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)

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.
 ...
PMID:Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia. 193 5

Two hybridomas producing monoclonal antibodies reactive with natural killer cells were selected after fusion of 129 anti-C57BL/6 immune spleen cells with P3X63-Ag8.653 myeloma cells. Treatment of normal or stimulated cells with the 4LO3311 or the 4LO439 mAb and rabbit complement inhibited natural killer and antibody-dependent cellular cytotoxicities, whereas cell lysis mediated by natural cytotoxic cells, cytotoxic T lymphocytes, or activated macrophages was unaffected. Lymphokine-activated killer activity was reduced after complement-mediated treatment of interleukin-2-stimulated spleen cells with the 4LO3311 mAb but not after treatment with the 4LO439 mAb. Similar treatment of spleen cells with either mAb had no effect on the mitogen-induced proliferation of T and B lymphocytes and did not alter the frequency of antibody plaque-forming cells in immune spleen cell suspensions. The 4LO3311 and 4LO439 mAbs thus appear to be specific for NK cells and their progeny. Flow cytometry analysis confirmed that 4LO3311+ and 4LO439+ cells are phenotypically identical to NK-1.1+ cells. The epitope recognized by the 4LO3311 mAb has the same strain distribution as the NK-2.1 alloantigen previously detected with NZB anti-BALB/c antiserum, whereas the 4LO439 mAb appears to identify a new NK cell marker exclusively expressed in mice of C57BL lineage. The relationship of the molecules detected with either the 4LO3311 or the 4LO439 mAb to polymorphic antigens of the Ly series is discussed.
 ...
PMID:Identification of murine natural killer cell subsets with monoclonal antibodies derived from 129 anti-C57BL/6 immune spleen cells. 201 2

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.
 ...
PMID:Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors. 203 17

Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies.
 ...
PMID:Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies. 204 62

The recombinant interleukin-2 (rIL-2) generation of lymphokine-activated killer (LAK) cells was investigated in peripheral blood T lymphocytes (PBT) of 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 32 patients with multiple myeloma (MM). LAK activity was significantly decreased in MM, but not in MGUS patients, and was partially recovered in MM in the remission phase. This finding was unexpected, because CD8+ CD11b+ cells, which contain LAK precursors, are significantly increased in MM. LAK activity was investigated in purified CD8+ CD11b+ lymphocytes to discriminate between an intrinsic defect or a defective regulation by other T cell subsets. These cells were intrinsically unable to generate LAK activity fully following rIL-2 stimulation. MM showed the more pronounced LAK deficiency, while MGUS patients showed intermediate values. Phenotyping revealed significantly increased proportions of Leu7+ and HLA-DR+ cells in MM patients. These data reveal another dysregulation of T cell effector functions in patients with monoclonal gammopathies and offer further evidence of the impairment of their cell-mediated immunity.
 ...
PMID:Defective interleukin-2 induction of lymphokine-activated killer (LAK) activity in peripheral blood T lymphocytes of patients with monoclonal gammopathies. 210 68

Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2.19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes an important mechanism of monocyte killing activity against microorganisms and probably against malignant cells, it is suggested that ranitidine may be of beneficial impact in the treatment of multiple myeloma.
 ...
PMID:The effect of ranitidine on cellular immunity in patients with multiple myeloma. 228 14

There has been little progress in the treatment of patients with multiple myeloma, and the average survival time is still only about 3 years. Although there have been significant therapeutic advances in recent years, clinical trials have only just begun. The major concern is, of course, the achievement of major disease control (which can be equated with a cure). The data available to date indicate that this is possible only with the use of allogeneic bone marrow transplantation, with which a survival plateau of around 30% can be attained. The trials should perhaps include the sequential use of all regimens with established efficacy in refractory myeloma. Immunoconjugate therapy with either radioisotopes or cytotoxic agents could also be envisioned, and expansion with suitable biological agents such as interleukin-2 could be considered. There is a plethora of promising treatment possibilities and novel concepts that may improve the dismal outlook for patients with multiple myeloma.
 ...
PMID:Management of multiple myeloma. 240 26

A method to efficiently antigen-prime B-lymphocytes with low amounts (less than 1 microgram/10(8) cells) of either immunogenic or non-immunogenic molecules is described. Keyhole limpet hemocyanin (KLH) and histone were used as prototypes for strongly immunogenic and for phylogenetically conserved non-immunogenic epitopes, respectively. Several modifications of previously reported methods were applied to the system and resulted in the requirement of antigen amounts sufficiently low to be obtainable by elution of proteins from electrophoretic gels. Antigen priming against highly purified antigen preparations is thereby feasible even when purified material cannot be obtained by conventional biochemical procedures. The amount of T- and B-lymphocytes and interleukin-2 production was estimated under various conditions during the priming procedure, and those optimal for generation of a high number of antigen-specific B-lymphocytes determined. In vitro antigen-primed B-lymphocytes were immortalized by conventional hybridoma technology. By fusion of lymphoid cells with myeloma cells at each day during the antigen-priming period, the optimal day of fusion to generate antigen-specific hybridomas was determined. Further, in 12 experiments with different antigens, 11 monoclonal antibodies to histones H3 and H4, two to the murine glucose transporter, 17 to trinitrophenyl-sheep red blood cells, and 20 to KLH were obtained. All specific hybridomas produced IgMs, as the antigen-priming period could not be extended for more than 9-10 days, whereafter a rapid decay in B-lymphocytes occurred.
 ...
PMID:In vitro B-lymphocyte antigen priming against both non-immunogenic and immunogenic molecules requiring low amounts of antigen and applicable in hybridoma technology. 243 6

Biological response modifiers can be divided into 2 groups; 1) immunomodulator (IM) or immunostimulator (IS) and 2) cytokines. Several IM or IS have been used clinically for the treatment of various cancers in combination with various chemotherapeutic agents. They are effective for prolonging the survival time or remission duration of cancer patients. However, no direct effect on cancer of the IM.IS has been proven. Cytokines such as interferons (IFNs) or interleukin-2 (IL-2) are effective against renal cell carcinoma, melanoma, hairy cell leukemia, multiple myeloma and other tumors even when they are used singly. IM.IS exert their anti-cancer effects through a combination of NK cell and macrophage activation or production of IFNs and ILs. Therefore, each effect is not strong enough to show a direct anticancer effect. Cytokines which are produced by recombinant techniques can be used in large doses and have been shown to have direct effects on certain types of cancers. The future approach is to devise the best combination between cytokines, cytokines and IM.IS, and cytokines and chemotherapeutic agents.
 ...
PMID:[BRM in the treatment of cancer]. 245 12

Previous work with continuously cultured multiple myeloma lines suggested that cytokine production by tumor cells may mediate some of the medical complications of this disease. To further investigate this issue, we assayed freshly obtained bone marrow (BM) cells from myeloma patients for the in vitro production of cytokines and the presence of cytokine RNA. Production of cytokine protein was assessed by bioassays with the aid of specific neutralizing anticytokine antibodies. These assays detected interleukin-1 (IL-1) and tumor necrosis factor (TNF) secretion by myeloma BM cells, which was significantly greater than secretion from similarly processed BM cells of control individuals. In contrast, lymphotoxin and interleukin-2 (IL-2) production could not be detected. The levels of IL-1 and TNF produced in vitro peaked at 24 hours of culture and correlated with stage and the presence (or absence) of extensive osteolytic bone disease. Northern blot analysis demonstrated the presence of IL-1 beta and TNF RNA in uncultured myeloma BM cells but no detectable IL-1 alpha or lymphotoxin RNA. In addition, the amount of cytokine RNA correlated with protein production, being significantly greater in patients' BM cells than in control marrow. These data suggest a role for IL-1 beta and/or TNF in the pathophysiology of multiple myeloma and argue against a role for lymphotoxin or IL-2.
 ...
PMID:Production of cytokines by bone marrow cells obtained from patients with multiple myeloma. 247 82


<< Previous 1 2 3 4 5 6 7 8 9 Next >>