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)

Enriched human interferon-gamma (HuIFN-gamma) receptor preparations were obtained by affinity chromatography of non-ionic detergent solubilized COLO 205 cell membranes on immobilized recombinant HuIFN-gamma. The active fractions, identified by a competition ELISA, were used as the immunogen in a BALB/c mouse. Fusion of its splenocytes with myeloma cells yielded several hybrids secreting antibodies that inhibit the antiviral activity of HuIFN-gamma; the two most active ones were selected for further characterization. This blocking activity was restricted to both the human species and the gamma type of IFN. Affinity purification of cell membrane extracts on the immobilized monoclonal antibodies resulted in the visualization of a major protein band with an Mr of 90,000, which is in good agreement with the results obtained by other authors [Aguet M. and Merlin G. (1987) J. exp. Med. 165, 988-999; Novick D., Orchansky P., Revel M. and Rubinstein M. (1987) J. biol. Chem. 262, 8483-8487; Sheehan K. C. F., Calderon J. and Schreiber R. D. (1988) J. Immun. 140, 4231-4237].
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PMID:Monoclonal antibodies against the human interferon-gamma receptor(s). 214 91

In a recent report, a construction containing the alpha chain-variable region (V alpha) coding sequence of a cDNA clone derived from a diphtheria toxoid-specific human T cell (P28), fused to a human immunoglobulin kappa light chain constant region (Ck), was used stably to transfect a murine myeloma cell. In the present study, these transfected cells were employed as an immunogen to raise a mAb, termed 1C5V alpha, specific both for the V alpha Ck chimeric protein secreted by the transfectant and the P28 T cell antigen receptor-V alpha region. mAb 1C5V alpha specifically immunoprecipitates the V alpha Ck protein as a family of 32-35 kDa bands present in the 35S-methionine-labeled culture supernatant from the transfected cells. It specifically binds clone P28. Surface molecules recognized by mAb 1C5V alpha are physically linked to the CD3 molecules since cell treatment with either 1C5V alpha or anti-CD3 mAbs caused the simultaneous down-regulation of the CD3/TCR molecular complex. This link is further supported by immunoprecipitation experiments. Thus, both the 1C5V alpha and the anti-CD3 mAbs precipitate the 16-28 kDa CD3 molecules and the disulfide-linked form of P28 TCR from 125I-labeled P28 T cells. Studies performed in order to define whether a stimulus directly acting on the TCR-V alpha region may trigger the intracellular events observed during human T cell activation showed that (a) mAb 1C5V alpha efficiently triggers the phospholipase C transduction pathway revealed by an accelerated phosphoinositides turn-over and an increased production of phosphorylated derivatives of inositol phosphates; (b) mAb 1C5V alpha induces an up-regulation of IL2R mRNA, accompanied by a slight increase of IL2 and IFN alpha mRNA transcripts evidently amplified in the presence of PMA; (c) soluble mAb 1C5V alpha is strongly mitogenic together with PMA. These results provide the first evidence for the structural authenticity of a secreted water-soluble chimeric form of the variable region of a human TCR alpha chain. They further demonstrate that such chimeric proteins may be valuable tool to further dissect the various functional structure of the human TCR.
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PMID:A human TCR-Ig chimeric protein used to generate a TCR alpha chain variable region-specific mAb. 214 29

A 46-year-old man was admitted because of lumbago and numbness of the left leg. Pelvic X-ray showed a large defect in the left sacrum and CT revealed multiple punched-out lesions. Serum IgA was 1,740 mg/dl with a monoclonal component of IgA kappa by serum electroimmunofixation. Bence Jones protein of kappa type was detected in urine. Diagnosis of myeloma was made on the basis of histology of the biopsied sacral tumor. Repeated melphalan/prednisolone intermittent therapy (MP) was done with concomitant administration of natural interferon-alpha (IFN-alpha) 3 X 10(6) U intramuscularly for 67 days. Performance status including gait markedly improved. Normal bone marrow morphology and disappearance of M-protein by electroimmunofixation were achieved after 13 cycles of MP, when pelvic X-ray revealed prominent recalcification. No further treatment was instituted for subsequent 6 months, without any demonstrable M-protein. Complete remission of myeloma is rare with conventional therapies and thus new therapeutic modalities have been waited for. IFN-alpha may promise better responses if appropriately combined with other chemotherapies.
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PMID:[Complete remission in multiple myeloma with natural interferon-alpha (HLBI) and melphalan/prednisolone intermittent therapy]. 221 76

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

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

Although IFN proteins were recognized first for their potent antiviral properties, it has now been established that they may profoundly affect other vital cellular functions. The IFNs are divided into three main classes, alpha, beta, and gamma, and are defined by their differences in amino acid sequences, physicochemical properties, and induction by different agents from different cell types. The inducing agents include viruses, bacteria, bacterial products, polymers, low molecular weight compounds, and antigens or mitogens. Studies on the mechanisms of action of IFNs have mainly been focused on their antiviral actions. However, many of the facts revealed by these studies are equally relevant for understanding other actions of IFN. IFNs are extremely potent, they interact with specific receptors, and they induce the expression of specific genes, the products of which mediate their various actions. There is almost a complete lack of knowledge of what happens between the interaction of IFN with its receptor and induction of new RNA synthesis. However, we are beginning to understand how some of the IFN-inducible enzymes impair viral replication. The discovery of the dsRNA-dependent enzymes has implications beyond the IFN system. It is quite possible that they are used for other physiologic regulatory systems as well. The identities and functions of many other IFN-inducible proteins remain to be elucidated. Principally, IFNs alpha and beta are cytokines in that they may be produced by the cellular components of the immune system and have immunoregulatory effects on the cells of the immune system. These effects include enhancement of surface structures such as histocompatibility antigens, pleiotropic hormone-like effects, and stimulation or inhibition of the activities of a number of different effector cells such as B cells, T cells, macrophages, and natural killing cells. IFN levels may be below detection and yet mediate important biologic functions. Perhaps the most interesting IFN subtype regarding immunoregulation is IFN gamma, which is a product of T lymphocytes. Few drugs have stimulated as much research interest or clinical promise as the IFNs. Clinical trials in patients have shown most promise in coryza, herpes virus infections, papilloma virus tumors, hairy cell leukemia, multiple myeloma, and renal cell carcinoma. IFN gamma employed alone and in combination with IFN alpha may dramatically increase IFN's activity. IFN treatment combined with chemotherapy also may give enhanced antitumor activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interferon review. 243 74

Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.
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PMID:New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells. 246 85

In vitro proliferation (3H-TdR-uptake) and M-protein secretion rate by highly purified myeloma cells from bone marrow aspirates were examined serially to evaluate the progression of multiple myeloma in a patient who was refractory to conventional alkylating agents. Following the administration of IFN-alpha, serum M-protein decreased significantly, with the reduced in vitro spontaneous M-protein secretion rate from the separated myeloma cells. Similarly, when IFN-alpha as low as 10 u/ml was added in vitro, it also suppressed M-protein secretion from myeloma cells of this patient, suggesting that, the observed decrease of serum M-protein was due to diminished M-protein secretion by the myeloma cells themselves, as well as the reduction of the tumor cell burden. On the other hand the in vitro 3H-TdR uptake by the myeloma cells increased markedly with the decrease in the M-protein secretion rate. Five months after the initiation of IFN-alpha treatment, tumor formation at the lumbar vertebrae occurred when serum M-protein level was still low, followed by a bone marrow relapse. These results suggest that serial assessments of proliferation and M-protein secretion potential of myeloma cells in vitro can be helpful in predicting the progression of multiple myeloma.
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PMID:[A case of refractory multiple myeloma demonstrating a relationship between the progression of the disease and in vitro myeloma cells activity]. 261 42

A randomized study comparing melphalan/prednisone (M/P) therapy with MP + natural alpha-IFN in untreated patients with multiple myeloma stages II and III started April 1, 1986. By March 1989, 78 patients were evaluable in the MP group and 80 in the MP/IFN group. 48% of the MP patients achieved a response and 66% in the MP/IFN group (p = 0.04). Stage II patients responded better to MP/IFN (76%) than MP alone (47%) (p = 0.02), while no statistically significant difference was noted for stage III patients. 90% of the IgA myelomas responded to MP/IFN and 52% to MP (p = 0.02). Both for IgG and BJ myelomas the response rates of MP/IFN were higher than of MP, although the differences were not statistically significant. The observation period is still short. There was no difference in total survival between the two treatment groups. However, in patients less than or equal to 65 years a tendency to a longer survival was seen for those receiving the IFN combination (p = 0.12).
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PMID:Induction treatment with alpha-interferon in multiple myeloma: an interim report from MGCS. 269 85

The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M-protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation.
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PMID:Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells. 279 Jan 96


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