Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of multiple myeloma was made in two white men, aged 55 and 59 years. They were treated with cyclophosphamide for 98 and 44 months respectively. Patient 1 also received a nine-month course of combined therapy with melphalan, procarbazine, and prednisone. Both developed acute erythroid leukemia, 98 and 71 months after the original diagnosis of myeloma, and died of subarachnoid hemorrhage and cardiac arrest. Patient 1 developed squamous cell carcinoma of the skin with recurrence, and Patient 2 developed anaplastic carcinoma of the urinary bladder. Palliative radiation therapy was given. The development of erythroid leukemia plus carcinoma in these two men suggests mutagenic change secondary to cyclophosphamide therapy.
 ...
PMID:Acute erythroid leukemia after cyclophosphamide therapy for multiple myeloma: report of two cases. 106 31

A patient with multiple myeloma in whom acute erythroleukaemia developed 5 years following treatment with irradiation and melphalan is reported. Immunoglobulin synthesis and immunofluorescence investigations provided evidence that the blast cells in the peripheral blood did not belong to the plasma cell series; ultrastructure examination demonstrated their myeloid origin. Chromosomally abnormal cells were observed in both the bone marrow and peripheral blood. Light-and electron microscopy of erythropoiesis in this case showed distinct features of dyserythropoiesis, similar to those described in other entities. The erythroid cell abnormalities are discussed in the light of their being either indications of malignancy or of a reactive process.
 ...
PMID:The morphology of dyserythropoiesis in a patient with acute erythroleukaemia associated with multiple myeloma. 107 Jan 41

The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was investigated in vitro in 21 patients with multiple myeloma to assess the clinical usefulness of rh-Ep in this disease. CFU-E and BFU-E assays were performed by methylcellulose culture methods. The myeloma patients were divided into two groups according to the percentage of plasma cells in the bone marrow (over 50% and under 50%). Among the patients with few plasma cells, some revealed normal CFU-E and BFU-E growth at 2 units of rh-Ep, and no further increase was observed even with an increasing dose of rh-Ep. Among the other patients, more than half demonstrated a good response to rh-Ep. Among the patients with a high percentage of plasma cells, some revealed no response to rh-Ep, but there were patients with a high percentage of plasma cells in the bone marrow who had a good response to rh-Ep. High doses of rh-Ep may be clinically effective in some patients with multiple myeloma independently of the level of plasma cells in the bone marrow.
 ...
PMID:Responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in multiple myeloma. 139 Feb 30

Mouse myeloma cells (SP2/0) were incubated with 125I-5s rRNA from rabbit reticulocytes and processed for autoradiography. The results indicated that 5s rRNA could pass into the nuclei of mouse myeloma cells. In a separate experiment, SP2/0 were incubated with cold 5s rRNA, then with 3H-TdR and processed for autoradiography. It was found that in the mouse myeloma cells, DNA synthesis and cell division were obviously suppressed. In another series of experiments, rRNA was extracted from rabbit bone marrow, reticulocytes and erythroid cells and from rat embryonic liver and erythroid cells. The rRNA was analyzed by agarose electrophoresis. It was found that the amount of 5s rRNA in various stages of erythroid development changed along with the denucleating process. Thus it seems likely that 5s rRNA from mammalian erythroid cells could play a role in reversing the malignant phenotype of tumor cells and denucleation of mammalian erythroid cells through inhibiting DNA synthesis.
 ...
PMID:The quantitative alteration of 5s rRNA during the development of mammalian erythroid cells and its effect on DNA synthesis in SP2/0 mouse myeloma cells. 142 58

Coexistence of myeloma and MDS was noted in a patient without history of exposure to cytotoxic drugs. A 73-year-old man was admitted because of fever and dyspnea on exertion. A complete blood count revealed macrocytic anemia with hemoglobin 7.1 g/dl, RBC 191 x 10(4)/microliters and MCV 111.2 fl. WBC was 6,000/microliters, with normal differentials. Bone marrow showed erythroid hyperplasia with M/E ratio of 1.36. There were marked tri-lineage cellular abnormalities, which included megaloblastic changes, multinucleated erythroblasts, hypersegmentation of neutrophils, giant neutrophils, and giant platelets. Ringed-sideroblasts were demonstrated in 20% of the erythroblasts. These findings were compatible with MDS. Although plasma cells accounted for only 9.7% of the nucleated marrow cells, there were many immature plasma cells with inclusion bodies, and the patient showed lambda-light chain type monoclonal gammopathy with corresponding Bence Jones protein. Immuno-histochemical staining of the bone marrow biopsy specimen revealed monoclonal growth of lambda-positive plasma cells. A punched-out lesion of the skull eventually developed. These findings suggest existence of myeloma. There have been some reports of coexistence of MDS and myeloma; supporting the idea of pluripotent stem cell origin of the disease. This is the first documentation of such a case in Japan.
 ...
PMID:[Coexistence of myeloma and primary myelodysplastic syndrome (MDS)]. 154 17

IgA1(kappa)-transferrin complex was ascertained in a case of multiple myeloma with hypersiderinemia. On gel filtration, this complex disclosed an orange-colored protein with two peaks between the 19S and 7S fractions. On polyacrylamide gel electrophoresis and Western blotting analysis, the complex migrated at molecular weights of 430 and 700 kD in the non-reducing condition. A small amount of free transferrin was detected simultaneously. The complex was further separated into monoclonal IgA1(kappa) and transferrin at pH 4.5; these recombined at pH 7.2 after incubation (37 degrees C, 2 h). We also showed that the pepsin-digested F(ab')2 fragment of IgA1(kappa) combined with the transferrin. From these results it can be suggested that monoclonal IgA1(kappa) has an antibody activity for the transferrin. Clinically, this complex distributed the iron transport to erythroid cells in the bone marrow, resulting in hypersiderinemia, anemia, and iron deposits in the liver.
 ...
PMID:Ascertainment of IgA1 (kappa)-transferrin complex in a case of multiple myeloma associated with hypersiderinemia. 179 8

Two novel retroviral vectors bearing lymphoid-specific enhancers were tested for improved expression of human adenosine deaminase (hADA) in tissue culture cells and in mouse bone marrow transplant recipients. These vectors carried either an added human T-cell receptor alpha-chain enhancer (delta N2TADA) or a substitution of the Moloney long terminal repeat (LTR) enhancer with the murine immunoglobulin mu heavy-chain first intron enhancer (delta N2 mu ADA). Each vector was produced at a titer of approximately 10(6) infectious units/ml and efficiently transduced hADA into murine fibroblast and myeloma cells in culture. No quantitative difference in expression was observed between the enhancer modified vectors and the basic retrovirus vector (delta N2ADA). In addition, each vector efficiently conferred hADA expression in lymphoid, myeloid, and erythroid cells of long-term transplanted mice. The majority of the transduced-marrow recipients demonstrated expression of the human enzyme for 4-8 months with each of the three vectors.
 ...
PMID:Evaluation of lymphoid-specific enhancer addition or substitution in a basic retrovirus vector. 183 33

Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients. Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast majority of neoplastic plasma cells appeared to be involved. Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10. The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration. Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function. The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen. Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro. Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals. The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody.
 ...
PMID:Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. 199 92

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.
 ...
PMID:Hemopoietins in clinical oncology. 204 61

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.
 ...
PMID:Multiple myeloma. 208 Oct 91


1 2 3 4 5 6 7 8 9 10 Next >>