Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. 753 May 7

The expression of 6 different oncoproteins and 2 tumour suppressor gene products in the plasma cells of 63 bone marrow samples was used to determine a profile of the oncogenic phenotype of patients with multiple myeloma. Dual label flow cytometry after periodatelysine paraformaldehyde fixation was used to detect cell surface phenotype and intracellular protein expression simultaneously. The normal range for both the incidence and intensity of expression was determined for each protein by analysing plasma cells (high CD38 intensity) in 22 normal bone marrow samples. The percentage of myeloma patients with a greater than normal incidence of plasma cells expressing these proteins was 53% for c-myc, 28% for Rb, 28% for bcl-2, 27% for c-fos, 24% for p53 wild, 22% for p53 mutant, 13% for c-neu and 13% for pan-ras. When a panel of 8 antibodies was used, 82% of the samples (n = 28) had an increased incidence of expression by at least one oncoprotein or tumour suppressor gene product. The 5 patients with a normal incidence of expression of all 8 proteins were in plateau stage and 4 had not received chemotherapy for more than 12 months. The number of patients with an increased incidence of expression by 2 or more oncoproteins was significantly greater (X2 = 9.0; p < 0.005) in progressive disease (55%) than in stable disease (14%) but there was no specific phenotype pattern associated with progressive disease. All 6 oncoproteins and both tumour suppressor gene products had a greater incidence and intensity of expression in progressive than in stable disease. The expression of c-myc oncoprotein correlated with c-myc mRNA expression in the same samples (n = 10) but c-myc did not correlate with either the plasma cell labelling index (r = -0.15) nor serum thymidine kinase (r = 0.10). Our results suggest that there is a heterogeneous, non-systematic but almost universal presence of activated oncogenes and tumour suppressor genes in the plasma cells of patients with multiple myeloma and that disease progression is associated with the accumulation of a variety of secondary genetic changes which confer increased malignant behaviour.
 ...
PMID:The oncoprotein phenotype of plasma cells from patients with multiple myeloma. 769 21

Thymidine kinase (TK) is a cellular enzyme required for the incorporation of thymidine into DNA. It catalyses the conversion of deoxythymidine to deoxythymidine monophosphate (dTMP). The synthesis of dTMP from deoxythymidine is called the salvage pathway. There are two types of thymidine kinase, distinguished by there biochemical and physico-chemical characteristics. Cytosolar TK is found in dividing cells in stages G1-S. Mitochondrial TK is found in mitochondria. Serum thymidine kinase (S-TK) levels can be determined by the use of a radioenzyme assay method. These are increased in proliferating cells (S phase). It is a useful tool for the clinical evaluation, staging, and follow-up of patients with multiple myeloma.
 ...
PMID:[The enzymatic character of myeloma cell]. 769 91

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.
 ...
PMID:[Biochemical markers of multiple myeloma]. 769 95

The clinical significance of plasma cell acid phosphatase (PCAP) was evaluated in 143 patients with monoclonal gammapathies, using a semiquantitative cytological scoring method. Significantly higher PCAP scores were measured in overt myelomas than in MGUS or in smouldering myelomas, during the phases of activity (diagnosis, progression, relapse), and in patients with extended disease. Among various clinical and laboratory parameters, PCAP was significantly related to the percentage of bone marrow plasma cells, the neoplastic growth fraction, as determined by Ki67 monoclonal antibody, and to serum levels of C-reactive protein. An inverse relationship was also found between PCAP and hemoglobin levels. Although the patients with "flaming" plasma cells exhibited low PCAP scores and poor prognosis, on the whole, myeloma patients with PCAP scores < 200 showed a significantly longer median overall survival than those with PCAP > 200 (46 vs 20 months, p < 0.003). However, in the multivariate analysis, beta 2-microglobulin, growth fraction, performance status, and serum levels of thymidine kinase and C-reactive protein, but not PCAP, maintained a significant prognostic relevance. In conclusion, although PCAP may be considered a marker of disease activity, other parameters provide better prognostic information in myeloma patients.
 ...
PMID:Plasma cell acid phosphatase and prognosis in multiple myeloma. 781 11

The expression of nucleoside transporters is a limiting factor in the pharmacology of the nucleoside analogue, cytosine arabinoside (AraC) and is associated with cellular proliferation. We investigated the expression of nucleoside transporters on plasma cells from the bone marrow of 51 patients with multiple myeloma by 2-colour immunofluorescence flow cytometry, utilising 5-(SAENTA-x8)-fluorescein, a fluorescent ligand for the nucleoside transporter and anti-CD38 conjugated to phycoerythrin, as CD38 expression has unique characteristics on plasma cells. Mean nucleoside transporter expression on bone marrow plasma cells from patients with myeloma (1777 +/- 2181 transporters/plasma cell) was not significantly different from expression on plasma cells from normal bone marrow (997 +/- 1096 transporters/plasma cell). However, analysis of disease subgroups revealed a significant trend towards increased transporter expression in patients with progressive disease compared to those with stable disease (chi 2 = 4.0, p < 0.05). Nucleoside transporter expression correlated significantly with the plasma cell labeling index (LI) (r = 0.45, p < 0.01) and serum thymidine kinase levels (r = 0.66, p < 0.01), both markers of cellular proliferation but not with c-myc oncoprotein expression. These findings suggest that flow cytometric measurement of nucleoside transporter expression on plasma cells provides a rapid and convenient measurement of disease activity or quiescence in myeloma.
 ...
PMID:Multiple myeloma: expression of nucleoside transporters on malignant plasma cells and their relationship to cellular proliferation. 806 94

In a group of 74 patients with multiple myeloma the authors revealed elevated values of serum thymidine kinase (REA kit ADICO Praha, range of normal values 0-5 U/l) in 40% of the patients-incl. a group of 22 subjects examined at the time of diagnosis of the disease in 50%, and a group of 52 subjects examined in different stages of the disease in 36% of the patients. If the upper range of S-TK 10 U/l was used, the ratio of patients with a raised value declined to 15%, in selected groups to 18 and 14% resp. The authors found a satisfactory correlation of serum thymidine values and values of S-beta-microglobulin, S-albumin, with the percentage ratio of plasmocytes in bone marrow and a less significant correlation was found with the red cell sedimentation rate (in IgG and IgA type) to the index of paraprotein and the serum interleukin-6 level. The authors did not reveal significant differences of serum thymidine kinase levels with regard to age, sex and immunochemical type of M-protein and type of light chains. The authors did not reveal any correlation of thymidine kinase serum levels and haemoglobin values, S-ferritin levels, the beta 2-microglobulin index and the synthetic score of plasma cells. It was found that examination of S-thymidine kinase extends in a useful way the existing spectrum of laboratory tests which help to elucidate the individual character of multiple myeloma.
 ...
PMID:[Serum thymidine kinase in multiple myeloma: I. Relation to selected laboratory indicators in the disease]. 818 66

In a group of 74 patients with multiple myeloma examined in different developmental stages of the disease the authors evaluated the clinical impact of assessment of the serum thymidine kinase (S-TK) activity. They recorded a significant relationship of S-TK values and the clinical activity of the disease (increase in 75% of the patients with the clinically active form of myeloma) and the general clinical condition ("performance status") evaluated by means of a five-grade scale. The authors tested the relationship of S-TK values and the degree of multiple myeloma, i.e. the clinical stage of the disease tested according to Durie-Salmon's classification (British Medical Research Council) and the authors' system modified according to Bataille. Individual stages of the disease (stage 1-3) differed as to the mean S-TK value and the median value and also as to the ratio of subjects with elevated values of this biochemical indicator. It was revealed that the cause of the relationship between S-TK and the stage of the disease is the increasing ratio of patients with the clinically active form of the disease in more advanced stages of myeloma. The S-TK activity in patients in the stable stage of the disease did not differ significantly in different stages (stage 1-3). From the practical aspect it is, however, an adverse finding that there is significant overlapping of S-Tk values in all mutually compared groups. According to preliminary experience S-TK is a simple readily accessible indicator related to proliferative characteristics of tumourous tissue which extends the hitherto available spectrum of evaluation criteria in multiple myeloma.
 ...
PMID:[Serum thymidine kinase in multiple myeloma: II. Relation to disease activity and stage]. 818 67

In multiple myeloma the duration of plateau is an important clinical and biological determinant of quality of life and survival. During plateau phase, the tumour is in an indolent state, as manifested by a low labelling index of plasma cells and other proliferative markers, e.g. the thymidine kinase level. The mechanism by which plasma cells escape from this indolent phase to a more aggressive phase of this disease is unknown, but a number of possible mechanisms have been postulated. These include loss of immunoregulation, clonal evolution, cytokine dysfunction and oncogene activation or tumour suppressor gene dysfunction. As current chemotherapy protocols do not appear to be able to eradicate the malignant clone, understanding the nature of the indolent phase of the malignant clone and the reasons for its escape from this phase are very important and may provide new options for disease control.
 ...
PMID:Mechanisms of the escape phase of myeloma. 820 6

Serum beta 2-microglobulin, serum thymidine kinase, and commonly used prognostic parameters were investigated for their prognostic value in a well-defined group of patients with multiple myeloma (n = 207). Multivariate analysis showed hemoglobin to be the parameter of strongest prognostic value. Only albumin, serum beta 2-microglobulin and serum thymidine kinase added further prognostic information. When tested for efficiency in recognizing patients with poor (average survival time < 1 year) and good (average survival time > 5 years) prognosis, serum beta 2-microglobulin was best (80%), followed by total urinary protein (78%), hemoglobin (76%), and albumin (75%).
 ...
PMID:Prognostic factors in multiple myeloma: role of beta 2-microglobulin and thymidine kinase. 831 85


<< Previous 1 2 3 4 5 Next >>