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)

Four patients with myelomatosis (one IgG-chi-type, two IgA-chi, and one Bence Jones-x) were given human leucocyte interferon as the only treatment for from 3 to 19 months. Remission was complete in two patients and partial in the other two. Normal bone-marrow haematopoiesis was slightly inhibited. The disease has not so far progressed in any of the patients.
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PMID:Interferon therapy in myelomatosis. 8 1

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.
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PMID:Interferon therapy in multiple myeloma. 10 25

Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.
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PMID:Modified polyriboinosinic-polyribocytidylic acid complex: sustained interferonemia and its physiological associates in humans. 50 Jan 89

Multiple myeloma can be regarded as model disease for quantification of tumor mass, investigation of tumor cell kinetics and of tumor response to therapy. The quantification of the tumor cell number allows evaluation of prognosis and monitoring of disease as well as of therapy induced responses. Treatment of multiple myeloma is primarily based on the alkylating drugs cyclophosphamide and melphalan. In recent years other cytostatic substances, also effective in the treatment of this disorder have been introduced. However, the sensitivity determination of the individual myeloma stem cells seems to be the only possible method which possibly increases the response rate significantly. In accordance with these considerations we have, in preliminary clinical investigations, observed a good correlation between the in vitro determined cytostatic drug sensitivity and the in vivo response to therapy. Further progress in the treatment of multiple myeloma is to be expected with the introduction of interferon into the therapeutic regimen. Administration of this glycoprotein has resulted in significant reduction of tumor mass in more than half of all patients treated up to this time.
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PMID:[New aspects in the clinical course determination and therapy in multiple myeloma]. 55 24

With the object of examining the anti-tumour effect of exogenous interferon therapy in man a research programme has been initiated at the Karolinska Hospital. Established cell lines obtained from patients with Burkitt's and other types of lymphoma, leukaemia, osteosarcoma, mammary carcinoma and fibrosarcoma and from fibroblast cultures displayed a variable sensitivity to the cell multiplication inhibitory activity of interferon. All the monolayer cultures tested were found to be sensitive to interferon at concentrations between 10 and 300 units/ml. Some lymphoma cell lines were not sensitive to interferon even at concentrations as high as 10.000 units/ml, while others were sensitive at concentrations between 2 and 300 units/ml. The interferons tested appeared to show a degree of tissue specificity. Controlled studies in vivo are being performed on osteosarcoma, juvenile papilloma of the larynx, multiple myeloma and small-cell carcinoma of the lung. The clinical results of this research obtained to date, together with the results obtained in model experiments, would appear to warrant accelerated production of human interferon.
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PMID:Interferon therapy for neoplastic diseases in man in vitro and in vivo studies. 72 40

The clinical application of anticancer cytokines (interferons, interleukin-1, interleukin-2 and tumor necrosis factor) are reviewed. Although anticancer cytokines have confirmed its usefulness against some tumors which are refractory to the treatment using anticancer drugs, the results of clinical trials have generally been disappointing because the target spectrum and efficiency is somewhat limited. Recently, combined efficacy between interferon and anticancer drugs was reported in some malignancies such as multiple myeloma and colorectal carcinoma. For the development of effective combination treatment, we need more basic and clinical information on dose, schedule and sequence of drug administration.
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PMID:[Clinical application of anticancer cytokines]. 127 41

Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents.
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PMID:Current status of interferons in the treatment of cancer. 128 Jan 53

The projected outcome of allogeneic BMT for myeloma based on the EBMT data is as follows: for patients transplanted after first line therapy there is a 30% risk of transplant related death, a 55% chance of being alive at 5 years and a 35% chance of being alive in complete remission at 5 years. If BMT is performed later in the course of the disease, the risk of transplant related death is increased and the chance of long term relapse-free survival correspondingly reduced. Conversely, ABMT has a low mortality risk, but there is currently no evidence that ABMT using unpurged marrow can produce long term cure as no series has shown any evidence of a plateau in remission duration. The early results of maintenance interferon are encouraging but longer follow-up is needed to determine whether the proportion of patients in continuing remission at 5 years will approach that seen after allogeneic BMT. Early results of peripheral blood stem cell transplantation are also encouraging but longer follow-up is required. It remains extremely important when comparing results of ABMT with chemotherapy alone to compare similar patient groups, bearing in mind that patients who have autologous transplantation in first response are by definition responders with good performance status and without significant renal failure. In order to address this problem in a prospective manner, a randomised study has been planned by the EORTC in collaboration with the EBMT. In this study, patients with adequate renal function will be randomised at diagnosis to chemotherapy followed by either autologous BMT or continuing chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The current position of allogeneic and autologous BMT in multiple myeloma. 128 47

Modulation of the expression of P-glycoprotein, a plasma membrane protein associated with multidrug resistance, was examined in drug-sensitive and drug-resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor cells facilitating the uptake of doxorubicin and other tumor-inhibitory antibiotics. P-glycoprotein expression was measured flow cytometrically by the binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562 erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant 8226/DOX40 myeloma cells. Cells were treated for up to 2 h with up to 80 units of leukoregulin/ml or one of a variety of unrelated cytokines including interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating factor, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha-interferon, epidermal growth factor, platelet-derived growth factor AA, platelet-derived growth factor BB, insulin-like growth factor I, insulin-like growth factor II, fibroblast growth factor, or transforming growth factor beta. Leukoregulin caused a concentration-dependent decrease in P-glycoprotein expression; however, P-glycoprotein expression was unaffected by the other cytokines (< 12% decrease in expression). Leukoregulin-induced membrane permeabilization, determined flow cytometrically by intracellular fluorescein efflux, and decreased P-glycoprotein expression occurred simultaneously within 15 min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured flow cytometrically by doxorubicin influx, was also present within 15 min. Leukoregulin enhancement of doxorubicin uptake and increased membrane permeability varied directly with the decrease in P-glycoprotein expression. Leukoregulin in combination with doxorubicin enhanced the inhibition of cell proliferation in 8226/DOX40 multidrug-resistant cells over expressing P-glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant human promyelocytic leukemia cells that do not overexpress P-glycoprotein in association with their multidrug resistance resulted in no greater growth inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone. This is the first demonstration that a naturally occurring macromolecule with anticancer activities can modulate the expression of P-glycoprotein concomitant with enhanced drug uptake and inhibition of cell proliferation.
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PMID:Decreased P-glycoprotein expression in multidrug-sensitive and -resistant human myeloma cells induced by the cytokine leukoregulin. 135 22

In 1992, the Melphalan-Prednisone (M. P.) protocol remains a standard treatment of multiple myeloma even if a lot of new ways have been investigated during the last years. Polychemotherapies may appear better than M.P. for high tumor mass myeloma. Interferon is useful as maintenance treatment after chemotherapy. Combinations of interferon and chemotherapy, during the induction phase, are under evaluation. Because of their toxicity, heavier treatments, with stem cells reinfusion, are being developed mainly with younger patients. Thanks to these approaches the response's rate is increasing but any improvement of survival is still to be demonstrated. Other recent investigations have concerned diphosphonates and immunoregulators. Larger use of these new treatments requires more informations about prognostic factors and their integration in therapeutic strategy of myeloma.
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PMID:[Treatments of multiple myeloma in 1992]. 136 52


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