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Human Myeloma Cells (human + myeloma_cell)

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Medical Sciences100%

Selected Abstracts

Arsenic trioxide is effective in the treatment of multiple myeloma in SCID mice

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004
Philippe Rousselot
Abstract: Objectives :,Pharmacological concentrations of arsenic trioxide (ATO) and organic arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to further document the interest of the arsenic in vivo, we treated severe combined immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or melarsoprol. Methods :,Fifty-two SCID mice were irradiated before intraperitoneal (i.p.) injection of plasma cells from five myeloma patients. Engraftment was assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG) concentration in mouse serum. Treatment with ATO (10 ,g/g i.p. 5 d a week), melarsoprol (30 ,g/g i.p. 5 d a week) or phosphate buffer saline was started when a sustained growth of the tumor cells was demonstrated. Results :,Seventeen mice developed the human tumor. A significant decrease in HuMIgG amounts was observed in three of five mice of the ATO group, including two that achieved an apparent complete remission persisting up to 5 months after ATO discontinuation. In these mice, no human plasma cells were detected in tissue samples collected postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as a surrogate marker of the plasma cell proliferation, varied in parallel with HuMIgG concentration. A significant difference in survival was observed between control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no difference could be evidenced in control and melarsoprol groups. Conclusion :,Present study confirms in vivo the in vitro effects of ATO on myeloma cells. Delayed relapses were observed suggesting that prolonged or maintenance therapy has to be considered in future clinical trials. Whether or not this will translate into clinically relevant effect of the drug in myeloma patients deserves further consideration. [source]

The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2004
Patricia Gomez-Bougie
Abstract Multiple myeloma is a fatal B,cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax. [source]

Galectin-1 supports the survival of CD45RA(,) primary myeloma cells in vitro

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2008
Saeid Abroun
Summary The survival and proliferation of human myeloma cells are considered to be heavily dependent on the microenvironment of bone marrow (BM). This study confirmed that galectin-1 (Gal-1) and SDF-1, were produced by bone marrow mononuclear cells of myeloma patients. The addition of Gal-1 and SDF-1, to a serum-free synthetic medium, maintained the viability of primary myeloma cells for 2 weeks similar to that before culture. While Gal-1 reduced the viable cell number in CD45RA(+) B cell lines, it maintained the viability of CD45(,) U266 and CD45RA(,)RO(+) ILKM3 myeloma cell lines in the synthetic medium. This was confirmed with the transfection of the PTPRC (CD45) RA, -RB, or -RO gene into CD45(,) U266 cells. The combination of Gal-1 and SDF-1, significantly induced phosphorylation of Akt and IkB, while the phosphorylation of ERK1/2 was significantly reduced in CD45RA(+) U266 and Raji cells but not CD45(,) or CD45RA(,) U266 cells. Furthermore, we confirmed that Gal-1 bound to CD45RA in CD45RA(+) Raji cells, and also physically interacted with ,1-integrin by immunoprecipitation followed by Western blotting and confocal microscopy. The results suggest that Gal-1 has two different actions depending on its binding partner, and supports the survival of CD45RA(,) myeloma cells. [source]

Expression of protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2004
T. Otsuki
Summary The neuron cytoplasmic protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9·5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9·5 in myeloma cells was examined. PGP9·5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9·5 was observed in association with that of p27Kip1, a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9·5. These results suggested that PGP9·5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors. [source]