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)

Three cases of canine multiple myeloma that showed monoclonal IgA gammopathy and bone lesions were examined. One dog was associated with Bence-Jones proteinuria as well. Radiographic examination revealed extensive skeletal involvement of flat bones such as scapula, pelvic bone, costa, and epiphysis of long bones where the hematopoiesis was active throughout the life. Histopathologically, small osteolytic lesions occurred from periosteum and Haversian canal as well as endosteum, and larger lesions were formed by gradual expansion or fusion of small lesions. Osteolytic lesions did not necessarily involve tumor growth, explaining the inconsistent confirmation of tumor cells in biopsy specimens for diagnosis of multiple myeloma and suggesting the possible mechanism for osteolysis by some other humoral factors.
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PMID:Bone lesions of multiple myeloma in three dogs. 821 53

Sodium cyanate is a selective inhibitor of protein synthesis in a variety of mammalian tumor cells without a corresponding effect on normal tissue of the tumor-bearing animals. In the present study, we investigated the potential role of sodium cyanate in the augmentation of the antitumor activity of melphalan in MOPC-460D myeloma-bearing BALB/c mice. The simultaneous intraperitoneal injection of sodium cyanate, 250 mg/kg, and melphalan, 12 mg/kg, followed by another dose of sodium cyanate, 200 mg/kg, administered 18 hours later, resulted in a tumor growth inhibition index (TGII) of 207%. In contrast, melphalan or sodium cyanate administered separately at the same dose induced a TGII of 133% and 15%, respectively, when compared to control animals. Furthermore, a direct comparison of the volume of tumor implants in mice treated with the combination of sodium cyanate and melphalan vs. those treated with melphalan alone showed a statistically significant growth inhibition in favor of the sodium cyanate and melphalan combination on days 35, 39, and 42 from initiation of treatment. The data presented here suggest that the antitumor activity of melphalan could be increased, with moderate toxicity, by the concomitant intraperitoneal administration of sodium cyanate in BALB/c mice bearing measurable subcutaneous MOPC-460D tumor transplants. This is the first report of an increase in melphalan antitumor activity by sodium cyanate at a tumor location distant from the site of injection.
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PMID:Alteration of the systemic antitumor activity of melphalan by sodium cyanate in MOPC-460D myeloma-bearing BALB/c mice. 846 73

Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin has been focused on as a target molecule for passive immunotherapy. We have cloned the cDNA encoding the immunoglobulin light and heavy chains of an anti-GD3 monoclonal antibody KM641 (murine IgG3, kappa), and constructed the chimeric genes by linking the cDNA fragments of the murine light and heavy variable regions to cDNA fragments of the human kappa and gamma 1 constant regions, respectively. The transfer of these cDNA constructs into SP2/0 mouse myeloma cells resulted in the production of the chimeric antibody, designated KM871, that retained specific binding activity to GD3. Indirect immunofluorescence revealed the same staining pattern for chimeric KM871 and the mouse counterpart KM641 on GD3-expressing melanoma cells. When human serum and human peripheral blood mononuclear cells were used as effectors in complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity respectively, the chimeric KM871 was more effective in killing GD3-expressing tumor cells than was the mouse counterpart KM641. Intravenous injection of chimeric KM871 markedly suppressed tumor growth in nude mice. The chimeric KM871, having enhanced antitumor activities and less immunogenicity than the mouse counterpart, would be a useful agent for passive immunotherapy of human cancer.
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PMID:A mouse/human chimeric anti-(ganglioside GD3) antibody with enhanced antitumor activities. 850 Jan 10

It remains to be clarified whether IL-6 acts on the growth of human myeloma cells by an autocrine or paracrine mechanism. Even in established myeloma cell lines, the autocrine growth by IL-6 appears unusual. In the present study, we deviced a model of IL-6 autocrine growth in vitro by transfecting IL-6 cDNA into a human myeloma cell line that had a proliferative response to IL-6 but did not produce IL-6. After IL-6 transfection, the cells (S6B45) proliferated in culture media without IL-6. IL-6 production by S6B45 was demonstrated both at protein and mRNA level. The growth of S6B45 was definitely inhibited by anti-IL-6 (MH166) or anti-IL-6 receptor (PM1) monoclonal antibodies. Furthermore, S6B45 was successfully transplanted to nude mice. The transplanted tumor growth was clearly inhibited by the administration of MH166 or PM1 to the mice. The in vivo antitumor activity of these antibodies suggest a new therapeutic strategy against tumors that proliferate by an autocrine mechanism through a cytokine such as IL-6.
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PMID:[Growth characteristics of a human myeloma cell line transfected with IL-6 cDNA]. 851 Mar 28

Interleukin-6 (IL-6), a product of bone marrow stromal cells (BMSCs), is a growth factor for multiple myeloma (MM) cells. Transforming growth factor-beta1 (TGF-beta1) is also produced by BMSCs and can regulate IL-6 secretion by several tissues, including BMSCs. The present study was designed to characterize in vitro tumor growth regulation by TGF-beta1 in MM. Sorted CD38+CD45RA- MM cells secreted significantly more TGF-beta1 (8.2 +/- 2.0 ng/mL) than peripheral blood mononuclear cells (P < .001), splenic B cells (P < .001), and CD40 ligand (CD40L) pretreated B cells (P < .05). TGF-beta1 secretion by MM-BMMCs (3.8 +/- 0.9 ng/mL) was significantly greater than by N-BMMCs (1.2 +/- 0.1 ng/mL, P < .001). MM-BMSCs also secreted significantly more TGF-beta1 (6.6 +/- 2.5 ng/mL, n = 11) than N-BMSCs (4.4 +/- 0.6 ng/mL, P < .02, n = 10) and N-BMSC lines (3.9 +/- 0.2 ng/mL, P < .02, n = 6). TGF-beta1 secretion was correlated with IL-6 secretion in MM-BMSCs. Anti-TGF-beta1 monoclonal antibody both blocked IL-6 secretion by BMSCs and inhibited the increments in IL-6 secretion by BMSCs induced by MM cell adhesion. Moreover, exogenous TGF-beta1 upregulated IL-6 secretion by MM-BMSCs, normal BMSCs, and CD38+ CD45RA- MM cells, as well as tumor cell proliferation. This is in contrast to the inhibitory effect of TGF-beta1 on proliferation and Ig secretion of normal splenic B cells. Finally, retinoblastoma proteins (pRB) are constitutively phosphorylated in MM cells; TGF-beta1 either did not alter or increased pRB phosphorylation. pRB are dephosphorylated in splenic B cells and phosphorylated in CD40L triggered B cells in contrast to its effects on MM cells, TGF-beta1 decreased phosphorylation of pRB in CD40L treated B cells. These results suggest that TGF-beta1 is produced in MM by both tumor cells and BMSCs, with related tumore cell growth. Moreover, MM cell growth may be enhanced by resistance of tumor cells to the inhibitory effects of TGF-beta1 on normal B-cell proliferation and Ig secretion.
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PMID:Transforming growth factor-beta1: differential effects on multiple myeloma versus normal B cells. 863 41

The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients.
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PMID:Erythropoietin and the anemia of cancer. 866 61

Our previous study showed that the injection of mouse myeloma VKCK/RM4-IFN-tau cells secreting the fusion protein RM4/IFN-tau to syngeneic BALB/c mice resulted in tumor regression in 70% of mice after tumor inoculation. In this study, the VKCK/RM4-IFN-tau cell line was used to characterize the protective immunity subsequent to tumor inoculation. Our histologic findings demonstrated that, in the primary response to VKCK/RM4-IFN-tau inoculation, tumor regression is associated with macrophage infiltration. This macrophage-dominated regression further leads to a protective immunity against the 2nd challenge of parental VKCK tumor cells. FACS analysis and chromium release assays showed that the majority of T lymphocytes that mediated this anti-tumor immunity were CD8+ cytotoxic T lymphocytes (CTLs). Our animal studies further showed that the VKCK/RM4-IFN-tau cells were able to grow as aggressively as the parental VKCK cells in T lymphocyte deficient nude mice. The protective immunity started 7 days, became complete 10 days following and lasted up to at least 12 months subsequent to the tumor inoculation. The adoptive transfer of T lymphocyte-enriched spleen cells or CTLs also conferred significant protection against tumor growth of parental VKCK cells (p < 0.01). These data thus support the notion that genetically engineered tumor cells secreting IFN-tau may have potential use as tumor vaccines in preventing the development of tumor recurrence and/or metastases following the surgical removal of the primary tumors.
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PMID:Characterization of anti-tumor immunity derived from the inoculation of myeloma cells secreting the fusion protein RM4/IFN-tau. 888 33

A 63-year-old Japanese male with a four-year history of asymptomatic hypogamma-globulinemia is presented. On admission, he had a mild bone marrow plasmacytosis at about 10% of the total nucleated cells, but had no anemia, no paraproteins nor bone lesions. Flow cytometric analysis showed a predominant proliferation of kappa chain-positive cells in the bone marrow and peripheral blood, and an increase in the proportion of natural killer cells in the peripheral blood. Furthermore, coexistent meningioma and transitional cell carcinoma of the bladder were subsequently found 9- and 15-months after the admission, respectively. We considered that a myeloma-induced, possible latent immunodeficiency may have allowed the additional tumor growth, and that this process may have been controlled by the cytotoxic subset of immune effector cells.
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PMID:Asymptomatic multiple myeloma with concomitant neoplasms of two different origins. 898 71

Although IL-6 has been identified as a major growth factor in multiple myeloma (MM), it is believed that maintenance of tumor growth in vivo depends on one or more additional stroma-derived factors. We describe a new human myeloma cell line (MM5.1) that can be maintained in the presence of bone marrow-derived stromal cell layers, and not only when cultured with exogeneous IL-6. This cell line expresses the same immunoglobulin kappa light chain RNA sequence as the patient's original tumor cells, has a plasma cell morphology and expresses plasma cell antigens (cytoplasmic kappa light chain, CD38, BB4). Without the presence of stromal factors, MM5.1 cells become apoptotic. A low proliferative effect was observed in the presence of oncostatin M (OSM) but other cytokines (IL-10, IL-11, stem cell factor (SCF) and leukemia inhibitory factor (LIF)) had no effect at all. We observed that MM5.1 cells also grow when physically separated from stromal cell layers by a 0.45 microm microporous membrane or when cultured in conditioned medium from stromal marrow cells. Unexpectedly, the growth in stromal supernatants was markedly inhibited by an anti-IL-6 antiserum and an anti-IL-6 receptor transducer chain (gp130) mAb in a dose-dependent manner. This implies that MM5.1 cells are IL-6 responsive only when exposed to one or more additional soluble factor(s) derived from bone marrow stroma. Coculturing MM5.1 cells with IL-6 and cytokines that were described to increase the IL-6 responsiveness of myeloma cells (G-CSF, GM-CSF and IL-3) had no effect on the growth or survival. A strong proliferative effect was observed when MM5.1 cells were cultured with IL-6 and soluble IL-6 receptor (sgp80). However no sgp80 could be detected in stromal supernatants using a sensitive immunoassay. This indicates that sustained proliferation of the MM5.1 cell line depends on a combination of IL6 and at least one, thus far unidentified, stroma-derived factor. After more than 1 year in continuous culture, we could obtain a variant of the line (MM5.2) that shows an improved growth rate and grows stroma independently. Molecular analysis revealed clonal identity with the early passage form and Epstein-Barr virus antigen expression was negative. The two variants of this cell line offer a useful model to identify molecular mechanisms involved in clonal evolution towards stroma-independent growth of myeloma cells.
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PMID:Establishment and characterization of a human stroma-dependent myeloma cell line (MM5.1) and its stroma-independent variant (MM5.2). 900 94

Although the underlying genetic defect in multiple myeloma is unknown, activating mutations in the N- and K-ras oncogenes are common. Recent studies have suggested that ras mutations are associated with disease progression. We have introduced an activated N-ras12, N-ras61, or K-ras12 cDNA into the interleukin 6 (IL-6)-dependent multiple myeloma cell line ANBL6 to determine the effect of N- and K-ras on the growth/death properties of ANBL6. All three transduced cell populations demonstrate a growth advantage over the parent ANBL6 when propagated on normal human bone marrow stromal cells. In the absence of bone marrow stromal cells, augmentation of growth was observed in all three mutant ras-expressing populations at optimal and suboptimal concentrations of IL-6. Furthermore, in the absence of IL-6, all mutant ras populations demonstrated an augmentation in DNA synthesis when compared to the parent ANBL6. However, growth of the K-ras12 population in the absence of IL-6 was significantly inhibited when compared to the mutant N-ras populations. This could be explained by the observation that in the absence of IL-6, N-ras12 and N-ras61 suppress apoptosis, whereas K-ras12 does not. We also found that mutant ras expression could result in early protection from glucocorticoid-induced apoptosis similar to that observed by the addition of IL-6. However, the combination of mutant ras and IL-6 could completely block the glucocorticoid induction of apoptosis in long-term cultures. These data suggest that mutations in different ras family members may have similar or distinct effects on myeloma tumor growth and death and may alter the response to glucocorticoid treatment.
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PMID:Activating mutations in the N- and K-ras oncogenes differentially affect the growth properties of the IL-6-dependent myeloma cell line ANBL6. 918 31

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