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)

FE-3 cells were established by Hanashiro et al. by hybridizing mouse myeloma cells (Sp2/0-Ag14/SF) with rat spleen cells that were freshly isolated from Brown-Norway rats sensitized with DNP-As. FE-3 cells can constitutively secrete IgE without stimulation by cytokines. Our preliminary experiments demonstrated that the IgE secretion was decreased at 3 days after start of culture and the addition of exogenous IgE into culture media depressed the secretion of IgE. Thus, we hypothesized that the IgE production in FE-3 cells may be regulated by a signal transduction through the binding of IgE to its high affinity receptor (Fc(epsilon)RI) or to an IgE binding protein on the cell surface. In this study, we aimed to identify the nucleotide sequence of IgE FE-3 and compared with those of mouse IgE and IgE IR162 to find a structural heterogeneity in the Fc region of IgE FE-3. We also tested if the mRNA of Fc(epsilon)RI was expressed in FE-3 cells using the reverse transcriptase-polymerase chain reaction (RT-PCR) method with the combination of sequencing analysis. Consequently, the cDNA sequence of IgE FE-3 was identical to that of the CH3 and CH4 domains in the epsilon-chain of rat IgE IR162, whereas the cDNA of Fc(epsilon)RI was identical to that of mouse, suggesting that the genes of IgE FE-3 and Fc(epsilon)RI was derived from that of rat spleen cells and mouse myeloma cells, respectively.
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PMID:The nucleotide sequence of dinitrophenyl-specific IgE and Fc(epsilon)RI alpha-subunit obtained from FE-3 hybridoma cells. 1183 54

As found in different studies, glucocorticoid hormones (GCs) as well as interleukin-6 (IL-6) are involved in the modulation of protein glycosylation. In this work we have investigated the immunomodulatory effect of dexamethasone by assessing in vitro IgG glycosylation by monoclonal antibody-producing hybridoma cells. As described in myeloma cell lines, cellular viability and proliferation rates of hybridoma 112D5 cells decrease when cultured with dexamethasone during 24 hours, in a dose-dependent way. Moreover, the corticosteroid triggered apoptosis of the hybridoma, which was observed as soon as 4 h after culturing cells in the presence of the drug. In line with these results, after 24 h, dexamethasone induced a drop in the anti-DNP level of antibodies synthesized by hybridoma 112D5. In previous works we described that asymmetric glycosylation of in vitro synthesized IgG correlated with induction of cell damage. Nevertheless, an increase in asymmetric IgG glycosylation was not observed here, but there was a decrease in the proportion of asymmetrically glycosylated IgG synthesized by the hybridoma after a 4-h culture with the drug. Finally, as results from assessing IL-6 production by ELISA, we conclude that the above described effects of dexamethasone on hybridoma 112D5 cells could not be due to the inhibition of IL-6 synthesis exerted by the corticoid but rather to a direct effect of the drug. Monoclonal antibody (MAb) producing hybridomas provide an excellent in vitro model for the study of the molecular mechanisms involved in immunoglobulin glycosylation.
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PMID:The immunomodulatory action of dexamethasone on monoclonal antibody-producing hybridoma cells. 1216 47

Hybridoma that produces rat anti-mouse interleukin 6 receptor (IL-6R) antibody, MR16-1, was established by the fusion of mouse P3U1 myeloma cells and spleen cells from mouse soluble IL-6R (sIL-6R)-immunized Wistar rat. In the present study, we examined the characteristics of MR16-1 in vitro and in vivo. MR16-1 bound to mouse sIL-6R dose-dependently. MR16-1 suppressed IL-6-induced proliferation of 7TD1 cells in a dose-dependent manner and this inhibitory effect was reversed by the addition of a higher concentration of IL-6. Cross-reactivity study using T cells from mouse, rat, and human revealed that MR16-1 did not cross-react with human and rat IL-6R. Binding region analysis using several human-mouse chimeric IL-6Rs showed that half of the fibronectin domain II of mouse IL-6R (amino acids 214-285) was required for MR16-1 binding. Furthermore, MR16-1 completely suppressed IL-6-induced antibody production in DNP-KLH immunized mice. These lines of evidence demonstrate that MR16-1 is useful to investigate the physiological and pathological roles of IL-6 and sIL-6R in mice.
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PMID:Characterization of anti-mouse interleukin-6 receptor antibody. 1241 42

Many types of leukemia including multiple myeloma remain essentially incurable despite recent developments in immuno- and chemotherapy. The effectiveness of these therapies might be greatly enhanced by targeting cell surface proteins unique to the malignant clone, which for leukemias of the B cell lineage means clonotypic surface immunoglobulin (sIg). As this immunoglobulin (Ig) is necessarily epitope specific, we are developing ligand-toxin conjugates (LTCs) as a strategy for delivering toxins and other drugs to clonotypic tumor cells. Here we report in vitro studies that illustrate the effectiveness of this approach. LTC comprising the DNP hapten conjugated to ricin A toxin (DNP-RTA) were shown to specifically and effectively kill anti-DNP secreting murine hybridoma (U7.6) cells but not other hybridoma cells (1B12), a murine erythroleukemia cell line (Friend's Leukemia or) normal mouse spleen cells. In addition to direct toxicity, LTC treatment negatively affected the growth characteristics of the few surviving cells as reflected in decreased growth index and an increase in growth inhibition over 72 h post treatment. Interestingly, U7.6 cells that survived one or two LD90 dose(s) of LTC showed no alteration in their dose response to a subsequent attack of LTC indicating that this treatment strategy may not induce drug resistance. These data suggest that LTC therapy may be a new and effective strategy for specific destruction of tumor cells such as myeloma plasma cells and could be extended to other tumors where clonotypic receptors can be identified.
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PMID:Specific destruction of hybridoma cells by antigen-toxin conjugates demonstrate an efficient strategy for targeted drug therapy in leukemias of the B cell lineage. 1276 46


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