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)

A dye exclusion method was used for testing the sensitivity of primary human myeloma and normal bone-marrow cells to interferon (IFN). Following 4 days of incubation with 5000 units/ml of natural (n) IFN-alpha, there was a greater than 90% decrease in the number of viable myeloma cells in cultures from some patients, whereas myeloma cells from other patients showed intermediate or no sensitivity to IFN. The number of viable non-malignant bone-marrow cells (from the same patients) following a 4-day exposure to nIFN-alpha (5000 units/ml) decreased by 10-60%. Exposure of malignant and non-malignant bone-marrow cells to natural beta- and recombinant alpha- and gamma-IFN, also induced a decrease in the number of viable cells. The decreased number of viable myeloma cells could be observed already after 1 day of exposure to IFN-alpha in vitro. To test whether inhibition of proliferation could account for the observed effects, proliferation, as measured by [3H]thymidine uptake, was studied in some experiments. Only approx. 1-2% of the myeloma cells were labeled with [3H]thymidine during the 4 days of culture in vitro, whereas the proportion of labeled non-malignant cells was approx. 40%. Thus, the IFN-induced reduction of cell number in normal bone-marrow cells could possibly be attributed to a cell multiplication inhibitory effect of IFN, whereas the effect observed in myeloma cells cannot be attributed to cell multiplication inhibition. To test the possibility that the reduction in the number of myeloma cells could be attributed to the activity of autologous cytotoxic T-cells, NK-cells or macrophages, these cells were depleted in some experiments. Depletion of these cells did not, however, influence the IFN-induced decrease in the number of viable myeloma cells. We thus conclude that IFN can reduce the number of viable tumor cells by a cytotoxic effect, unrelated to cell multiplication inhibition.
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PMID:Interferon exerts a cytotoxic effect on primary human myeloma cells. 314 Nov 98

A discrete subpopulation of lymphocytes sharing several phenotypic characteristics with natural killer (NK) cells was identified within the circulating pool of human lymphocytes that bear the T helper marker Leu-3. This Leu-3+ subpopulation of cells formed cell conjugates with the NK target cell lines K562 and MOLT-4, but did not bind to mouse myeloma and hybridoma cell lines that are insensitive to NK cells. The Leu-3+ lymphocytes binding to NK cell targets contained cytoplasmic granules similar in ultrastructure and cytochemistry to those previously defined in granular lymphocytes with NK function, except that the granules in Leu-3+ cells were smaller and fewer in number. Unlike classical NK cells, however, the granular Leu-3+ cells did not kill the target cells to which they bound, even after treatment with interferon. The proportion of granular Leu-3+ cells with the capacity to bind to NK cell targets was approximately 7% at birth and increased to approximately 21% of the Leu-3+ cells in adults. These observations suggest the possibility of a lineal relationship between the granular Leu-3+ cells and granular Leu-3- cells with NK capability.
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PMID:A large subpopulation of lymphocytes with T helper phenotype (Leu-3/T4+) exhibits the property of binding to NK cell targets and granular lymphocyte morphology. 315 72

The use of murine monoclonal antibodies in the immunotherapy of human disease has prompted interest in the interactions of murine IgG with Fc receptors (FcR) expressed on human effector cells. We examined the heterocytophilic interactions between monomeric murine IgG subclass proteins and the FcR expressed on human monocytic cells (peripheral blood monocytes and interferon (IFN)-gamma-induced U937 cells). All four murine IgG2a antibodies and both murine IgG3 antibodies that were tested bound to human monocyte FcR with high affinity (10(8) to 10(9) M-1). By contrast, the affinities of four murine IgG1 and four IgG2b monomers were 100-fold to 1000-fold lower than the affinity of the human IgG1-FcR interaction. A 68,000 to 72,000 dalton protein was isolated by affinity chromatography from blood monocytes and from IFN-gamma-induced U937 cells on murine IgG2a, IgG3, and human IgG immunoadsorbents. In binding assays with IFN-stimulated U937 cells, murine IgG2a and IgG3 antibodies showed complete cross-blocking with a human IgG1 myeloma protein, indicating that murine and human IgG interact with the same population of Fc-binding proteins. No evidence for heterogeneity of cross-reactive FcR was observed. The ability of murine IgG2a and IgG3 monomers to compete with human IgG1 monomers for binding to human monocyte FcR suggests the potential usefulness of antibodies of these isotypes in the immunotherapy of diseases in which monocyte- or macrophage-mediated, antibody-dependent cellular cytotoxicity may play a role in the modification or remission of disease.
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PMID:The interaction of murine IgG subclass proteins with human monocyte Fc receptors. 315 90

Since 1970, several trials conducted with natural alpha interferon have allowed the recognition of sensitive disorders to this new type of treatment. These studies are ongoing now with recombinant alpha interferons in hairy cell leukaemia, low grade lymphomas, myeloproliferative disorders and myeloma.
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PMID:[Treatment of hematologic diseases with alpha interferon]. 320 95

Almost all patients with multiple myeloma still relapse or become refractory in 2 to 3 years. Interferon (IFN) therapy has clearly influenced the levels of abnormal serum proteins in some patients. A multi-institutional phase II clinical trial used alfa-2b recombinant interferon (Intron A, Schering, Kenilworth, NJ) in 38 evaluable patients with relapsing and refractory multiple myeloma; two thirds of the patient population had received extensive prior treatment. Seven responded, of whom three continued to do so beyond 1 year--one with an ongoing complete remission. An additional 13 had at least a 25% decrease in abnormal paraproteins. Of nine patients who were initially refractory to chemotherapy, two responded to IFN. Of nine relapsing patients returned to chemotherapy following IFN therapy, six then responded. Thirty previously untreated patients with multiple myeloma were treated with IFN followed by melphalan and prednisone; of 24 evaluable patients, 18 responded with a median duration of 10+ months. Alfa-2b IFN apparently does not antagonize melphalan or prednisone, nor does it appear to worsen the response of the two drugs alone. Effectiveness of recombinant alfa-2b IFN in pretreated relapsing patients suggests additional trials are needed to study its effects in previously untreated patients. A significant number of patients who relapsed on their original chemotherapy and subsequent interferon will apparently respond to the reinstitution of chemotherapy.
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PMID:The use of interferon in the treatment of multiple myeloma. 329 11

Both in vitro and in vivo studies have demonstrated antiproliferative effects of interferon alfa-2b (Intron A; Schering-Plough) when tested with human tumor cells. A clonogenic assay has been widely used to determine its direct antiproliferative effects on human tumor cells in vitro using colony reduction as a reproducible endpoint. As a single agent, interferon alfa-2b shows maximum tumor cell colony reduction when used in high concentrations with continuous cell exposure. Short-term exposure to interferon alfa-2b does not produce significant tumor cell colony reduction. Clonogenic assays have also been used to test combinations of interferon alfa-2b with cytotoxic drugs. Variations in drug scheduling, sequencing and concentrations have indicated the best combinations which maximize tumor cell colony reduction. Combinations of interferon alfa-2b with doxorubicin, cisplatin, vinblastine, melphalan and cyclophosphamide have been shown to have at least additive and occasionally synergistic antiproliferative effects. In clinical trials, optimal pairs of agents have been identified frequently combining either doxorubicin, cisplatin or vinblastine with interferon alfa-2b. Pretreatment with interferon alfa-2b has been adopted from in vitro studies and applied to most clinical trials. One study has enrolled 135 patients having a variety of advanced or recurrent solid tumor types, using a schema which combines interferon alfa-2b and doxorubicin administration, both given on a weekly basis for three weeks, followed by treatments every two weeks in responding patients. Clinical responses have been seen using this regimen in patients with ovarian, cervical, colorectal and pancreatic carcinomas and in one lymphoma patient. Another study has been designed combining melphalan, prednisone and interferon alfa-2b for the treatment of patients with relapsing multiple myeloma. This is also based upon preclinical data. New methods of administration are being studied giving interferon alfa-2b as a single agent or in combination with cisplatin by the intraperitoneal route to patients with relapsing ovarian carcinomas limited to the peritoneal cavity. This method can maximize both the levels of interferon alfa-2b as well as the tumor cell exposure time.
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PMID:Overview of preclinical and clinical studies of interferon alfa-2b in combination with cytotoxic drugs. 329 33

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blasts, myeloma colony-forming cells and normal hemopoietic precursor cells have shown that interferon does not specifically inhibit the growth of the malignant cells in culture, i.e. the growth of the malignant and the normal precursor cells are inhibited equally. However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blasts and myeloma cells. This observation suggested that interferon should be tested for its ability to prolong remissions rather than as a remission-inducing agent. We have tested the ability of interferon alfa-2b (Intron A; Schering-Plough) to prolong remissions induced by busulfan in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time (Td) and remission duration on no therapy was compared to the values observed during interferon alfa-2b maintenance therapy. Fourteen patients have been started on study and seven have received interferon alfa-2b for three months or more. All seven have shown slowing of the leukocyte Td and prolongation of the remission duration after interferon alfa-2b therapy. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow or prevent progression of CGL to the blast phase and prolong survival.
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PMID:Interferon alfa-2b in the treatment of chronic granulocytic leukemia. 329 36

Interferon has been reported to have activity in the treatment of multiple myeloma. We studied 24 myeloma patients treated with human lymphoblastoid interferon (Wellferon) by intramuscular injection twice weekly at an initial dose of 3 MU/M2 (three patients) or 15 MU/M2 (21 patients). One of 17 evaluable patients achieved a partial remission, three others were stable over a 16-week period of treatment, and 13 others had progressive disease. Subjective toxicity was frequent and substantial, particularly at the 15 MU dose level. Hematologic toxicity was mild and reversible. Two patients experienced acute renal failure. The low rate of response (6%) and substantial level of toxicity fail to support further exploration of these schedules of interferon as a single agent in myeloma.
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PMID:Phase II study of human lymphoblastoid interferon in patients with multiple myeloma. 339 54

alpha-interferon (alpha-IFN) is a biological response modifier with a dose-dependent activity. The present study on the treatment of patients with multiple myeloma with high doses of natural alpha-IFN was designed to meet this dose-dependent concept. 50 previously untreated patients with IgA and BJ myelomas and a s-Creatinine less than or equal to 200 mumol/l entered the study. Various treatment schedules were tested. The initial plan was to give the patients 30 X 10(6) U alpha-IFN daily. This dosage, however, gave unacceptable toxicity. Step-by-step decreasing dose schedules were given to the patients, 10 X 10(6) U of alpha-IFN daily for 7 consecutive d repeated every 3rd week was found to be the maximal tolerable dose that could be given to most patients. 36% (95% confidence levels: 22%-50%) of the patients responded: 41% of the IgA myelomas and 23% of BJ myelomas. Median time to response was 1.5 months and median response duration was 20 months. Impaired general condition and central nervous system and gastrointestinal-related toxicity were the main adverse reactions. Hematological side-effects were mild.
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PMID:High doses of natural alpha-interferon (alpha-IFN) in the treatment of multiple myeloma--a pilot study from the Myeloma Group of Central Sweden (MGCS). 341 7

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blast cells, myeloma colony-forming cells, and normal hemopoietic precursor cells have demonstrated that interferon shows no specificity in inhibiting the growth of these cells in culture (ie, growth of the malignant and normal precursor cells is equally inhibited). However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blast cells and myeloma cells. This observation suggested that interferon's ability to prolong rather than induce remissions should be tested. We have studied the ability of interferon alfa-2b (Intron A) to prolong remissions induced by busulfan (Myleran) in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time and remission duration among patients receiving no therapy was compared with the values observed during interferon alfa-2b maintenance therapy. Nine patients have begun the study; five have completed 3 months of interferon alfa-2b therapy. In four (80%) of the five patients, there has been a significant slowing of the leukocyte doubling time and prolongation of the remission duration. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow progression of CGL to the blast phase and prolong survival.
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PMID:Interferon alfa-2b in the treatment of chronic granulocytic leukemia. 346 99


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