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 DNA technology has made adequate quantities of human interferons available for both in vitro and in vivo testing. In the clonogenic assay, RPMI-8226 myeloma cells were tested with recombinant interferon alfa-2b (Intron A), melphalan, cyclophosphamide, and prednisone. Prednisone used as a single agent had the least cytotoxic effect. Concentrations of alfa-2b as low as 1 unit/mL (international antiviral activity) showed a reduction in colony number of less than 30% of the untreated controlled cultures. Melphalan and cyclophosphamide showed measurable cytotoxic activity, expressed in terms of 50% inhibition of colony growth, at doses of 0.15 microgram/mL and 0.4 microgram/mL, respectively. Additive antiproliferative effects were noted with combinations of alfa-2b plus cyclophosphamide and alfa-2b plus prednisone. However, the alfa-2b-melphalan combination had a synergistic effect on tumor-cell colony reduction. Even greater cytotoxic activity was seen with the three-drug combination of alfa-2b, melphalan, and prednisone. Clinical trials have shown that alfa-2b may be effective in patients with relapsing and refractory multiple myeloma. Of 38 patients evaluated, seven responded to treatment. Three of the seven responders have continued to respond for over 33 months, with monoclonal proteins approaching undetectable levels. A pilot study of the feasibility of combining alfa-2b with melphalan and prednisone in previously untreated patients with multiple myeloma has been completed. Although response was not the primary objective of this study, an overall response rate of 78% was achieved using criteria established by the Chronic Leukemia Task Force. Phase II trials conducted thus far have established tumor responsiveness to interferons in human myeloma. To clearly define the role of these agents in the treatment of myeloma, well-planned multicenter studies are needed.
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PMID:Interferons in the treatment of multiple myeloma. 376 41

PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.
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PMID:[Restoration of immunologic responsiveness by PSK in tumor-bearing animals]. 378 58

Three types of hybridomas were obtained by fusion of murine myeloma cells (NSI-1-Ag4-1) with splenocytes from mice immunized with human lymphoblastoid cells (RPMI-6410t line, acute myeloblastic leukemia). Hybridomas of the first type synthesize monoclonal antibodies Ma-1, which interact with 6410t-cells, but are not bound to the cells of human Burkitt lymphoma-Raji. Raji cells contain HLA-DRw5 and -DRw6 antigens on cell surface but there are no HLA-A2, -B7 and -B12 antigens (specific for 6410t). Thus, Ma-1 are probably derected against some of HLA antigens of loci A or B. Hybridomas of the second type synthesize Ma-2 antibodies which react with 6410t and Raji cells, but are not bound to peripheral blood lymphocytes (PBL). We suppose that Ma-2 antibodies to tumor specific antigens which have common antigen determinants both for Raji and RPMI-6410t cells. The third type of hybridomas synthesizes monoclonal antibodies Ma-3 reacting with all the three types of target cells: 6410t, Raji, and PBL. Ma-3 seems to be directed against human species-specific lymphocyte antigens which remained in 6410t and Raji cells.
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PMID:[Hybridomas synthesizing monoclonal antibodies to surface antigens of human lymphocytes]. 379 64

Recently, recombinant DNA methods have been successfully applied to interferon production, making adequate quantities available for both in vitro and in vivo testing. Although interferons are in the class of biologic response modifiers, they do have some direct cytotoxic effects on human tumor cells that can be quantitated in vitro with the colony-forming assay. In the clonogenic assay, RPMI-8226 myeloma cells were tested with interferon alfa-2b (Intron A, Schering Corp., Kenilworth, NJ), melphalan, cyclophosphamide, and prednisone. With concentrations of interferon alfa-2b as low as 1 U/ml (international antiviral activity), colony number was reduced to less than 30% of the untreated control cultures. Both melphalan and cyclophosphamide showed measurable cytotoxic activity, with the ID50 of melphalan at 0.15 microgram/ml and that of cyclophosphamide at 0.4 microgram/ml. Prednisone had the least cytotoxic effect when tested with these myeloma cells as a single agent. Additive antiproliferative effects were noted with combinations of interferon alfa-2b plus cyclophosphamide and interferon alfa-2b plus prednisone. However, the interferon-melphalan combination showed synergistic effects on tumor colony cell reduction. Even greater cytotoxic activity was seen with the three-drug combination of interferon alfa-2b, melphalan, and prednisone. Clinical trials have shown that interferon alfa-2b may be effective in relapsing and refractory patients with multiple myeloma. Of 38 evaluable patients, a total of seven responded to treatment; one patient had a complete response, and six had a partial response. Three of the seven responders have continued to respond for over 33 months, with monoclonal proteins approaching undetectable levels. A pilot study of the feasibility of combining interferon alfa-2b with melphalan and prednisone in previously untreated patients with multiple myeloma has been completed. It is concluded that interferon alfa-2b, in dosages not exceeding 2.0 X 10(6) IU/m2, can be safely given in combination with melphalan and prednisone, without compromising melphalan dosage. Although response was not the primary objective of the study, an overall response of 75% was achieved using the criteria established by the Chronic Leukemia-Myeloma Task Force.
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PMID:Interferons in the treatment of multiple myeloma. 380 25

The culture supernatants of Con A-activated human peripheral blood mononuclear cells (PBM) contained at least two regulatory factors upon B cell proliferation. One was B cell growth factor (BCGF), which activated antigen-stimulated B cells to proliferation and clonal expansion, and the other was its inhibitory factor, arbitrarily named B cell growth inhibitory factor (BIF). This BIF inhibited the effect of BCGF on anti-mu-stimulated B cells or the monoclonal mature B cell line (CLL-T.H.) obtained from the peripheral blood lymphocytes of B cell-type chronic lymphocytic leukemia patients, which were activated only with BCGF and without adding other proliferating stimuli (e.g., anti-mu). BIF activity was detected in the 24 hr culture supernatants of Con A-activated human PBM in FCS containing medium and also in serum-free RPMI 1640 medium. This substance with BIF activity could not be derived from FCS. Con A-induced BIF (m.w. of 80,000 and an isoelectric point of pH 5.4) was analyzed by Sephadex G-200 gel filtration and chromatofocusing. BIF was stable at pH 2.0 and at 56 degrees C for 30 min. Partially purified BIF had no effect on cell viability and almost no interferon activity (less than 1 IU/ml). BIF with high titer had a slight but significant inhibition on TCGF-dependent T cell growth and on PHA or Con A responses, but the extent of these inhibitions was far less than that of BCGF-dependent B cell growth. Absorption of BIF with Con A blasts made its inhibition on T cell growth even less. On the other hand, BIF activity could not be absorbed with Con A blasts but was almost absorbed with large numbers of CLL-T.H. cells. BIF had almost no inhibitory effect on the proliferation of a mouse fibroblast cell line (NIH 3T3), a mouse myeloma cell line (NS-1), human lymphoid cell lines (MOLT-4, HSB-2, and Daudi), or a human myeloid cell line (K-562). BIF-producing cells were estimated to be T cells and were identified as T8+ T cells. On the other hand, Con A-induced BCGF was demonstrated to be produced predominantly by T4+ T cells. These results show that human B cell proliferation is regulated by interaction between T4+ and T8+ cells via soluble factors, namely BCGF and BIF, respectively.
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PMID:Identification and characterization of a B cell growth inhibitory factor (BIF) on BCGF-dependent B cell proliferation. 387 Nov 8

A simple and convenient method for efficiently establishing 8-azaguanine-resistant mutant leukemia and myeloma cell lines (for example, the T cell lines Jurkat and CCRF-CEM, human myeloid/macrophage-like cell lines HL60 and U937, Burkitt lymphoma line Raji and the human myeloma line RPMI 8226), is described. The method relies on culturing the cell lines in RPMI 1640 medium containing 8-azaguanine and supplemented with 15% heat-inactivated fetal calf serum and large amounts of amino acids and vitamins, and removes the necessity for pretreatment with mutagenic reagents such as ethyl methylsulfonate or X-irradiation. The possibility of obtaining mutant cell lines using the method described here is about 15 times greater than using media without high levels of amino acids and vitamins. Hybridomas produced between mitogen-activated human peripheral blood lymphocytes and an 8-azaguanine-resistant Jurkat mutant cell line (established by this method) were shown to produce soluble T cell-derived macrophage activating factor (MAF)-like material.
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PMID:A simple method for efficiently establishing 8-azaguanine-resistant mutant human leukemia and myeloma cell lines. 390 63

Two distinct cell lines (OPM-1 and OPM-2) were established from the peripheral blood of a 56-year-old female myeloma patient at the stage of terminal leukemic evolution associated with loss of cytoplasmic immunoglobulin heavy chain (G lambda----lambda). The lines grew in suspension with a doubling time of 36-42 hr and 30-36 hr, respectively. EBNA was absent from both lines. The lines synthesized cytoplasmic lambda-chain, but had no detectable surface immunoglobulins. Fc receptors and complement receptors could not be detected in either line. The lines had very complex chromosomal abnormalities, but the patterns of chromosomes differed greatly between the two lines. The two lines, together with the RPMI 8226 line established by Matsuoka et al. (1967), were analyzed for phenotypic expression as defined by a panel of monoclonal antibodies to B cells (B1, BA-1, BA-2, BA-3, OKIa-1 and OKT10/BMA0100). Neither OPM-1 nor OPM-2 reacted with any of the antibodies tested except OKT10. OPM-1 cells reacted weakly (less than 30%) with OKT10/BMA0100, while OPM-2 cells showed a fluctuating reactivity, ranging from 40 to 80%, with OKT10/BMA0100. In contrast, RPMI 8226 reacted strongly with OKT10 and BA-2. These results demonstrate the presence of phenotypic heterogeneity in all 3 myeloma cell lines, suggesting that the lines might represent different stages of terminal B-cell development.
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PMID:Two distinct human myeloma cell lines originating from one patient with myeloma. 392 60

In this study the exposure period of the lymphocyte-myeloma cell mixture to the fusogen was evaluated for its influence upon the yield of total hybridoma colonies and those which secreted monoclonal antibodies. Sp2/0 and FOX-NY myeloma cells were fused for varying periods with murine splenic lymphocytes immunized with sheep red blood cells. The optimal fusion period consisted of adding the fusogen (5.0 ml Kodak 1450 PEG, 0.5 ml dimethylsulfoxide, and 4.5 ml of phosphate-buffered saline, pH 7.0) to the cell mixture over a 45 s period at 37 degrees C. The fusion process was stopped by gradually diluting the mixture in 50 ml of RPMI-1640. After 10 min, the cells were centrifuged, resuspended in selective medium with feeder macrophages and cultured. In comparison to common, longer fusion techniques, this procedure produces approximately a 5-fold increase in the number of hybrids produced when using the Sp2/0 cells and a 30-fold increase in the number of hybrids produced when using the FOX-NY cells as the fusion partner. In both cases, virtually all the wells contain monoclonal antibody-secreting hybridoma colonies. This high efficiency fusion technique can be used most advantageously to produce monoclonal antibodies against weak immunogens or to reduce the time needed for immunization with stronger immunogens.
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PMID:A short-duration polyethylene glycol fusion technique for increasing production of monoclonal antibody-secreting hybridomas. 402 Jan 50

Female Balb/c mice were immunized with human thyroid stimulating hormone (hTSH). The spleen cells of responding mice were used in a cell fusion with NS1 mouse myeloma cells to define 27 stable anti-hTSH hybridomas. The antibody-secreting cell lines, designated SY/T8/1-6, were characterized and three were found to be completely specific for h-TSH while the other three showed some cross reactivity with LH and hCG. Six of the monoclonal antibodies have been well characterized and their parent hybridomas isolated and banked at -196 degrees C for future studies. The hybridomas have been raised from liquid nitrogen and recultured in RPMI 1640 medium. Progress is being made in the investigation of the growth characteristics of these hybridoma cell lines.
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PMID:Production and growth of hybridomas secreting monoclonal antibodies to human thyroid stimulating hormone. 404 40

Estrogen receptors (ER) and androgen receptors (AR) were determined in a series of 23 leukemia or lymphoma cell lines including 8 T-cell lines, 12 B-cell lines, and 3 non lymphoid cell lines. The phenotypic characterization of these cells by currently available immunological markers provides an estimate of their stage of differentiation. The result indicate that none of the investigated cell lines bear simultaneously ER and AR. Four were found to bear ER: U266, RPMI 8226, HL60, IARC/310/LT2, and four to express AR: RAJI, IARC/301/LTI, U937, REH6. The presence of cytosolic receptors was always associated with that of nuclear receptors. The expression of either ER or AR is restricted to discrete maturation stages of different haemopoietic cell lineages. Thus AR were found among the most immature lines of the T, B or monocytic lineage but they could be detected neither in the promyelocytic line HL60, nor in the pluripotential K562. The present results are in keeping with the demonstration of AR in some leukaemic blasts or in non Hodgkin's lymphomas. In contrast with AR, ER are present in two myeloma cell lines, in the promyelocytic cell line, HL60 and in a T-cell line bearing the phenotype of mature suppressor/cytotoxic T cells.
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PMID:Distribution of androgen and estrogen receptors among lymphoid and haemopoietic cell lines. 407 52


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