Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY-CFUc) from bone marrow aspirates were compared. At presentation, MY-CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY-VAMP or VERCY-VAMP, MY-CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY-VAMP and VERCY-VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission. There was no concomitant increase in normal tissue toxicity as measured by granulocyte-macrophage colony (GM-CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.
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PMID:Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone. 228 58

The effectiveness of ex vivo chemotherapy with drugs, such as vincristine, etoposide, and Adriamycin (doxorubicin, Adria Labs, Columbus, OH) for elimination of residual tumor cells from human bone marrow grafts could be undermined by the presence of multidrug-resistant tumor cells in the bone marrow. Therefore, to supplement chemoseparation, we investigated whether MRK-16, a monoclonal antibody (MoAb) to the surface moiety of multidrug resistance-associated P-glycoprotein antigen, can eliminate drug-resistant tumor cells in the presence of rabbit complement (RC). Two doxorubicin (DOX)-resistant human myeloma tumor cell line, 8226/DOX40 (resistant to 4 x 10(-7) mol/L DOX) and 8226/DOX6 (6 x 10(-8) mol/L DOX) with high and low amounts of cell surface P-glycoprotein, respectively, and the drug-sensitive parent cell line 8226/S were used as tumor models in this study. Using the limiting dilution assay, we have shown that three cycles of treatment with 25 micrograms/mL of MRK-16 MoAb and a 1:4 final dilution of RC eliminated 2.90 +/- 0.10 logs of 8226/DOX40 cells and 1.94 +/- 0.18 logs of 8226/DOX6 cells. One and two cycles of treatment were less effective, eliminating 0.47 +/- 0.40 and 1.94 +/- 0.36 logs of 8226/DOX40 and 0.12 +/- 0.20 and 1.63 +/- 0.58 logs of 8226/DOX6 cells, respectively. The 8226/S cell growth was unaffected by one to three cycles of treatment. The cell kill was not impaired when the antibody plus complement treatment was carried out on a mixture of 8226/DOX40 or 8226/DOX6 cells with a ninefold excess of irradiated bone marrow mononuclear cells (MNCs). The three cycles of treatment with antibody plus complement did not adversely affect granulocyte-macrophage colony-forming unit (GM-CFU) survival in hematologically normal marrows (92.5% to 104% survival) or in myeloma patient marrows (85% to 100%). These results show that it is possible to eliminate drug-resistant myeloma tumor cell lines from the admixed human bone marrow by treatment with MRK-16 MoAb plus RC. This method could prove to be effective for elimination of other drug-resistant tumor cell lines including those of leukemia and solid tumors, and will be further useful for supplementing chemopurging, and immunopurging of bone marrow with other antitumor cell antibodies.
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PMID:Elimination of drug-resistant myeloma tumor cell lines by monoclonal anti-P-glycoprotein antibody and rabbit complement. 257 83

To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and Etoposide (VP-16) as a purging agent for myeloma cells in bone marrow ex-vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal bone marrow (BM) cells were treated at different concentrations of 4-HC, VP-16. In separate experiments, LAK cells or antibodies were also used to treat the above cell lines. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal bone marrow cells at a 4-HC concentration of 60 mumol/l. Under similar conditions, approximately 1% of normal BM myeloid progenitor granulocyte-macrophage colony forming cells (CFU-GM) survived. The results with LAK cells and antibodies were also encouraging. These observations support the use of various purging methods for myeloma cells for autologous bone marrow transplantation.
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PMID:Ex vivo treatment of myeloma cells by 4-HC, VP-16, LAK cells and antibodies. 262 87

Avidin-biotin immunoadsorption, a technique based on the high affinity between the protein avidin and the vitamin biotin, has been used to remove neoplastic plasma cells from the bone marrow of patients with multiple myeloma. Buffy coat cells obtained from 25 patients were first incubated with monoclonal antibodies (MoAb) capable of recognizing plasma cell-associated antigens (i.e., 8A, 8F6, 62B1, and cocktails of 8A plus 8F6 or 62B1), then with biotinylated goat antimouse immunoglobulin, and passed over a column containing avidin conjugated to Sepharose GMB. Both non-linked and linked cells were analyzed by immunofluorescence and morphological staining. The results showed that over 98% of plasma cells were removed by using 8A or 8F6 alone, while 99.5% +/- 0.4 SD of plasma cell purging was achieved with 2 associated MoAb. In addition, the overall recovery of committed granulocyte-macrophage (CFU-GM),* erythroid (BFU-e), and multilineage (CFU-GEMM) progenitors after column treatment ranged from 39% +/- 15 SD to 50% +/- 6 SD, from 15% +/- 2 SD to 39% +/- 7 SD, and from 16 +/- 4 SD to 64% +/- 10 SD, according to the MoAb employed. On this basis avidin-biotin immunoadsorption appears to be a suitable technique for ex-vivo manipulation of bone marrow infiltrated by neoplastic plasma cells.
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PMID:Bone marrow purging for multiple myeloma by avidin-biotin immunoadsorption. 264 22

Normal granulocyte-macrophage precursors (CFU-GM) were studied in 65 multiple myeloma patients by means of culture assays. The patients were divided into separate groups on the basis of previous therapy (i.e. analysis performed at diagnosis or after chemotherapy), time elapsed from the last therapy (i.e. more or less than 1 month) and clinical features of the disease (i.e. tumor stage, immunoglobulin type, bone marrow plasma cell infiltration). The results were evaluated by Wilcoxon rank sum test and linear regression analysis. There was no statistical difference in CFU-GM cloning efficiency or in the number of CFU-GM/ml of bone marrow, even though a larger CFU-GM recovery was found in patients evaluated at diagnosis or at least 1 month or more from previous chemotherapy. In addition, no correlation was demonstrated between bone marrow plasma cell percentage and CFU-GM cloning efficiency. This finding was confirmed by the number of myeloid bone marrow cells in S-phase, assessed by the bromodeoxyuridine labeling index, which showed similar results in patients with different degrees of plasma cell infiltration. In conclusion our data indicate that the granular-monocytic lineage keeps its cell-line potentiality regardless of the degree of marrow plasma cell infiltration and the type of therapeutic approach. These data suggest that autologous bone marrow transplantation might be feasible even in patients with a large neoplastic infiltration.
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PMID:Normal myeloid progenitors (CFU-GM) in multiple myeloma: a preliminary study in view of autologous BMT. 267 56

As a result of the striking discrepancy between the substantial amount of information on the role of natural killer (NK) cells derived from in vitro experimentation and the corresponding lack of data demonstrating their physiologic relevance, we have examined the importance of NK cells for the steady state production of hematopoietic stem and progenitor cells in situ. B6D2F1 mice received two 0.2-ml injections of ascites containing anti-NK 1.1 monoclonal antibody (anti-NK) directed to murine NK cells. Another group was treated similarly but received "control" ascites (CA) that was induced solely by injection of a mouse myeloma cell similar to the fusion partner of the NK 1.1 hybridoma. Two days after the last injection, we determined the number and cycling fraction (i.e., percentage of cells in S-phase determined by in vivo hydroxyurea suicide) of femoral stem cells (spleen colony-forming units; CFU-S) and committed granulocyte-macrophage (granulocyte-macrophage colony-forming units; CFU-GM), megakaryocytic (megakaryocyte colony-forming units; CFU-Meg), and erythroid (erythroid burst-forming units; BFU-E and erythroid colony-forming units; CFU-E) progenitor cells. The striking finding was the almost complete abolishment of the proliferation of CFU-Meg in the anti-NK group, resulting in a statistically significant (p less than 0.02) decrease in number to 37% of the CA control. In contrast, the cycling fraction of BFU-E was significantly (p less than 0.05) increased to 205% of the CA control with no increase in number. The number and cycling fraction of CFU-S, CFU-GM, and CFU-E in the anti-NK group were not significantly different from values in the control group. These findings add a novel aspect to the understanding of hematopoietic regulation by providing the first evidence for a differential effect of NK cells on the steady-state proliferation of CFU-Meg and BFU-E in situ.
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PMID:Differential effect of natural killer cells on modulating CFU-Meg and BFU-E proliferation in situ. 280 34

To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) as a purging agent for myeloma cells in bone marrow (BM) ex vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal BM cells were treated at different concentrations of 4-HC or VP-16. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal BM cells at a 4-HC concentration of 60 microM. Under similar conditions, approximately 1% of the normal BM myeloid progenitor granulocyte-macrophage colony-forming cells survived. These observations support the use of 4-HC for purging myeloma cells for autologous BM transplantation.
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PMID:Ex vivo treatment of myeloma cells by 4-hydroperoxycyclophosphamide and VP-16-213. 313 88

A double layer agar technique has been developed to grow myeloma colonies (MY-CFUc) from human bone marrow aspirates and peripheral blood. Heavily irradiated HL60 cells (5 x 10(5)/plate) are added to an agar underlay in growth medium containing 0.5% agar. Mononuclear cells from the test bone marrow or blood are overlayered in either 0.2 ml HL60-conditioned medium (HL60-CM) or in 0.5 ml growth medium containing 0.23% agar, and the cultures are incubated at 37 degrees C in an atmosphere of 5% CO2, 10% O2 and 85% N2. Colonies (greater than 50 cells) form between 2 and 3 weeks. Using this method 60/68 samples of bone marrow and 7/12 samples of blood from 54 patients have produced colonies in soft agar and in liquid on an agar underlay. The cells which form these colonies are of two distinct sizes, the larger cells being plasmacytoid and the smaller lymphoid. The two cell types are usually, but not always, present in separate colonies. Both plasmacytoid and lymphoid cells carry the isotype of the respective patient's myeloma protein and the plasma cell marker (HAN PC1). This technique has enabled us to culture myeloma cells from patients with as few as 2% plasma cells in the bone marrow but it does not permit the growth of normal B, T or granulocyte-macrophage colonies (GM-CFUc). The drug sensitivity of myeloma cells (MY-CFUc) compared with normal haemopoietic cells (GM-CFUc) can be measured using dose-response curves in individual patients. Furthermore, this method can detect resistant subpopulations within a given myeloma sample.
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PMID:A simple method for culturing myeloma cells from human bone marrow aspirates and peripheral blood in vitro. 339 Mar 92

Hybridomas derived from the fusion of murine myeloma cells with splenocytes from mice immunized with human cultured lymphoid cells secreted monoclonal antibodies to human cell surface antigens. Serologic and immunochemical assays showed that 4 monoclonal antibodies (Ab Q2/47, Q2/61, Q2/70, Q2/80) recognize framework determinants of Ia-like antigens and 1 monoclonal antibody (Ab Q1/28) reacts with determinants expressed on the heavy chain of HLA-A,B antigens. Both anti-HLA-A,B and anti-Ia-like antigen monoclonal antibodies caused complement-dependent inhibition of granulocyte-macrophage colony formation by human bone marrow grown in soft agar. Mixing experiments excluded the possibility of an indirect effect on progenitor cells by lysis of auxiliary cells. These results indicate that human myeloid progenitor cells express HLA-A,B and Ia-like antigens.
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PMID:Monoclonal antibodies to HLA-A,B, and Ia-like antigens inhibit colony formation by human myeloid progenitor cells. 615 98

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89


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