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)

This paper over-viewed the clinical studies on various interferons including HLBI (human lymphoblastoid interferon), HuIFN-beta (human fibroblast interferon) and r-IFN-alpha A (recombinant leukocyte A interferon) which have been tried widely in Japan. These interferons have shown some antitumor effects on various malignancies such as malignant lymphoma, multiple myeloma, renal cell carcinoma, leukemias, brain tumors, malignant melanoma, mycosis fungoides and others. Adverse reactions included fever, general fatigue, leukopenia and thrombocytopenia, and abnormal liver function tests were experienced.
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PMID:[Effects of interferon on various malignancies]. 669 57

Purified blood lymphocytes from 30 patients with myelomatosis were studied. B lymphocytes with sIg were identified by direct IFL after staining with F(ab')2-fragments of antibodies against heavy or light chain specificities. Forty per cent of the patients had B lymphocyte values above the normal range; the median percentage of B cells was 7.25 as compared to 4.5 for control donors (p less tha 0.01). Lymphocytes bearing the light chain isotype of the myeloma protein were selectively increased in 20 of 30 patients suggesting monoclonality. The heavy chain specificities on such lymphocytes were usually that of the serum myeloma globulin sometimes together with mu and/or delta. Tentatively, mu and/or delta carrying monoclonal lymphocytes may represent early precursors to the malignant plasma cells. In patients with IgG myelomas, gamma-bearing blood lymphocytes may be late during maturation. The presence of monoclonal lymphocytes with surface bound gamma chains in untreated patients was associated with unfavourable prognosis.
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PMID:Immunoglobulin isotypes on monoclonal blood lymphocytes in human plasma cell myeloma. 678 49

A hybrid murine myeloma (2-13F5) secreting a monoclonal antibody that specifically bound and neutralized murine interferon beta has been isolated. Affinity chromatography with immobilized 2-13F5 monoclonal antibody of murine IFN (containing both IFN-alpha and IFN-beta) separated an IFN-beta preparation that demonstrated one band with Coomassie Brilliant Blue staining of SDS-PAGE at a molecular weight of 35000 and a specific activity of 4.3 x 10(8) units/mg of protein. This monoclonal antibody neither bound nor neutralized murine IFN-alpha. In addition, it bound only 87% of the interferon demonstrating a molecular weight of 35K. Possible explanations of this partial binding are discussed.
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PMID:Production, screening and characterization of a monoclonal antibody to murine interferon-beta. 682 50

Purified human leukocyte interferon produced by recombinant techniques (IFN-alpha A) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL). The activity of these agents alone or in combination was tested against various human tumor cell lines, using a modified soft agar clonogenic assay. Three human tumor cell lines (myeloma, RPMI 8226; breast, MCF-7; and colon, WiDR) showed sensitivity to these agents at clinically achievable drug concentrations. Statistically significant synergistic activity against in vitro colony formation was observed with the combination of VLB and IFN-alpha A. An additive or sub-additive effect was usually observed with the other agents tested. Continuous exposure of the 8226 myeloma cell line to both IFN-alpha A and PLAT showed evidence of a more significant potentiation. It is hypothesized that the synergistic effect observed between VLB and IFN-alpha A is due to some of their common mechanisms of action.
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PMID:Interactions of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay. 686 Dec 60

The therapeutic potential of six cytokines, eight cytotoxic drugs and two effector cell populations for the treatment of multiple myeloma was assessed in vitro using the 5T33 murine myeloma model. The efficacy of combination IFN-alpha and melphalan therapy was also evaluated in vitro and in vivo. Of the cytokines tested in vitro using the MTT assay, only IFN-alpha demonstrated significant inhibition of myeloma cell growth at non-toxic concentrations (ED50 = 1508.3 +/- 181.3 U/mL and 2617.9 +/- 334.0 U/mL for murine IFN-alpha [mIFN-alpha] and human IFN-alpha hybrid B/D [hIFN-alpha B/D], respectively). The ED50 for the eight cytotoxic drugs tested ranged from 2.3 x 10(-9) to 4.3 x 10(-13) mol/L and all were within the therapeutic range for humans. Combination hIFN-alpha B/D and melphalan were found to be additive in their inhibitory effects on myeloma cell growth in vitro and this finding was confirmed in vivo in C57BL/KaLwRij mice bearing disseminated 5T33 myeloma. Control animals demonstrated a median survival duration of 25.3 days whereas hIFN-alpha B/D or melphalan treatment alone increased survival to 30.5 and 33.3 days, respectively (P < 0.001). Combination IFN-alpha/melphalan therapy increased median survival duration to 38.5 days (P < 0.001) which was also significantly greater than that obtained with single agent therapy (P < 0.01). The murine myeloma cells were found to be resistant to NK cell lysis but susceptible to lysis by LAK cells (49.3 +/- 6.3% lysis at an effector to target ratio of 100:1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of the therapeutic potential of cytokines, cytotoxic drugs and effector cell populations for the treatment of multiple myeloma using the 5T33 murine myeloma model. 749 69

The vav proto-oncogene product (p95vav) is specifically expressed in cells of the hematopoietic system, contains one Src homology 2 and two Src homology 3 domains, and is a substrate for receptor and non-receptor tyrosine kinases. Immunoblotting experiments using an anti-phosphotyrosine monoclonal antibody showed that interferon alpha (IFN alpha) induces rapid tyrosine phosphorylation of p95vav after binding to its cell surface receptor in the U-266 human myeloma cell line. The IFN alpha-induced tyrosine phosphorylation of p95vav was time- and dose-dependent, confirming the specificity of the process. IFN alpha-dependent tyrosine phosphorylation of p95vav was also observed in other hematopoietic cell lines of B-cell origin (Daudi), T-cell origin (MOLT-4), and promyelocytic origin (HL-60). Immunoprecipitation experiments performed with 32P-labeled U-266 cells and phosphoaminoacid analysis of the bands corresponding to p95vav showed that p95vav is phosphorylated on serine residues prior to IFN alpha stimulation of the cells. After IFN alpha stimulation significant amounts of phosphorylation of p95vav on tyrosine residues were detectable. Tyrosine phosphorylation of p95vav in U-266 and HL-60 cells was also induced by two other Type I IFNs, IFN beta and IFN omega. Altogether these data suggest that the vav proto-oncogene product is a substrate for a Type I IFN-regulated tyrosine kinase(s) and may be involved in the signal transduction pathway of Type I IFNs in hematopoietic cells.
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PMID:Interferon alpha induces rapid tyrosine phosphorylation of the vav proto-oncogene product in hematopoietic cells. 750 9

Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to > 1000/mmc and > 50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w. and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.
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PMID:Treatment of multiple myeloma with autologous blood stem cell transplantation. Preliminary results of an Italian multicentric pilot study. 751 17

A 68-year-old man who was admitted to our hospital because of general fatigue and anorexia. He was diagnosed as suffering from neuron specific enolase (NSE)-producing IgD-lambda type multiple myeloma with high activity of serum amylase, based on the detection of monoclonal IgD-lambda M-protein in the serum and urine, markedly high activities of salivary-type amylase and NSE in the serum, and immunohistochemical evidence of NSE and IgD in the myeloma cells. After two courses of alpha-IFN and VMCP chemotherapy, serum IgD, amylase and NSE decreased to normal levels. These observations indicate that NSE was ectopically produced by myeloma cells.
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PMID:[Neuron specific enolase-producing IgD multiple myeloma with high serum amylase activity]. 754 Feb 26

In 1988, a prospective, randomized multicenter study was initiated to determine the efficacy of a combined induction regimen with recombinant interferon-alpha-2b (IFN-alpha) and maintenance with IFN-alpha on the response and survival rates in multiple myeloma (MM) patients. Induction therapy consisted of VMCP (vincristine, melphalan, cyclophosphamide, prednisone), randomized to combine IFN-alpha at a dose of 2 x 10(6) U, 5 days per week throughout the induction period of 12 months. Patients who achieved plateau phase were subsequently randomized again between IFN alpha maintenance (2 x 10(6) U, 3 days a week) for 12 months and no maintenance therapy. Of the previously untreated patients, 84 were initially randomized for induction therapy, and 31 for the maintenance phase with IFN-alpha. Results of the cohort median survival, based on the intention to treat, have shown that those on the VMCP/IFN-alpha arm had a median survival of 53 months, compared with patients on the VMCP induction arm who a median survival of 26 months (P = 0.052). The median survival of stage 3 evaluable patients who were on the VMCP/IFN induction arm was 43 months, and 13 months for patients treated by VMCP alone (P = 0.008). No significant difference in survival was detected among patients in partial remission (after induction) who had a second IFN-alpha randomization at the plateau phase. Hematologic toxicity, mild to moderate fever, and fatigue were more common in the VMCP/IFN induction arm. The results show that VMCP/IFN is a well-tolerated treatment regimen, and is superior to VMCP for patients with stage 3 myeloma.
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PMID:Interferon-alpha-2b with VMCP for induction in multiple myeloma: the Israel Myeloma Cooperative Group experience. 759 91

The effects of interferon-alpha (IFN-alpha) on the interleukin-6 (IL-6) receptor in a multiple myeloma cell line, U266, have been examined. IFN-alpha inhibits [3H]thymidine incorporation in U266 cells in a time- and dose-dependent manner. Furthermore, IFN-alpha inhibits the ability of IL-6 to induce increases in [3H]thymidine incorporation. While IFN-alpha suppresses the ability of 125I-IL-6 to bind to the IL-6 receptor on U266 cells, this effect is not due to competition of IFN-alpha with IL-6 for the IL-6 receptor. Although IFN-alpha induces IL-6 synthesis in the U266 cell, inhibition of IL-6 binding occurs when IL-6 synthesis is minimal. Furthermore, after pretreatment of U266 cells with neutralizing anti-IL-6 antibodies, IFN-alpha still inhibits 125I-IL-6 binding. These data suggest that IFN-alpha inhibition of 125I-IL-6 binding does not involve IL-6 synthesis. IFN-alpha reduces 125I-IL-6 binding without affecting its affinity, suggesting that IFN-alpha inhibits IL-6 receptor expression. Although pretreatment with cycloheximide inhibits 125I-IL-6 binding, IFN-alpha does not cause a selective decrease in the levels of gp130 or IL-6 receptor mRNA at times when 125I-IL-6 binding is inhibited. These observations indicate that IFN-alpha lowers IL-6 receptor density on U266 cells by mechanisms other than competitive binding or lowering IL-6 receptor mRNA production. Receptor down-regulation may be a mechanism of IFN-alpha-induced inhibition of growth in U266 cells.
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PMID:Interferon-alpha down-regulates the interleukin-6 receptor in a human multiple myeloma cell line, U266. 761 53


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