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)

Human serum amyloid P-component (SAP) and C-reactive protein (CRP) are structurally similar pentraxins composed of five identical subunits in a disc-like configuration and display Ca(2+)-dependent binding reactivity to a variety of unrelated ligands. CRP is generally classified and defined as a phosphocholine (PC)-binding protein, whereas SAP is identified as a polysaccharide-binding protein. We examined the PC-binding activity of human SAP and compared it to human CRP since many of the biological activities of CRP are triggered upon PC-binding. SAP was able to bind to immobilize PC in a saturable, Ca(2+)-dependent manner but with lower avidity than CRP in direct competitive binding assays. The affinity of the binding of SAP to soluble [14C]PC was slightly lower than the affinity of CRP; however, the valence of SAP was only one PC-binding site/pentraxin or 2/protein vs 5 such sites per CRP molecule. Both SAP and CRP displayed a similar binding preference for PC vs phosphoethanolamine (PE). Two monoclonal antibodies (mAb) generated against the PC-binding site of SAP also reacted with the PC-binding site of CRP and inhibited PC-binding by both pentraxins. A mAb specific for the PC-binding site on CRP also inhibited SAP binding to PC. SAP was also recognized by two anti-idiotypic mAb that shared reactivity with the TEPC-15 PC-binding myeloma protein and the PC-binding site of CRP. Both pentraxins could be isolated from human serum by affinity chromatography on either PC- or PE-substituted agarose beads. The findings indicate that SAP is also a PC-binding protein.
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PMID:Binding of human serum amyloid P-component to phosphocholine. 797 74

Serum levels of various immunochemical markers of clinical interest, as interleukin-6 (IL-6), C-reactive protein (CRP) and beta 2-microglobulin (beta 2M), were measured in sera from 98 subjects affected with monoclonal gammopathy of undetermined significance (MGUS; 80% of which bearing cancer too) and from 39 patients with multiple myeloma (MM). In addition, the ratio between serum IgG/IgA amounts (GAR) was also calculated in monoclonal gammopathies of IgG type. Consistent with our previous investigations, we found that tumor presence significantly influenced the serum levels of the various markers (except GAR) in MGUS patients; in fact, only when comparing MGUS without tumor and MM patients, was a clear difference observed for all markers considered. The data presented discourage the use of IL-6, CRP and beta 2M as discriminant indices between MGUS and MM patients, unless a careful selection of MGUS subjects is performed. Further investigations on these potential markers are therefore needed for a more rational clinical application.
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PMID:Selection of patients with monoclonal gammopathy of undetermined significance is mandatory for a reliable use of interleukin-6 and other nonspecific multiple myeloma serum markers. 798 75

The immunological phenotype of bone marrow myeloma cells and peripheral blood lymphocytes was evaluated in 38 untreated myeloma patients. A striking increase of monotypic cells expressing the same light chain as the M component was observed in bone marrow from 18/38 (47%) patients. A two-colour analysis clarified that the majority of myeloma cells co-expressed plasma cell and B lymphocyte markers (cyIg, CD38, CD56 and sIg), and were regarded as early-plasma cells (early-PC). In the remaining patients, myeloma cells expressed plasma cell markers only (late-PC). Phenotype corresponded to a distinct morphological pattern: early-PC showed a lympho-plasmocytoid feature with significantly lower diameters than late-PC (12.1 v 14.8 microns, P < 0.007). Moreover, the plasma cell labelling index was significantly increased in early-PC patients (1.2 v 0.5%, P < 0.04). In peripheral blood from patients with early-PC, monotypic cells co-expressing sIg and CD38, CD56, but not CD19, were also detected. These data suggest a recirculation of early-PC. Myeloma cells maintained their phenotypic pattern during the course of the disease. This observation suggests that the degree of maturation is an intrinsic characteristic of the myeloma cell population in individual patients. The evaluation of prognostic factors, such as beta 2-microglobulin, C-reactive protein and neopterin, showed a statistically significant increase in the early-PC patients, suggesting a poor outcome. In conclusion, myeloma cell phenotype allows identification of a myeloma variant with aggressive biological and clinical characteristics.
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PMID:Multiple myeloma: 'early' plasma cell phenotype identifies patients with aggressive biological and clinical characteristics. 813 73

Patients affected with multiple myeloma constitute an heterogeneous population with very different clinical patterns, varying from asymptomatic to very compromised patients with severe and uncontrolled disease. Most common clinical and biological staging systems have been in use for many years. Recently new prognostic factors have been identified; among them, serum levels of beta-2 microglobulin, C-reactive protein and interleukin-6 employed with already known parameters have been useful in the new staging system, permitting a more focalized therapy. As today is not yet possible to define the best treatment schedule, as the most common treatments are incapable to eradicate myeloma neoplastic clone even in responsive patients. Nevertheless extensive use of biologic response modifiers in the last years, as alpha interferon, have added new powerful and hopeful therapeutic tools even if the results need to be confirmed in future trials. It is important to remind the primary role of bone marrow transplantation associated with high dose polychemotherapy even if just a minority of patients is eligible for this therapeutic chance.
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PMID:[Multiple myeloma. Role of prognostic factors and staging in a therapeutic program]. 818 81

Serum bioactive but not immunoreactive interleukin-6 (IL-6), and serum C-reactive protein (CRP), have been reported to be of prognostic significance in multiple myeloma (MM). We measured serum immunoreactive IL-6 by a sensitive enzyme-linked immunosorbent assay in 30 MM patients at diagnosis. In 30% of the patients serum immunoreactive IL-6 exceeded the upper reference limit. The concentrations of CRP and IL-6 showed a linear association. Logarithmically transformed IL-6, CRP and beta 2-microglobulin were significant variables by univariate survival analysis; by multivariate analysis CRP was a slightly stronger prognostic factor than IL-6 and the only one of independent prognostic significance.
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PMID:Serum immunoreactive interleukin-6 and C-reactive protein levels in patients with multiple myeloma at diagnosis. 798 40

A component exhibiting toxicity to B cell hybridoma cells was isolated and purified from fetal calf serum (FCS) by immunoaffinity chromatography using a monoclonal antibody (mAb) which reacted with the high-molecular-weight glycoprotein (6B3.Ag) recognized by a mAb, 6B3, to human large cell lung carcinoma cells (HLC-2). The component (FCS-6B3.Ag) was a high-molecular-weight antigen (approximately 1,000,000), consisting mainly of 76,000 subunits. FCS-6B3.Ag showed the same mobility in the pre-beta globulin region as that of 6B3.Ag on electrophoresis in 1.2% agarose gel. When FCS-6B3.Ag was analyzed by double immunodiffusion, it reacted with anti-6B3.Ag antiserum and the precipitin line fused partially with that formed between 6B3.Ag and anti-6B3.Ag antiserum. FCS-6B3.Ag was found to be toxic to hybridoma cells (anti-6B3.Ag, anti-alpha-fetoprotein, anti-carcinoembryonic antigen or anti-C-reactive protein mAb producing cells) specifically in vitro at 5 micrograms/ml. The antigen also strongly suppressed their growth. The toxic effect of FCS-6B3.Ag appeared immediately after addition, and death of the target cells was complete only after 36-48 h. However, the antigen exhibited only weak suppression of Ig-non-secretory mouse myeloma (P3U1), thymic lymphoma (EL4) of mastocytoma (P815) cell growth. Five lots of FCS contained 2.1 to 4.1 micrograms/ml of FCS-6B3.Ag.
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PMID:Identification and purification of a toxic component to B cell hybridoma cells in fetal calf serum. 820 Aug 50

Interleukin 6 (IL-6) is a major in vitro growth factor for tumoral cells in human multiple myeloma and myeloma cell lines, whose growth is completely dependent on exogenous IL-6, can be reproducibly obtained. IL-6 is overproduced in patients with active myeloma, mainly by the tumoral environment. Injection of anti-IL-6 antibodies to myeloma patients with terminal disease and extramedullary proliferation completely blocked myeloma-cell proliferation in vivo and completely inhibited the C-reactive protein production. Moreover, the serum CRP level is a strong prognostic factor in myeloma, increased serum CRP levels (reflecting an increased IL-6 production) being associated with a poor prognosis. Other cytokines control the IL-6 mediated myeloma cell proliferation. GM-CSF, IL-3 and G-CSF stimulate the IL-6 responsiveness of myeloma cells without affecting the endogenous IL-6 production. Interferon-gamma completely inhibits the IL-6 mediated myeloma-cell proliferation without affecting the endogenous IL-6 production and IFN alpha and TNF alpha stimulate the proliferation of our IL-6 dependent myeloma-cell lines by inducing an autocrine production of IL-6 in these cell lines.
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PMID:[Cytokines and lymphoplasmocytic proliferations: essential role of interleukin 6]. 850 54

The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.
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PMID:Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. 824 20

The median duration of survival for patients with multiple myeloma ranges from 2.5 to 3 years. However, there is considerable variability from one patient to another. Renal function as determined from blood urea nitrogen or serum creatinine values, hemoglobin value, calcium level and performance status have been recognized as prognostic factors for more than 20 years. A study of 107 patients with newly diagnosed multiple myeloma at the Mayo Clinic showed that plasma cell labeling index (PCLI); levels of thymidine kinase, beta 2-microglobulin (beta 2-M), serum albumin, and C-reactive protein; and age were all significant univariate prognostic factors. Only PCLI and beta 2-M levels had independent prognostic significance. Among nine patients younger than 65 years with low PCLI and low beta 2-M levels, eight were alive almost six years after starting chemotherapy. Interleukin 6 (IL-6) is a significant univariate predictor of survival in myeloma. An elevated lactate dehydrogenase content is associated with a poor prognosis. An elevated soluble IL-6 receptor (sIL-6R) level is an independent factor associated with shorter survival. In one study, the addition of sIL-6R to PCLI and beta 2-M to the analysis doubled the proportion of patients identified as high-risk. In this study, the two-year survival was 41% at two years if the PCLI was > or = 2%, beta 2-M was > or = 4.0 micrograms/dl, or sIL-6R was > 300 ng/ml. When none of these three factors were increased, the estimated two-year survival was 83%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic factors in multiple myeloma. 852 May 13

Serum neural cell adhesion molecule (NCAM) has been described as a prognostic marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2-microglobulin (beta 2M) are established prognostic markers in MM. We tested the diagnostic value of these markers in 212 serum samples of patients with paraproteinemia registered prospectively in a population-based registry. Sixty patients had MM and 152 had other monoclonal gammopathies (hematologic diseases [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal gammopathy of undetermined significance [56]). CRP and beta 2M had wide and overlapping ranges in all diagnostic categories. However, serum neural cell adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non-Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM, CRP, beta 2M, paraprotein type and concentration, hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium, lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM, with 89% of cases being correctly classified. Even without bone marrow and x-ray examinations, serum NCAM, in combination with paraprotein type and concentration, can differentiate between MM and nonmyeloma patients.
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PMID:Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes. 855 95


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