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 rearranged human immunoglobulin gamma 1 heavy-chain gene (HIG1) was cloned from a human plasma cell leukemia cell line, ARH-77. The cloned gene possessed a unique direct repeat sequence of 84 bp in the 5' flanking region as well as an enhancer-like element in the JH-C gamma 1 intron. The latter sequence is located 1 kb downstream of 3' end of the J6 exon. The direct-repeat sequence in the 5'-flanking region contained a core-like sequence resembling that of viral enhancer elements. It is located in the intron between two leader exons. P1 nuclease mapping and exonuclease VII digestion experiments showed that most of the direct repeats are noncoding regions and spliced out from the transcript. These data suggested that HIG1 gene might have two kinds of enhancer-like elements at both sides of the V region gene. HIG1 gene has been introduced by the protoplast fusion into mouse myeloma cells (NSI and J558L cells) and mouse fibroblasts. A pSV2gpt vector containing HIG1 gene (pSV2-HIG1) was used to transform the cells. The amounts of mRNA synthesized in the transformed cells were at least 50 to 100 times larger than those in ARH-77 cells, although about one copy of HIG1 gene was present in DNA of a transformed cell. HIG1 gene was not expressed in fibroblasts, indicating that the enhancer of HIG1 gene acts in a tissue-specific manner but not in a species-specific one. The role of two kinds of enhancer-like elements in HIG1 gene is discussed in connection with the high-level expression of this gene in mouse myeloma cells.
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PMID:A cloned human immunoglobulin heavy chain gene with a novel direct-repeat sequence in 5' flanking region. 392 55

Monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, display a variety of morphologic entities ranging from small lymphocytes to classic plasma cells. The cells show intense pyronin and periodic acid-Schiff affinity but are negative for colloidal iron, sudan black, and naphtol AS-D chloroacetate esterase. The cells exhibit phenotypic markers pertaining to each stage of the B-cell lineage. They fail to display sheep erythrocyte and bovine erythrocyte-IgG antibody complex rosettes, common acute lymphocytic leukemia (ALL) antigens and T-cell antigens, but most cells display surface complement receptors, Ia-like antigens, and surface and intracytoplasmic Ig. Monoclonal antibodies were negative for T-antigens, myelomonocytic cell antigens, leukemia-associated antigens, and BA-1 and OKT-10 antigens. However, 100% of the cells were positive with OKT-9 and B3/25 antibodies that are specific for transferrin receptors. About 50% to 80% of the cells were positive for surface membrane immunoglobulin (kappa IgG) and about 10% to 50% for cytoplasmic immunoglobulin (kappa IgG). Virtually all cells were positive when tested for nuclear Epstein-Barr virus antigens.
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PMID:ARH-77, an established human IgG-producing myeloma cell line. I. Morphology, B-cell phenotypic marker profile, and expression of Epstein-Barr virus. 609 3

The growth curve of monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, is represented by an everbending curve on a semilogarithmic plot; however, the curve can be fitted by a straight line on a linear-linear plot. This unusual growth pattern suggests that, instead of a fixed proportion of the population, a fixed number of ARH-77 cells divide per unit time. The following are cell cycle transit time parameters calculated from percent labeled mitosis experiments: TG1, 10.0 +/- 3.5 hours; Ts, 14.3 +/- 2.3 hours; TG2, 4.3 hours; TM, 1.4 +/- 1.3 hours; and Tc, 30.0 +/- 6.1 hours. For cells exposed continuously to 3H-thymidine the values are: growth fraction, 67%; TG1, 6.5 hours; Ts, 13.0 hours; and TG2 + M, 3.0 hours. The average doubling time is 4.6 days (range, 3.8-4.7 days); after about 10 to 15 days in culture, the growth rate of freshly passaged cells declines markedly, as reflected by a growth curve with a much shallower slope. The changes are accompanied by a marked decline in the labeling index from 41.3% (range, 28.9%-53.7%) during the first 3 days of culture to less than 5% measured on day 21. Flow cytometry for DNA content-dependent cell cycle compartment distribution demonstrates an obvious decline in the proportion of S-phase cells and a marked accumulation of G2 phase cells as the cultures age. When the supernatant medium of ARH-77 cells grown for 10 days is replaced by fresh medium, a new burst of vigorous cellular growth is observed with a curve slope similar to that observed during the first 5 days of culture. If the 10-day-old supernatant medium is used to set up cultures with freshly harvested ARH-77 cells, their growth curve resembles that of 10-day-old cultures. However, this supernatant medium induces no decrease in the growth rate of other human tumor cells, suggesting that inhibition of cellular growth does not result from exhaustion of nutrients, but that ARH-77 cells produce a molecular mediator that specifically inhibits the growth of these cells. ARH-77 cells could be synchronized with a single treatment of 3 or 5 mM thymidine; (dThd) and cloning efficiency was 2% to 4% in a double-layer soft agar assay. Treatment for 1 hour with increasing concentrations of melphalan produced a threshold exponential survival curve (Dq = 0.45 microgram/ml and D0 = 0.35 microgram/ml, 1 hour).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:ARH-77, an established human IgG-producing myeloma cell line. II. Growth kinetics, clonogenic capacity, chalone production, xenogeneic transplantations, and response to melphalan. 623 73

A complete set of a rearranged human gamma 1-heavy chain gene, HIG1, was cloned from human plasma cell leukemia line, ARH-77, and transferred into mouse cells. It was strongly expressed in mouse myeloma cells but not in mouse L cells, indicating that immunoglobulin gene expression is not species-specific but cell-specific. However, a remarkable production of human gamma 1 chain was induced in mouse L cells containing HIG1 gene when the cells were treated with cycloheximide for a short period. The role of a labile repressor molecule in the expression of the immunoglobulin gene is proposed.
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PMID:Induction of immunoglobulin gene expression in mouse fibroblasts by cycloheximide treatment. 651 93

Hybridoma clones were established by fusing spleen cells from mice hyperimmunized with human breast cancer cells of MDA-MB-231 line with murine myeloma cells P3-X63-Ag8-653. Ten permanent hybridomas were stabilized. The monoclonal antibodies of three of them, i.e. HBCA-6, HBCA-4 and HBCA-12 were tested against 20 various established cell lines. The most restricted binding properties showed HBCA-12 antibody which reacted positively only with two types of target cells. The cross-reactivity of HBCA-12 with human breast cancer cell line MDA-MB-231 and human myeloma derived cells ARH-77 is discussed in view of the pertinent target structure, i.e. differentiation antigens, allospecific antigens, hormone receptors and shared tumor associated antigens. It was shown that the target structure for HBCA-12 is localized on the cell surface.
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PMID:Monoclonal antibodies to membrane components of human breast cancer cell line MDA-MB-231. Production and reactivity with various cells in culture. 670 Jul 97

Ligand binding of the B-cell lineage antigen CD40 enhances growth and interleukin-6 (IL-6) secretion in human B cells (the CD40/IL-6 loop). IL-6 has an autocrine and paracrine role in human multiple myeloma (MM) cell growth. With the use of the CD40 monoclonal antibody (MoAb) G28-5, we examined CD40 expression and the effect of CD40 binding on MM clonogenic colony (MCC) formation to characterize the IL-6/CD40 loop activity in MM. CD40 was expressed on plasmacytoid cells in 21 of 28 plasma cell dyscrasia (PCD) bone marrow (BM) biopsies tested (10 of 14 MM, 2 of 2 Waldenstrom's macroglobulinemia [WM], 2 of 2 plasma cell leukemia [PCL], 6 of 8 monoclonal gammopathy of undetermined significance [MGUS], and 1 of 2 primary amyloidosis [AL]). G28-5 binding increased MCCs by 35% to 150% in 11 of 17 CD40+ PCD BM cultures, but did not affect MCC formation in CD40- specimens or normal BM colony forming units (CFU-GEMM, CFU-GM, BFU-E). Responsive cultures originated from BM of patients with MM (2 of 5 cases tested), WM (2 of 2), PCL (2 of 2), and MGUS (5 of 6). CD40-responsiveness was not significantly inhibited by the presence of an anti-IL-6 MoAb (2 of 2 MGUS cultures tested), and did not correlate with the capacity to respond to IL-6 stimulation (n = 17, P > .05) or a detectable level of endogenous IL-6 (n = 15, P > .05). Additional studies were performed with PCD cell lines to characterize the interrelationship of CD40 activation and IL-6 production. Fifty percent to greater than 95% of cells from the RPMI 8226 and ARH77 lines expressed CD40, whereas 6% of U266 cells were CD40+. For RPMI 8226, ARH-77, and U266 cells, the increased MCC formation after anti-CD40 stimulation was not affected by the presence of an anti-IL-6 neutralizing MoAb and was not accompanied by detectable IL-6 secretion. There was no apparent increase in IL-6 mRNA transcription following G28-5 treatment of U266 or RPMI 8226 cells. Our observations indicate that CD40 is expressed in a subset of human myeloma cells present in various PCDs. Cell-line studies suggest that the CD40+ myeloma cell may regulate MM clonogenic colony formation without activating the IL-6 pathway.
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PMID:Anti-CD40 antibody binding modulates human multiple myeloma clonogenicity in vitro. 752 65

Recent studies have suggested that ICAM-1 (CD54) is involved in the pathogenesis of human multiple myeloma. A monoclonal antihuman CD54 antibody has been generated by immunizing BALB/c mice with human myeloma cell lines. SCID mice injected with human ARH-77 myeloma cells develop disseminated myeloma which is similar in several respects to multiple myeloma in humans. The mice have monoclonal gammopathy and succumb to hind leg paralysis caused by infiltration of tumor cells into the thoracolumbar vertebrae, resulting in compression of the spinal cord. In the absence of treatment, the mean paralysis time of the SCID/ARH-77 mice is 29 days. When the SCID/ARH-77 mice received four consecutive daily i.v. injections of anti-CD54 mAb commencing 1 day after tumor inoculation, they survived for 150 days, at which time the experiment was terminated. Histopathological analyses indicated that prior to death all control SCID/ARH-77 mice had myeloma cells in the vertebrae and skull. At this time, the anti-CD54-treated mice had no evidence of tumor. High levels of human immunoglobulin were detected in the sera of control, but not treated mice. F(ab')2 fragments of the anti-CD54 antibody also had similar, albeit, slightly less antitumor activity in vivo, suggesting that antibody effector function may account for some, but not all the antitumor activity of anti-CD54. In vitro studies indicate that anti-CD54 does not inhibit homotypic adhesion, the binding of myeloma cells to murine bone marrow stromal cells, or cell proliferation. By exclusion, we propose that the CD54-mediated homing of these ARH-77 cells to certain anatomical sites is crucial for their growth in vivo.
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PMID:Anti-CD54 (ICAM-1) has antitumor activity in SCID mice with human myeloma cells. 783 32

We have generated a murine monoclonal antibody (UV3) which recognizes an epitope on ICAM-1 expressed on myeloma cells. By flow cytometric analysis, the epitope on ICAM-1 recognized by this antibody is strongly expressed on human myeloma cells, pre-B leukemia cells and Burkitt's lymphoma cell lines. Most human T cell lines are weakly positive. The antibody does not react with red blood cells, polymorphonuclear leukocytes (PMNs) or resting B lymphocytes from normal donors, and reacts very weakly with resting T cells. Immunohistochemical assays indicate that the antibody does not react with normal liver, kidney, heart, brain, thymus or lung. An immunotoxin (IT) was prepared by coupling UV3 to deglycosylated ricin A-chain (dgA). In protein synthesis inhibition assays it was highly cytotoxic to the human myeloma cell lines HS-SULTAN (IC50 = 1 x 10(-11)M) and ARH-77 (IC50 = 9 x 10(-11)M), but not to cell lines of T cell lineage or most cell lines of the B lineage. Our results suggest that the UV3-dgA may have therapeutic potential for the treatment of human multiple myeloma.
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PMID:Cytotoxicity of a novel anti-ICAM-1 immunotoxin on human myeloma cell lines. 790 88

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA-5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.
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PMID:Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. 791 45

In the present study we examined the production of fibronectin (FN) in 10 human myeloma cell lines (HMCL). By Northern blot analysis we could detect the presence of FN-mRNA in most of these lines. A majority of the cell lines (LP-1, OPM1, SKMM-2, EJM, JJN3 and ARH-77) hybridized with two probes recognizing total FN while the mRNA of one cell line (LB84-1) was shown to hybridize also with a probe recognizing the EDA segment of cellular FN. In one cell line (L363) FN-mRnA could only be detected after PCR amplification. Using an enzyme-linked immunosorbent assay, we could also demonstrate that HMCL secrete FN in their culture medium. Seven myeloma cell lines that produce FN showed a significant adherence to soluble FN. By blocking experiments, this adhesion was found to be mediated by the VLA-4 (alpha 4 beta 1) receptor. The production of fibronectin and the expression of a functional receptor for this protein may represent independent features of myeloma cells but may also be functionally linked. Since fibronectin has recently been identified as a crucial co-factor of IL6 in the regulation of the terminal B cell differentiation, the endogenous FN production may be part of an autocrine-line process mediating the autonomous growth of these cell lines. Alternatively, the FN production may also reflect a mechanism that myeloma cells use to communicate with their natural environment, i.e. the bone marrow stroma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of fibronectin and adherence to fibronectin by human myeloma cell lines. 794 65

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