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

Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity.
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PMID:Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells. 753 8

Insulin receptors and insulin-like growth factor-1 (IGF-1) receptors are present in circulating human B lymphocytes (B cells) and certain B cell malignancies, but no function has been attributed to either receptor. We report a human myeloma cell line, RPMI 8226, that exhibits insulin and IGF-1-dependent receptor and substrate tyrosine phosphorylation as well as hormone-responsive cellular metabolism. Competitive hormone-binding analysis revealed that the cell line expressed approximately 4 x 10(3) high affinity insulin binding sites and 1.1 x 10(4) high affinity IGF-1 binding sites per cell. The Kd of the insulin-binding sites for insulin was 0.32 nM. The Kd of high affinity IGF-1 binding sites for IGF-1 was 0.89 nM. Insulin receptor autophosphorylation was maximum at 200 nM as was tyrosine phosphorylation of the 180-kDa cytosolic receptor substrate. Insulin-dependent activation of phosphatidylinositol 3-kinase paralleled receptor phosphorylation. In contrast, IGF-1 produced its maximum effects at 200 nM for receptor phosphorylation and 20 nM for substrate phosphorylation and PI 3-kinase activation. In growth synchronized cells, IGF-1 and insulin at 200 nM increased DNA synthesis by 122 +/- 18% and 101 +/- 27%, respectively. IGF-1 increased DNA synthesis 88 +/- 21% at 2 nM and the effect of insulin at 2 nM was 34 +/- 12%. Flux through the glycolytic pathway was also increased by insulin and IGF-1. At 200 and 2 nM, insulin increased production of lactate by 33 +/- 9% and 19 +/- 11%, respectively. IGF-1 increased lactate production 47 +/- 3% and 23 +/- 3% at identical hormone concentrations. Finally, in two additional myeloma cell lines, U266 (human) and Ag8.653 (mouse), insulin and IGF-1 increased tyrosine phosphorylation of receptor beta-subunit (95 kDa), the prominent 180-kDa substrate (pp185), and several other substrates. Thus, functional insulin and IGF-1 receptors are present in myeloma cell lines. Through these receptors, insulin and IGF-1 regulate mitogenesis and glucose metabolism, and may be important in potentiating plasma cell malignancy.
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PMID:Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. 768 86

The ratio of hapten to bovine serum albumin in an antigen conjugate was exactly determined by matrix-assisted laser desorption/ionization mass spectrometry. A hybridoma secreting monoclonal antibodies against forskolin was produced by fusing splenocytes immunized with a forskolin-bovine serum albumin conjugate with HAT-sensitive mouse myeloma cells. The cross-reaction of anti-forskolin antibodies with 7-deacetyl forskolin was 5.57%. A very small cross-reaction appeared with 1-deoxy, 9-deoxy and 1,9-dideoxy forskolin derivatives. The full measuring range of the assay extends from 6 ng to 200 ng of forskolin. The competitive ELISA assay used for this analysis was found to be more sensitive than TLC (10 micrograms), GLC (30 ng) and HPLC (1 microgram) methods.
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PMID:Production of monoclonal antibodies and enzyme immunoassay for typical adenylate cyclase activator, Forskolin. 776 88

It is now well documented that apoptosis represents the prevalent mode of cell death in hybridoma cultures. Apoptotic or programmed cell death occurs spontaneously in late exponential phase of batch cultures. Until lately, no specific triggering factors had been identified. Recently, we observed that glutamine, cystine or glucose deprivation induced apoptosis in both hybridoma and myeloma cell lines whereas accumulation of toxic metabolites induced necrotic cell death in these cells. Other triggering factors such as oxygen deprivation might also be responsible for induction of apoptosis. In the present study, induction of cell death by exposure to anoxia was examined in batch culture of the SP2/0-derived hybridoma D5 clone. The mode of cell death was studied by morphological examination of acridine orange-ethidium bromide stained cells in a 1.5 L bioreactor culture grown under anoxic conditions for 75 hours. Under such conditions, viable cell density levelled off rapidly and remained constant for 25 hours. After 45 hours of anoxia, cell viability had decreased to 30% and the dead cell population was found to be 90% apoptotic. In terms of cellular metabolism, anoxia resulted in an increase in the utilization rates of glucose and arginine, and in a decrease in the utilization rate of glutamine. The lactate production rate and the yield of lactate on glucose increased significantly while the MAb production rate decreased. These results demonstrate that glycolysis becomes the main source of energy under anoxic conditions. Cells incubated for 10 hours or less under anoxic conditions were able to recuperate almost immediately and displayed normal growth rates when reincubated in oxic conditions whereas cells incubated for 22 hours or more displayed reduced growth rates. Nonetheless, even after 22 h or 29 h of anoxia, cells reincubated in oxic conditions showed no further progression into apoptosis. Therefore, upon removal of the triggering signal, induction of apoptosis ceased.
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PMID:Induction of apoptosis in oxygen-deprived cultures of hybridoma cells. 776 24

The effects of the glucose supply on growth and metabolism of an SP2/0 derived recombinant myeloma cell line were studied in chemostat culture during growth on IMDM medium at a fixed dilution rate of 0.032 h-1. Lowering of the feed medium glucose concentration from 25.0 to 1.4 mmol/L resulted in a decrease of steady-state viable cell concentration from 1.9 x 10(9) to 1.0 x 10(9) L-1, whereas viability remained above 90%. Mass balances indicated that only a minor amount of glucose was utilized via the TCA cycle irrespective of the glucose concentration in the feed medium. The apparent biosynthetic yield of cells from ATP was independent of the ratio between the specific glucose and glutamine consumption rate. It is concluded that the primary role of glucose is the provision of intermediates for anabolic reactions. In addition, glucose may play an indirect catabolic role in the process of glutaminolysis by providing the pyruvate for the transamination of glutamate to alanine and alpha-ketoglutarate. At low glucose concentrations in the feed medium, glutamine is probably the sole energy source for this myeloma in chemostat culture.
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PMID:Effects of glucose supply on myeloma growth and metabolism in chemostat culture. 782 30

The phenomenon of cell resistance to prolonged energy deprivation after mild thermal stress was studied in vitro. Murine P3O1 myeloma and Ehrlich ascites carcinoma cells were treated with rotenone (an inhibitor of respiration) in glucose-free medium to block ATP generation. ATP rapidly decreased in these cells to 3-6% of the initial level that resulted in powerful aggregation of cytoskeletal proteins, blebbing, and necrotic death of 60-70% cells within 2 h. Prior heat shock (43 degrees C for 10 min) with a subsequent 3-h recovery in a rich medium considerably suppressed the rotenone-induced actin aggregation and rate of necrosis in the energy-deprived cells without effecting the ATP drop in them. Using [14C]leucine labeling, gel electrophoresis, and fluorography, stimulation of the heat-shock protein (HSP) synthesis and total suppression of any other translation were revealed in the cells during recovery after the heat pretreatment. Significantly elevated levels of HSP70 but not HSP90 and HSP27 were found by means of immunoblotting in both cell cultures rendered resistant to necrosis under ATP-depleting conditions. Inhibition of the thermo-induced HSP synthesis by cycloheximide fully prevented development of the tolerance to energy deprivation. A novel function of HSP70 consisting of protection of ATP-deprived cells from "lethal" aggregation of cytoskeletal proteins is suggested.
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PMID:Heat shock-induced accumulation of 70-kDa stress protein (HSP70) can protect ATP-depleted tumor cells from necrosis. 786 13

We report the sudden and dramatic reversal of maturity onset diabetes in a 57-year-old woman in association with relapse of IgA myeloma diagnosed 3 years earlier. Prior to the relapse of the myeloma, twice daily insulin had been administered at a dose which had been stable for 3 years. However, the same dose produced hypoglycaemic coma at the time of relapse and, subsequently, blood glucose was controlled by diet alone. There had been no significant change in weight or renal function prior to the hypoglycaemic episode. Investigations showed a suppressed fasting serum insulin level in association with an inappropriately high serum level of IGF-II compared with IGF-I and a 'big' IGF-II concentration at the upper end of the normal range. Pituitary, adrenal and liver disease, as well as the autoimmune insulin syndrome, were excluded. The findings are consistent with the hypothesis that the plasma cell tumour was associated with excessive production of insulin-like peptides with consequent reduction in the blood glucose level.
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PMID:Reversal of diabetes associated with escape of myeloma: evidence for inappropriate IGF-II secretion. 794 48

We report here that cultured human lymphoma cells in the absence of sonicated eosinophils are sensitive to killing by glucose oxidase (beta-D-glucose:oxygen-oxido reductase; EC 1.1.3.4) at concentrations as low as 0.025 microgram/ml, a level that can be rapidly attained in s.c. tumor implants in mice that receive a single nonlethal injection of enzyme. Multiple clonogenic assays were used to measure the survival of human lymphoma cell lines (H9 and ARH-77) cultured for 14 days in complete RPMI 1640 supplemented with exogenous glucose oxidase (0.025-2.5 micrograms/ml) or an immunoconjugate containing glucose oxidase (0.25-25 micrograms/ml) in the presence or absence of catalase (10 micrograms/ml) or an equal number of sonicated human eosinophils with or without supplemental 100 microM Br-, I-, or SCN-. In addition, we used an immunoassay to measure the concentration of glucose oxidase in s.c. implants of the Sp 2/0 myeloma tumor at 0-30 min after an i.v. injection of 50 micrograms of enzyme into 21 BALB/c mice. Doses of glucose oxidase as small as 0.025 microgram/ml killed more than 3 logs of tumor cells. Catalase completely inhibited, and sonicated human eosinophils partially inhibited, the killing by glucose oxidase or immunoconjugate, whereas supplemental halides had no effect. Glucose oxidase i.v. produced levels > 0.04 microgram/g of tumor for 30 min after injection with a peak concentration of 0.079 microgram/g of tumor within 5 min of injection. These results are important because certain human lymphomas contain extensive extracellular deposits of eosinophil peroxidase, thereby making these tumors potentially less susceptible to killing by otherwise therapeutic doses of glucose oxidase.
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PMID:Effects of sonicated eosinophils on the in vitro sensitivity of human lymphoma cells to glucose oxidase. 816 93

While IGF-1 plays a role in early B-cell development, little is known of insulin and insulin-like growth factor-1 (IGF-1) action in post-marrow B-cells. Recently, our laboratory demonstrated that mouse and human multiple myeloma (MM) cell lines possess functional insulin receptors (IRs) and IGF-1 receptors (IGF-1Rs). In this study, we show that responsiveness to insulin and IGF-1 is more developed in human MM cell lines than in human B-lymphoblastoid cell lines. Two human MM cell lines (U266 and RPMI 8226) were compared to three B-lymphoblastoid cell lines [Epstein-Barr virus immortalized B-cells (EBV), a Burkitt lymphoma cell line (Ramos), and a non-EBV lymphoblastoid cell line (HS Sultan)]. Surface IR and IGF-1R expression, measured by flow cytometry, demonstrated that the MM cell lines expressed more IRs and IGF-1Rs than did the EBV, Ramos, or HS Sultan cell lines. In vitro receptor kinase activity of affinity-purified receptors showed that the MM cells had more phosphorylated receptors than did the EBV, Ramos, or HS Sultan cells. Intracellular receptor signaling was also markedly different between the two cell groups. Whole cell phosphorylation studies showed that MM cells possessed not only hormone-dependent receptor autophosphorylation (M(r) 97,000) but also substrate phosphorylation (M(r) 185,000; 60,000). The lymphoblastoid cells, while demonstrating receptor autophosphorylation (IR autophosphorylation in the EBV cell line at 200 nM hormone was similar to MM receptor phosphorylation at 2 nM), lacked hormone-responsive substrates. The MM cell lines contained significantly more hormone-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity than the B-lymphoblastoid cell lines. In the MM cells, PI 3-kinase was activated by at least 10-fold, but, in the B-lymphoblastoid cell lines, it was activated by no more than 2-fold. Hormone-responsive glucose metabolism was also greater in the MM cell lines. In the U266 cells, insulin increased lactate production 62 +/- 9 and 101 +/- 12% (mean +/- SE) at concentrations of 2 nM and 200 nM, respectively. IGF-1 produced 72 +/- 9 and 99 +/- 13% increases at similar concentrations. In the 8226 cells, insulin increased lactate production 4 +/- 4 and 36 +/- 15% at 2 and 200 nM, respectively. IGF-1 produced a 13 +/- 6 and 70 +/- 18% increase. In the EBV and Ramos cells, neither hormone increased lactate production by more than 10 +/- 3%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines. 820 37

The bioconversion of 5-aminolevulinic acid (ALA) into hydrophobic protoporphyrin IX and other water-soluble porphyrins was investigated in Ehrlich ascite carcinoma (EAC) cells and in a myeloma cell line. The effects of irradiation (514 nm), temperature, incubation time and added glucose on the relative porphyrin concentrations (protoporphyrin vs. water-soluble porphyrins) were examined. Variations in these parameters induced a change in the amount of water-soluble porphyrins relative to protoporphyrin IX. The main component of the hydrophilic porphyrins was found to be uroporphyrin (Up), with minor components of coproporphyrin (Cp) and other carboxyporphyrins. The enhanced production of water-soluble porphyrins appears to be associated with alterations in the activities of the various enzymes in the heme biosynthetic pathway, resulting, for example, in the reduction in the activity of mitochondrial enzymes.
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PMID:Formation of water-soluble porphyrins and protoporphyrin IX in 5-aminolevulinic-acid-incubated carcinoma cells. 868 98


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