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 a synthetic peptide with the amino acid sequence corresponding to residues 78-109 of human TGF-beta 1 (A78/109 peptide) as an immunogen, we generated and characterized monoclonal antibodies (Mabs) against transforming growth factor-beta 1 (TGF-beta 1). Spleen cells from a mouse immunized with carrier-free A78/109 peptide were fused with a myeloma cell line, P3U1. Two hybridoma cell lines were selected with A78/109 peptide used as the antigen, and the Mabs were designated as 3H10 and 4C10. Mab 4C10 recognized TGF-beta 1 only in immunoblotting analysis, but not in ELISA. In contrast, Mab 3H10 recognized it in not only ELISA but also immunoblotting analysis. Neither Mab was capable of recognizing both porcine TGF-beta 2 and chicken TGF-beta 3, and, therefore, both Mabs were TGF-beta 1 specific. From the results of epitope-mapping analysis, both Mab 3H10 and Mab 4C10 recognized the 78-87 portion of TGF-beta 1. The epitope recognized by Mab 4C10 was mapped specifically to amino acids 85-87. These results suggest that the region within 78-87 is exposed in the dimeric TGF-beta 1 and is one of the antigenic determinants in this molecule.
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PMID:Synthetic peptide-generated monoclonal antibodies to transforming growth factor-beta 1. 750 42

Recombinant human transforming growth factor soluble receptor Type II (rhTGF-beta sRII) corresponding to the 159 amino acid extracellular domain of hTGF-beta RII has been expressed in insect cells using the baculovirus expression system or in a mouse myeloma cell line. N-terminal sequence analysis of the purified protein revealed the removal of the 23 amino acid signal peptide. In SDS-PAGE, the rhTGF-beta sRII resolves into multiple bands due to N-linked glycosylation. Recombinant hTGF-beta sRII is a TGF-beta antagonist and will inhibit the biological activities of TGF-beta 1, TGF-beta 3, and TGF-beta 5 on TGF-beta-responsive cell lines, such as murine HT-2 or human TF-1 with an ED50 of approximately 0.3 micrograms/mL. However, hTGF-beta sRII does not inhibit TGF-beta 2 bioactivities in these cell lines, suggesting that hTGF-beta RII has low affinity for TGF-beta 2. Polyclonal antibodies to hTGF-beta sRII have been produced in goats and purified on Protein-G affinity columns. This antibody can inhibit TGF-beta 1,2,3,5-dependent bioactivities on human cell lines such as TF-1. Additionally, this antibody has species cross-reactivity and will also inhibit TGF-beta-dependent bioactivities on murine cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of recombinant soluble human transforming growth factor-beta receptor type II (rhTGF-beta sRII). 757 76

Less is known about the cytokine expression and regulation of normal plasma cells compared to that of activated B cells or myeloma cells. This study shows that nonproliferating (hydroxyurea-treated), immunoglobulin (Ig)-secreting cells generated from human B cells in the EL-4 culture system no longer express interleukin (IL)-6 mRNA, progressively lose IL-10 mRNA, but continue to express transforming growth factor (TGF)-beta 1 mRNA. Secretion of TGF-beta 1 protein was demonstrated. On the other hand, and in contrast to the suppression of B cell proliferation and Ig secretion, the basal or the IL-6/IL-10 stimulated Ig secretion of nonproliferating cells was not inhibited by recombinant TGF-beta 1. Plasma cells isolated from human bone marrow expressed neither IL-6 nor IL-10 mRNA; only TGF-beta 1 mRNA was detected by reverse transcription-polymerase chain reaction analysis. Such plasma cells may be on average more "aged" cells than those generated in vitro. Thus, plasma cells persistently express TGF-beta 1, a known suppressor of various lymphoid and hemopoietic cell activities, but do not limit their own Ig secretion via this cytokine.
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PMID:Cytokine expression and regulation of human plasma cells: disappearance of interleukin-10 and persistence of transforming growth factor-beta 1. 787 13

Expression of mRNA for eight cytokines was analyzed in an in vitro response-proliferation and Ig-secretion--of normal human B lymphocytes. This was made possible by the use of murine thymoma cells as helper cells in conjunction with human T cell supernatant, and the design of human DNA sequence-specific primers for RT-polymerase chain reaction. mRNAs for interleukin (IL)2 and IL-4, but also for IL-1 alpha and IL-1 beta remained undetectable during the whole culture period in highly purified B cells prepared by a three-step purification protocol. However, tumor necrosis factor alpha and IL-6 mRNAs peaked during days 1-3 after culture start and became undetectable after 5-6 d, shortly before bulk B cell proliferation started to decline. In contrast, transforming growth factor beta 1 mRNA, after a progressive increase during the first few days, and IL-10 mRNA, after a peak on days 1-3, remained detectable in immunoglobulin (Ig)-secreting cultures throughout the observation period of 22 d. Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA. These findings show a differentiation stage-related cytokine program during a B cell response, whereby (a) B cells can become activated without IL-1 alpha or IL-1 beta expression; (b) mRNA for positive (IL-10) and negative (TGF-beta 1) autoregulatory factors coexists in cell populations during the later phase of the response, although not necessarily in all B cell clones; and (c) normal Ig-secreting cells cease IL-6 expression in contrast to their malignant counterparts, myeloma cells.
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PMID:Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs. 810 60

A hybridoma TB 21 clone was derived from fusion between Sp 2/0-Ag 14 myeloma cells and spleen cells of BALB/c mice immunized with transforming growth factor-beta 1 (TGF-beta 1) purified from human platelets. The TB 21 clone was identified to produce monoclonal antibody with IgG1 subclass and had sufficient titer for immunoreactivity to both human platelets-derived TGF-beta 1 and recombinant human TGF-beta 1 by enzyme-linked immunosorbent assay (ELISA). Western blotting studies demonstrated that two immunoreactive bands corresponding to 25 Kda and 12.5 Kda molecules were observed in the sample of acid/ethanol extracts from human platelets. The affinity constant (Kaff) was determined as 1.47 x 10(8) M-1 with non-competitive ELISA. Moreover, using bioassay for the effects of TGF-beta 1 on the growth of mink lung epithelial cells (CCL/64 cell line) and fibroblast cells (NRK 49 F cell line), TB 21 IgG was shown to be able to neutralize the action of TGF-beta 1 on the growth of these target cells. Therefore, this monoclonal antibody may be a useful probe for studying the growth modulatory activity of TGF-beta 1 in a variety of cells and tissues.
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PMID:[Biological characterization of a monoclonal antibody TB 21 against human transforming growth factor-beta 1]. 823 23

To evaluate possible involvement of a paracrine/autocrine inhibitory growth factor in myeloma cell growth, we studied the expression and actions of two forms of transforming growth factor beta (TGF-beta 1 and TGF-beta 2) on two closely related myeloma cell lines, OPM-1 and OPM-2. Earlier studies showed that both cell lines contain glucocorticoid receptors, but only OPM-2 cells are growth inhibited by dexamethasone (Dex). We found that OPM-2 growth was inhibited by TGF-beta, with TGF-beta 1 exerting a greater effect than TGF-beta 2, and Dex plus TGF-beta 1 acting synergistically. In OPM-1 (Dex insensitive), TGF-beta mRNA was not expressed, whereas it was induced by Dex in OPM-2. It was also possible to block partially the growth inhibition of Dex in OPM-2 cells by the addition of anti-TGF-beta 1 antibodies. These data suggest that the glucocorticoid effect(s) on myeloma cells may be mediated at least in part through modulation of internal and/or external levels of TGF-beta 1.
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PMID:Actions and interactions of glucocorticoids and transforming growth factor beta on two related human myeloma cell lines. 842 3

The osseous manifestation of multiple myeloma is well known as the osteolytic or osteoporotic feature. On the other hand, there are rare cases of general osteosclerotic manifestation as myeloma variants. We report a case of multiple myeloma with solitary osteosclerotic legion in the cervical vertebra. A 60-year-old-man was admitted with paralysis of both arms. The cervical roentogenogram showed the osteosclerotic change of the seventh cervical vertebra. The pathological study of surgical bone biopsy from the vertebra revealed osseous and severe fibrotic change and accumulation of plasma cells in the residual bone marrow. Clusters of plasma cells were also observed in the bone marrow of ileac bone. In addition, IgG-lambda type M protein was seen in the serum. Therefore we diagnosed this case as the osteosclerotic multiple myeloma. We then analyzed the cytokines known to influence bone formation, and found that the bone marrow serum TGF-beta and PDGF levels were increased compared with normal control. These results may suggest that the preferential increase of osteosclerotic cytokines caused the osteosclerotic changes of bone marrow.
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PMID:[Multiple myeloma with a solitary osteosclerotic legion on seventh cervical vertebra]. 942 41

Decreased bone formation plays an important role in the development of lytic lesions during the late stage of multiple myeloma (MM). Release of insulin-like growth factor binding protein-4 (IGFBP4) by tumour cells adjacent to bone may inhibit IGF-I-stimulated osteoblast growth and contribute to decreased bone formation. The present study demonstrates that the human MM cell line, ARH-77, expresses IGFBP4 and, to a lesser extent, IGFBP6 mRNA and protein. IGFBP4 expression in myeloma cells may be modulated by cytokines released by stromal cells and T cells in the microenvironment. We tested the effect of recombinant interferon-gamma (INF) on IGFBP4 expression in ARH-77. INF increased IGFBP4 mRNA and protein levels at 12 h, with a decline to baseline by 24 h. In contrast, IGFBP4 was not regulated in response to IL-6, TNF-alpha, PDGF BB, bFGF, TGF-beta or the cAMP agonist, forskolin. In other systems. IGFBP4 may also be regulated post-transcriptionally by a protease that is activated by IGF-I or -II. Conditioned medium from ARH-77 cultures incubated with IGF-I or -II for up to 24 h failed to demonstrate proteolytic activity. Proteolysis was also not observed when conditioned medium containing exogenous rhIGFBP4 was incubated with IGF-I or -II under cell-free conditions. To determine if human myeloma tumours also express IGFBP4, total RNA was isolated from four tumour biopsies. All samples expressed detectable levels of IGFBP4 mRNA. These findings indicate that interferon-gamma may indirectly modulate bone formation via the the release of tumour-derived IGFBP4. suggesting that the immune system may influence bone turnover in MM. Failure of myeloma cells to release protease activity may promote IGFBP4 accumulation in the microenvironment during tumour growth.
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PMID:Potential role of insulin-like growth factor binding protein-4 in the uncoupling of bone turnover in multiple myeloma. 1019 30

Multiple myeloma (MM) is a cancer of plasma cells, characterized by profound suppression of host immune responses. Here we show that MM cell lines significantly suppress the proliferation, blasting, response to interleukin-2 (IL-2), and expression of CD25 by concanavalin A (Con A)-activated or allostimulated peripheral blood T lymphocytes. T cells arrest in the G1 stage of the cell cycle, and do not enter the IL-2 autocrine growth pathway. T cell inhibition was mediated by a soluble factor. MM cell lines did not produce IL-10 but did produce large amounts of transforming growth factor beta1 (TGF-beta1). T cells were assessed for their ability to respond to IL-2 when co-cultured with MM cells in the presence or absence of the TGF-beta inhibitor, TGF-beta latency-associated peptide (LAP). MM cells suppressed IL-2 responses but this inhibition was completely reversed by TGF-beta LAP. A CD25-, IL-2-dependent blast cell line was not inhibited by MM cells or rhTGF-beta, confirming the specificity of the inhibition mechanism for the IL-2 autocrine growth pathway. We conclude that MM cells suppress T cells in their entry into the autocrine IL-2/CD25 pathway and in response to IL-2, and that TGF-beta has a significant role to play.
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PMID:Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes. 1061 81

To elucidate the role of PTHrP in myeloma, we examined the expression levels of PTHrP and its receptor in human myeloma cell lines and clinical specimens from 13 myeloma cases. In vitro modification of PTHrP expression and production induced by TGF-beta and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six out of seven myeloma cell lines with an inverse correlation with the expression of its receptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHrP expression and secretion into culture medium were enhanced by supplemental TGF-beta and PMA. PMA also seemed to affect PTHrP upregulation via TGF-beta activation. The fundamental role of PTHrP in bone lesions and hypercalcemia in myeloma may be important to consider even during the initial phase of the disease and particularly in the progression of bone complications with hypercalcemia.
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PMID:Expression and in vitro modification of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor in human myeloma cells. 1137 53


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