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)

Twenty previously treated patients with multiple myeloma were treated with rDNA human alpha-2 interferon (INTRON A) in a phase II trial. Patients received an induction phase of therapy consisting of 3-100 X 10(6) IU/m2 iv given every other day pending myelosuppression. Patients then received 10 X 10(6) IU/m2 three times a week sc. In patients not responding to the iv and sc protocol, prednisone (20 mg orally) was given with each dose of INTRON A to determine whether additional responses could be produced and whether toxicity could be reduced. During the sc phases of therapy, INTRON A was escalated pending hematologic and nonhematologic toxicity. Three partial remissions were achieved in patients receiving the initial iv/sc therapy, and one additional patient responded when prednisone was added (durations of remission, 5, 6, 8, and 9 months). Myelosuppression was the dose-limiting toxic effect in both the iv and sc phases of therapy. Constitutional symptoms (flu-like) were seen in the majority of patients, but were tolerable. With the utilization of prednisone, flu-like symptoms were reduced in frequency and degree. Escalation of the dose of INTRON A was possible in the majority of patients when prednisone was added; however, only one patient (of seven) responded to combination therapy. INTRON A can produce remissions in 20% of patients with previously treated multiple myeloma. No improvement in the response rate was achieved utilizing a high-dose induction program. Although the dose of INTRON A could be escalated when prednisone was added, the response rate was not enhanced.
 ...
PMID:Phase II study of rDNA alpha-2 interferon (INTRON A) in patients with multiple myeloma utilizing an escalating induction phase. 376 70

Six hybrid clones producing monoclonal antibodies (MCA) to influenza A/FMI/47 virus and 9 hybrid clones producing MCA to influenza A/USSR/090/77 virus have been developed. The resulting MCA have been shown to be highly specific for influenza viruses of H1N1 serotype and differentiating H1N1 viruses from H0N1 and H3N2. In 3 out of 11 hybrid clones under study, unique marker chromosomes not occurring in cells of the myeloma parents have been found.
 ...
PMID:[Hybridomas producing monoclonal antibodies to influenza viruses]. 388 55

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
 ...
PMID:The new alpha interferons. 391 Mar 84

A Phase I study of interferon alfa-2a was conducted in 20 patients with disseminated cancer to establish the relationship between dose and interferon-related side effects. Fever was the most common side effect, and was not dose-related. Other side effects not related to dose included flu-like symptoms, gastrointestinal symptoms, and numbness of fingers and toes. A dose-response relationship was seen for leukopenia, thrombocytopenia, and the elevation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). A Phase II study was then conducted in 641 patients to evaluate the efficacy of interferon alfa-2a in a number of disseminated malignant neoplasms. The 415 male and 226 female patients, almost all of whom had malignancies refractory to standard therapy, were treated with interferon alfa-2a at an initial daily dose of 3 X 10(6) U for 3 days. Doses were increased gradually at 3- to 7-day intervals until the therapeutic dosage was established. The daily dose could not exceed 50 X 10(6) U, and treatment was continued for at least one month. Efficacy rates, for 65 patients who achieved partial or complete responses, based on the total number of evaluable patients by cancer type were: 11/49 (22.4%), multiple myeloma; 4/21 (19%), lymphomas; 15/108 (13.8%), renal cell carcinoma; 2/30 (6.6%), bladder cancer; 4/39 (10.2%), brain tumors; 5/26 (19.2%), melanoma; 12/12 (100%), cutaneous lymphoma; 10/19 (52.6%), other skin cancers; 2/30 (6.6%), bone and soft tissue sarcomas. Overall, 65/371 (17.5%) of evaluable subjects responded.
 ...
PMID:Clinical studies of recombinant interferon alfa-2a (Roferon-A) in cancer patients. 394 42

A new human cell surface antigen (Hu Ly-m5) detected by a murine monoclonal antibody (E4.3) is described. The tissue distribution of the Hu Ly-m5 antigen is similar to the HLA antigens (with which it was initially confused) but it is not present on all bone marrow cells nor the U266 myeloma, and is expressed on the HLA-negative K562 cell line. Nevertheless, the Hu Ly-m5 antigen has some affinity for HLA molecules as the two entities cocap and the Hu Ly-m5 antigen copurifies with the HLA antigens on an anti-beta 2-microglobulin immunoabsorbent column; however, the antigen complexes did not withstand the procedures used for coprecipitation. Despite their similarities, the Hu Ly-m5 and HLA antigens are distinct molecular entities--Hu Ly-m5 consists of two bands of apparent molecular weight 69 and 60 K while HLA is comprised of the 43 and 12 K bands of the HLA heavy chain and beta 2-microglobulin, respectively. The function of the Hu Ly-m5 antigen is unknown, but no involvement in the cytotoxic T-lymphocyte response to influenza virus-infected cells could be demonstrated. The two properties described (apparent molecular weight and physical association with the HLA antigens) suggests that the Hu Ly-m5 antigen may be a viral-encoded protein.
 ...
PMID:Hu Ly-m5: a unique antigen physically associated with HLA molecules. 618 9

Hybridomas were prepared by fusion of mouse myeloma cell line Sp2/0 with lymphocytes from mice immunized with avian myeloblastosis virus (AMV). The specificity of each monoclonal antibody was characterized by radioimmunoassay (RIA) using purified viral core proteins, immunoprecipitation of radioactively labeled virus (35S-methionine-labeled AMV, 125J-labeled AMV) and immunoblotting. One monoclonal antibody (IC11) which is of IgG1 subclass, and two other monoclonal antibodies (IF9 and IB8), both of IgG3 subclass, were directed against the p19 protein of AMV. The remaining eight monoclonal antibodies (most of them of IgM class) did not precipitate viral proteins under the experimental conditions used, except IIG12 hybridoma antibody which irregularly precipitated glycoprotein gp85. Since most of them (seven, including IIG12) gave positive reactions in RIA with antigenically unrelated influenza virus, these monoclonal antibodies were directed against virus components specified by chick cells (host cell antigen).
 ...
PMID:Production and characterization of monoclonal antibodies against avian myeloblastosis virus. 631 35

T cells are normally activated when the peptide for which they are specific is presented to them in the context of the appropriate major histocompatibility complex (MHC) (class I and Class II for CD8+ and CD4+ T cells, respectively). An increasing body of evidence indicates that structural homologues of the immunogenic peptide can partially activate or antagonize CD4+ T cells. CD8+ T cells may also be partially antagonized by such peptides, and self-derived peptides of this type may play a role in CD8+ T cell selection in the thymus. Activated CD8+ T cells lyse their targets by perforin-dependent granule exocytosis and by inducing apoptosis mediated by CD95 (also known as Fas or APO1) with its ligand (CD95L). Here we show that a clone of Kd-restricted CD8+ T cells specific for influenza haemagglutinin, which can also be activated in a crossreactive manner by a peptide derived from a myeloma tumour immunoglobulin heavy-chain variable region (IgVH) to kill by both routes, kills only by the CD95-CD95L pathway when stimulated by the corresponding germline IgVH peptide. As this germline IgVH peptide differs from the tumour peptide only at a single position buried in the MHC-binding groove, this indicates that CD95-CD95L-mediated killing can be triggered independently of the perforin-mediated pathway, and can be selectively affected by changes in MHC conformation.
 ...
PMID:Partial activation of CD8+ T cells by a self-derived peptide. 747 51

There are two immunogenic sites on the type A influenza A/Japan/57 (H2N2) hemagglutinin (HA) that can be recognized by class I major histocompatibility complex (MHC), H-2Kd-restricted cytolytic T lymphocytes (CTLs). One of these sites encompasses two distinct partially overlapping epitopes, which span HA residues 204-212 and 210-219. During the analysis of the fine specificity of CTL clones directed to the HA 210-219 epitope, we found that one clone 40-2 also recognized the myeloma cell line P3x63-Ag8. P3x63-Ag8 is derived from the MOPC 21 myeloma and expresses an immunoglobulin (Ig) heavy chain variable region (VH) gene which is a member of the murine 7183 VH gene family. Recognition was specific for the endogenously processed MOPC 21 heavy chain in association with the Kd molecules, since the SP2/0 derivative of P3x63-Ag8, which does not make a functional Ig H chain, is not recognized. The VH epitope recognized by clone 40-2 could be mapped to a 10 amino acid peptide spanning MOPC 21 VH residues 49-58. Cross-reactivity for the VH gene product was also demonstrable in some heterogeneous populations of CTL generated in response to influenza virus infection. These results represent the first demonstration of cross-reactivity for an endogenously processed product of a self-Ig by the CTL directed to a foreign antigen and raise the possibility that the Ig VH expression may regulate the CD8+ T cell response to foreign antigens.
 ...
PMID:Recognition of an immunoglobulin VH epitope by influenza virus-specific class I major histocompatibility complex-restricted cytolytic T lymphocytes. 750 98

We reported a 74-year-old woman with plasmacytoid lymphocytic lymphoma who initially presented with exertional dyspnea, conscious disturbance, ascites, and lytic skull lesions. Protein electrophoresis and immunoelectrophoresis showed monoclonal IgG-lambda gammopathy with IgG level of 13300 mg/dl and marked suppression of the residual normal immunoglobulins. Abdominal computed tomography (CT) revealed a pattern mimicked cancerous peritonitis. She responded to plasmapheresis with much clinical improvement of the hyperviscosity syndrome but died of H. influenza sepsis 3 weeks after diagnosis. The unusual and interesting features of this case included: (1) IgG hyperviscosity syndrome and diffuse peritoneal involvement as the initial manifestations in plasmacytoid lymphocytic lymphoma, and (2) presence of lytic bone lesions in conjunction with high level of M--component and marked suppression of normal residual immunoglobulins in a patient with lymphoma rather than multiple myeloma.
 ...
PMID:Plasmacytoid lymphocytic lymphoma presenting with IgG hyperviscosity syndrome and peritoneal lymphomatosis. 764 Nov 9

Interferon alpha is a biologic agent with demonstrated anti-tumor activity in a variety of hematologic and solid malignancies. Many patients treated with interferon experience acute toxicity manifested as a flu-like syndrome of fever, chills, myalgias, and malaise. However, fatigue, anorexia, bone marrow suppression, nausea, vomiting, dizziness, and confusion may also occur. Cardiotoxicity is a rare complication of interferon therapy that most frequently presents as transient episodes of hypotension and tachycardia, with few significant life-threatening cardiovascular effects reported. A small number of cases of suspected interferon-induced cardiomyopathy, all of which improved after discontinuing interferon, have recently been documented. We report a patient with multiple myeloma who developed severe congestive cardiomyopathy while receiving interferon alpha that did not reverse subsequent to discontinuation of interferon therapy. Although the patient had previously received doxorubicin, the presence on endomyocardial biopsy of a prominent intracellular lipid accumulation within myocytes and only grade 2 anthracycline cardiotoxicity suggested that other or additional factor(s) contributed to the severity of this patient's cardiomyopathy. Etiologies of cardiac dysfunction other than interferon and doxorubicin were excluded. While a direct cause-effect relationship between interferon alpha and irreversible congestive cardiomyopathy cannot be firmly established in this case report, patients who either concurrently or sequentially receive interferon and anthracyclines should be carefully monitored for evidence of cardiac toxicity.
 ...
PMID:Irreversible, severe congestive cardiomyopathy occurring in association with interferon alpha therapy. 771 76


<< Previous 1 2 3 4 5 6 7 Next >>