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)

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.
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PMID:Monoclonal antibodies to human prostate and bladder tumor-associated antigens. 704 15

Currently we are using two different ISO-DALT two-dimensional gel electrophoresis systems, designated MC-Iso 1 and MC-Iso 2, for the analysis of serum and plasma samples. Here we report quality-assurance data for both of these systems. CV values for the slopes of the pH gradient (ISO dimension) are 5.6% of less; CV values for the slopes of the molecular-mass curves (log Mr vs relative mobility in the DALT dimension) are 3.4% or less. We examined the various steps of the analysis in detail for reproducibility and protein loss, using radiolabeled albumin, alpha 2-macroglobulin, and beta 2-microglobulin. Generally, in the first dimension, less protein enters the MC-Iso 2 gels (our routine system in which silver stain is used) than enters the MC-Iso 1 gels (our wide-range system for myeloma serum samples, in which the gel is stained with Coomassie Blue), on the average, 87% as much. The CV at this stage for both systems is 5--8%. During equilibration, considerable amounts of protein are lost (approximately 30% in 10 min) from the ISO gel, and the reproducibility is also decreased. Resolution in the DALT dimension has, in most cases, little or no effect on either recovery or reproducibility. Overall, for most proteins expected to appear in an ISO gel of a given pH range, approximately 50--60% of the starting material may be expected to reside in the sodium dodecyl sulfate slab gel, under our conditions. The two most important variables affecting recovery are the concentration of the NaOH (used as catholyte) and the pH of the starting sample. The overall CV for the process is between 8 and 12%.
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PMID:Reproducibility and quality assurance of two-dimensional gel electrophoresis of serum specimens. 707 81

Serum levels of lactate dehydrogenase (LDG) and beta 2-microglobulin (beta 2-MG) were measured in 164 and 128 patients with multiple myeloma (MM), respectively. High levels of LDG were recordable in 15.4% of patients at diagnosis and 36.8% of terminal stage patients. The frequency of extraosseous foci in untreated patients with high LDG activity made up 36.8%, survival median 19 months. In normal LDG activity the above values were 6.8% and more than 36 months, respectively. The highest LDG level occurred in patients with terminal plasmic cell leukemia. MM with IgD secretion was characterized by a a more frequent rise in LDG concentrations. Normal LDG amounts in active MM were seen in 58 (54.2%) out of 107 patients. beta 2-MG levels exceeded 6 mg/l in 75 of 128 patients with normal creatinine. These patients had a short survival median 24 months. Those patients who had beta 2-MG levels under 6 mg/l have not reached survival median for 36 months of follow-up. The authors hold that beta 2-MG concentrations are of prognostic value in all myeloma secretions and in nonsecretory myeloma as well though their indications are not absolute as 14% had low beta 2-MG levels in high MM activity. Comparative results are presented for 40 high-risk MM patients. Group 1 (20 patients) have received standard chemotherapy. Group 2 (20 patients) have undergone intensive polychemotherapy. Survival median made up 12 and 26 months for group 1 and 2, respectively.
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PMID:[The significance of lactate dehydrogenase and beta 2-microglobulin levels for the assessment of the prognosis and choice of therapy in multiple myeloma]. 748 3

In a group of 111 patients with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients evaluated in different stages of the disease, the author examined the relationship between the interleukin-6 serum level (IL-6), assessed by the method of enzyme immunoanalysis and selected laboratory indicators of the disease. Elevated IL-6 values were recorded in 38% of the patients. In neither of the groups significant relations were found between IL-6 and calcium, urea, creatinine levels, the amount and type of monoclonal immunoglobulin, lacticode dehydrogenase, beta 2-microglobulin, ferritin, IL-2 and its soluble receptor in serum and the incidence of myeloma plasmocytes in bone marrow. In the second (but not in the first) group a significant relationship was recorded between IL-6 levels and the red cell sedimentation rate, the Hb value, the CRP level and serum albumin and the value of thymidinekinase in serum of patients with a value beyond the normal range. From the investigation ensues that examination of IL-6 serum levels in MM contributes so far mainly to improvement of the diagnosis and expedient classification of this disease in clinical practice.
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PMID:[Serum interleukin-6 in multiple myeloma: I. Relation to selected laboratory indicators of disease]. 748 49

Human CD1 genes are a family of five non-polymorphic genes that, although homologous to both class I and II major histocompatibility complex genes, map to chromosome 1. Only three of the antigens, CD1a, -b, and -c, have been clustered with monoclonal antibodies. They are noncovalently associated with beta 2-microglobulin and may function as nonclassical antigen-presenting molecules. Here we analyze their expression in mouse myeloma transfectants and human thymocytes and find mRNA splicing complexity. This manifests itself as incomplete splicing, alternative splicing, utilization of cryptic splice sites, and the generation of alternative reading frames. In the case of CD1A transfectants, we demonstrate that the major protein product is secreted and show by amino acid sequence analysis that this is derived from an unspliced transcript. A second major CD1a component appears to be retained intracellularly. The production of alternatively spliced transcripts in the thymus is not a feature of all CD1 genes. Although in the case of CD1A only the transcript encoding the cell surface CD1a isoform is found, CD1C and -E produce complex intrathymic splicing patterns. The CD1C transcripts predict the expression of a secreted CD1c isoform in the human thymus, which we detect in CD1C transfectant culture supernatants. CD1 gene expression is thus characterized by considerable splicing complexity, and the difference between the splicing patterns found in different environments suggests that this is tissue specific.
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PMID:Alternative splicing generates secretory isoforms of human CD1. 751 59

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.
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PMID:Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. 753 May 7

To assess the efficiency and toxicity of alternating combination chemotherapy plus interferon-alpha-2b (IFN) in the treatment of poor prognosis multiple myeloma, we began a prospective clinical trial. The study involved 103 previously untreated patients with poor prognosis: Stage III, haemoglobin below 8.5 g/dl, beta 2-microglobulin > 5.0 micrograms/ml and multiple lytic lesions. All patients were treated with an alternating combined regimen given monthly for 2 years. After randomization, 52 patients also received IFN at a dosage of 5.0 MU three times weekly during the first year of the therapy. The remaining 51 patients received chemotherapy alone. Compared with patients treated with chemotherapy alone, those treated with chemotherapy plus IFN had a higher overall rate of response: (80% versus 47%), a longer duration of remission (36 months versus 18.5 months) and a higher rate of survival at 5 years (74% versus 39%; P < 0.001). Toxicity was similar in both arms. All patients received the planned dose of IFN. There were no deaths related to treatment. The addition of IFN to a regimen of alternating chemotherapy increased the rate of response, duration of remission and survival in patients with poor prognosis multiple myeloma, without serious side effects.
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PMID:Alternating combination chemotherapy and interferon improves survival in poor prognosis multiple myeloma. 754 73

Thirteen patients with light chain (LC) proteinuria (11 with multiple myeloma and two with monoclonal gammopathy of undetermined significance) were followed up for one to 3.5 (median 2.5) years and studied for urinary excretion of LCs, alpha 1-microglobulin (alpha 1 M), beta 2-microglobulin (beta 2M), albumin, and serum creatinine concentration at intervals of 6 +/- 2 months. At the beginning of the follow-up, urinary alpha 1M excretion correlated with that of beta 2M (r = 0.81, p = 0.0007) and LCs (0.69, p = 0.0084), and with the serum creatinine level (r = 0.56, p = 0.047). During the follow-up period, renal function remained stable in eight patients despite high or fluctuating LC excretion. In seven of them, urinary alpha 1M was repeatedly below 150 mg/24 h and in one it transiently exceeded that level. The remaining five patients had an unstable renal function (deterioration in four, improvement in one) although their urinary LC and albumin excretion during the study period was comparable to those in patients with stable renal function. In the five patients with unstable renal function, high (> 150 mg/24 h) urinary alpha 1M excretion was associated with a rise in the serum creatinine level. alpha 1M excretion was thus found to be a useful indicator of renal damage caused by LCs.
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PMID:Urinary alpha 1- and beta 2-microglobulin in light chain proteinuria. 755 29

We investigated the clinical significance of the serum soluble interleukin-6 receptor (sIL-6R) in 42 patients with plasma cell dyscrasias (27 with multiple myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS), and two with plasma cell leukaemia (PCL)). Serum levels of sIL-6R in normal individuals were 77 +/- 21 ng/ml (mean +/- SD, n = 18); those in patients with MGUS and with MM were elevated (102 +/- 33 ng/ml, mean +/- SD, P < 0.05 and 126 +/- 60 ng/ml, mean +/- SD, P < 0.01, respectively). Significant correlations were not found between the serum levels of sIL-6R and known prognostic factors (C-reactive protein, haemoglobin levels, calcium, creatinine, beta 2-microglobulin, amounts of M-protein, or percentages of plasma cells in bone marrow). Elevated serum sIL-6R did not affect the survival of the patients with MM. Serial measurements of sIL-6R together with the clinical course of patients with plasma cell neoplasias revealed a good correlation between the sIL-6R level and disease activity. We conclude that sIL-6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.
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PMID:Clinical significance of elevated soluble interleukin-6 receptor levels in the sera of patients with plasma cell dyscrasias. 861 53

Biochemical markers of multiple myeloma (MM) including beta 2-microglobulin (beta 2MG), C-reactive protein, neopterin, fibronectin, lactate dehydrogenase (LDH), thymidine kinase, connective tissue components, osteocalcin, amylase, etc. are reviewed. To date, no reliable biochemical markers have been reported for the diagnosis of MM. beta 2MG and LDH are widely used to predict the prognosis of the patients with MM. The value of other parameters is however, controversial. The cytochemical diagnosis of MM, using acid phosphatase, beta-glucronidase and lysozyme are also mentioned. Furthermore, the significance of the assay of various hormones, ammonia, cobalamin and electrolytes in MM are discussed.
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PMID:[Biochemical markers of multiple myeloma]. 769 95


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