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)

A monoclonal antibody (MAb) was prepared by the fusion of murine SP2-O myeloma cells with BALB/cByJ spleen cells that were immunized with the glycolipid asialo GM1 adsorbed to naked Salmonella. The specificity of the IgM antibody obtained was defined using various glycolipids, cell extracts and saccharides in ELISA assays and thin-layer chromatography (TLC) immunoblots. The non-reducing terminal galactose is the immunodominant residue for this antibody; however, there is undetectable reactivity to free galactose, galactosylceramide or compounds with an alpha-linked galactose. The SH-34 antibody specifically lyses asialo GM1-expressing macrophages in the presence of complement and removes NK cells in vitro from spleen cell populations. When the specificity of the MAb was compared to that of a commercially available rabbit antiserum to asialo GM1, it was found that both cross-reacted with GM1 and asialo GM3 at high antibody concns; however, the MAb did not bind asialo GM2 while the rabbit antiserum showed substantial reactivity to this glycolipid. It is anticipated that this MAb will be useful for the study of murine and rat natural killer cells.
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PMID:A monoclonal antibody with reactivity to asialo GM1 and murine natural killer cells. 361 6

Monoclonal B cell hybridoma cell lines express glycolipids characteristic of both the myeloma and normal lymphocyte parents. The neutral glycolipids from hybridoma cell lines metabolically radiolabeled with [14C]galactose plus [14C]glucosamine separate by high performance thin layer chromatography into patterns that may reflect differences in glycolipid expression among B cell subsets. Gas chromatography/mass spectrometry of oligosaccharides released by trifluoroacetolysis from neutral glycolipids extracted from 10(9) clonally expanded hybridoma cells reveals the carbohydrate composition of the major glycolipid components detected by thin layer chromatography. Glycolipids differentially expressed among six cell lines analyzed include monohexosylceramide, lactosylceramide, globotriaosylceramide, globoside, asialo-GM2, and 2'fucosyllactosylceramide. The latter compound has not been described previously in cells from the mouse.
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PMID:Gas chromatography/mass spectrometry analysis of oligosaccharides from neutral glycosphingolipids of murine B cell hybridomas. 660 22

Purified GM1 and GM2 gangliosides incorporated into liposomes were injected subcutaneously in BALB/c mice every 3-4 days after pretreatment of the animals with low-dose cyclophosphamide. Serum samples were collected at different intervals and tests by ELISA for the presence of anti-ganglioside antibodies. Four doses (50 micrograms each) were sufficient to raise a measurable primary type of response to GM1, while nine doses were required to obtain measurable IgM antibody titers to GM2. Three monoclonal antibodies (MAbs) wer generated by fusing splenocytes with mouse myeloma cells. The specificity of MAbs was determined by ELISA and HPTLC-immunostaining using a panel of purified glycolipids. The MAb designated E1 showed a high degree of specificity because it reacted only with N-acetyl GM2. Monoclonal antibody A3 reacted predominantly with GM2 and GM1, but also reacted moderately with the GM3 ganglioside. The epitope recognized by this MAb is suggested to be the trisaccharide sequence GalNAc beta 1-4(NeuAc alpha 2-3)Gal. The third MAb (F6) reacted strongly with GM1 but a weak reactivity was also observed with GD1b as well as with asialo-GM1, indicating that the terminal tetrasaccharide Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal- structure is probably involved in antigenic recognition. Formalin-fixed and paraffin-embedded tissue sections were stained with the E1 and A3 MAbs, using the avidin-biotin complex (ABC) technique. Strong immunoreactivity for E1 appeared in the tumor cells of five primary lung carcinomas and in five malignant melanomas. No immunoreactivity was demonstrated in the parenchyma of a lung without malignancy, or in a metastasis from a colon carcinoma.
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PMID:T cell-independent B cell response to self-monosialogangliosides: primary response monoclonal antibodies. 759 Jul 82

We have previously reported that human B cell differentiation is accompanied by sequential changes in glycosphingolipid expression. Pre-B cells contain lacto-series type II chain-based glycolipids and GM3 ganglioside; mature/activated B cells do not synthesize lacto-series compounds but express GM3 and globo-series glycolipids (Gb3 and Gb4); terminally differentiated B cells, in addition to these compounds, also contain GM2 ganglioside. At the cell surface, Gb3, Gb4 and GM2 constitute stage-specific antigens. To elucidate the biosynthetic mechanism leading to these modifications we have compared activities of the glycosyltransferases involved in the core structure assembly and the first elongation steps of neo-lacto, ganglio- and globo-series glycolipids. These glycosyltransferase activities have been measured in B cell lines and normal B lymphocytes at various stages of differentiation. We first determined the optimal requirements of the four glycosyltransferases which synthesize Lc3, GM3, Gb4 and GM2 glycolipids in B lymphocytes and then tested these enzymes and the Gb3 synthetase in the selected B cells. The following results were obtained: beta 1-->3 N-Acetylglucosaminyltransferase (Lc3 synthetase) has a high activity in pro- and pre-B cells whereas it is undetectable in more differentiated cells; alpha 2-->3 sialytransferase (GM3 synthetase) is activated from the pre-B cell stage to the terminally differentiated myeloma cells; alpha 1-->4 galactosyltransferase (Gb3 synthetase) is only detected in cells representing the late stages of B cell differentiation; beta 1-->3 N-Acetylgalactosaminyltransferase (Gb4 synthetase) is only found in some lymphoblastoid cell lines, representative of activated B cells whereas the beta 1-->4 N-Acetylgalactosaminyltransferase (GM2 synthetase) has a high activity in these lymphoblastoid cell lines and in terminally differentiated myeloma cells. These results suggest that the sequential shifts in the three major glycosphingolipid series observed during B cell differentiation are mostly due to sequential activations of the corresponding glycosyltransferases.
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PMID:Sequential changes in glycolipid expression during human B cell differentiation: enzymatic bases. 781 47

Three kinds of anti-GM1 monoclonal antibodies, AGM-1, -2, and -3, of the IgM class were produced by the immunization of BALB/c mice with ganglioside GM1 inserted into liposomes with Salmonella minnesota R595 lipopolysaccharides and fusion of the spleen cells with a mouse myeloma cell line. The specificities of the monoclonal antibodies obtained were elucidated through complement-dependent liposome immune lysis assay and enzyme immunostaining on thin-layer chromatograms. All of the monoclonal antibodies reacted only with ganglioside GM1, and structurally related glycosphingolipids, such as fucosyl-GM1, asialo-GM1, GM2, and GD1b, and the other gangliosides (GM3 and GD1a) tested showed no reactivity to the 3 monoclonal antibodies. These findings suggest that the monoclonal antibodies obtained may be specific for ganglioside GM1. These anti-GM1 monoclonal antibodies were used to define the expression of ganglioside GM1 on small cell lung carcinoma (SCLC) cell lines and tissues. In flow cytometric analysis and immunostaining studies, we observed that ganglioside GM1 was highly expressed on the SCLC cell lines. Results obtained with flow cytometry and immunohistochemistry agreed well with the immunochemical determination of ganglioside GM1 in lipid extracts of cell lines. Furthermore, expression of ganglioside GM1 in tumor tissues from patients with SCLC was ascertained by the immunohistochemical examination of acetone-fixed paraffin-embedded tissue sections. Ganglioside GM1 was detected in 5 of 19 SCLC tissues. These results suggest that ganglioside GM1 is expressed in SCLC cells.
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PMID:Establishment of monoclonal antibodies specific for ganglioside GM1: detection of ganglioside GM1 in small cell lung carcinoma cell lines and tissues. 789 55

Twenty seven B cell neoplasms were examined by high performance thin layer chromatography (HPTLC) and immune thin layer chromatography (ITLC) to determine ganglioside expression. Patterns of expression in the cells were compared with conventional morphology, genotype, and glycoprotein immunophenotype. Patterns of ganglioside expression were found for each of the tumor types analyzed (5 acute lymphoblastic lymphomas (ALL), 5 Burkitt's Lymphomas (BL), 4 chronic lymphocytic leukemias (CLL), and 3 diffuse poorly differentiated lymphomas (DPDL), 7 diffuse histiocytic lymphomas (DHL), and 3 multiple myelomas (MM). GM3 was the predominant ganglioside found in all B cell neoplasms except multiple myeloma where GM2 was equivalent to GM3. GM1 was detected by ITLC in all B cell tumors, but significant amounts were found by HPTLC only in ALL, CLL, and DHL. Small amounts of GD3 and GD2 were found in several B cell neoplasms. Significant amounts of other gangliosides were not found. The expression of GM2 on the MM cell lines, a cell type derived from outside of the nervous system, is unusual. This high level of expression was also seen in metabolic labeling studies. GM2 was readily detectable in the SKMM1 human multiple myeloma cell line by flow cytometry and served as a target for human complement-mediated cytotoxicity. Although the functions of gangliosides are largely known, the patterns of gangliosides found for this system of human B cell malignancies may serve to provide targets for specific immunotherapy and clues to their functions.
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PMID:Patterns of ganglioside expression in B cell neoplasms. 872 7

Increased levels of NeuGc-containing gangliosides have been described in human breast cancer. A controlled Phase II clinical trial was conducted in patients with metastatic breast cancer to evaluate immunogenicity, safety and to identify evidences of biological activity of a cancer vaccine composed by NeuGcGM3 in a proteoliposome of Neisseria meningitidis together with Montanide ISA 51 as adjuvant. After first line chemotherapy, 79 women were randomized 1:1 to receive the vaccine candidate or best supportive care. All patients achieved at least stable disease to the first line therapy for the metastatic condition. Treatment consisted on 5 vaccine doses every 2 weeks and then, monthly re-immunization to complete 15 doses. Vaccination with the NeuGcGM3 based vaccine was safe and the most frequent adverse events consisted on injection site reactions, fever, arthralgia and chills. The vaccine was immunogenic and a sustained increase of both IgG and IgM antibody titters against NGcGM3 was observed after the second vaccination month. Antibodies were able to recognize the NeuGcGM3(+) murine tumor cell line L1210 and the myeloma cell line P3X63. Humoral response was specific since vaccination did not result in Neu-Acetyl GM3 or GM2-antibody response. Hyperimmune sera from vaccinated patients were able to prevent the NeuGcGM3 mediated CD4 down-modulation on T lymphocytes. In the intent to treat analysis, there was a trend toward a survival advantage for the vaccine group and this effect was significant for women bearing non-visceral metastasis. Two phase III clinical studies with this vaccine candidate are ongoing.
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PMID:Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: Results from a controlled study in metastatic breast cancer patients. 2085 39


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