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)

Modulation of the expression of P-glycoprotein, a plasma membrane protein associated with multidrug resistance, was examined in drug-sensitive and drug-resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor cells facilitating the uptake of doxorubicin and other tumor-inhibitory antibiotics. P-glycoprotein expression was measured flow cytometrically by the binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562 erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant 8226/DOX40 myeloma cells. Cells were treated for up to 2 h with up to 80 units of leukoregulin/ml or one of a variety of unrelated cytokines including interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating factor, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha-interferon, epidermal growth factor, platelet-derived growth factor AA, platelet-derived growth factor BB, insulin-like growth factor I, insulin-like growth factor II, fibroblast growth factor, or transforming growth factor beta. Leukoregulin caused a concentration-dependent decrease in P-glycoprotein expression; however, P-glycoprotein expression was unaffected by the other cytokines (< 12% decrease in expression). Leukoregulin-induced membrane permeabilization, determined flow cytometrically by intracellular fluorescein efflux, and decreased P-glycoprotein expression occurred simultaneously within 15 min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured flow cytometrically by doxorubicin influx, was also present within 15 min. Leukoregulin enhancement of doxorubicin uptake and increased membrane permeability varied directly with the decrease in P-glycoprotein expression. Leukoregulin in combination with doxorubicin enhanced the inhibition of cell proliferation in 8226/DOX40 multidrug-resistant cells over expressing P-glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant human promyelocytic leukemia cells that do not overexpress P-glycoprotein in association with their multidrug resistance resulted in no greater growth inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone. This is the first demonstration that a naturally occurring macromolecule with anticancer activities can modulate the expression of P-glycoprotein concomitant with enhanced drug uptake and inhibition of cell proliferation.
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PMID:Decreased P-glycoprotein expression in multidrug-sensitive and -resistant human myeloma cells induced by the cytokine leukoregulin. 135 22

Two hybridomas producing monoclonal antibodies against mouse beta nerve growth factor (NGF) were obtained from the fusion of hyperimmune splenocytes from rats immunized with polymerized beta-NGF and Sp2/0.Ag mouse myeloma cells. The monoclonal antibodies coded IgG 24 and 30 produced and secreted by the hybrid cells are both of the IgG2a subclass. Both monoclonal antibodies are capable of recognizing native NGF coated on microassay plates as well as the denatured factor on Western blots. However, only IgG 30 has been found to block NGF-induced process outgrowth from the rat pheochromocytoma cell line (PC12) as well as NGF-induced increase in choline acetyltransferase activity in rat primary septal cell cultures. In addition, only IgG 30 was able to detect immunocytochemically NGF-immunoreactive sites in fixed tissue. And, finally, IgG 24 could not compete for IgG 30 binding to immobilized native NGF. Consequently, it appears that these antibodies are recognizing different epitopes on the NGF molecule. Neither monoclonal antibody displayed any crossreactivity with serum albumin, aprotinin, epidermal growth factor or insulin. A hybrid-hybridoma producing bi-specific anti-NGF anti-horseradish peroxidase (HRP) monoclonal antibodies was generated from the fusion of an azaguanine resistant anti-HRP hybridoma, coded RAP2.Ag and the anti-NGF IgG 30 hybridoma treated with emetine. The potential merits of using these bi-specific antibodies in combination with their mono-specific anti-NGF parent in a homogeneous sandwich immunoassay for the quantitation of NGF are discussed.
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PMID:Two distinct monoclonal antibodies raised against mouse beta nerve growth factor. Generation of bi-specific anti-nerve growth factor anti-horseradish peroxidase antibodies for use in a homogeneous enzyme immunoassay. 199 53

The monoclonal antibody to the epidermal growth factor (EGF) receptor was generated after fusion of PAI myeloma cells with immunized BALB/c mouse spleen cells, using intact A431 epidermoid carcinoma cells as an immunogen. The antibody, denoted 5A9, is an IgG, which recognizes a protein with molecular mass 170 kDa during immunoblot analysis, immunoprecipitates phosphoprotein with molecular mass 170 kDa from the membrane preparations of A431 cells, and, according to immunofluorescence experiments, is distributed in the cell similar to the EGF-rhodamine conjugate. It is concluded that the produced antibodies are specific to EGF-receptor. At the same time the 5A9 (50 nM) do not compete with EGF for binding with high and low affinity receptors. They fail to induce internalization of the EGF-receptor and do not exert influence on intracellular degradation of EGF-receptor. Monoclonal antibodies 5A9 are also unable to inhibit the EGF-induced protein kinase activity of the receptor and do not stimulate protein kinase activity by themselves. Thus, the prepared monoclonal antibodies can be used to register the EGF-receptor cellular localization without affecting biologic activity of the receptor.
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PMID:[Isolation and characteristics of monoclonal antibodies to the external domain of the EGF receptor in human A431 epidermoid carcinoma]. 247 49

Hybridomas that secrete monoclonal antibodies specific for the high molecular weight (HMW) form of human epidermal growth factor (hEGF) were established by fusing spleen cells obtained from mice immunized with purified urinary HMW-hEGF with myeloma P3 x 63Ag8.653. The resulting monoclonal antibodies were characterized basically into two groups. One group recognized both EGF and HMW-hEGF, while the other recognized HMW-hEGF specifically on radio immunoprecipitation. Surprisingly, the majority of the isolates was positive by western blotting. Utilizing these monoclonal antibodies for affinity chromatography, we purified HMW-hEGF successfully from urine. These antibodies may be an extraordinarily powerful tool for histological study related to both forms of EGF.
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PMID:Monoclonal antibodies specific for high molecular weight form of human epidermal growth factor. 281 6

An epidermal growth factor (EGF) receptor-interactive monoclonal antibody (151-IgG) that inhibits EGF binding to PC12 rat pheochromocytoma cells and to various other cell types has been produced. The hybridoma clone was obtained by fusing Sp2/O-Ag14 myeloma cells with splenocytes from Balb/C mice which had been immunized with n-octyl glucoside-solubilized protein from isolated PC12 cell plasma membranes. The antibody is an IgG which binds to protein A. 151-IgG did not bind EGF. At 0.5 degrees C 151-IgG was directly competitive for EGF binding to PC12 cells. It also inhibited EGF binding to bovine corneal endothelial cells, rabbit corneal fibroblasts, human foreskin fibroblasts, and normal rat kidney cells, and it slightly enchanced EGF binding to SW 3T3 cells. PC12 cells have the same number of binding sites for 151-IgG as for EGF (approximately 27,000 sites/cell). 151-IgG inhibited the photoactivatable cross-linking of EGF to a protein of Mr 170,000 in PC12 cells. 151-IgG inhibited the EGF-stimulated incorporation of [3H]thymidine into quiescent bovine corneal endothelial cells, rabbit corneal endothelial cells, epithelial normal rat kidney cells, and SW 3T3 cells while it enhanced the EGF-stimulated [3H]thymidine incorporation into quiescent human foreskin fibroblasts. 151-IgG by itself possessed intrinsic EGF-like activity for human fibroblasts but not for the other cells tested. This suggests that there is a difference in EGF receptors and/or processing in these normal cell types.
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PMID:A monoclonal antibody which inhibits epidermal growth factor binding has opposite effects on the biological action of epidermal growth factor in different cells. 298 58

A monoclonal antibody to the epidermal growth factor (EGF) receptor of A431 cells, denoted 2D1-IgM, was generated after fusion of immunized BALB/c mouse spleen cells with SP2/0-Ag14 myeloma cells. Specific binding of 2D1-IgM to the A431 cell-surface receptor for EGF was demonstrated by indirect immunofluorescence, immunoprecipitation, and immunoblot analysis. Scatchard analysis of 125I-EGF binding to A431 cells demonstrated that 2D1-IgM treatment did not change the number of EGF receptors, but caused an increase in the affinity of EGF receptors from a population of low affinity to a uniform population of high affinity. Like EGF, 2D1-IgM induced phosphorylation of EGF receptors and EGF receptor clustering. As in the case of EGF, a biphasic growth response with stimulation of DNA synthesis at low and inhibition at high concentrations of 2D1-IgM was evident in A431 cells. The intrinsic "EGF-like" bioactivity of 2D1-IgM was enhanced by the presence of EGF. These results suggest that the binding of 2D1-IgM to the EGF receptor at a different site from that to which EGF binds can initiate an effective EGF-like biological response; and the EGF-like biological effects of 2D1-IgM may be mediated by a population of high affinity EGF receptors which may be involved in the control of cellular growth.
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PMID:Epidermal growth factor receptor of A431 cells. Characterization of a monoclonal anti-receptor antibody noncompetitive agonist of epidermal growth factor action. 298 73

Monoclonal antibodies can be produced in large amounts, are homogenous and can be highly purified. A specific monoclonal antibody against glandular kallikrein could be very useful in studies of the kallikrein-kinin system, both in vivo and in vitro. Two monoclonal antibodies against rat glandular kallikrein (rgKK) were produced by immunized mouse spleen and lymph node fusion with myeloma Ag8.653. Both antibodies, named 2E9.8 and 2E9.9, bound active 125I-kallikrein and phenylmethylsulfonyl fluoride (PMSF)-inactivated 125I-kallikrein. A radioimmunoassay (RIA) was developed with each of the antibodies using rabbit anti-mouse gamma globulin to separate bound from free 125I-rgKK. The standard curve (range 10-1000 ng/tube) was curved even when subjected to logit-log transformation. Using 3% polyethylene glycol (PEG) to assist separation of bound from free, the standard curve became straight for 2E9.8 and the RIA was more sensitive, with a binding range of 0.35-2.4 ng/tube. Both antibodies were specific for rgKK since they had negligible cross-reaction with purified proteases from the submandibular gland of the rat (tonin, esterases B and E). They did not cross-react with mouse nerve growth factor, epidermal growth factor, nor with pig pancreatic kallikrein. Antibody 2E9.9 did appear to bind some human kallikrein when tested with high concentrations of this enzyme, while 2E9.8 did not. When preincubated with purified rgKK, both antibodies prevented the enzyme from releasing kinins from semi-purified dog kininogen and from cleaving [3H]-L-arginine methyl ester (3H-TAME). These results suggested that both antibodies bind an epitope near to, and maybe including, the active site of the enzyme. Monoclonal antibody 2E9.8 appears to be specific for rgKK, can be used in a sensitive RIA, and is capable of inhibiting the enzymatic activity of kallikrein. It should prove to be useful in vivo for examining the role of kallikrein in physiological processes.
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PMID:Characterization of monoclonal antibodies against rat glandular kallikrein. 363 49

A monoclonal antibody directed to a species-specific determinant of human epidermal growth factor (h-EGF) was obtained by fusing murine myeloma cells with BALB/c mouse splenocytes sensitized to h-EGF. This antibody, referred to as 863.D4, did not react with either rat or mouse epidermal growth factor or with 11 other polypeptide hormones tested as shown by solid-phase radioimmunoassay (SPRIA), and immunoprecipitation followed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Scatchard analysis of the antibody binding to purified h-EGF revealed an apparent equilibrium dissociation constant of 1 X 10(-8) M. The antibody blocked both the binding of h-EGF and h-EGF stimulation of 3H-thymidine incorporation into DNA by greater than 90% in confluent cultures of human foreskin fibroblasts.
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PMID:Monoclonal antibody to human epidermal growth factor. 620 80

Mice were immunized with human epidermoid carcinoma cells (A-431 cell line) that possess an unusually high number of membrane receptors for epidermal growth factor (EGF). Spleen cells from these mice were fused with NSI cells, a nonsecreting murine myeloma. The immunoglobulins secreted by the obtained hybridomas were screened for specific binding to A-431 cells and selected according to their ability to inhibit the binding of radiolabeled EGF to the membrane of A-431 cells. Several antibodies secreted by cloned hybrid lines were found to inhibit the binding of radiolabeled EGF to membrane receptors of living A-431 cells, human foreskin fibroblasts, and mouse 3T3 fibroblasts and also to membrane preparations from A-431 cells. These monoclonal antibodies induced the early and delayed biological effects mediated by EGF. Like EGF, the antibodies induced morphological changes in A-431 cells and enhanced the phosphorylation of endogenous membrane proteins in membranes from these cells. They also stimulated DNA synthesis in human foreskin fibroblasts. These observations support the notion that the biological information of the EGF-receptor complex resides in the membrane receptor. Furthermore, the antibodies offer a powerful tool to study the structure, processing, and mode of action of EGF receptors.
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PMID:Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor. 627 78

A monoclonal antibody to the epidermal growth factor (EGF) receptor of A431 cells was obtained after fusion of immunized BALB/c mouse spleen cells with NS-1 myeloma cells. Specific binding of the antibody to the plasma membrane of A431 cells was demonstrated by indirect immunofluorescence and electron microscopy. The antibody did not react with human KB cells, normal rat kidney cells, or Swiss 3T3 cells. The antibody is an IgG3K; it specifically immunoprecipitated a Mr approximately 170,000 protein from radiolabeled A431 cell extracts. This protein is phosphorylated in a EGF-dependent manner in intact A431 cells and in Triton X-100-solubilized plasma membranes. The specificity of the interaction of the antibody with the Mr = 170,000 protein was confirmed by electrophoretic transfer of A431 cell proteins to nitrocellulose followed by incubation with the antibody and 125I-protein A. When 125I-EGF was covalently cross-linked to its receptor, the 125I-EGF-receptor complex was specifically precipitated by the antibody. The monoclonal antibody did not inhibit the binding of 125I-EGF to its receptor in intact A431 cells and also failed to stimulate the phosphorylation of the Triton X-100-solubilized EGF receptor. The results indicate that the antibody and EGF bind to different sites on the EGF receptor. The antibody will be useful for isolating the EGF receptor in an unactivated form.
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PMID:Epidermal growth factor receptor. Characterization of a monoclonal antibody specific for the receptor of A431 cells. 630 2


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