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)

Clinical staging, such as with the Durie-Salmon clinical staging method, remains the most easily usable available method to classify patients with untreated multiple myeloma. However, for the development of new treatment strategies and comparison with prior results, new and powerful prognostic factors are now available. Serum beta 2 microglobulin alone represents the most reliable prognostic factor in multiple myeloma. Beta 2 microglobulin alone allows simple and reproducible classification of patients into low grade myeloma with low serum beta 2 microglobulin versus high grade myeloma with high serum beta 2 microglobulin. Plasma cell labelling index is an additional factor which allows identification of patients with MGUS as well as subclassification of patients with low serum beta 2 microglobulin into those with relatively better or worse prognosis. For each grade of myeloma young (less than 63 years of age) patients have a slightly better survival. Independently of serum beta 2 microglobulin and labelling index, DNA content values allow the identification of a subset of patients with biclonal or hypodiploid tumors and high grade disease. New or more sophisticated methods for evaluating myeloma cells such as by immunophenotyping or assessment of multi drug resistance enable the development of specific approaches to treatment in individual cases. It should also prove possible to identify patients especially suitable for newer biologic agents such as alfa interferon, G or G-MCSF and the various interleukins.
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PMID:Therapeutic implications of myeloma staging. 269 83

In multiple myeloma (MM), low-cost maintenance treatment has some attractions, since maintenance of a small tumor is usually compatible with a fairly healthy state. However, the great majority of the studies of maintenance treatment have failed to show any clinical benefit. Based on simple theoretical consideration, it is shown that in MM response duration and survival are affected primarily by the residual tumor mass after primary treatment, and by the kinetics of the tumor. Continuation of maintenance treatment is likely to have a moderate effect. The main cause of that is identified in the presence or in the development of a substantial proportion of drug-resistant cells. Preliminary data suggest that only alpha-interferon can be useful for maintenance, and that it can act by slowing down the kinetics of the tumor.
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PMID:Maintenance treatment of multiple myeloma. 269 86

Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and hemibody irradiation received recombinant alpha-interferon as salvage therapy. The median duration of treatment was 8 weeks. One patient had an objective response and survived 8 months, whereas in the remaining 9 patients the disease progressed and median survival was 11.5 weeks. Side-effects were substantial and included confusion with extreme weakness, resulting in 5 patients refusing further therapy. The low response rate and the morbidity in this pilot study resulted in its discontinuation and the conclusion that recombinant alpha-interferon as single-agent therapy used for salvage in patients with refractory myeloma is of no value.
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PMID:Recombinant alpha-interferon as salvage therapy in multiple myeloma. A pilot study. 276 38

Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morphology, and response to various culture conditions. The tumor marker was the paraprotein idiotype. Low numbers of tumor cells were found in the blood of most of the patients. In some patients, the circulating tumor cells were solely B lymphocytes, whereas in other patients, they were lymphoid, lymphoplasmacytoid, and plasmacytoid. Dual surface antigen analysis of blood and bone marrow cells confirmed that the tumor may be composed of a spectrum of cell types. Thus, cells may range from surface-idiotype+,CD19+,CD20+, PCA-1-,cytoplasmic-idiotype- lymphocytes, to CD19-,PCA-1+,cytoplasmic-idiotype+ plasma cells that are surface-idiotype- or weakly surface-idiotype+. In one patient, some of the tumor cells co-expressed surface idiotype and CD10. The tumor B lymphocytes were activated in vitro to synthesize paraprotein by pokeweed mitogen (PWM), and by low molecular weight B cell growth factor (BCGF). In contrast, spontaneous synthesis of paraprotein by more mature tumor cells was inhibited by agents that also inhibit nonmyeloma plasma cells. These agents included PWM, gamma interferon, and phorbol ester. The results demonstrate that in multiple myeloma there exist different tumor cell types that are similar, by a variety of criteria, to normal B lineage cells at different stages of differentiation. Thus, further evidence is provided for the hypothesis of myeloma cell differentiation.
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PMID:Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow. 278 20

Hybridomas producing monoclonal antibodies against human alpha interferon (hu-IFN alpha) were constructed by fusion of NSO myeloma cells with spleen cells of BALB/c mice immunized with purified hu-IFN alpha. Altogether, 527 hybridomas were prepared in two separate experiments. From this cohort of hybridomas, 51 produced monoclonal antibodies against hu-IFN alpha. Seventeen out of fifty one hybridomas produced antibodies with neutralizing capacity for IFN while 34 hybridomas produced monoclonal antibodies with binding ability not accompanied with the neutralization of biological activity of IFN. The specificity of antibodies was determined with 3 types of tests: ELISA, ELISAN (modified ELISA) and neutralization test. Using isotype analysis, it has been found that 23 monoclonal antibodies were of IgM class, 20 were of IgG1 subclass, 4 were of IgG2b and 4 of IgG3 subclass. The average number of chromosomes in hybridomas was between 61.35 and 78.55. Their average doubling time was between 13.95 and 25.76 hrs.
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PMID:Preparation and characterization of hybridomas producing monoclonal antibodies against human alpha interferon. 287 27

To prepare hybridomas secreting monoclonal antibodies (MoAb) against human alpha-interferon (alpha-IFN), BALB/c mice were immunized with IFN produced in Namalwa cells. Native alpha-IFN, as well as partially purified or on cellulose adsorbed alpha-IFN preparations were used for immunization. Seven hybridomas continuously secreting IgG against human alpha-IFN were prepared by fusion of splenocytes from immunized donors with the mouse myeloma cells. MoAb reacted in ELISA as well as in neutralization test with human lymphoblastoid, leukocytic and recombinant alpha-IFN.
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PMID:Preparation of Hybridomas producing monoclonal antibodies against human interferon. 290 19

Natural leukocyte interferon and recombinant interferon alpha-2 have effected remission rates between 10 and 20% in the treatment of multiple myeloma. Response rates have been higher in untreated patients than in relapsing or primarily refractory cases. Patients with slowly proliferating tumors, early tumor stage or IgA-monoclonal protein seem to show increased sensibility to interferon as compared to patients without those characteristics. First trials using combined interferon chemotherapy regimens suggest that the toxicity associated with this treatment modality remains acceptable. At present, however, one cannot definitely decide whether and to which degree the combination therapy will improve the response rates.
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PMID:[Interferon therapy in multiple myeloma]. 305 70

Purified, recombinant human gamma-interferon (rIFN-gamma) was tested at clinically achievable doses for direct and indirect antiproliferative activity against human tumor cell lines using a clonogenic assay. One-h treatment with rIFN-gamma showed direct dose dependent inhibition of tumor colony growth in cell lines established from human melanoma, myeloma, renal cell, and cervical cancers. Longer treatments resulted in suppression of ovarian and breast carcinoma clonogenicity. In order to test for indirect antiproliferative effects of rIFN-gamma, feeder cells were included in a separate agarose underlayer in the cloning assay. These feeder cells included mouse peritoneal macrophages, U-937 (human histiocytic lymphoma cell line), and adherent cells from human malignant ascites specimens. Colony growth of ovarian carcinoma and melanoma cell lines was stimulated by each of these feeder cell types. Cultures containing mouse peritoneal macrophages or U-937 cells showed the same antiproliferative responses to rIFN-gamma as did control cultures without feeder cells. In contrast, human adherent ascites cells (greater than 80% macrophages) became strongly inhibitory to tumor colony growth when treated with rIFN-gamma. These results suggest that human tumor associated macrophages may become tumoricidal under the influence of rIFN-gamma, producing a diffusable substance in agarose culture which causes the observed antiproliferative effects on tumor cells.
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PMID:Direct and indirect effects of human recombinant gamma-interferon on tumor cells in a clonogenic assay. 308 Feb 33

The aim of this study was to determine the effects of interferon on in vitro immunoglobulin synthesis by the plasma cells of patients with multiple myeloma. Bone marrow cultures were set up in the presence of media alone or alpha-interferon. Supernatants were harvested over a 24-hour period and assayed for paraprotein immunoglobulin synthesis using radio-immunoassays developed in this department. The 24-hour paraprotein synthesis ranged from 9 to 493 micrograms/10(6) plasma cells in patients with IgG myeloma (n = 11), and from 0.3 to 8.3 micrograms/10(6) plasma cells in those with IgA (n = 4). Alpha-Interferon had variable effects on paraprotein synthesis in IgG myelomas, causing an inhibition of synthesis (up to 61%) in 3 patients and an enhancement of synthesis (up to 95%) in 5 cases. In IgA myelomas, on the other hand, alpha-interferon caused inhibition of synthesis in 1 case. In the 2 patients studied during alpha-interferon administration, IgG synthesis was significantly reduced. More cases are currently being investigated. Clearly, immunoglobulin synthesis by plasma cells shows variable modulation by alpha-interferon in vitro.
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PMID:Effect of interferon on the in vitro synthesis of paraprotein by plasma cells in myeloma. 312 75

A phase I and a phase II study of recombinant gamma-interferon (S 6810) were conducted on a cooperative basis involving 11 and 57 institutions, respectively. In the phase I study, a total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills was observed in approximately 80%. Other toxicities were fatigue (50%), gastrointestinal symptoms (30-40%), changes in hepatic enzymes, and hematological toxicities (20-30%). Dose-limiting factors were judged to be hypotension, leucopenia and CNS toxicity. Since the optimal dose for the phase II study was considered to be 5 X 10(6) U/m2 by daily chronic schedule, a further study was conducted using this dose. Response rates were as follows: 14.3% (renal cell cancer), 11.8% (multiple myeloma) 40.0% (chronic lymphocytic leukemia), 16.7% (non-Hodgkin lymphoma), and 67% (mycosis fungoides). Complete response was obtained in one case each of renal cell cancer, malignant lymphoma and mycosis fungoides. Moreover, intermittent high-dose gamma-interferon against renal cell cancer induced a response rate of 21.4%, significantly higher than the 8.6% obtained by continuous administration. Local injection against cutaneous malignancies resulted in a 55.3% response rate. Anti-viral effect against herpes zoster infection was also preliminarily evaluated. Among 4 cases, 3 responded subjectively well to local injection of gamma-interferon, which is a hopeful result, although a randomized trial is still needed.
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PMID:[Gamma interferon therapy of cancer patients]. 313 83


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