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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally recognized that no one cell culture system can be universally applied to all cell types commonly used for biopharmaceutical manufacture. The analogous concept that no single cell type may be useful for the expression of all biopharmaceutical products may also gain credence in the biotechnology community. It may be that like specialized bioreactors, there will come to exist a variety of cell types that will be used for the production of different types of biopharmaceutical products. In addition, it may not be enough in the future just to demonstrate the stability of expression of the amino acid backbone of the protein only; the carbohydrate portion of the molecule may become the subject of real scrutiny. Questions such as how the carbohydrate side chain affects the performance of the molecule in vivo are being asked of more DNA constructs. The next question becomes, how can we control the expression of carbohydrate moieties on the molecule? Such questions are in the future of the biotech manufacturing field. Aside from those examples mentioned above dealing with the insertion of receptors, other more subtle attempts at modifying cellular metabolism are taking place. It was reported at a recent meeting that the sialyltransferase gene was inserted into a CHO line which did not normally express this enzyme (116). The transfected line was capable of expressing the transferase and, more importantly, the enzyme functioned correctly in sialylating glycoproteins. Other very complex relationships exist between the substratum and the cell that could have very direct consequences on culture maintenance. For example, researchers recently published results indicating that collagenase synthesis and secretion is stimulated in rabbit fibroblasts by autocrine factors. They determined that these autocrine proteins had sequence homology to serum amyloid-A and beta-2-microglobulin. It may be that using serum supplements in the medium in those systems that couple fibroblast and collagen substratum may not be prudent, especially for long-term culture. The traditional selection of a cell type for expressing heterologous proteins has generally been limited to the more "common" cell types such as CHO cells, C127 cells, and myeloma cells. In many cases these cell types were selected because there was a great deal of preexisting literature on the cell type (i.e., "cookbook" methods of transfection for the cell) or the cell was simply being carried in the lab at the time the effort was made to express a biopharmaceutical product.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Large-scale animal cell culture: a biological perspective. 136 73

We tested the significance of the Ki-67 plasma cell growth fraction in 49 bone marrow samples from 42 patients with multiple myeloma (MM). As a new approach to study myeloma cell proliferation, strong positivity of the CD38 antigen as plasma cell related feature was simultaneously evaluated with nuclear Ki-67 expression in a flow cytometric double immunofluorescence assay. Mean Ki-67 values were significantly higher in MM at relapse (22.4 per cent +/- 10.4) as compared with MM at diagnosis (11.9 per cent +/- 8.4, p less than 0.005) and plateau-phase (10.0 per cent +/- 5.5, p less than 0.001), respectively. Serial observations in six patients confirmed this change in cell kinetic behaviour during the course of the disease. Elevated Ki-67 values correlated significantly with stage III (versus stage I, p less than 0.05), beta-2-microglobulin serum levels greater than 6 (p less than 0.001), plasmablastic morphology (p less than 0.001), and diploid myeloma cell DNA-content (p less than 0.005). No correlation was found between Ki-67 and immunoglobulin isotypes as well as immunophenotypic features (expression of CD10, CD33, and CD56) of myeloma cells. Clinically, six of seven patients with Ki-67 greater than 14 per cent at diagnosis had an unfavourable course (primary resistant disease or early relapse), and three of four patients with elevated Ki-67 values at plateau-phase relapsed within 3 months. Our results demonstrate the usefulness of Ki-67 in determining proliferative activity in MM and emphasize its value in the evaluation of the risk profile of MM patients.
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PMID:The biological and clinical significance of the KI-67 growth fraction in multiple myeloma. 159 63

In a retrospective and prospective follow-up study from 1968 to 1989, bone marrow biopsy specimens, serum beta-2-microglobulin (SB2M) levels, and the clinical features of 251 patients with multiple myeloma (MM) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS) were investigated. The main histologic variables (tumor cell type, tumor growth, tumor load, and fibrosis), SB2M level, serum thymidine kinase (STK) level, and various clinical parameters were analyzed to determine factors of value in monitoring the clinical phases of activity in MM. Our recently proposed prognostic strategy combining bone marrow histologic type, SB2M level, and signs of organ failure was tested for its ability to (1) diagnose the early and smoldering variants; (2) facilitate decisions on the time of initiation, the type and duration of initial induction therapy in the pretreatment phases (active and rapidly progressive phases); and (3) characterize variations in tumor regression and tumor-host interactions during chemotherapy (early treatment, plateau, relapse, transition, and refractory phases). The results indicate that this clinicopathologic monitoring combines information both on stage and aggressivity of MM and thus facilitates therapeutic decisions in the various clinical phases of MM.
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PMID:Histologic, biochemical, and clinical parameters for monitoring multiple myeloma. 191 61

Over the course of a 2-year period (September 1987 to September 1989) a total of 432 patients with multiple myeloma were registered in a study comprising 39 Swedish and one Italian clinics. Six of these were university hospitals, the others were county (community) hospitals. A total of 308 patients fulfilled the eligibility criteria of the protocol, and were started on traditional intermittent melphalan-prednisone therapy. Response, defined as a reduction in the concentration of the M-component in serum or urine, was observed in 58% of patients, and a clearly defined plateau phase was noted in 38% of the cases. Of the patients who achieved a plateau phase, 120 individuals (with a median age of 71 years) were at this point randomized between no further therapy and continuous interferon-alfa-2b at a dose of 5 x 10(6) IU subcutaneously three times per week. At relapse the interferon therapy was discontinued, and melphalan-prednisone restarted. Only preliminary data and interim results are at this point available. The final evaluation of the study will be performed after June 1, 1991. The treatment arms are comparable with regard to age, stage according to Durie-Salmon, renal function, immunoglobulin class, and type of response to the cytostatic therapy (rapid versus slow). A median number of six courses of melphalan-prednisone were administered before randomization. For those patients in whom pretreatment serum beta-2-microglobulin was analyzed, no difference in the median values between the treatment arms was found. The median observation time from randomization is 20 months. At the time of this analysis, 85 had relapsed: 33 of 59 (56%) in the interferon arm, and 52 of 61 (85%) in the no therapy arm. An interim analysis of the duration of the plateau phase (from the time of randomization) was performed in October 1990, showing a highly significant difference between the two treatment arms (P less than .001). The median duration of plateau was 59 weeks in the interferon arm, and 26 weeks in the no therapy arm. To date there have been 34 deaths, 13 in the interferon arm and 21 in the no therapy arm. All patients in the no therapy arm died from multiple myeloma (n = 19), or from another cause, but with the myeloma in an uncontrolled, progressive state (n = 2). In the interferon arm, only 10 patients died from progressive myeloma, and four of these either did not start interferon therapy at all (n = 1), or discontinued therapy early (n = 3).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interferon therapy during the plateau phase of multiple myeloma: an update of a Swedish multicenter study. 194 28

Serum beta-2-microglobulin (B2m) concentrations were determined in 43 southern African black patients with multiple myeloma (MM), in 130 black patients with monoclonal gammopathy of undetermined significance (MGUS) and in 70 control subjects. The results showed median values for serum B2m in patients with MM, MGUS and the control group to be 8.10 mg/l, 3.05 mg/l, and 2.35 mg/l, respectively; these values differed significantly from one another (P less than 0.01), even when patients with normal renal function (serum creatinine value less than 110 mumol/l) were considered separately. The median serum B2m concentration for IgG MM (22 cases) was 4.3 mg/l, for IgA MM (8 cases) 7.3 mg/l, and 24.2 mg/l for Bence Jones MM (12 cases). These differences were also significant (P = 0.001), but not in the restricted group of MM patients with normal renal function. In the 43 MM patients serum B2m concentrations had a significant positive correlation with serum creatinine (r = 0.706; P less than 0.005) and a significant negative correlation with haemoglobin values (r = -0.459; P = 0.006). In 28 MM patients with normal renal function, serum B2m values had a significant negative correlation with serum albumin (r = -0.602, P = 0.003). Sixty-five per cent of the 43 MM patients and 18.5% of the MGUS patients had raised serum B2m values (greater than 4.7 mg/l). An optimum cut-off value for serum B2m of 6.9 mg/l for differentiating MM from MGUS was determined using a classification rule. Despite lacking specificity, serum B2m measurement was useful in differentiating MM from MGUS, and was the best second choice variable in relation to serum albumin and haemoglobin in patients with normal renal function.
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PMID:Serum beta-2-microglobulin in the differential diagnosis of monoclonal gammopathies. 156 80

The distribution of serum cobalamin-binding proteins was studied in 30 patients with low-grade multiple myeloma and in 26 patients with high-grade myeloma. The mean total cobalamin concentration (holotranscobalamin I and II) was similar in both groups of patients. We found a marked rise in total unsaturated binding cobalamin capacity mainly due to an increase in apotranscobalamin II (apo-TC II) in patients with high-grade myeloma. There was also a positive correlation between serum beta-2-microglobulin (B2M) and apo-TC II in myeloma patients. Our results indicate that pretreatment measurement of serum apo-TC II could supplement B2M as a prognostic guide.
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PMID:Additional predictive value of serum unsaturated vitamin B12 proteins in multiple myeloma. 207 17

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.
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PMID:Multiple myeloma. 208 Oct 91

Solitary plasmocytoma is a rare plasma cell disorder as compared with multiple myeloma. In order to evaluate their relationships, the clinical findings in 51 patients with solitary plasmocytoma were analyzed. The median follow-up was 7.8 years (range 3 to 14). Twenty patients (39%) developed multiple myeloma in a average of 3.8 years. The risk factors associated with the development of multiple myeloma were an initial abnormal electrophoresis (M peak), age (less than 40 years) and an increase in beta-2-microglobulin. Although radiotherapy remains the initial treatment of solitary plasmocytoma, a careful evaluation should be performed in order to consider chemotherapy in selected patients with high risk of developing multiple myeloma.
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PMID:[Solitary plasmacytoma. A retrospective analysis of 15 cases]. 209 Nov 78

Multiple myeloma remains a universally fatal malignancy with a median survival time not exceeding 3 years. A clinical trial was undertaken to determine feasibility and efficacy of marrow-ablative chemoradiotherapy supported by unpurged autologous bone marrow (ABMT) and to define prognostic variables. Total body irradiation and either melphalan or thiotepa were administered to 55 patients (median age 53 years; range 20 to 66 years). The group of 21 patients with resistance to standard melphalan-prednisone and to continuous infusions of vincristine and Adriamycin with high dose dexamethasone (VAD) included 7 with primary unresponsive disease and 14 with resistant relapse; among the 34 patients achieving remission with the VAD regimen, 14 were in first and 20 in a subsequent remission. Marked cytoreduction by greater than or equal to 75% was observed among all 21 patients with refractory myeloma, whereas further cytoreduction of this magnitude was noted in only 56% of the 34 patients already in remission after VAD. Five of the 6 early deaths among all 55 patients occurred in the 14 patients with resistant relapse, none of whom achieved complete remission and who, as a group, had median durations of relapse-free and overall survival of only 8 and 7 months, respectively. Among the 41 remaining patients, there was only one early death, and 27% achieved complete remission including a 36% incidence among the 14 patients treated in first remission; their projected 4-year survival rate was 82% regardless of their disease status (first or later remission or primary resistance). When information about sensitivity to prior therapy is unavailable, the presence before ABMT of both high beta-2-microglobulin levels (greater than 3 mg/L) and non-IgG isotype helped identify 9 among the 55 patients with a very poor prognosis: all 8 responders relapsed within 9 months, and 8 patients died within 15 months. By contrast, a 4-year projected survival rate of over 70% for the other patients (about 80% of this series) justifies further investigation of this novel treatment approach in comparison with standard dose regimens. Our results indicate that marrow-ablative therapy cannot be recommended for myeloma patients with resistant relapse or those with a combination of risk factors (advanced tumor burden, absence of IgG isotype). The apparent lack of an adverse effect of even marked plasmacytosis in autografts (up to 30%) emphasizes the need for better cytoreduction rather than bone marrow purging.
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PMID:Autologous bone marrow transplantation in multiple myeloma: identification of prognostic factors. 222 33

In this study we analysed serum IL-2 levels in 61 patients with multiple myeloma (MM). Patients serum IL-2 levels were significantly higher than normal controls. Moreover, higher serum IL-2 levels were associated with a prolonged actuarial survival. In particular, 87% of the MM patients with IL-2 greater the or equal to 10 U/ml are still alive at 5 years while only 13% of the remaining patients with IL-2 less than 10 U/ml are alive. The multivariate analysis confirmed these data indicating that high serum IL-2 levels are the most useful predictor index of longer survival in MM patients. Furthermore, among the 50 patients in whom serum beta-2-microglobulin (SB2M) determination was available we observed that all patients with serum IL-2 levels greater than or equal to 10 U/ml had SB2M less than 6 micrograms/ml, whereas in patients with serum IL-2 less than 10 U/ml SB2M ranged from 1.3 to 15 micrograms/ml. Using these two parameters we were able to identify three groups of patients with different survival duration. Group A (9 patients) defined by serum IL-2 greater than or equal to 10 U/ml and SB2M less than 6 micrograms/ml in which all patients are alive: group B (26 patients) characterized by serum IL-2 less than 10 U/ml and SB2M less than 6 micrograms/ml in which 24% of patients are alive and group C (15 patients) characterized by serum IL-2 levels less than 10 U/ml and SB2M greater than or equal to 6 micrograms/ml in which the actuarial survival curve drops to 0 at 2.5 years. A statistically significant difference was observed between groups A and B (P less than 0.05), groups A and C (P less than 0.01) and groups B and C (P less than 0.01). These data could reflect the existence of an active T cell control on B cell neoplasia and may suggest the opportunity of a more extensive use of recombinant biological modifiers such as IL-2 in the therapeutic strategy of MM.
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PMID:High serum IL-2 levels are predictive of prolonged survival in multiple myeloma. 238 71


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