UMLS:C0026764 - FACTA Search

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

A membrane protein (33 kDa) that binds to the globular "heads" of C1q (gC1q-R) has been recently described. The full length cDNA encoding gC1q-R has been cloned, expressed in E. coli and using the purified recombinant protein (rgC1q-R) as an immunogen, a panel of IgG monoclonal antibodies (MAb) has been produced by fusion of spleen cells from hyperimmunized BALB/c mice with NSO mouse myeloma partners. From this fusion, 60 anti-gC1q-R hybridomas were selected and evaluated for their ability to (1) discriminate between the mature form (MF) of gC1q-R (residues 74-282) and a truncated form (TF) lacking residues 74-95, which contains a major C1q binding site, (2) recognize two functionally defined synthetic peptides derived from the NH2-(XN18) and COOH-(XC15) terminus of gC1q-R, and (3) bind to microtiter well fixed intact Raji cells. Several clones were identified: MAbs 46.23 and 60.11 (IgG1 kappa), reacted strongly with ELISA plate-fixed intact Raji and K562 cells, MF, and the XN18 peptide, but had poor or no reactivity with TF; MAbs 74.5.2 > 25.15 (IgG1 kappa) recognized both MF and TF and are directed against epitopes in the XC15 peptide that contains a binding site for high-molecular-weight kininogen and Factor XII.
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PMID:Identification of functional domains on gC1Q-R, a cell surface protein that binds to the globular "heads" of C1Q, using monoclonal antibodies and synthetic peptides. 891 82

A human monoclonal antibody (mAb), designated mNKES, was generated by fusing B cells isolated from an enlarged cervical lymph node of a patient with a carotid body tumor (CBT), with human myeloma cell line KR-12 (6TG). The reactivity of mNKES was tested by the indirect immunofluorescence method. The antigen defined by mNKES was expressed on Burkitt's lymphoma cell lines Raji, Daudi, and Ramos and on B lymphoblastoid cell line IM-9. In addition, mNKES reacted with T cells stimulated with recombinant interleukin-2 (rIL-2) obtained from normal healthy donors. However, mNKES did not react with normal resting human T, B, or adherent cells (monocytes/macrophages). When the reactivity of mNKES and mouse mAbs recognizing the human adhesion-associated antigen (CD10, CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, and HLA class I, and HLA class II antigen) with various cell lines was compared, mNKES reactivity was found to be unique, not resembling that of any of these mouse mAbs. Interestingly, mNKES specifically and rapidly (within 2 hr) induced homotypic cell aggregation of IM-9 cells. This mNKES-induced cell aggregation was completely blocked by the addition of EDTA and when incubated at 4 degrees C. The mAbs reactive with CD11a/CD18 (leukocyte function-associated antigen-1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) completely blocked the IM-9 cell aggregation induced by mNKES, and induction of IM-9 cell aggregation by mNKES was significantly blocked in the presence of the protein kinase C inhibitors sphingosine and H-7 and completely blocked by cytochalasin B and cytochalasin D, which inhibit microfilament formation. Regarding biological function, IM-9 cells bearing surface IgG (sIgG) effectively promoted IgG-secreting activity underlying the homotypic cell aggregation induced by mNKES. The surface antigen recognized by mNKES has a molecular size of about 55 kDa, as determined by immunoblotting analysis. These findings indicate that mNKES recognizes a novel adhesion-associated antigen distinct from any previously reported adhesion-associated antigens in terms of pattern of cellular distribution and biological function and that mNKES is the first human mAb found that rapidly induces homotypic cell aggregation and effectively promotes the IgG-secreting activity of human B lymphoblastoid cell line IM-9.
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PMID:A novel human monoclonal antibody rapidly induces homotypic cell aggregation and promotes antibody-secreting activity by human B lymphoblastoid cell line IM-9. 908 89

Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt's lymphoma), LIK and SB cell lines (B-cell lymphoblastic leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis, and morphogenesis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases, while Daudi, CEM, and Jurkat cells produced metalloproteinase-2 but not-9. In contrast, urokinase-type plasminogen activator was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat cells secreted both basic fibroblast growth factor and vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly, the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells grown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266, CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered by host inflammatory cells and by an intervening ensemble of angiogenic factors.
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PMID:Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis. 959 64

Arsenic trioxide (As2O3) has recently been shown to induce complete remission in acute promyelocytic leukemia (APL). As2O3 reportedly has dose-dependent dual effects on APL cells, triggering apoptosis at relatively high concentrations and inducing differentiation at lower concentrations. However, its effect is still controversial for other AML cells and hematological neoplasms. We studied the in vitro effect of As2O3 on lymphoid lineage cells: lymphoma cell lines, NOL-3, Raji and Daudi, a myeloma cell line, NOP-1, normal peripheral blood lymphocytes (PBL), non-Hodgkin's lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells, and compared it with the effect on APL cell line, NB4, as well as other myeloid cell lines, HL-60 and NKM-1. As2O3 at a concentration of 1 micromol/l markedly inhibited both proliferation and viability of NB4, NOP-1, NOL-3 and NKM-1 cells, but it reduced only viability in normal PBL, CLL cells and NHL cells. As2O3 induced apoptosis and down-regulated bcl-2 expression in NB4, NOP-1 and NKM-1 cells. On the other hand, in HL-60, Raji and Daudi cells, 1 micromol/l As2O3 inhibited only the proliferation weakly, and neither induced apoptosis nor down-regulated bcl-2 expression, but arrested only cell cycle at G1 phase. As2O3 at a low concentration of 0.1 micromol/l had no effect on proliferation and viability of these cells except for NB4. These results showed that As2O3 exerted variable and definite effects on lymphoid cells and indicated that As2O3 might be clinically useful in lymphoid neoplasms such as malignant lymphoma and CLL.
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PMID:The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms. 973 86

Peripheral blood T cells from a patient with multiple myeloma in complete remission were selected in vitro against an autologous myeloma cell line (SBN-1), using a protocol designed for the selection of relatively rare precursor cytotoxic T cells (pCTL). Delayed addition (2 weeks) of interleukin 2 induced T-cell proliferation, and a bulk culture (T-cell line) was obtained 2 days later. This T-cell line displayed cytotoxicity against SBN-1. A CD8+ CD4- cytotoxic T-cell clone (CT5) was then obtained that recognized SBN-1 but not autologous EBV+ B-lymphoblastoid cells, autologous T PHA-blasts, or Daudi, Raji, K562, and 11 allogeneic myeloma cell lines. Moreover, CT5 cytotoxic activity against SBN-1 was blocked by monoclonal antibodies recognizing human lymphocyte antigen class I molecules. This seems to be the first demonstration of myeloma-specific pCTL in peripheral blood T cells of patients with multiple myeloma.
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PMID:Isolation of human lymphocyte antigens class I-restricted cytotoxic T lymphocytes against autologous myeloma cells. 1010 Jul 25

Chronic lymphocytic leukaemia (CLL) is a most common form of adult leukemia. No specific marker for CLL has been defined until today. We attempt to produce a specific monoclonal antibody (mAb) to CLL B cells. For this purpose, Balb-C mice were immunised with peripheral blood lymphocytes of a patient with CLL. After the fusion, the immunised mouse spleen cells and SP2/0 myeloma cell line, antibody secreting clones were selected by ELISA and specific antibody was determined by flow cytometry. Leukemic cells from different patients, different cell line and lymphoid tissue were tested with this mAb using flow cytometry and immunoperoxidase methods. Ligand of the mAb on cell surface was identified using epitope analysing method. We have shown that this mAb is specific to a molecule with 6.5 kDa molecular weight, which is present mainly on B CLL cells (63.7+/-16.4%). It has also been shown that this molecule was a glycoprotein. Amongst the different cell lines that were tested, Raji cell, Molt-3 and P3HR-1 cells were expressing this molecule. We, therefore, suggest that it is a novel molecule with unknown function and is mainly present on the B cells of CLL.
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PMID:New monoclonal antibody specific for a 6.5 kDa glycoprotein which presents mainly on a B cell of chronic lymphocytic leukemia (CLL). 1122 6

The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.
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PMID:Mutational analysis of IkappaBalpha in hematologic malignancies. 1252 85

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor family that forms heterodimers with retinoid X receptor. These heterodimers bind to DNA and activate the transcription of target genes. Here, we report that the PPAR gamma receptor protein is expressed in primary myeloid and lymphoid leukemias and in lymphoma and myeloma cell lines. In this study, we compared the activity of several PPAR gamma ligands including BRL49653 (rosiglitazone), 15-deoxy-Delta 12,14-prostaglandin J(2), and the novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid on leukemia cells. Exposure to these PPAR gamma ligands induced apoptosis in myeloid (U937 and HL-60) and lymphoid (Su-DHL, Sup-M2, Ramos, Raji, Hodgkin's cell lines, and primary chronic lymphocytic leukemia) cells. A similar exposure to these PPAR gamma ligands induced the differentiation of myeloid leukemic cells. A combination of PPAR gamma ligands with a retinoid X receptor agonist (i.e., LG100268) or a retinoic acid receptor agonist (i.e., all trans-retinoic acid) enhanced differentiating and growth-inhibitory effects. 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced differentiation and apoptosis with much greater potency than the other PPAR gamma ligands in established cell lines and primary chronic lymphocytic leukemia samples. Exposure to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced mitochondrial depolarization and caspase activation, which was associated with apoptosis induction. In Bcl-2-overexpressing chronic lymphocytic leukemia cells, the small-molecule Bcl-2 inhibitor HA14-1 sensitized these cells to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-induced apoptosis. These results suggest that PPAR gamma ligation alone and in combination with retinoids holds promise as novel therapy for leukemias by activating the transcriptional activity of target genes that control apoptosis and differentiation in leukemias.
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PMID:Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. 1548 92

An anti-CD38 mAb (IB4) coupled to saporin-S6, a type 1 ribosome-inactivating protein (RIP), was designed for ex vivo or loco-regional therapeutical applications in myeloma and lymphoma. The ability of this immunotoxin to eliminate CD38+ cells was studied in vitro on selected CD38+ human cell lines (Raji, HBL6, L540 and CEM) and on CD38+ neoplastic cells from a Non Hodgkin Lymphoma (NHL) patient. HBL6, Raji and L540 cells resulted very sensitive to the IB4/saporin-S6 conjugate, concentrations as low as 100 pM of the immunotoxin completely inhibited protein synthesis. CD38+ neoplastic cells from the NHL patient were completely eliminated after treatment with immunotoxin at 10 nM concentration. CFU-c rescue by bone marrow precursors was maintained after exposure to the immunotoxin. These results indicate that IB4/saporin-S6 is endowed with strong and specific cytotoxic effects on selected CD38+ tumor cells lineages. Consequently, it is reasonable to propose a clinical use of the IB4/saporin-S6 for ex vivo purging of unwanted cells (e.g. depletion of contaminating neoplastic cells in aphereses obtained from G-CSF-treated patients) or for loco-regional therapies of CD38+ tumors.
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PMID:CD38 as a target of IB4 mAb carrying saporin-S6: design of an immunotoxin for ex vivo depletion of hematological CD38+ neoplasia. 1660 30

Although there is convincing evidence of a link between B lymphocyte stimulator (BLyS) and the proliferation and survival of malignant B cells, previous observations about BLyS expression on B lymphoma cells were contradictory. In this study, BLyS expression on human lymphoma and myeloma cell lines was evaluated by Fluorescence-Activated Cell Sorter (FACS). First, specificity of a monoclonal antibody (MAb) against BLyS, was analyzed. The results showed that MAb B7 was immunoglobulin G(3) (IgG(3)) and recognized recombinant human BLyS specifically. In addition, MAb B7 bound to the histiocyte lymphoma cell line U937 in dosage-dependent manner, but not the T lymphoma cell line Jurkat, suggesting that the cellular binding of MAb B7 was specific. Using this MAb, BLyS expression on two multiple myeloma cell lines (XG-7 and SKO-007) and two Burkitt's lymphoma cell lines (Daudi and Raji) was evaluated. MAb B7 did bind to XG- 7 and SKO-007 (66.84% and 79.38% positive cells, respectively). But MAb B7 did not bind Burkitt's lymphoma cell lines, Daudi and Raji (4.09% and 3.02% positive cells, respectively). It will be interesting to further analyze the expression of BLyS on B malignant cells of multiple myeloma and lymphoma patients, and to evaluate the correlation of its expression and patient prognosis.
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PMID:Analysis of an anti-B lymphocyte stimulator monoclonal antibody B7 and its binding activity to myeloma and lymphoma cell lines. 1693 21

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