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)

Using human myeloma cell line, LICR-LON-HMy2, and human lymphocytes, we have produced human monoclonal auto-antibodies against skin-components by human-human hybridoma technique. Resulting monoclonal antibodies are classified as follows; 1. Antibodies which recognize cytoplasmic filamentous antigen(s) in epithelial and non-epithelial cells, which are presumably keratin cross-reacting with other classes of intermediate filament(s), 2. Antibody to keratinocyte cellular membrane which is specific to upper epidermal layers, 3. Antibody to sebaceus gland with some cross-reaction in horny layers, 4. Antibody to the innermost cell layer of outer root sheath. The immunoglobulin class of all the antibodies was human IgM. Although pathological roles of these monoclonal antibodies are unknown, it is suggested that auto-antibodies against skin components are more commonly produced in human than previously understood and may be associated with various skin diseases.
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PMID:[Production of human monoclonal auto-antibodies which recognize skin components]. 258 79

LICR-LON-HMy2 cells (HMy2 cells), an established line of human myeloma lymphoblasts, produce and secrete IgG, and have been used for production of human-human hybridomas. We have previously shown that HMy2 cells are growth-inhibited by glucocorticoids and contain high affinity, saturable, steroid-specific glucocorticoid receptors. Here we report that treatment for 0-4 days with the synthetic glucocorticoid dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl-11 beta,17 alpha,21-triol-3,20-dione) leads to time-dependent increases in IgG secretion rates as measured by goat anti-human IgG antibodies in an enzyme-linked immunosorbent assay. Stimulation of IgG secretion is dependent on the concentration of dexamethasone employed, with half-maximal stimulation occurring between 1.10(-9) and 1.10(-8) M, and maximal stimulation occurring at 1.10(-7) M. Stimulation of IgG secretion is specific for active glucocorticoids such as cortisol and dexamethasone; treatment of cells with 17 beta-estradiol, progesterone, dihydrotestosterone, and aldosterone has little, if any, effect on IgG secretion. Finally, dexamethasone markedly stimulates both secreted and newly synthesized IgG, as determined by continuous and pulse labeling of extracellular and intracellular proteins, respectively, followed by binding to protein A-Sepharose, gel electrophoresis, and autoradiography. Thus, although dexamethasone effects on post-translational or secretory processes have not been ruled out, our data indicate that increased biosynthesis of IgG accounts for most, if not all, of the observed increase in IgG secretion rates. In summary our results demonstrate that despite the known immunosuppressive effects of glucocorticoids, these hormones can stimulate IgG biosynthesis and secretion in human myeloma lymphoblasts in vitro.
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PMID:Stimulation of IgG production by glucocorticoids in human myeloma lymphoblasts. 334 8

Intratumoral lymphocytes from 12 patients undergoing craniotomy for malignant glioma were fused with a specially derived human myeloma line LICR-LON-HMy2. 71 stable hybridomas were obtained from 5 of the 12 patients. Such hybridomas had a DNA content equal to the sum of that present in lymphocytes and the parent myeloma. The hybridoma supernatants contained human monoclonal immunoglobulins. Glioma-binding activity was detected in 7 out of the 71 supernatants. These results suggest that malignant gliomas contain a population of B lymphocytes which may be involved in host defence against the tumour.
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PMID:Human hybridomas from malignant gliomas. 611 12

A monoclonal antibody (K-1-21) raised against a kappa Bence Jones protein exhibits unique binding properties to malignant plasma cells. K-1-21 is an IgG1 kappa antibody that reacts with human kappa light chains in free form, but shows no reactivity with heavy chain-associated kappa light chains. By immunofluorescence, K-1-21 binds to the surface of LICR LON/HMy2 (HMy2) kappa myeloma cells and to plasma cells from a majority (8/11) of patients with various types of kappa myeloma; it did not bind to the surface of normal cells, nor to malignant cells of non-kappa myeloma origin. Flow cytometry analysis of K-1-21 binding to HMy2 cells indicated that the surface reactivity of K-1-21 could be completely inhibited by preincubation of the antibody with purified kappa light chains, whereas no inhibition occurred after preincubation with lambda chains or intact human IgG. Thus, the epitope recognized by K-1-21 on the cell surface may be similar, if not identical, to the determinant recognized on soluble free kappa light chains, and constitutes a tumor-associated antigen with selectivity for kappa myeloma cells. K-1-21 may therefore have clinical potential in patients with kappa myeloma.
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PMID:A tumor-associated antigen specific for human kappa myeloma cells. 619 95

Human lymphocytes from tumor-bearing patients and normal individuals have been fused with the NS-1 mouse myeloma line or the LICR -LON- HMY2 ( LICR -2) or SK0 -007 human cell lines. For a given number of lymphocytes, fusions with NS-1 produced 8 times more clones than fusions with LICR -2 and greater than 20 times more clones than fusions with SK0 -007. The percentage of clones that secrete human immunoglobulin (Ig) and the range of Ig production were comparable for clones derived from the three myeloma/lymphoblastoid lines. Clones derived from fusions with LICR -2 and SK0 -007 were found to secrete new species of light and heavy Ig chains in addition to those of the myeloma/lymphoblastoid lines, and clones derived from fusions with NS-1 secreted human Ig and contained both mouse and human chromosomes, which indicates that true hybrid cells were derived from fusions with each of the myeloma/lymphoblastoid lines under study. The stability of Ig production was similar for clones derived from fusions with NS-1, LICR -2, or SK0 -007; these results were comparable to those obtained with standard mouse/mouse hybrids. Stable clones producing human monoclonal antibodies that react with cell surface, cytoplasmic, cytoskeletal, nuclear, or nucleolar antigens have been isolated from tumor-bearing patients and normal individuals. A number of human monoclonal antibodies reactive with cytoskeletal antigens appear to be directed against components of the intermediate filament family. Techniques for the production of human monoclonal antibody appear to be sufficiently advanced to initiate a serological dissection of the humoral immune response to cancer.
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PMID:Analysis of human monoclonal antibodies derived from lymphocytes of patients with cancer. 632

Lymphocytes from 180 patients with a variety of malignant diseases were collected and fused with a human myeloma-derived line, LON-LICR-HMy2/CAM1. A total of 162 hybridomas was obtained. Only B lymphocyte markers were found on the surface of the fusion products. Flow cytometric analysis revealed a stably increased DNA content in the hybridoma cells. Some hybridoma supernatants were found to contain new Ig chains. Anti-tumour binding activity was found in 12 supernatants.
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PMID:Human hybridomas from patients with malignant disease. 633 43

The monoclonal antibody K-1-21 defines an antigen, KMA (kappa myeloma antigen) on the surface of human kappa myeloma cells. K-1-21 also recognizes human kappa light chains in free form but not when covalently bonded to heavy chains. To examine the relationship between KMA and this determinant on free kappa chains, the surface expression of KMA was examined on the IgG, kappa myeloma line LICR LON/HMy2 (HMy2). No patching or capping was observed in the presence of K-1-21 alone, but KMA could be capped if the cells were incubated with K-1-21 followed by fluorescein isothiocyanate-conjugated sheep F(ab')2 anti-mouse immunoglobulin. Capping was not affected by the inhibitors calcium ionophore or dibucaine. When IgG molecules were removed from the cell surface by capping with anti-IgG antiserum both KMA and free kappa light chains could still be detected with K-1-21 and a polyvalent anti-kappa antiserum, respectively. By contrast, after removal of all surface kappa chains with the polyvalent anti-kappa serum, no staining was observed with K-1-21 indicating that KMA may be an epitope on free kappa chains inserted in the membrane of kappa myeloma cells but absent from normal cells. KMA cell surface expression varied with the stage of the cell cycle. Flow cytometric analysis of K-1-21-stained HMy2 cells from either continuous cultures or from elutriated fractions enriched for various cell cycle phases showed that, within the cycling population, cells in G2 + M expressed KMA at a higher frequency and density than did cells in G1.
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PMID:The surface expression of a tumor-associated antigen on human kappa myeloma cells. 642 92

Human lymphocytes from lymph node, peripheral blood, spleen, and tumor specimens have been fused with the LICR-LON-HMy2 (LICR-2) or SKO-007 human cell lines or the NS-1 mouse myeloma line. Over 75 fusions with the three myeloma-lymphoblastoid lines have been performed. Several factors appeared to improve the fusion outcome, including maintenance of the myeloma-lymphoblastoid lines in logarithmic phase growth at greater than or equal to 95% viability, a delay of 24 hr in the introduction of aminopterin to the fused cells, and preselection of the fetal calf serum used in the medium. For a given number of lymphocytes, fusions with NS-1 produced 5-20 times more clones than fusions with LICR-2 or SKO-007, and LICR-2 produced 4 times as many clones as SKO-007. The percentage of clones secreting human immunoglobulin, the range of immunoglobulin production, and the proportion of IgM, IgA, and IgG secretors were comparable for clones derived from the three myeloma-lymphoblastoid lines. Stable Ig-secreting clones were isolated with approximately equal frequency from LICR-2 and NS-1 fusions. A number of stable clones producing human monoclonal antibodies reacting with cell-surface, cytoplasmic, or nuclear antigens have been isolated from tumor-bearing patients and normal individuals. A surface antigenic system present on normal and malignant cells has been defined with a human monoclonal antibody derived from a patient with breast cancer. Techniques for producing human monoclonal antibody now appear to be sufficiently advanced to initiate a serological dissection of the humoral immune response to cancer.
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PMID:Generation of human monoclonal antibodies reactive with cellular antigens. 657 59

This study represents an initial attempt to analyze the humoral immune reactions of patients with malignant melanoma by hybridoma methodology. Using lymphocytes from regional lymph nodes, peripheral blood and tumor infiltrates, 158 fusions were performed with SKO-007 (human myeloma line), LICR-LON-HMy2 (LICR-2), GM 4672 (human lymphoblastoid lines), or NS-1 (mouse myeloma line). Fusion of lymph node lymphocytes with NS-1 resulted in a 3-4 times higher frequency of clones than fusion with LICR-2, and a 10 times higher frequency than fusion with SKO-007 or GM 4672. In the case of peripheral blood lymphocytes, fusion with NS-1 gave greater than 25 times higher frequency of clones than fusion with LICR-2 or SKO-007. Production of human mu, gamma, or alpha heavy chains was detected in 50-80% of wells containing growing clones, and the levels of immunoglobulin ranged from 0.3 micrograms to 40 micrograms/ml. NS-1-derived clones could be easily subcultured, while LICR-2 and SKO-007 clones grew more slowly on subculturing. In this study, Ig secretion appeared to be a more stable property of LICR-2-derived clones than NS-1-derived clones. A panel of 20 human cancer cell lines was used to screen 771 Ig-secreting cultures for antibody to cell surface or intracellular antigens. Reactivity with cell surface antigens was found infrequently (6 cultures), whereas reactivity with intracellular antigens was more common (27 cultures). A new cell surface antigen with properties of a glycolipid was defined with an IgM monoclonal antibody secreted by a tetraploid cell derived from a fusion of LICR-2 with lymphocytes from the axillary lymph node of a patient with melanoma. The hybrid cell line has been subcloned four times and secretes 5 micrograms IgM/ml. The antigen detected by this IgM antibody was found on 5 of 23 melanoma cell lines and 12 of 30 epithelial cancer cell lines. No reactions were found with 11 cultures derived from normal cells. Stable cell lines secreting human antibody that detected nuclei, nucleoli, cytoskeletal elements, Golgi complex, or other cytoplasmic components were also isolated in this study. One of these antibodies detected an intracellular antigen that is restricted to cells of neuroectodermal derivation, and a second antibody reacted primarily with cells of epithelial origin. Using these methods to isolate and analyze human monoclonal antibody, it should now be possible to define the repertoire of the humoral immune response to melanoma.
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PMID:Detection of cell surface and intracellular antigens by human monoclonal antibodies. Hybrid cell lines derived from lymphocytes of patients with malignant melanoma. 686 64

Osteoclastogenesis is commonly associated with various age-related diseases, including cancer. A member of the tumor necrosis factor superfamily, receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL), has been shown to play a critical role in osteoclast formation and bone resorption. Thus, agents that suppress RANKL signaling have a potential to suppress bone loss. In this report, we investigated the effect of 1'-acetoxychavicol acetate (ACA), a component of Alpina galanga, on RANKL signaling and consequent osteoclastogenesis in RAW 264.7 cells, a murine monocytic cell line. Treatment of these cells with RANKL activated NF-kappaB, and coexposure of the cells to ACA completely suppressed RANKL-induced NF-kappaB activation in a time- and concentration-dependent manner. The suppression of NF-kappaB by ACA was mediated through suppression of RANKL-induced activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, and IkappaBalpha degradation. Furthermore, incubation of monocytic cells with RANKL induced osteoclastogenesis, and ACA suppressed it. Inhibition of osteoclastogenesis was maximal when cells were simultaneously exposed to ACA and RANKL and minimum when ACA was added 2 days after RANKL. ACA also inhibited the osteoclastogenesis induced by human breast cancer MCF-7 cells, multiple myeloma MM1 cells, and head and neck squamous cell carcinoma LICR-LON-HN5 cells. These results indicate that ACA is an effective blocker of RANKL-induced NF-kappaB activation and of osteoclastogenesis induced by RANKL and tumor cells, suggesting its potential as a therapeutic agent for osteoporosis and cancer-associated bone loss.
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PMID:1'-Acetoxychavicol acetate inhibits RANKL-induced osteoclastic differentiation of RAW 264.7 monocytic cells by suppressing nuclear factor-kappaB activation. 1660 41


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