown that they may have a role in the treatment of multiple myeloma. Twelve studies, each of which involved at least 10 evaluable cases (352 in total) with various dose schedules involving leukocyte, lymphoblastoid and recombinant alpha-IFNs, reported 8-33% objective responses. The response duration was rather short but, in a few cases, it lasted for more than a year. In addition to a decrease in the levels of M-protein and/or urine Bence-Jones protein, a decrease in the number of plasma cells in the bone marrow, disappearance of bone pain, healing of bone lesions, increase of hemoglobin and/or restoration of normal immunoglobulins were observed. Higher doses of recombinant alpha-interferons seemed to exert a stronger effect. No clear difference in response rate was observed between myeloma which had been previously treated and that which was not treated. At least clinically, therefore, there seems to be no cross-resistance between alpha-interferons and conventional anti-tumor drugs. A randomized study comparing low-dose leukocyte interferon with intermittent high-dose melphalan-prednisone has given a lower response rate for interferon. Beta- and gamma-interferons have not yet been extensively studied. They have been used at low doses producing an objective response in 7% of 68 and 2% of 45 evaluable cases, respectively. Since the myelosuppression of interferons is transient and, after discontinuation of interferon therapy, peripheral blood cells usually recover within a week, it may be possible to use interferon in combination with agents that have strong myelosuppressive effects provided there is no synergism.
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PMID:Interferons in the treatment of multiple myeloma. 244 12

Receptors for IgE (Fc epsilon R) on rat bone marrow-derived macrophages (BMDM phi) were demonstrated by a rosette assay employing trinitrophenyl-coated ox erythrocytes (EoTNP) sensitized with mouse IgE anti-dinitrophenyl monoclonal antibody (EoTNP-IgE). Virtually all BMDM phi emerging from bone marrow cells cultured for 1 week in the presence of mouse L929 cell supernatant, with partially purified murine CSF-1 or recombinant murine GM-CSF, formed IgE rosettes. To study the effect of interferons (IFNs) on Fc epsilon R expression, 1-week-old rat BMDM phi were incubated with murine recombinant IFN-gamma, purified IFN-alpha or IFN-beta, and were tested for their capacity to bind and ingest EoTNP sensitized suboptimally with IgE. A marked increase in the percentage of cells forming IgE rosettes or phagocytosing EoTNP-IgE was noted after 8-72 hr incubation of BMDM phi with 0.1-1000 U/ml of IFNs. At similar concentrations IFN-gamma and IFN-beta triggered EoTNP-IgE binding or ingestion more efficiently than IFN-alpha. The enhancing effect was blocked by the respective anti-IFN antibodies, cycloheximide or actinomycin D but not by mitomycin C. The IgE rosette formation and IgE-mediated phagocytosis were dose-dependently inhibited by native rat IgE but not by heat-denaturated IgE myeloma protein IR162 or monomeric rabbit IgG. Our results demonstrate that rat BMDM phi express constitutively Fc epsilon R, and that murine IFNs augment Fc epsilon R-mediated binding and ingestion in a time- and dose-dependent manner. This effect probably reflects an increase in the number of Fc epsilon R per cell, as a result of de novo synthesis of Fc epsilon R.
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PMID:Augmentation of IgE receptor expression and IgE receptor-mediated phagocytosis of rat bone marrow-derived macrophages by murine interferons. 245 Aug 38


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