losartan-potassium and Plasmacytoma

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Diphosphonates; Erythropoietin; Humans; Interferons; Interleukin-2; Middle Aged; Multiple Myeloma; Plasmacytoma; Prospective Studies; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Transplantation, Autologous

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoproliferative Disorders; Mice; Mice, Inbred BALB C; Plasmacytoma; Recombinant Proteins

To study the role of some soluble factors in the process of angiogenesis that accompanies multiple myeloma (MM).. The concentrations of three well-known angiogenic peptides, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) were evaluated by an ELISA method. All of these factors were measured in the plasma obtained from peripheral blood (PB) and bone marrow (BM) aspirates of 34 patients affected by plasma cell disorders. This series included one patient with a solitary extramedullary plasmacytoma, 17 patients with MM at diagnosis, and 16 with previously treated MM.. In all the patients, the concentration of each angiogenic factor was higher in bone marrow than in peripheral blood. Mean values of the three angiogenic factors in BM or in PB were lower in stage I than stage II-III. One patient with extramedullary solitary myeloma had high levels of VEGF and bFGF but this increase was not found in the other 6 patients with extramedullary disease when compared with patients without extramedullary disease. VEGF and bFGF did not correlate with each other while HGF showed a weak correlation with VEGF and a stronger one with bFGF. Moreover, VEGF correlated with features of disease activity, such as C-reactive protein, and 2-microglobulin, while both bFGF and HGF showed an inverse correlation with albumin level. No correlation was found between VEGF, bFGF and HGF levels and age, M protein level, osteolytic lesions, or percentage of BM plasma cells. Since angiogenic factors may be released by normal cells in response to hypoxia, we also evaluated erythropoietin (EPO) levels (which correlate with the hypoxic stimulus) both in PB and BM plasma of these patients but none of the measured angiogenic factors correlated with EPO levels. Interpretation and Conclusions. Several soluble factors may play a role in the angiogenic activity described in MM but their contribution to the progression of disease may be different. The finding of higher levels of these factors in BM than in PB might indicate that the bone marrow environment is their major source. Concentrations of angiogenic factors parallel the activity of disease and are independent of the hypoxic stimulus.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone Marrow; Cell Count; Endothelial Growth Factors; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fibroblast Growth Factor 2; Hepatocyte Growth Factor; Humans; Interferon-alpha; Lymphokines; Male; Middle Aged; Multiple Myeloma; Neoplasm Proteins; Neoplasm Staging; Neoplastic Stem Cells; Neovascularization, Pathologic; Plasma Cells; Plasmacytoma; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To compare the signal transduction pathways used by erythropoietin (Epo) and interleukin-6 (IL-6), the cDNA for the murine Epo receptor (Epo-R) was introduced into an IL-6-responsive plasmacytoma cell line (TEPC-2027) by retrovirally mediated gene transfer. G418-resistant clones were amplified in IL-6 and studied for their ability to grow and differentiate in response to Epo. Epo-R synthesized from the viral gene showed the same affinity for Epo as did the receptor on erythroid cells; however, the numbers of Epo receptors expressed on the cell membrane varied among clones. After a delay of 3 to 5 days in the presence of Epo, all the clones studied proliferated as well in response to Epo as in response to IL-6. In response to IL-6, Stat3 was activated and JunB mRNA was accumulated, whereas in response to Epo, Jak2 and Stat5 were activated and JunB mRNA was not accumulated in Epo-R-expressing TEPC (Epo-R/TEPC) cells. These results suggest that Epo and IL-6 transduced their proliferative signals through different pathways. Further studies showed that, in Epo-R/TEPC cells, Epo neither induces the synthesis of erythroid-specific mRNA nor modifies the synthesis of gamma 1 lg heavy chain, suggesting that ectopic expression of the Epo-R in plasmacytoma cells does not modify their differentiative potential. The data show that Epo induces a proliferative response without differentiation providing a new cellular model for evaluating molecular events specific for proliferation.

Topics: Animals; Cell Division; Erythropoietin; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Humans; Interleukin-6; Mice; Plasmacytoma; Receptors, Erythropoietin; Signal Transduction; Tumor Cells, Cultured

Hybrid cells that synthesize a monospecific antibody directed toward erythropoietin have been produced by the fusion of mouse plasmacytoma cells with spleen cells from rats immunized against human erythropoietin. The antibody binds the alpha and beta forms and the asialo alpha form of erythropoietin to the same extent. It is an immunoglobulin of the IgG class and binds only erythropoietin in an impure preparation of the hormone. Biologically active unlabeled erythropoietin competes with biologically inactive radiolabeled hormone for monoclonal antibody binding sites. In addition, the biological activity of erythropoietin measured in vitro is not inactivated when it is bound by the monoclonal antibody.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Binding, Competitive; Chromatography, High Pressure Liquid; Erythropoietin; Humans; Hybridomas; Lymphocytes; Mice; Plasmacytoma; Radioimmunoassay; Rats

Topics: Anemia; Animals; Blood Cell Count; Blood Volume; Erythropoiesis; Erythropoietin; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma

Topics: Adenocarcinoma; Animals; Erythropoietin; Humans; In Vitro Techniques; Mammary Neoplasms, Experimental; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Rabbits