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)

An increased glucose metabolic rate is observed with various degrees of intensity in different subtypes of aggressive lymphomas. [(18)F]Fluorodeoxyglucose (FDG)-positron emission tomography (PET; FDG-PET) allows functional imaging of this phenomenon through 3-dimensional tomographic slices, which are now easily fused with computed tomography (CT) images. [(18)F]Fluorodeoxyglucose-PET staging appears superior to conventional staging modalities for detecting nodal and extranodal lymphoma. When performed after first-line chemotherapy, FDG-PET is more efficient than CT and conventional diagnostic methods to predict the disease outcome. Some studies have reported that the relapse rate is 100% in patients with positive PET findings after treatment and 17% in patients with negative PET findings. This imaging modality can also assess early response after 1-2 cycles of chemotherapy, thus identifying responders from patients whose cancer will fail to respond to first-line therapy or will relapse shortly after having exhibited a partial or complete remission. [(18)F]Fluorodeoxyglucose-PET also seems useful for an accurate selection of patients who will benefit from highly intensive treatment.
Clin Lymphoma Myeloma 2006 Jan
PMID:Value of [18F]fluorodeoxyglucose-positron emission tomography in managing patients with aggressive non-Hodgkin's lymphoma. 1650 8

A macrokinetic model for a myeloma cell line is proposed. The model describes the dynamic balances of lactate, alanine, ATP and NADH during the metabolsim of glucose, glutamine and other amino acids. The metabolic pathways mainly include glycolysis, glutaminolysis, the trcicarboxylic acid cycle, the formation and utilization of amino acids, the respiratory chain, cell growth and cell death. The metabolic shift of glucose is especially considered because of a change in the rate of glycolysis. Thus the model functions in three modes to describe the behaviour of the myeloma cell line. On the basis of this model the macrokinetic bioreaction rates such as the specific substrate consumption rate, the specific growth rate, the specific acetyl-CoA formation rate, as well as the specific oxygen uptake rate, are estimated. The specific substrate consumption rate and the specific growth rate are then coupled into a bioreactor model such that the key variables, i.e., the cell density, the substrate and metabolite concentrations, are obtained. Experiments with batch and fed-batch cultures of a myeloma cell line (X63-Ag8.653) were used to validate the model. The prediction of the model was simulated by the rolling prediction approach.
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PMID:A macrokinetic model for myeloma cell culture based on stoichiometric balance. 1680 Aug 13

Insulin-like growth factor-binding protein-1 (IGFBP-1) is secreted in a highly phosphorylated form that binds IGF-I with high affinity and is resistant to proteolysis. We have purified IGFBP-1-specific protease activity from the urine of an individual with multiple myeloma. This protease efficiently cleaves both phosphorylated and non-phosphorylated IGFBP-1 at Ile130-Ser131, generating fragments that together have higher association and dissociation rates for IGFs compared with intact IGFBP-1. The proteolytic fraction contained azurocidin, a protease homologue hitherto considered inactive. After cleavage of IGFBP-1, there was a lower affinity, but higher capacity for IGF-I binding, suggesting both N- and C-terminal fragments may interact with ligand independently. There was decreased inhibition of IGF-II-stimulated cell growth and glucose uptake. Alone, proteolysed IGFBP-1 stimulated glucose uptake in muscle. We conclude that specific cleavage of IGFBP-1 at target tissues is important in cellular growth and metabolism and opens novel strategies for targeting IGFBP-1 in treatment of disease.
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PMID:Specific cleavage of insulin-like growth factor-binding protein-1 by a novel protease activity. 1700 28

In this study we have analyzed the dynamic covariation of the mammalian cell proteome with respect to functional phenotype during fed-batch culture of NS0 murine myeloma cells producing a recombinant IgG(4) monoclonal antibody. GS-NS0 cells were cultured in duplicate 10 L bioreactors (36.5 degrees C, 15% DOT, pH 7.0) for 335 h and supplemented with a continuous feed stream after 120 h. Cell-specific growth rate declined continuously after 72 h of culture. Cell-specific recombinant monoclonal antibody production rate (qP) varied sixfold through culture. Whilst qP correlated with relative recombinant heavy chain mRNA abundance up to 216 h, qP subsequently declined, independent of recombinant heavy chain or light chain mRNA abundance. GS-NS0 cultures were sampled at 48 h intervals between 24 and 264 h of culture for proteomic analyses. Total protein abundance and nascent polypeptide synthesis was determined by 2D PAGE of unlabeled proteins visualized by SYPRO Ruby and autoradiography of (35)S-labeled polypeptides, respectively. Covariation of nascent polypeptide synthesis and abundance with biomass-specific cell growth, glucose and glutamate consumption, lactate and Mab production rates were then examined using two partial least squares regression models. Most changes in polypeptide synthesis or abundance for proteins previously identified by mass spectrometry were positively correlated with biomass-specific growth rate. We conclude that the substantial transitions in cell physiology and qP that occur during culture utilize a relatively constant complement of the most abundant host cell machines that vary primarily with respect to induced changes in cell growth rate.
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PMID:Dynamic analysis of GS-NS0 cells producing a recombinant monoclonal antibody during fed-batch culture. 1711 45

This case report describes a patient who presented with severe anemia, monoclonal gammopathy, a high erythrocyte sedimentation rate and significant weight loss. These features were highly suggestive of multiple myeloma. Bone marrow aspiration was negative for myeloma on two occasions. A positron emission tomography (PET) scan showed extensive 2-flourodeoxy-glucose uptake in the vascular tree consistent with arteritis. A temporal artery biopsy established the diagnosis of giant cell arteritis (GCA). There were no typical symptoms of GCA, such as headache, visual disturbance, or polymyalgia rheumatica. The patient was treated with steroids, which resulted in the resolution of anemia, monoclonal gammapathy, and other symptoms.
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PMID:Giant cell arteritis mimicking multiple myeloma; diagnosed by PET scan. 1719 11

A perfusion system is described for the production of a human monoclonal antibody in non-secreting murine myeloma (NS0) cells that was previously shown to be difficult to produce at high levels using fed-batch culture. The perfusion system was based on the use of a commercially available cell settler as the separation device to separate the cells from the culture. Separation efficiency of the cell settler was above 98%. Based on the growth and glucose consumption rates, fresh media was added to the culture and the turnover rate for the bioreactor was set at a maximum of 1.5 times the bioreactor volume per day. The perfusion process resulted in twice the maximum viable cell densities and up to three times the total protein production in a 53-day run period when compared to the fed-batch process. In addition, charge heterogeneity of the antibody as measured by ion exchange chromatography was lower for material purified from the perfusion runs compared to fed-batch. Perfusion mode of culture using a commercially available gravity settler is therefore a viable alternative to fed-batch mode for high-level production of this monoclonal antibody in NS0 cells.
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PMID:High-level production of a monoclonal antibody in murine myeloma cells by perfusion culture using a gravity settler. 1726 92

A deterioration of glucose tolerance is one of the most important side-effects ofglucocorticoid therapy. Disorders of glucose metabolism are present in almost all patients treated with glucocorticoids and 25% of these develop manifest diabetes mellitus. Glucocorticoids increase gluconeogenesis in hepatis and decrease insulinosensitivity in peripheral tissues and probably also decrease the release of insulin from pancreatic beta cells. The deterioration of glucose tolerance leads to worsening of morbidity and mortality of seriously ill patients. In glucocorticoid-induced diabetes mellitus the highest levels of glucose are seen in the afternoon, in the evening and postprandially: Normal levels of glucose are seen in the morning. Excluding 11 patients with diabetes (16%), we idenfied 7 (10%) patients with normal glucose tolerance, 13 (19%) patients with impaired fasting glucose or/and impaired glucose tolerance and glucocorticoid-induced diabetes mellitus we found in 37 (55%) patients treated in our department with diagnosis of myeloma multiplex in the year 2004 intermitently with 40 mg dexamethason p.o.
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PMID:[Disorder of glucose metabolism regulation in patients with multiple myeloma treated with high doses of corticosteroids at our clinic in 2004]. 1747 11

We have recently shown significant renoprotective effects with the administration of pituitary adenylate cyclase-activating polypeptide (PACAP) in models of myeloma kidney. PACAP markedly inhibited the production of proinflammatory cytokines stimulated by immunoglobulin light chains in human renal proximal tubule epithelial cells and in the kidneys of rats infused with myeloma light chains. PACAP was also shown to suppress the proliferation of human kappa and lambda light chain-secreting multiple myeloma-derived cells. In this case study, an 81-year-old male patient with active multiple myeloma and myeloma kidney was infused intravenously with synthetic human PACAP38 at a rate of 4 pmol/kg/min for 120 min. The continuous infusion increased the level of PACAP38 in blood, with a plateau at about 0.2 nM during the infusion. The level of PACAP in the blood rapidly declined after the cessation of administration with a half-life of about 5-10 min. The continuous infusion did not significantly alter the basal glucose level, blood gases or blood pressure. There was a large reduction in free lambda light chains in urine after the start of the treatment with PACAP. These studies show that PACAP can be safely used in humans and suggest that it could be used as a novel therapeutic agent for the treatment of multiple myeloma and myeloma kidney.
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PMID:Intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP) in a patient with multiple myeloma and myeloma kidney: a case study. 1758 55

The advent of positron emission tomography-computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) has introduced tumor imaging with a systemic and functional approach compared with established sequential, multimodal diagnostic algorithms.Whole-body PET with [18F]-fluoro-2-desoxy-glucose is a useful imaging procedure for tumor staging and monitoring that can visualize active tumor tissue by detecting pathological glucose metabolism. The combination of PET with the detailed anatomical information of multislice computed tomography as dual-modality scanners has markedly increased lesion localization and diagnostic accuracy compared with both modalities as standalone applications.Hardware innovations, such as the introduction of multi-receiver channel whole-body MRI scanners at 1.5 and, recently, 3 T, combined with acquisition acceleration techniques, have made high-resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution, and contrast media dynamics can be combined with whole-body anatomical coverage in a multiplanar imaging approach. More flexible protocols (eg, T1-weighted turbo spin-echo and short inversion recovery imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen) can be performed within 45 minutes.Whole-body magnetic resonance imaging has recently been proposed for tumor screening of asymptomatic individuals, and potentially life-changing diagnoses, such as formerly unknown malignancy, have been reported. However, larger patient cohort studies will have to show the cost efficiency and the clinical effectiveness of such an approach.For initial tumor staging, PET-CT has proved more accurate for the definition of T-stage and lymph node assessment, mainly because of the missing metabolic information in WB-MRI. However, new applications, such as magnetic resonance whole-body diffusion-weighted imaging or lymphotropic contrast agents, may significantly increase sensitivity in near future. Whole-body magnetic resonance imaging has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and as a whole-body bone marrow screening application. Within this context, WB-MRI is highly accurate for the detection of skeletal metastases and staging of multiple myeloma. This article summarizes recent developments of CT/PET-CT and WB-MRI and highlights their performance within the scope of systemic oncological imaging.
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PMID:Whole-body magnetic resonance imaging and positron emission tomography-computed tomography in oncology. 1776 83

A simple kinetic model is developed to describe the dynamic behavior of myeloma cell growth and cell metabolism. Glucose, glutamine as well as lysine are considered as growth limiting substrates. The cell growth was restricted as soon as the extracellular lysine is exhausted and then intracellular lysine becomes a growth limiting substrate. In addition, a metabolic regulator model together with the Monod model is used to deal with the growth lag phase after inoculation or feeding. By using these models, concentrations of substrates and metabolites, as well as densities of viable and dead cells are quantitatively described. One batch cultivation and two fed-batch cultivations with pulse feeding of nutrients are used to validate the model.
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PMID:A simple kinetic model for myeloma cell culture with consideration of lysine limitation. 1825 55


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