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)

Interferons (IFN) are potent antiviral, cytostatic-cytotoxic and immunomodulatory agents. Although gene technology has made available an unlimited supply of all different kinds and types of IFN, their basic modes of action have not been clarified up to now. The therapeutic effects proven differ gradually between the individual disease entities. They comprise prophylaxis, prevention of recurrences and direct therapeutic effect, either of reducing the actual disease symptoms, or of inducing a complete recovery. For the following viral diseases a positive therapeutic effect has been shown: infections by herpes-viruses (herpes simplex keratitis , herpes zoster, herpes simplex), cytomegalovirus infections, chronic-hepatitis B virus infection, acute respiratory virus infections by rhino-, corona- and influenza viruses. Especially for the group of virus-associated tumors and papillomas, IFN is considered to be therapeutically effective. IFN has been accepted to be the first line treatment for laryngeal papillomatosis. In condylomata acuminata too, IFN is a potent therapeutic agent. Moreover, IFN represents the most effective therapeutic modality for Kaposi's sarcoma in patient with AIDS. Hairy cell leukemia, malignant lymphoma, multiple myeloma, melanoma and hypernephroma are the malignancies, for which a therapeutic effect of IFN could be proven. Furthermore, IFN is considered to be the therapy of first choice for hairy cell leukemias. Although there are some signs, that IFN could be a potent agent for adjuvant therapy, this question can not be answered - not even on principle - because of lacking sufficient data so far. Up to date, the therapeutic efficacy of IFN seems to be established only for hairy cell leukemia, laryngeal papillomatosis, Kaposi's sarcoma in patients with AIDS and partly for condylomata acuminata. For all other indications, first of all, sufficient phase-II-study data will have to be evaluated, before prospectively controlled studies, comparing the IFN treatment results with placebo and standard therapy results, can be initiated for the individual disease entities. Then, it will be possible to assess the therapeutic efficacy of IFN. Already now, IFN represent a valuable enrichment of the therapeutic modalities for malignancies and viral diseases.
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PMID:[Current status of interferon therapy]. 242 97

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.
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PMID:[Interferon therapy in hematologic neoplasms]. 245 54

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Two monoclonal IgM natural autoantibodies (E7 and D23) obtained from the fusion of normal, nonimmunized, BALB/c mouse spleen cells and nonsecreting myeloma cells were selected on the basis of their polyreactivity with auto- and xenoantigens and chemical haptens. Nucleotide sequence analysis of the variable and constant regions of the heavy and light chains showed the following. (i) The antibodies arise from different genetic elements with very low or no homology--E7 from a heavy-chain variable region (VH) of family 36-60 and kappa light-chain variable region (V kappa) from a group 19--whereas D23 derives from a VH of family Q52 and V kappa derives from group 8. (ii) E7 and D23 are probably of germ-line origin, as suggested by high homology with VH genes from the unrearranged genome. Compared with the germ-line VH 1210.7 gene, E7 has a single nucleotide difference leading to a silent mutation at position 15, whereas D23 seems to be encoded by germ-line VH 101 with one nucleotide difference causing replacement of Ser-84 by Ala. (iii) The genetic V kappa and VH elements for E7 and D23 also give rise to different responses to phenyloxazolone, dinitrophenyl, 5-(dimethylamino)naphthalene-1-sulfonyl, arsonate, phosphocholine, and influenza virus hemagglutinin. Antibodies from normal and autoimmune mice with rheumatoid factor-like activity are also homologous to E7 and D23. These results indicate that polyreactive autoantibodies are encoded by germ-line genes and that, starting with the preimmune poly- and autoreactive repertoire, mutated forms of antibodies recognizing exogenous antigens can be obtained and selected.
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PMID:Two murine natural polyreactive autoantibodies are encoded by nonmutated germ-line genes. 249 87

Peripheral blood leucocytes from a pony previously exposed to equine influenza virus (H3, N8) and vaccinated with killed virus (H3, N8 and H7, N7 subtypes) were cultured in vitro with live A/equine/Prague/56 (H7, N7). On the sixth day of culture, cells were harvested and fused with mouse myeloma cells (X63-Ag8.653). From this fusion, one hemagglutinin specific, equine IgG monoclonal antibody secreting hybridoma was identified and cloned twice by limiting dilution. The antibody inhibited hemagglutination by nine H7 equine influenza virus isolates obtained over a 21-year period, but did not inhibit A/equine/Miami/63 (H3, N8), or A/PR/8/34 (H1, N1). The neutralizing titer of hybridoma induced, nude mouse ascitic fluid was 10(-4.5) when tested in eggs against 100 egg infective doses (EID50) A/equine/Prague/1/56. The hybridoma continued to synthesize antibody during more than 4 months in continuous culture.
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PMID:Production of an equine monoclonal antibody specific for the H7 hemagglutinin of equine influenza virus. 262 95

Interferon-alpha 2b (IFN-alpha) was administered by continuous subcutaneous (s.c.) infusion to 23 patients with hematologic malignancies or metastatic solid tumors: 5 patients with multiple myeloma, 3 with malignant melanoma, 2 with chronic myelogenous leukemia (CML), 10 patients with renal cell cancer, and 3 patients with other solid tumors. Drug was delivered by continuous s.c. infusion for 28 days (1 cycle) at daily dose levels of 0.7, 1.4, 2.5, 3.6, or 5.0 X 10(6) IU/m2 to 3, 3, 3, 8, and 6 patients, respectively. At the highest dose level, a severe flu-like syndrome was seen in 3 patients and severe gastrointestinal toxicity in 2 patients. The maximally tolerated dose (MTD) was 3.6 X 10(6) IU/m2.day and the principal toxicity was a mild to moderate flu-like syndrome. Local skin reactions were occasionally noted at all dose levels if the s.c. needle site was not rotated every 3-4 days. At dose levels of 2.5-3.6 X 10(6) IU/m2.day, IFN-alpha serum levels at steady state ranged from 19 to 61 IU/ml. The time to achieve steady-state conditions ranged from 40 to 72 h and at steady state, 24 h area under the concentration time curve (AUC24 h) ranged from 480 to 1,464 IU/ml.h. Objective responses were seen 3 of 17 evaluable patients: 1/7 in renal cell cancer (14%); 1/2 in CML and in one patient with ependymoma. Remissions lasted 4, 8, and 15 months in renal cell, CML, and ependymoma, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I-II trial of interferon-alpha 2b by continuous subcutaneous infusion over 28 days. 323 Mar 30

Two immunization techniques that enable production of mouse monoclonal antibodies were evaluated in terms of small quantities of antigen. Various amounts of purified influenza A virus particles were applied either for in vitro sensitization in cultured splenocytes or for intrasplenic immunization, followed by hybridization of the immunized cells with mouse myeloma cells. Hybridomas producing specific antibodies for influenza viral proteins were detected by enzyme-linked immunosorbent assay when more than 50 micrograms of antigens was used for the in vitro immunization method, and at least 5 micrograms was necessary for a single intrasplenic immunization. On the other hand, as little as 60 ng of antigen administered in two intrasplenic injections was sufficient to produce specific hybridomas. Two out of six randomly selected monoclonal antibodies obtained using the repeated intrasplenic immunization method were IgG and the other four were IgM. Immunoprecipitation analyses revealed that the recognized antigens involved a viral inner protein (nucleocapsid protein), as well as an envelope glycoprotein (hemagglutinin). We conclude that immunization by two direct injections of antigen into the spleen is the most effective method for sensitization with nanogram quantities of insoluble antigen such as influenza viruses.
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PMID:Effective production of mouse monoclonal antibodies against influenza virus by repeated intrasplenic immunization. 323 22

A mouse-human hybridoma has been produced by fusing human splenocytes from a Cooley's anemia patient with the murine myeloma P3-NS1/1-Ag 4-1. The hybridoma is stable after 18 months and secretes human IgM. The antibody reacts with some H3N2 influenza A strains and detects an epitope that is part of the hemagglutinin antigen, but does not affect virus infectivity.
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PMID:A nonneutralizing human IgM monoclonal antibody inhibiting hemagglutination of H3N2 influenza A strains. 354 6

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.
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PMID:Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 369 41

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44


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